Evaluation of single oral dose metyrapone tests in children with hypopituitarism. Evaluation of single-dose metyrapone tests in children with hypopituitarism; comparison with the prolonged metyrapone and insulin induced hypoglycaemia tests and their relationship with the etiology of hypopituitarism. Acta Paediatr Scand, 65:177, 1976.--Pituitary-adrenal reserve was evaluated in control and hypopituitary subjects by comparing the 8 a.m. plasma 11-deoxycorticoid response (11-DOCS) to a single midnight oral dose of metyrapone (short test) with 1) the 8 a.m. 11-DOCS increase under repeated oral doses of metyrapone (prolonged test) and 2) with the plasma corticoid response during arginine-insulin test. In the short and the prolonged metyrapone tests, the same response was obtained in 25 out of 27 patients. The short test was repeated in 22 patients and the 11-DOCS response did not show a significant difference. In 34 of 40 patients, the response to the short test was comparable to the response during the arginine-insulin test; only 3 patients with a normal 11-DOCS rise to the short test had a low response to insulin and vice versa. Among the low responders to the short test, the mean 11-DOCS value was significantly lower in subjects with operated craniopharyngiomas than in idiopathic hypopituitary patients (p less than 0.001). In the short test, the 8 a.m. baseline cortisol value was positively correlated with the 8 a.m. 11-DOCS response (p less than 0.001), the cortisol level allowing to predict the 11-DOCS response in 28 out of 53 patients. Thus, the short oral metyrapone stimulation was found to be a reliable test in hypopituitary children.


Hypohistidinemia in juvenile rheumatoid arthritis. The mean level of plasma histidine in 86 children with rheumatoid arthritis was found to be significantly lower in comparison with that of controls. The possible influence of various drugs on the plasma histidine concentration is discussed.


Health screening of four-year-olds in a Swedish county. III. Variation of effectiveness among examining teams. The data gathered in connection with a routine health screening program for 4-year-olds were used in order to test a number of hypotheses concerning factors which might have influenced the effectiveness of the program, as well as concerning the quality of preventive care delivered to the children before the age of 4 years. It was found that preventive care of relatively high quality delivered to children 0-3 years of age had not reduced the prevalence of previously undetected health problems at 4 years of age. Furthermore, the analysis demonstrated substantial differences between physicians in the rates of correct and unnecessary referrals. Only a small part of these differences could be attributed to professional status or specific experience with the program. They consisted essentially in varying thresholds for what was perceived as a health problem needing treatment, and were considered as a matter of personal temperament. True differences of quality did occur but were less prominent. The implications of these findings with regard to the continuation of the program are discussed.


Cerebellar-ataxic syndrome in children and adolescents with hypothyroidism under treatment. Animal experiments and observations on quantitative growth of human cerebellum suggest a critical period when its development is particularly vulnerable to hypothyroidism. Sixty-seven patients aged 7-24 years with hypothyroidism under long-term treatment were examined for ataxic symptoms. These were found in 24 of 39 patients (60%) hypothyroid before or during the third month of life. Only 4 of 18 patients (20%) hypothyroid later had cerebellar symptoms. Such symptoms could be evidence for the onset of hypothyroidism before or during the 3rd month of life. Seventeen (80%) of mentally retarded patients had cerebellar symptoms compared with 11 (30%) of 45 attending normal school. Even retrospectively, these data might permit a more accurate prognosis of further mental development in hypothyroid children.


A case of impaired chemotaxis and lymphocyte transformation. The report describes the clinical syndroms of a 14-year-old boy which suffered from recurrent infections since early infancy. The clinical and general laboratory findings were similar to "the granulomatous disease of childhood" as described by Bridges et al. (8). The following serum factors were determined: Immunoglobulins, complement factors, isoagglutinins. The following assays with normal or patient's granulocytes were done: Chemotactic activity, nitroblue-tetrazolium test, bactericidal assay, fungicidal assay, myeloperoxidase, monocytes fungicidal assay. Immunological studies include kinetics of phytohaemagglutinin response, effect of serum of the patient on lymphocytic reactivity in vitro and skin tests. The following results were obtained: 1) Assays with normal or patient's granulocytes showed an impaired chemotatic activity, when serum of the patient was added. There was strong indication by treatment of the patient with plasma infusions, that the chemotactic defect is a serum dependent factor. 2) It could be demonstrated that the patient's serum also inhibited the response of lymphocytes to tuberculin and phytohaemagglutinin. Therefore the patient report focuses attention upon the possibility of serum related abnormalities that may influence granulocytic as well as lymphocytic functions leading to recurrent bacterial, fungal and viral infections.


Massive chronic feto-maternal bleeding associated with placental chorioangiomas. After pregnancy complicated by polyhydramnios and the antenatal discovery of a very large placenta a newborn infant suffered from anemia, thrombocytopenia and hypoproteinemic edema, and was successfully treated by exchange transfusion. The placenta contained two chorioangiomas and there was diffuse placental hypertrophy with edema and patchy chorioangiomatosis. There was evidence of major chronic feto-maternal bleeding which could be the explanation for most of the hematological and biochemical problems which occurred. The child was developing normally at subsequent follow-up aged 15 weeks.


Acid activation of renin in rabbit uterus. During the first 2 days post-partum there is a rapid fall in the uterine renin content of the rabbit. A similar loss of renin can be reproduced in vitro when pregnant and post-partum and to a lesser degree non-pregnant uterine tissue slices are incubated at pH 7.4 at 37 degrees C. When a secondary incubation of these previously incubated preparations is performed at pH 4.8 an activation of renin is seen. There was not an inverse correlation between the amounts of renin lost during the primary incubation at pH 7.4 and the amounts of renin activated during the secondary incubation at pH 4.8. In similarly incubated preparations of kidney cortex, where only a small per cent of the initial renin content is lost during the primary incubation at pH 7.4, no activatable renin is seen.


The extent of carcinoma in situ in urinary bladders with primary carcinomas. The occurrence of carcinoma in situ was examined in a consequtive series of cystectomy specimens from 43 patients. All patients were suffering from or had been suffering from primary bladder cancer. Carcinoma in situ was defined as a definitive polymorphia of enlarged nuclei with abnormal chromatin structure in non-tumour bearing areas. It was found in 26 bladders. By means of a systematic technique of cutting the specimens, the extent of the alterations was quantitied, relating the number of blocks containing the alteration to the total number of blocks in which the changes possibly might be present. The extent of carcinoma in situ ranged from 2 to 81% with an average of 20%. The distribution of the alterations was unpredictable, often strongly focal, most often in continuation of the tumour. In one specimen, the margins of resection were involved. The extent was largest in bladders with poorly differentiated tumours. A temporal relationship between in situ carcinoma and invasive carcinoma could not be shown, as regards tumour size and duration of clinical symptoms. The morphology of the changes is discussed seen in the light of variations in the normal epithelium lining the lower urinary tract. Minor degrees of atypia of the epithelium showed rather bad reproduction. The dominating occurrence of carcinoma in situ in bladders with poorly differentiated tumours may either be a manifestation of a biological difference between tumours of different grades of differentiation or that the morphological criteria used correspond to the in situ type of poorly differentiated tumours.


Types of metaplasia in forty urothelial bladder carcinomas. A systematic histological investigation. In a systematic study of bladders from consecutively cystectomized patients, 40 primary urinary bladder carcinomas were examined with regard to the type of differentiation. Metaplastic areas were found in 24 of the tumours. A positive reaction of keratin to Kreybergs stain was required for the definition squamous metaplasia. Squamous areas were found in 16 of the tumours. In 4 tumours there was, in addition to squamos metaplasia, glandular metaplasia which was defined as definite glandular tissue with dysplasia of the epithelium. In 4 tumours, glandular metaplasia was also present in addition to the urothelial carcinoma. In 18 cases, metaplastic changes were present in the luminal portion of the tumour from which the biopsy material and desquaminated material originated. The occurrence of metaplasia was related to the degree of differentiation of the urothelial part of the tumour. Metaplastic changes were most frequent in the poorly differentiated tumours. The biopsies obtained pre-operatively permitted of the diagnosis metaplasia being made in 15 cases, while the cytological material suggested metaplastic changes in 4 cases only. The biological function of metaplasia is unknow. The possibility that these areas will react differently to radiation and chemotherapy is present and the frequency of such changes would suggest that their importance should be studied by their registration as mixed forms as stated by WHO.


Correlation of enzyme histochemical and structural segmentation in the proximal convoluted tubule of the rat kidney. Enzyme activity compared to the freeze-dried structure of serial-sectioned normal rat nephrons. In the normal rat kidney enzyme histochemical activity was correlated with the structural segmentation of the convoluted part of the proximal tubule, as seen in freeze-dried sections. Serial sections were employed for alternate morphological and enzyme histochemical studies. The tubules were investigated for activity of the following enzymes: 1) non-specific acid phosphatases, 2) non-specific alkaline phosphatases, 3) succinate dehydrogenase and 4) non-specific esterases. Close to the urinary pole acid phosphatase activity was slight in all instances, whilst in the first and second segment a gradual increase in tubular cells with heavy enzyme activity was seen. All tubular cells at the urinary pole showed heavy alkaline phosphatase activity, but there was a gradual increase of cells showing slight enzyme activity in the first and second segments. Succinate dehydrogenase activity was constantly heavy at the urinary pole, and there was a gradual decrease in these cells with heavy enzyme activity along the course of the first and second segments. The pattern of tubular enzyme activity for these three enzymes  was independent of the nephron level in the renal cortex. The non-specific esterase activity was, in comparison, uniform throughout the length of the proximal tubule in nephrons from all levels of the renal cortex. This combined enzyme histochemical and morphological investigation demonstrates conclusively that there is a close correlation between structural segmentation and the pattern of enzyme activity of non-specific acid and alkaline phosphatases and succinate dehydrogenase in the proximal convoluted tubule of normal rat kidney.


Atypical fibroxanthoma of the skin. A clinico-pathological study of 57 cases. A retrospective study of 57 patients with atypical fibroxanthoma of the skin is presented. The light microscopy is described and the differential diagnosis is discussed. Most of the atypical fibroxanthomas (32 out of 57 cases) were originally diagnosed as soft tissue sarcomas, e.g. fibrosarcoma, dermatofibrosarcoma, neurofibrosarcoma, myosarcoma and unspecified sarcoma. The tumour occurred chiefly in middle-aged and elderly patients; three patients were 15 years old or younger. The median age was 73 years in patients in whom the tumour occurred in the head and neck, and 34 years in patients in whom the tumour developed on the extremities and trunk. The sex ratio (male to female) was almost equal. Follow-up information about 43 patients was available. The follow-up period ranged from 1 year to 25 years with a median of 9 years. Eight patients died from intercurrent disease; all the other 35 patients are alive and well. The clinical course was benign in all but one patient in whom a recurrence developed and metastases to the regional lymph nodes appeared 7 years after the initial excision. The tumour in this case did not differ histologically from the other atypical fibroxanthomas with respect to cellularity, cellular and nuclear atypia or mitotic activity. It is suggested that the recurrence per se might be of prognostic importance.


Cytoplasmic effects of x-irradiation on cultured cells in a nondividing stage. 1. Establishment of an experimental model. The investigation was initiated with the aim of establishing a suitable experimental model with respect to mode of radiation and radiation dose for elucidating morphologically the sequential development of radiation induced damage of interphase cells (human glia cells in vitro). Adequately defined and reproducible cellular changes were obtained using X-radiation generated by an 8 MeV linear accelerator at a dose of 20,000 rad. The cellular alterations were studied in the light microscope and by scanning and transmission electron microscopy. The most conspicuous changes--first appreciable about 5 hours after irradiation--occurred in the lysosomal vacuome, and the plasma membrane and associated structures.


Experimental avian nephropathy. Changes of renal function and structure induced by ochratoxin A-contaminated feed. One-day-old chickens were fed ochratoxin A-contaminated diets at 2 levels: 0.3 and 1 mg ochratoxin A per kg feed, for 341 days. The only observable lesion to develop was a kidney damage comparable with the naturally occurring avian nephropathy. The changes in renal function were characterized by impairment of glomerular and tubular function, indicated by a decreased inulin clearance, TmPAH and decreased urine concentrating capacity. The changes of renal structure included degeneration of the tubular epithelium accompanied by regeneration. At slaughter, the kidneys, liver and muscular tissue of the birds contained residues of ochratoxin A (up to 50 mug per kg). As all the birds would have passed the meat inspection because no macroscopical lesions were present, this represents a possible health problem.


Sex differences in renal damage induced in the rat by the Finnish mushroom, Cortinarius speciosissimus. The sensitivity of male and female rats to Cortinarius speciosissimus toxins was compared. Dried, homogenized mushroom was given orally by stomach tubing at a dose of 250 mg dried mushroom/kg body weight. Both in males and in females, the kidneys were the only organs showing macroscopical changes. Sex differences in renal damage were observed in the area of the inner cortex.


Formation and action of prostaglandin endoperoxides in the isolated human umbilical artery. The effects on the isolated human umbilical artery (HUA) of the recently isolated endoperoxide intermediates in prostaglandin (PG) biosynthesis, PGG2 and PGH2, were studied. Both endoperoxides were potent contractors of the artery strips, the threshold concentrations being 3 (1-4) ng/ml for PGG2 and 1 (1-12) ng/ml for PGH2, as compared with 200 (40-400) ng/ml for PGE2. The hemiacetal derivative of 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (thromboxane B2), a metabolite of PGG2, appeared in the bath medium indicating PG and thromboxane generation in the isolated HUA. The formation of thromboxane B2 was inhibited by indomethacin (8-40 mug/ml) and by eicosa-5,8,11,14-tetraynoic acid (ETA) (25 mug/ml), ETA also inhibited the contractile responses to both endoperoxides. The results support the view that local generation of PGs might be involved in the closure of the HUA at birth.


A method for preparing isolated glands from the rabbit gastric mucosa. A method for isolating gastric glands from the corpus of the rabbit gastric mucosa is presented. The stomach of an anesthetized rabbit was perfused with saline under high pressure through the aorta, taken out and emptied. The mucosa was stripped off, minced into small pieces and transferred to a 1 mg/ml collagenase solution. After 90 min at 37 degrees C, a large number of isolated gastric glands and cells were separated free. By a simple washing procedure the glands were freed from cell contamination and collagenase. The gastric glands were viable, as demonstrated by dye exclusion technique, oxygen consumption and electrolyte content. For identification of the glandular cells both common staining techniques and electron microscopy were used. Four types of cells were identified, viz. parietal cells, zymogen cells, mucous neck cells and some endocrine cells. The intracellular morphology of the glandular cells did not differ significantly from that seen in intact gastric mucosa. The glands could be stimulated with histamine, in a dose-response manner, as revealed by the increase in oxygen consumption (ED-50 equal 3 X 10(-6) M). This isolated gastric gland preparation may serve as a useful tool for new approaches in gastric physiology.


Convergence on interneurones mediating the reciprocal Ia inhibition of motoneurones. I. Disynaptic Ia inhibition of Ia inhibitory interneurones. Interneurones identified as mediating the disynaptic reciprocal Ia inhibition of motoneurones (referred to as "Ia inhibitory interneurones") were recorded in the lumbar spinal cord of the cat. It was revealed that the Ia inhibitory interneurones themselves receive disynaptic Ia inhibition. The muscles from which this inhibition is evoked are strictly antagonistic to those supplying their Ia excitation. Similar to the Ia inhibition in motoneurones the Ia inhibition in the Ia inhibitory interneurones is decreased when preceded by an antidromic stimulation of ventral roots. Furthermore, transmission of Ia inhibition to the Ia inhibitory interneurones is facilitated from ipsilateral and contralateral primary afferents as well as several supraspinal pathways analogous to earlier findings for the Ia inhibition of motoneurones. The pattern and control of the Ia inhibition of motoneurones and of Ia inhibitory interneurones display so striking similarities that it is suggested that identical interneurones are responsible. The conclusion thus emerges that "opposite" Ia inhibitory interneurones (i.e. interneurones monosynaptically connected to antagonistic muscles) are mutually inhibiting each other. The functional significance of this organization is discussed.


Towards a valid technique of sampling fish muscle to determine redox substrates. The redox substrates--lactate, malate, alpha-glycerophosphate, dihydroxy acetonephosphate and pyruvate--have been determined in liver and muscle tissue from young salmon. The redox quotients have also been calculated. The freeze clamping technique was used and reliable samples of fish muscle for the determination of lactate were obtained with the aid of a pair of pliers with a gear mechanism. It was established that the lactate content in the body muscle is in close agreement with that in the blood from rested salmon parr. The concentrations of redox substrates are in good agreement with those found in mammalian tissue. The determination of the content of glycogen in fish muscle is discussed in the light of the results obtained in this study.


Regional distribution of blood flow in calf muscles of rat during passive stretch and sustained contraction. The regional distribution and number of microspheres in the calf muscles of rat has been studied during isometric sustained contraction and in stretched uncontracted muscles in situ. Carbonized microspheres, 15 +/- 5 mum, were injected into the aortic arch and muscle blood flow arrested 6 sec later. The calf muscles were freeze sectioned (12 slices of 40 mum) and the microspheres counted microscopically. The microsphere concentration in the gastrocnemius and plantaris muscles during rest was 4.6 +/- 1.6 spheres/mm3 (mean +/- S.E.). One min after a standardized exercise programme the sphere concentration was increased to 20.5 +/- 3.9 spheres/mm3. At increasing force of contraction following the standard exercise programme, the microsphere concentration fell from 11.6 +/- 2.5 at 25% of maximal force of contraction (MFC) to 2.2 +/- 0.6 spheres/mm3 at 100% MFC (5.6 kg/cm2). Corresponding measurements in stretched, uncontracted muscles showed a similar fall in microsphere concentration in the central inner zone and in the peripheral outer zone was slightly higher than unity (1.08-1.16) in muscles at rest and at light postexercise hyperemia. At 75 and 100% MFC the ratio was 0.76 +/- 0.07 and 0.57 +/- 0.13, significantly lower than unity. Stretching of the uncontracted muscle group to 175% MFC reduced the ratio towards zero. The greater reduction in blood flow to the inner central zone of contracted calf muscles shown by microsphere distribution was confirmed by measurement of 125 I-antipyrine distribution. These results show an increased resistance against blood flow during active contraction or stretching of the calf muscles, most pronounced in the central inner zone at high tensions.


Signal characteristics of EMG at different levels of muscle tension. Electromyographic activity of m. rectus femoris at submaximal and maximal voluntary contractions was quantified by conventional integration technique and also be a more "qualitative" procedure of automated motor unit averaging and frequency spectrum analysis. By relating the EMG parameters to produced muscle tension it was observed that the integrated EMG increased in a slightly nonlinear fashion with the increase in muscle force. The other EMG variables also showed clear changes as a function of muscle tension. The averaged motor unit potential (AMUP) and its specific parameters (number of spikes, amplitude, rise time and amplitude-rise time ratio) showed such changes with muscle tension that they may be useful in estimation of the recruitment pattern of the different types of motor units.


Myocardial blood flow in the diving seal. Grey seals exhibit a marked drop in heart rate, a slight decrease in ventricular contractility, and an essentially unchanged stroke volume upon diving. In the present study, we have demonstrated that the resulting drop in cardiac output is associated with a 90% reduction of coronary blood flow. Such reduction of myocardial blood flow takes place despite a significant increase in effective coronary driving pressure, and is indicative of a 800% increase in coronary vascular resistance. This means that the circulatory adjustments displayed by the diving seal (i.e. a reduction of the workload on the heart) are so effective that myocardial blood flow can be reduced to 10% of the pre-dive value without loss of cardiac function and blood pressure. It is suggested that even partial simulation of such a circulatory state might be a successful approach in the treatment of ischemic injuries in the heart of man.


Bacteriological and clinical evaluation of different dialysate delivery systems. In the period 1964-74 four different dialysate delivery systems have been used in our department. 1) Central mixing of dialysate using tap water and a dialysate delivery line with "dead ends" resulting in stagnant dialysate. 2) Central mixing of dialysate with cold distilled water, otherwise equal to system 1. 3) Local mixing of dialysate with cold distilled water, delivered through a line with "dead ends" resulting in stagnant water. 4) Local mixing of dialysate with distilled water, cooled to 25 degrees C just prior to use, reduced "dead ends" and monitored constant overflow to drain through the water supply line. The bacterial contamination of the four systems was examined and related to the clinical occurrence of pyrogenic and other reactions. An improvement was noted with the change from central to local mixing of dialysate (system 3) but complete sterility and virtual freedom from clinical reactions were first obtained in system 4. It is concluded that the use of sterile or near sterile dialysate is recommendable.


Survival after portacaval shunt: who and how? In a series of 74 portacaval-shunted patients no statistically significant differences in long-term survival or in incidence of postoperative encephalopathy have been observed between electively and emergency operated patients, between patients with slight and moderate impairment of liver function (groups A and B according to Child) or between patients with alcoholic and non-alcoholic cirrhosis. Patients older than 60 years had a higher risk of postoperative encephalopathy and a border-line significantly lower survival rate six months after the operation. Among the patients with more than six months' survival, about 50% returned to work.


Peripheral circulation, particularly heat regulation reactions, in patients with amyloidosis and polyneuropathy. As patients with amyloidosis and polyneuropathy often have signs and symptoms of circulatory disturbances in the extremities, especially the legs, we have examined such patients and controls with oscillometry and digital pulse plethysmography in order to estimate the occurrence of any arterial circulatory insufficiency. No signs of significant obliterative arterial changes were found. Skin temperature was also determined in fingers and toes during body-cooling and at subsequent indirect heating. At low environmental temperature the skin temperature was higher in  patients than in controls. In a few patients there was almost no decrease in skin temperature, despite a long period of cooling and a low rectal temperature. Indirect heating elicited a marked increase in the skin temperature of the toes and fingers of the controls. In most patients this reaction  was completely absent in the toes and absent or reduced in the fingers. These deviations can be explained by nerve damage caused by amyloid deposition in the nerves. Amyloid deposits in the wall of small blood vessels may be an additional factor. Maximum blood flow in the anterior tibial muscle after combined ischemia and exercise, investigated with radioactive xenon, was reduced in half of the patients.


Skin lesions of the legs and feet and skeletal lesions of the feet in familail amyloidosis with polyneuropathy. Twenty-one patients with familial amyloidosis and polyneuropathy have been examined for the presence of skin lesions, localized to the lower legs and feet. The lesions were classified as atrophic skin lesions, hypertrophic scar-like skin lesions, rubeosis plantarum, spontaneous blisters, necrotic skin lesions, yellow nails, traumatic skin lesions, purpura and abundant pigmented small non-atrophic spots. Skeletal destructions in the feet were also demonstrated. In many respects these lesions are similar to those of long-standing diabetes mellitus. I studied the cutaneous reactions to local thermal trauma with heat and cold to the legs and forearms in 11 patients. Petechiae were observed within the area of traumatization with either heat or cold more often in patients than in controls. Four of the 11 patients developed atrophic circumscribed skin lesions at the site of traumatization.


Purpura, pigmentation and yellow nails of the lower extremities in diabetics. This article describes purpura and pigmentations of the lower extremities as well as yellow nails mainly in elderly diabetics but also in persons not known to have diabetes. When the latter were compared to controls, it appeared that their glucose tolerance was altered in a diabetic direction. Precipitating factors could generally be established for these lesions, predominantly cardiac decompensation with edema of the legs, and were more common  in patients not known to have open diabetes than in  patients with open diabetes. Petechiae were transformed into small, pigmented, non-atrophic spots. Petechiae and pigmented spots were often seen simultaneously. In a few patients small, pigmented, non-atrophic spots were seen as pronounced brown-black pigmentation of the lower legs and feet. In a number of patients with open diabetes or diabetic glucose tolerance, erysipelas with purpura within the area of erysipelas was observed on the lower extremities. Patients with no purpura within the area of erysipelas generally had normal glucose tolerance. The pathogenesis of these lesions is discussed. Atrophic circumscribed skin lesions (Melin), cutaneous erythema, with or without necrosis, purpura, pigmentation, red toes, as well as rubeosis plantarum, yellow nails and neuropathy are often seen simultaneously on the lower extremities of patients with open diabetes as well as of those without open diabetes but with diabetic glucose tolerance.


Sarcoidosis. A clinical study with special reference to the choice of biopsy procedure. In a 10-year review of the records of 146 young male patients suspected of sarcoidosis on the basis of radiographic intrathoracic changes, the chest X-ray findings have been analysed in relation to the results of different biopsies. Most of the patients were military men, and almost all were apparently affected by the disease. Sixty-six per cent had bilateral hilar lymphadenopathy (BHL) only, 12% had isolated pulmonary lesions and 22% had both BHL and pulmonary lesions. In all patients at least one biopsy was performed, in most cases a scalene fat pad biopsy and/or a liver biopsy. Epitheloid cell granulomas were demonstrated in 86 biopsies from 64 of the 146 patients. Granulomas were obtained more frequently by scalene fat pad biopsies than by liver biopsies in the same group of patients. During the first 4--5 years of the 10-year period the scalene fat pad biopsies were done in local anesthesia in different general surgical departments without special experience of this biopsy procedure. In the last 5--6 years the scalene fat pad biopsies were done in general anaesthesia in a head and neck surgical department specially trained in this biopsy technique. Granulomas were obtained more frequently in the latter than in the former group. The highest frequency of granulomas was found among patients with both BHL and pulmonary lesions. Of the 71 patients in whom liver biopsy was performed, 43% had granulomas in the liver. A few patients had signs--although only slight--of liver affection. The results of the different biopsies are discussed in relation to the clinical picture. It is concluded that scalene fat pad biopsy in some cases can still be of some diagnostic aid in patients with radiographic intrathoracic changes suspected of sarcoidosis, although this type of biopsy has to a great extent been replaced by biopsy through mediastinoscopy. Furthermore it is concluded that comparison of different biopsies in one and the same patient could elucidate a possible relationship between the radiographic intrathoracic manifestations and the occurrence of granulomas in different intra- and extra-thoracic tissues. In this study there were only few and insignificant complications of the biopsies.


Vectorcardiographic-hemodynamic correlations in adult aortic stenosis. Thirty-nine vectorcardiographic (VCG) data from 45 patients with pure adult aortic stenosis have been tested as to their ability to reflect quantitatively the peak systolic left ventricular pressure (LVPSP), the left ventricular end diastolic pressure (LVEDP), and the X-ray estimated heart volume. VCG was recorded with the axial lead system and simple and multiple linear regression analyses were applied. Eight VCG data correlated significantly (p less than 0.001) with LVPSP, the best indicator being the maximum posterior dislocation in the Z lead (r = 0.65). Through multiple regression analysis a formula was derived which gave a correlation coefficient between observed and calculated pressures of 0.82. The best indicator of LVEDP was the maximum positive P amplitude in the X lead (r = 0.41). The relationship was, however, too poor to have practical significance. A good correlation was found between ST segment dislocation and heart volume (r = 0.65), in good accordance with previous observations as to the effect of right ventricular dilatation on the ECG. The study illustrates how ventricular volume and pressure exert different effects on the ECG, and how all the important hemodynamic aspects in aortic stenosis to some degree are reflected. Only the pressure correlations have, however, practical importance.


A nitrofurantoin-induced disorder simulating chronic active hepatitis. A case report. A 78-year-old woman with liver damage resembling chronic active hepatitis and occuring during long-term nitrofurantoin treatment is described. On admission to hospital she displayed jaundice, ascites and high serum levels of GOT, GPT, bilirubin and gamma-globulin as well as high titres of ANF and antibodies against smooth muscle cells. After withdrawal of nitrofurantoin the clinical and laboratory picture normalized without corticosteroid treatment, suggesting that the liver reaction was drug-induced.


Factors controlling growth and age involution of the rat thymus. Thymic development and somatic growth were investigated in three strains of rat. The well established influence of sex and age on somatic growth was confirmed. It was also found that the rate of thymic growth was not influenced by the sex of the animal until four weeks of age, but thereafter, the thymus grew faster in males compared with females of the same strain. Gonadectomy had a marked effect on the thymus, resulting in a higher rate of growth than in normal animals; but a slower initial rate of involution. The maximum thymus weights attained in gonadectomized animals were found to be independent of the age at which the animals were gonadectomized or of the sex of the animal. Gonadectomy did not influence the point at which involution began. Thymic mitotic indices of gonadectomized animals were found to be higher than those of normal animals. The influence of sex hormones on somatic growth and the development of the thymus is discussed, and it is concluded that cell loss is the regulator of thumus growth and involution.


Red-blood-cell potassium as a practical index of potassium status in elderly patients. Red-blood-cell potassium has been measured using a simplified technique on 292 geriatric patients. The measurement was found useful in reflecting changes in potassium status whereas serum potassium was unhelpful.


Hypoglycaemic coma due to chlorpropamide: observations on twenty-two patients. Twenty-two patients with chlorpropamide-induced hypoglycaemic coma were seen at a medical centre serving a region with a large geriatric population. The median age of the patients was 72; seven were over 80 and only one was under 60. Four patients died and in three of them death appeared to be connected with the hypoglycaemia. In two cases, the hypoglycaemia appeared in the postoperative period. Generally accepted contra-indications to the use of chlorpropamide were present in five of the eight patients under 70 and in four of the 14 patients over 70. If full precautions had been taken in presecribing chlorpropamide and if old age had been regarded as a contra-indication, the hypoglycaemia might have been prevented in 19 out of the 22 patients.


The problems of motor neurone disease.

The problems of motor neurone disease. The course of Motor Neurone Disease (MND) is described in 22 patients in respect of the extent and duration of the disabilities. The average stay in hospital in the terminal phase in 20 patients followed to the time of their death was 6.6 months for men and 4.7 months for women. The total duration of the disease ranged from 11 to 45 months, with an average of 28.7 months for men and 22.2 months for women. Between the bulbar cervical lumbar and mixed forms of the disease at the onset there emerged no difference in average survival. On woman of 32 is still alive 10 years after the onset, and one after 2-1/2 years. The hospital staff were exposed over many months to the progressive deterioration in breathing, swallowing, posture and mobility, and emotional crises and dysarthria aggravated the problems of management. Pain was a feature in one-third of the patients. In the treatment, physiotherapy with the accent on passive movements was found helpful. Although formal occupational therapy was not accepted by half of the patients, it was important to talk to them frequently, and encourage any means of expression such as painting, writing or dictating diaries, poems or essays. The indications for gastrostomy feeding are discussed, and the problem is raised of assisted respiration in this disease.


Geriatric admissions in East London 1962-72. Geriatric admissions over the period 1962-72 in East London were studied. Patients, for the most part, presented combinations of physical, mental and social disability. 6286 admissions of 3988 patients were analysed with regard to length of stay, outcome, number of repeat admissions, age and sex. Numbers were large enough for trends to be clear. For example, 550 admissions were of persons over 90. The largest group were aged 75-84. The likelihood of death in hospital increased with age while the percentage of discharges home fell. With age there was a gradual increase in the percentage of those in hospital 28 days or less. Eight per cent of males and 10 per cent of females remained in hospital over one year. Seventy per cent of patients were admitted to hospital once only, while fewer than 2 per cent were admitted more than five times. A sample of new patients admitted from one borough in 1968, was traced in hospital and after discharge. The 50 per cent survival time for men was 6.5 months and for women 12.9 months.


Contraception for adolescents.

Contraception for adolescents. The two major groups of contraceptives available to adolescents are simple and prescribed methods. Of the former, spermicidal agents and condoms alone or in combination offer some protection. Of the prescribed methods, oral contraceptives and intrauterine devices offer best protection. The risk of pregnancy and the mortality and pathologic risks involved in the use of each method must be considered. The indications, contraindications and specific guidelines for prescribing contraceptives in this age group cannot be uniformly applied to all adolescents; therefore, individualization is always necessary.


Hospital electrical safety.

Hospital electrical safety. Electrocution is an environmental hazard for hospital personnel and patients. The source is low-level alternating current, accidentally applied through indwelling electrodes which invade the normally protective high resistance of the body. Probably the greatest offender is the combination of electronic monitoring and the electrically operated bed. Preventive measures include education of medical personnel and the establishment of guidelines on leakage, coupled with periodic maintenance and inspection by trained technicians.


Tetanus.

Tetanus. While the incidence of clinical tetanus had decreased greatly, efforts to eradicate the disease will depend mainly upon continued stress on prophylaxis. Recent cases demonstrate the need for both continued vigil in prophylaxis and sensitivity to the early signs of the clinical disease. The fundamentals of treatment are: neutralize formed toxin, eradicate Clostridium tetani, debride tissues adequately, control spasm and start immunization. Complications are legion. Mortality is highest in the very young and in the elderly.


Constipation in childhood.

Constipation in childhood. Most commonly, constipation in the infant is functional, with increased tone of colonic smooth muscle. Hirschsprung's disease is the best known of the infrequent organic causes. Treatment includes reassurance of parents, use of sugars, fluids and bulk and care of fissures. Voluntary stool withholding occurs in older children, who present with a variety of symptoms. Medicines are required to restore the functional capacity of the colon after chronic distortion by stool. This must be combined with psychologic help.


Erythema nodosum.

Erythema nodosum. Erythema nodosum (EN) is now more commonly associated with streptococcal disease than with tuberculosis. Sarcoidosis is the third most frequently associated systemic disease. Oral contraceptives now lead the list of drugs associated with EN. The appearance and disappearance of crops of nodules is extremely variable. Salicylates and rest are useful. Steroids are not recommended because they may compromise defenses against an underlying disease process.


Preclinical cardiomyopathy in chronic alcoholics: a sex difference. Alcoholic subjects differ in the incidence of cardiomyopathy. Of potential variables, sex may be important since few females are seen with cardiomyopathy, even adjusting for the lower incidence of alcoholism. To examine this question, noninvasive systolic time intervals were measured in 22 males and 14 females of similar age, heart rate, and arterial pressure, without clinical evidence of heart disease or hypertrophy. Duration and intensity of ethanol intake and the interval from last drinking episode were apparently equivalent. In male alcoholics, the left ventricular preejection period and ejection time (PEP/LVET) ratio of 0.410 +/- 0.020 was significantly higher than in the 11 normal males (0.316 +/- 0.007) (P less than 0.001). In female alcoholics, the ratio was 0.322 +/- 0.015, compared to 0.310 +/- 0.01 for 11 normal females, and was significantly less than in the male patients (P +/- 0.001). In addition prolonged intraventricular conduction by high-frequency ECG was more prevalent in the male group. To further ensure equivalency of alcoholism, patients with biopsy-proved cirrhosis were selected. In nine males, PEP/LVET was significantly higher than in the 10 females. Thus, abnormal myocardial function was evident in males but not in females, suggesting that sex is a determinant of the toxic effects of ethanol on myocardium.


Atrioventricular conduction patterns in patients with paroxysmal supraventricular tachycardia. Atrioventricular conduction patterns suggestive of dual A-V nodal pathways have been reported in patients with and without a history of paroxysmal A-V nodal re-entrant tachycardia (PSVT). The purpose of this study was to determine whether significant association exists between this conduction pattern and the occurrence of PSVT in man. The pattern of A-V conduction was evaluated at similar pacing rates in 13 patients with documented PSVT and 135 patients with PSVT. Patients without PSVT were divided into groups with normal PR intervals (106 patients), PR intervals of 120 msec. or less (12 patients), and PR intervals of 200 msec. or greater (17 patients). Evidence of dual A-V nodal pathways was found in seven of 13 patients with PSVT and nine of 135 patients without PSVT, including eight of 106 patients with normal PR intervals, none of 12 patients with short PR intervals, and one of 17 patients with PR intervals of 200 msec. or greater. The incidence of dual A-V nodal pathways was significantly greater (P less than 0.01) in patients with PSVT when compared with all other groups. In two of four patients with PSVT, propranolol was found to unmask evidence of dual pathways; no evidence of dual pathways was produced by propranolol in 23 patients without PSVT. The data show that the pattern of dual A-V nodal pathways is common only in patients with PSVT and is significantly less frequent in patients without PSVT regardless of the presence of short or long PR intervals. The results of this study establish a strong association between this conduction pattern and the occurrence of PSVT in man.


The significance of mitral valve prolapse in middle-aged and elderly men. The clinical, roentgenographic, phonocardiographic, ECG, and echocardiographic data were evaluated in 40 consecutive middle-aged and elderly male patients with echocardiographically detectable systolic prolapse of mitral valve leaflets. Prolapse was present during more than half of systole in 31 patients and was holosystolic in six patients. In most instances, both leaflets prolapsed during systole. The closing velocity and excursion of the anterior leaflet were frequently increased particularly in association with evidence of mitral insufficiency. A majority of the patients had cardiac symptomatology. Moreover, roentgenographic and/or ECG evidence of cardiac enlargement or hypertrophy was evident in 45 percent of patients with mitral valve prolapse.


Adrenergic beta blockade and ECG changes in the systolic click murmur syndrome. In an attempt to elucidate the ECG changes associated with the SCMS, we have applied the propranolol test in 35 of our patients suffering from this syndrome. To the best of our knowledge this is the first such report in the English literature. Twenty-eight patients showed improvement and this points against an ischemic etiology. The test may be applied to differentiate ischemic ST-T changes from those associated with the SCMS. We have suggested the possibility of sympathetic overactivity and autonomic imbalance as the basis for the ECG and other features related to the SCMS. We have noted the striking similarities in the symptomatology and ECG changes associated with the SCMS and those of neurocirculatory asthenia. The implication of this was discussed.


First-degree sinoatrial heart block: sinoatrial block in the sick-sinus syndrome. Sinoatrial conduction time (SACT) was estimated from the delay in the atrial recovery period after premature depolarization applied in that portion of atrial diastole when increasing prematurity resulted in a constant recovery interval. In 20 normal patients SACT was 169 msec. +/- 91 (2 S.D.). At least nine of 19 patients with "sick-sinus syndrome" (SSS) demonstrated SACT that were longer than seen in these normal subjects. SACT was prolonged in seven of nine SSS patients with abnormal A-V nodal conduction. Among 10 SSS patients with normal A-V conduction, only two had prolonged SACT. This study identifies first-degree sinoatrial block as a frequent manifestation of SSS associated with the presence of A-V node conduction abnormalities.


Long-term survival following aortic valve replacement. Study was made of 95 survivors of aortic valve replacement during the early years of this procedure (1964 to 1970). The average follow-up time was 50.2 months. Survival was not related to hemodynamic parameters, such as cardiac index or left ventricular pressure, and did not appear to be influenced by the type of preoperative valve lesion. A history of angina pectoris and a New York Heart Association Class IV grouping were associated with shorter survival. Associated coronary artery disease was a leading cause of death in those patients surviving less than 2 years and angina pectoris the leading cause of morbidity in the long-term survivors. Sudden death occurred in five patients. Once a patient survived 36 months after the operation, the prognosis was excellent.


Diagnosis of Björk-Shiley aortic valve dysfunction by echocardiography. Echocardiography was performed on 26 patients with prosthetic Björk-Shiley aortic valves (BSAV). Technically satisfactory records were obtained in 22 patients. The systolic displacement of the valve disc varied from 1 to 1.8 cm. (mean, 1.4 cm.). Six patients developed valve dysfunction. Two patients had complete absence of Björk disc motion and dense echoes in the aortic root were noted on the echocardiogram. Extensive clot formation in and around the valve was seen at operation. After clot removal, these two echocardiograms showed excellent disc motion (1.5 and 1.8 cm.). In a third patient with a clotted valve, marked reduction of the velocity of opening and closing of the valve was noted. Three patients had aortic incompetence without evidence of clot formation. Normal disc motion (DM) was observed in all three. A seventh patient presented with a low output state and markedly reduced valve clicks. Echocardiography revealed normal DM with marked dilatation of the left ventricle. These features were confirmed by angiography. We conclude that: (1) satisfactory echocardiograms can be obtained in most patients with BSAV; (2) echocardiography may be a useful method of detecting Björk valve dysfunction.


Dopamine effects on the intestinal circulation. The effects of intra-arterial infusion of dopamine on superior mesenteric artery blood flow, intestinal flow, intestinal oxygen consumption, and capillary density were studied in anesthetized dogs before and after blockade of dopamine receptors with haloperidol and after beta-adrenergic receptor blockade with propranolol. Mesenteric blood flow to a distal segment of the small intestine was measured with an electromagnetic blood flow-meter and intestinal oxygen consumption was calculated from the measured arteriovenous oxygen difference across the intestine and total blood flow. Intestinal capillary density was estimated from the clearance of 86Rb. In normal animals prior to dopaminergic or beta-adrenergic blockade, dopamine caused a dose-related decrease in mesenteric blood flow, intestinal oxygen consumption, and 86Rb clearance. Only the lowest dose of the drug, 1 mug/Kg.-min., did not significantly change the intestinal capillary density. In dogs pretreated with the dopamine receptor, antogonist, haloperidol, dopamine (20 mug/Kg.-min.) caused a significant increase in blood flow and oxygen consumption and did not significantly alter the number of perfused intestinal capillaries. These increases in haloperidol-blocked animals administered dopamine were reversed by propranolol. Our results indicate that dopamine caused smooth muscle contraction in mesenteric arterioles and precapillary sphincters, thereby producing intestinal ischemia and hypoxia. These findings with haloperidol and propranolol indicate that dopamine stimulates at least two different receptors in the canine mesenteric vascular bed: a constrictor receptor blocked by haloperidol and a dilator receptor blocked by propranolol.


Sinus slowing produced by intracoronary arterial injections of hyperosmotic solutions in man. The effect of intracoronary arterial injections of normal saline, contrast agent, hyperosmotic glucose, and mannitol solutions on the sinus rate was studied in 18 patients. Sinus slowing was not produced by isosmotic saline (0.3 Osm. per kilogram of water) when injected into either coronary artery, whereas 76% Urografin (1.9 Osm. per kilogram of water), 20% glucose (1.3 Osm. per kilogram of water), and mannitol (1.2 Osm. per kilogram of water) decreased the sinus rate significantly (P less than 0.001). Among these solutions, Urografin with the highest osmolality produced the most marked sinus slowing, whereas no significant difference was detected between change in the sinus rate with hyperosmotic glucose and mannitol solutions (P greater than 0.5). Moreover, there was no significant difference between the degree of sinus slowing produced by intracoronary injections into the coronary artery of the side which the sinus node artery originated from and the slowing produced by contralateral injections with hyperosmotic solutions (P greater than 0.2). Therefore, it seems unlikely that this sinus slowing would be a result of a direct action on the sinus node including hypoxia and elevated perfusion pressure. Reflex-mediated parasympathetic stimulation may be operative.


An inexpensive receiver for ECG telemetry. A simple, inexpensive ECG demodulator circuit has been described which may be used in conjunction with an ECG telephone transmitter, telephone amplifier, and ECG recorder to form a telemetry system capable of ECG monitoring.


Artifacts in portable electrocardiographic monitoring. The development of portable ECG monitoring techniques has brought with it new insights into the electrical activity of the heart, and new problems in interpretation of artifacts. This article summarizes and classifies 15 different types of artifacts observed from dynamic electrocardiography. The artifacts appear partly as pseudo-arrhythmias mimicking supraventricular, ventricular, junctional, and dissociative rhythms. There are also non-arrhythmic artifacts which can be misleading in the interpretation of Q-waves, S-T-segments, and T-waves. Eight of the 15 artifacts have potentially serious consequences if not understood, and in 2 instances an artifact almost led to the unnecessary implantation of an artificial cardiac pacemaker.


Systolic time intervals in induced atrial fibrillation in the dog. The effect of induced atrial fibrillation on ventricular performance in the dog as measured by changes in the systolic time intervals (STI), was investigated. Atrial fibrillation was induced by enhancement of vagal tone with morphine sulfate, followed by direct mechanical stimulation of the atrium. Dogs received 15 mg. per kilogram of morphine sulfate subcutaneously, followed by 3 mg. per kilogram of pentobarbital sodium. ECG, atrial electrogram, phonocardiogram, and direct arterial blood pressure were recorded during periods of sinus rhythm and during periods of induced atrial fibrillation. Data were analyzed by selecting 20 representative cardiac cycles from each condition in each of 15 dogs. Cycles were selected so that the broadest spectrum of rates was examined for each animal. Three hundred cycles were examined from each condition, or a total of 600 cycles. Heart rate (HR), left ventricular end-diastolic pressure, and aortic end-diastolic pressure were unchanged during atrial fibrillation. The left ventricular pre-ejection period (LVPEP), externally derived isovolumic contraction time (EICT), and total mechanical systole (S1-S2 interval) were all found to increase significantly in duration after the induction of atrial fibrillation. The left ventricular ejection time (LVET) and the electromechanical delay (Q-S1 interval) were significantly decreased in duration following the induction of atrial fibrillation.


Acute myocardial infarction following wasp sting. Report of two cases and critical survey of the literature. Over the span of two or three days in August, 1972, in two separate communities in eastern Massachusetts two men, one aged 39, the other 66, each without previous overt heart disease, were stung by wasps. Each went into shock rapidly after an interval of over a half-hour developed chest pain and, later, sequential electrocardiographic changes diagnostic of acute myocardial infarction. Each survived; each had normal electrocardiograms before the sting. Though preexistent coronary artery disease can be excluded in neither, the view is favored that acute myocardial infarction in each was caused by deficient coronary perfusion secondary to anaphylactic shock induced by the wasp stings. An intriguing case was just recently reported58 of a 62-year-old man with previous angina who developed pulmonary edema but no chest pain following wasp sting and went on to show rapidly reversed electrocardiographic changes attributable to subendocardial ischemia or infarction. In a sense, this sequence fills the gap as an intermediate phase between the normal and the two individuals described here who developed pain after anaphylactic shock, then proceeded, perhaps through this phase, to develop transmural infarction.


Primary risk factors in patients with myocardial infarction. A predicted probability of suffering myocardial infarction based on a multiple risk function involving serum cholesterol, systolic blood pressure, and tobacco consumption, was allocated retrospectively to 270 men who survived a primary myocardial infarction. The infarction patients were representative of all surviving, diagnosed cases of primary infarction in men in certain age groups in Göteborg, Sweden, during the years 1968-70. The patients were divided into three groups-low, moderate, and high risk. A large number of patients had suffered infarction despite relatively low risk, but the patients showed a tendency toward higher risk in comparison with the risk distribution in a representative population sample. In order to study whether other variables, not included in the risk function, could "explain" the infarction in patients with relatiely low risk, the different risk groups were compared. A high degree of mental stress, diabetes mellitus, and dyspnea on exertion, and possibly also raised triglycerides, contributed to "explain" the infarctions in the low-risk group. Low physical activity during leisure time was probably also of importance.


The ECG of constrictive pericarditis--pattern resembling right ventricular hypertrophy. The ECG changes in 122 cases of constrictive pericarditis have been reviewed. Ninety-five per cent of tracings were typical and showed a normal QRS axis, low voltage, and generalized T wave flattening or inversion. The remaining six tracings showed evidence of right ventricular hypertrophy and half of these showed right axis deviation in addition. In only one could these findings be readily accounted for by the presence of severe fibrotic annular subpulmonic constriction; the remainder are unexplained and it is postulated that cardiac rotation and distrotion is causative since none of the other mechanisms of right axis deviation or right ventricular hypertrophy were operative.


The effect of vitamin E on platelet aggregation. Platelet aggregation studies were performed in five men with coronary artery disease and angina pectoris and five men with nonspecific chest pain before and after receiving 1,000 I.U. of alpha-tocopherol acetate orally per day for 8 days. There was no significant difference in the platelet aggregation response to three concentrations of ADP and two concentrations of epinephrine between the pre- and post-vitamin E periods among the 10 patients. If tocopherol acetate (vitamin E) has any beneficial effect on the prevention of thromboemolism or in the treatment of angina pectoris and peripheral vascular disease, it is not via inhibition of platelet aggregation.


A controlled trial of intramuscular lidocaine in the prevention of premature ventricular contractions associated with acute myocardial infarction. Intramuscular lidocaine administration is known to produce blood concentration levels considered to be therapeutic for prevention of premature ventricular contractions. This double blind study was designed to study the effect of intramuscular lidocaine in the prevention of PVC's in acute myocardial infarction. Forty-six patients with confirmed acute myocardial infarction, without congestive heart failure, shock, or major arrhythmias were admitted to the trial. Twenty-one patients received 4.5 mg. per kilogram of intramuscular lidocaine and 25 patients received placebo in the deltoid muscle within 14 hours of the onset of symptoms. Rhythm strips of 2 minutes' duration, blood pressure, heart rate, and blood specimens for blood concentration levels were obtained prior to and 5, 10, 15, 30, 60, 90, and 120 minutes after injection. The mean blood concentration level of lidocaine was 1.81 +/- 0.22 mug per milliliter at 5 minutes, reached a maximum of 2.18 +/- 0.22 mug per milliliter at 10 minutes, and was still 0.81 +/- 0.05 at 120 minutes. Analysis of rhythm strips revealed that only three of 21 patients (14 per cent) in the intramuscular lidocaine group developed at least one PVC as compared to 13 of 25 (52 per cent) in the placebo group (p less than 0.0005). No significant toxic effects were noted. This study suggests that intramuscular lidocaine may significantly reduce potentially fatal arrhythmias in early phases of acute myocardial infarction.


The localization of coronary artery stenoses by 12 lead ECG response to graded exercise test: support for intercoronary steal. In 39 consecutive patients with unequivocally positive postexercise ECG we have correlated the location and severity of the coronary artery stenoses with the ECG leads in which ischemic ST changes occured. Patients with major stenoses of the right coronary artery, with or without disease of the left coronary system, showed ischemic ST changes in Leads II, III, and aVF. Patients with major stenoses of the left coronary system, many of whom had suffered old inferior wall infarction, showed ST changes in Leads I, aVL, and the chest leads. A group of 11 patients showed ischemic ST changes in leads other than those expected on the basis of the location and severity of coronary artery stenoses. In each of these 11 patients large collateral channels were donated by the vessel in whose territory the ischemic changes occurred. This finding lends support to the concept of intercoronary "steal" during exercise in coronary artery disease, at the same time reducing the value of the postexercise 12 lead ECG in predicting the location and severity of coronary artery stenoses.


Long-term survival of elderly patients after pacemaker implatation. The follow-up of 80 patients above the age of 70 years with implanted pacemakers is described. These patients were the most advanced in age from a total group of 150 with implanted pacemakers. Their ages ranged from 70 to 87 years, with an average of 75.4 years; 50 were male and 30 were female. An epicardial electrode was implanted in 13 patients and an endocardial electrode in 67. The pacemaker was implanted in 76 patients for symptomatic atrioventricular block and in four patients for sick-sinus syndrome. Two patients (2.5 per cent) died during the postoperative period and 19 patients within a period of 3 months to 6 years after the implantation. The survival rates were: 1 year, 90.0 per cent; 2 years, 82.1 per cent; 3 years, 74.1 per cent; 4 years, 67.2 per cent; 5 years, 58.3 percent. These survival rates were surprisingly similar, for the first 3 years of follow-up, to those of our and others' previous studies, which included all age groups. The survival rates in the most advanced age groups decreased in comparison only in fourth and fifth years after the implantation. There was no evidence of new episodes of myocardial infarction among this group of patients during the follow-up period. We conclude that even in patients of the most advanced age groups the implantation of an endocardial pacemaker significantly prolongs life, improves its quality, and this at a low operative risk.


Facilitation of A-V nodal reciprocation by procainamide. Procainamide is known to depress conduction through the A-V node, and this property may facilitate the development of ventricular reciprocal beats or echoes. The occurrence of ventricular reciprocal beats was studied in 20 open-chest dogs before and after the administration of procainamide. While the ventricle was paced by basic stimuli, early ventricular premature beats were introduced at various coupling intervals to induce ventricular echoes. When ventricular echoes could be induced in a given heart, there was a continuous range of coupling intervals (or echo zone) within which ventricular echoes occurred. In the control state, no echo occurred in eight dogs and the echoes developed in 12 dogs with the mean echo zone of 38.3 msec. The effect of procainamide was studied at its therapeutic blood levels about 25 minutes after an intravenous injection of the drug in a dose of 10 mg. per kilogram. Of the first group of eight dogs, in which no echo occurred in the control state, four dogs developed ventricular echoes after the administration of procainamide with the mean echo zone of 29.3 msec. for the group. Of the second group of 12 dogs, in which ventricular echoes were induced in the control state, the administration of procainamide increased the echo zone in 10 dogs with the mean echo zone of 67.8 msec. for the group. Ventricular reciprocal beats were often sustained to produce short runs of supraventricular tachycardia in five dogs after the administration of procainamide. The results demonstrated a potentially deleterious effect of procainamide in facilitating the inducation of A-V nodal reciprocation by closely coupled ventricular premature beats.


The effects of acetylstrophanthidin on the response of the AV junction to adrenergic stimulation studied in dogs. The response of the AV junction to adrenergic stimulation was studied in 35 anesthetized open-chest dogs before and after the injection of acetylstrophanthidin (5mug) directly into the AV node artery. An AV junctional rhythm was obtained under control conditions by injecting norepinephrine (n = 9) or isoproterenol (n = 8) into the AV node artery and by stimulation of the left stellate ganglion (n = 11) after selectively injecting propranolol into the sinus node artery. Acetylstrophanthidin brought about various degrees of conduction block from simple PR interval prolongation to complete heart block, and decreased the chronotropic response of the AV junction to adrenergic stimulation. In seven animals the appearance of a spontaneous second degree AV block did not reduce the AV junctional response to adrenergic stimulation. Acetylstrophanthidin also reduced the ventricular acceleration produced by adrenergic stimulation during atrial fibrillation. These results suggest that the anti-adrenergic effect of cardiac glycosides may not only be involved in the mechanism of AV conduction disturbances during digitalis intoxication, but may also play a role in slowing the ventricular rate during atrial fibrillation.


Atrial T (Ta) loop in patients with A-V block: a trial to differentiate normal and abnoral groups. The P and the Ta waves were recorded with high fidelity and high amplification. The P and the Ta loops were constructed from these waves. Human subjects with A-V block were used, so that the Ta waves could be completely visualized. Subjects were separated into two groups: one group with minimal clinical evidence of heart disease and another with more severe disease. There were great and important differences in the Ta loops between the two groups with minimal differences in the P loops. In the patients with minimal heart disease, the Ta loop was always oriented to the right and superiorly. The P-Ta angle was approximately 180 degrees and all patients in this group showed a small spatial atrial gradient oriented to the left and inferiorly. These findings are similar to those found in normal dogs reported separately in the Journal. In the group of four patients with more severe heart disease, the P-Ta angle varied widely and deviated greatly form 180 degree. The satial atrial gradient was very large in three cases. The findings and others such as the direction of the maximum Ta vectors were diagnostically useful in separating the Ta loops of the two patient groups. Results indicate that the Ta loop may be very useful in separating normal from diseased atria in individuals with A-V block. There are some frequency differences between the Ta wave and the QRS complex. If the Ta wave could be extracted from the QRS complex by the use of some kind of filter when A-V block dose not exist, most of the Ta wave could be visualized. This, along with high fidelity recording techniques, may help detect atrial abnormalities in patients without A-V block. Future development of this equipment as a clinical tool is hoped for.


Coronary artery spasm as the cause of myocardial infarction during coronary arteriogarphy. Catheter-induced coronary artery spasm has been observed frequently. It is usually transient, reacts to the administration of nitroglycerin, and its distribution is generally confined to an area in proximity ot the intubated catheter. A 43-year-old woman with recurrent chest pain was found to have a rather long segment of tight proximal obstruction of the right coronary artery and experienced a myocardial infarction during coronary catheterization. Because of recurrent attacks of severe chest pain, coronary artery bypass surgery was performed which failed to result in significant improvement of her symptoms. Two repeat coronary cineangiograms seven weeks and three years after surgery revealed the proximal right coronary artery to be free of stenotic lesions or of luminal irregularities. After considering possible mechanisms of myocardial necrosis in the presence of normal coronary arteries it is concluded that myocardial necrosis can result from catheter-induced coronary artery spasm in spite of administration of nitroglycerin.


Spectrum of sinus node dysfunction in two siblings. Two siblings, ages 14 and 23, with various features of sinus node dysfunction have been reported. Sinus bradycardia was the presenting feature in both patients. During the follow-up period both patients developed various types of ectopic rhythms which increased with exercise. One of them developed "silent atrium" at the age of 23 and had cerebral embolus as a complication. The other patient had frequent syncopal episodes and had to be treated with a combination of electronic pacemaker and antiarrhythmic drugs.


Functional significance of coronary collateral vessels in patients with acute myocardial infarction: relation to pump performance, cardiogenic shock and survival. In 20 patients with acute myocardial infarction requiring emergency left heart catheterization and coronary arteriography, ventricular function and clinical course were related to collateral vessels supplying the infarcted area. The major coronary artery to the infarcted region was severely obstructed in all patients. Patients with adequate collateral vessels (Group I, no. = 6) and those with no or inadequate collateral channels (Group II, no. = 14) had similar findings with respect to age, site of infarction, prevalence of prior infarction and presence of multivessel disease. However, there were significant differences between Groups I and II in left ventricular end-diastolic pressure (13 versus 30 mm Hg), cardiac index (3.05 versus 2.04 liters/min per m2), stroke work index (45 versus 13 g-m/m2), ejection fraction (42 versus 20 percent) and area of dyssynergy (14 versus 47 percent). Moreover, in Group I all patients survived and none had cardiogenic shock, whereas in Group II 10 of 14 patients had shock and 8 of 14 died. The rapidity of vessel obstruction appeared to influence collateralization since infarction was preceded by angina pectoris more frequently in Group I than in Group II. These results indicate that well functioning anastomotic channels to the distal trunk of the blocked coronary artery may afford some protection of pump function and improve the prognosis in acute myocardial infarction.


Functional abnormalities in nonoccluded regions of myocardium after experimental coronary occlusion. The performance characteristics of both ischemic and "adjacent" and "remote" nonischemic myocardium were studied in open chest dogs by three mercury-in-Silastic length gauges sutured to the anterior surface of the left ventricle before and after occlusion of the distal left anterior descending coronary artery. The adjacent gauge was separated from the ischemic segment by one large nonoccluded diagonal branch of the left anterior descending artery. Remote myocardium was separated from the ischemic area by two such branches. At the time of occlusion epicardial S-T segment elevation appeared in the ischemic region but not in the adjacent or remote regions. Immediately after occlusion, typical changes of ischemic dysfunction appeared. Late systolic lengthening, depression of systolic shortening and increased diastolic compliance occurred consistently and simultaneously in ischemic and adjacent regions and inconsistently in the remote region. Five minutes after occlusion, fiber shortening was depressed to 21, 58 and 67 percent of control values in ischemic, adjacent and remote regions, respectively. Heart rate did not change, and mean arterial pressure decreased slightly. These changes persisted over time. In 11 of these dogs, end-diastolic pressure was maintained constant 20 minutes after occlusion. Systolic shortening was depressed to 40 and 74 percent of control values in the ischemic and adjacent regions, respectively. In six dogs, end-diastolic pressure was varied form 5 to 20 mm Hg by rapid volume loading during the control state and 30 minutes after occlusion. Systolic shortening in ischemic, adjacent and remote regions was depressed to 20, 40 and 65 percent of control values, respectively. The severity of all functional alterations after coronary occlusion was directly related to proximity to the ischemic region. These results indicate that depression of left ventricular function after coronary occlusion may be partially related to previously unrecognized depression of function in apparently "nonischemic" myocardium.


Alterations in myocardial function during bacterial infective cardiomyopathy. The status of myocardial function in rabbits subjected to cardiac catheterization and infection with Streptococcus viridans was assessed at 3 and 6 days. Sham-operated control animals as well as uninfected catheterized animals were used for comparison. Although left heart hypertrophy and interstitial edema were evident in both uninfected and infected animals, the infected animals exhibited in addition mononuclear cell infiltration and muscle degeneration as well as lung congestion and accumulation of pleural fluid. Both uninfected and infected animals has elevated levels of serum creatine phosphokinase, lactic dehydrogenase and glutamic oxaloacetic transaminase as well as electrocardiographic abnormalities such as increased amplitude of the ORS complex and flattening or inversion of the T wave. Unlike findings in the uninfected animals, the serum calcium, magnesium and sodium levels were slightly but significantly decreased and serum potassium levels were increased in the infected rabbits. Both heart rate and pulse pressure were higher in 6 day uninfected and 3 day infected animals whereas 6 day infected animals showed a decrease in heart rate. In comparison to the sham-operated control rabbits and the uninfected animals, the infected animals exhibited depression in the rates of left ventricular pressure development and relaxation as well as prolongation in time for half relaxation in situ. Relative maximal contractile element velocity extrapolated from intraventricular pressure-velocity curves was decreased by 24, 52 and 76 percent, respectively, of control values in the uninfected hearts and those with 3 and 6 days of infection. The isolated perfused hearts from infected animals also generated less contractile force and showed a decrease in the rates of contraction and relaxation, but half-relaxation time was increased. These results demonstrate myocardial dysfunction during experimental bacterial endocarditis and provide evidence that infective cardiomyopathy is associated with heart failure.


"Agenesis" of ductus arteriosus associated with the syndrome of tetralogy of Fallot and absent pulmonary valve. Four infants with the severe form of the syndrome of tetralogy of Fallot and absent pulmonary valve are described. All had severe respiratory distress due to bronchial compression from massively dilated pulmonary arteries. The clinical diagnosis was confirmed by cardiac catheterization and angiocardiography. The infants died at age 3, 5, 30 and 90 days, respectively. Autopsy revealed, in addition to the usual components of the syndrome, absence of the ductus arteriosus or its remnants. The possible relation of "agenesis" of the ductus arteriosus to the pathogenesis of the severe form of this syndrome is discussed and pertinent studies are reviewed.


Truncus arteriosus communis: truncal valve anomalies associated with small conal or truncal septal defects. Selected specimens of truncus arteriosus communis illustrate a spectrum of anomalous truncoconal septation in which the conal and truncal septal defects are so closely approximated to the truncal valve that portions of the valve tissue extend along the free margins of the adjacent ventricular or truncal septum.


Duration of hospitalization in "uncomplicated completed acute myocardial infarction". An Ad Hoc Committee review. The clinical and laboratory findings diagnostic of acute myocardial infarction include at least two of the following: (1) a history of pain consistent with myocardial ischemia, (2) electorcardiographic findings consistent with infarction, and (3) a rise in the serum level of specific cardiac enzymes. By the 4th or 5th day of illness, specific criteria can be applied to assign certain patients to a subset with "uncomplicated completed acute myocardial infarction." These criteria include the absence of evidence of (1) continuing cardiac ischemia, (2) left ventricular failure, (3) shock, (4) important cardiac arrhythmias, (5) conduction disturbances, and (6) other serious illnesses in patients with an established acute myocardial infarction. In terms of prognosis and management, patients in this subset should be regarded as substantively different from patients in other subsets. They should respond favorably to short periods of immobilization and hospitalization than those generally used. They may remain at bed rest (modified in regard to sitting and the use of a commode) for 4 days. Subsequently, mobilization with a program of progressive activity over the ensuing 5 to 10 days should reduce the duration of hospitalization to less than the current average of 17.5 to 20.8 days for patients with acute myocardial infarction. Nine to 14 days should suffice in most instances. Current and future trials may indicate that still earlier mobilization and shorter hospitalization periods can be applied to certain patient groups, but the evidence on this point is incomplete. For the individual patient, many factors will determine the optimal duration of bed rest and hospital stay. The patient's physician must consider the therapeutic benefits that may attend earlier mobilization and shorter hospitalization while weighing potential disadvantages. When the responsible physician does not regularly care for the patient, consultation with an experienced cardiologist is desirable. Patients whose condition is classified as "uncomplicated" may manifest deterioration during their illness and require assignment to a subset with a different prognosis and requiring different forms of treatment. For patients with uncomplicated acute myocardial infarction, as well as those in other subsets, absolute rules for therapy are unwise and application of broader principles by the alert physician is more likely to be beneficial.


"Presystolic" augmentation of diastolic heart sounds in atrial fibrillation. In the presence of atrial fibrillation, the diastolic murmur of mitral stenosis can appear augmented during early systole before the mitral valve closure sound. This phenomenon has previously been thought to be due to increased blood flow velocity across the narrowing mitral valve orifice. We have observed patients in whom the third heart sound (S3) gallop, the diastolic flow murmur of atrial septal defect and mitral insufficiency and the initial muscular component of the first heart sound become more intense during this period with short, critically timed cycle lengths. This phenomenon appears to be neither peculiar to nor indicative of mitral stenosis and is probably a direct result of the initial muscular contraction of an underfilled ventricle. Either the contraction itself or the sudden deceleration of the rapidly moving flow of blood across the atrioventricular orifice may produce the sound.


Eosinophilia and endomyocardial fibrosis. A 12 year old boy died after a 3 year course of recurrent and progressive heart failure. His cardiac symptoms began with a marked leukocytosis (white blood cell count 188,500/mm3) due to eosinophilia (90 percent). In 6 months, the leukocytosis and eosinophilia subsided, but the patient's heart failure progressed over the next 2 1/2 years. At autopsy there was no evidence of leukemia, but a severe endocardial fibrosis extending into the myocardium was found. The origin of endomyocardial fibrosis, although unknown, appears to have been related to the eosinophilia in this patient.


Tricuspid insufficiency due to nonpenetrating trauma. This case of tricuspid insufficiency due to nonpenetrating trauma involved a male patient who had received major chest trauma in an automobile accident, had a nonholosystolic murmur that increased slightly during inspiration on standing, and tranient electrocardiographic findings of right bundle branch block. Unlike findings in previous cases, the right atrial V wave was not dominant and was less than 8 mm Hg. An echocardiogram indicating right ventricular volume overload was an essential diagnostic tool that led to cardiac catheterization and definitive diagnosis.


Right ventricular infarction with tricuspid insufficiency and chronic right heart failure. A patient with chronic right heart failure and probable tricuspid insufficiency associated with an inferior myocardial infartion is described. Angiograms demonstrated total occlusion of the right coronary artery at its origin, a patent venous bypass graft to the mid-right coronary artery and hypokinesia of the inferior wall of both the right and left vebtricles. Clinical data indicated a greater impairment of right than of left ventricular function. It is proposed that infarction of the right ventricle resulted in chronic right heart failure and tricuspid insufficiency.


Characterization of the ischemic process by regional metabolism. The myocardial cell requires energy for contractile activity and for the work of internal maintenance. With the onset of ischemia mechanical performance is compromised. If the ischemia is severe and persistent, the energy necessary to maintain the internal millieu proves inadequate and cell death ensues. Ischemic heart disease is a regional phenomenon with normal and abnormal cell metabolism occurring side by side. The ischemic cell demonstrates hemodynamic, electrical and biochemical instability; its passage from a state of reversible to irreversible injury may persist for as long as 7 days and offers an opportunity to introduce interventions that may protect it and reduce ultimate infarct size. There is as yet no adequate objective means for predicting the mass of infarcted tissue. However, studies of regional metabolism, if properly conducted, may help define the adequacy of coronary vascular reserve and characterize the ischemic process. Current techniques utilize a myocardial pacing stress to induce an ischemic response. Although virtually every metabolic pathway is disrupted by severe ischemia, the assay of selected metabolities in arterial and coronary venous blood samples has provided information of diagnostic significance.


Estimation of infarct size from serum MB creatine phosphokinase activity: Applications and limitations. Results of enzymatic estimates of infarct size have been verified under defined experimental conditions, and close correlations have been obtained between enzymatically and morphologically estimated infarct size in patients. Nevertheless, to provide a basis for improved enzymatic estimates we explored several aspects of the original model. The first order disappearance rate of creatine phosphokinase (CPK) was verified by observed high correlation coefficients of the logarithm of CPK versus time after myocardial infarction in patients or intravenous injection of purified myocardial CPK in dogs. Selected hemodynamic interventions simulating derangements accompanying myocardial infarction including acceleration of heart rate, diminution of cardiac output and reduction of renal or hepatic perfusion in conscious dogs did not markedly alter CPK disappearance. To exclude contributions from noncardiac CPK to enzymatic estimates we performed studies with the MB CPK isoenzyme. Under standard assay conditions, MB CPK was found virtually exclusively in myocardium. Serial serum MB CPK curves paralleled those of total CPK from patients with uncomplicated infarction. Similar MB curves were obtained even in patients whose noncardiac CPK values distorted the total CPK curve after intramuscular injections. The correlation coefficient between infarct size estimated from total CPK and MB CPK was 0.97 in 12 patients with hemodynamically uncomplicated infarction. Thus, hemodynamic perturbations associated with infarction are unlikely to affect CPK disappearance and hence should not lead to spurious enzymatic estimates of infarct size. Furthermore, improved enzymatic estimates can be obtained by quantitative assay of MB CPK, a more specific myocardial marker, avoiding spurious estimates due to contributions from noncardiac enzyme.


Temporal relation of epicardial electrographic, contractile and biochemical changes after acute coronary occlusion and reperfusion. The increasing use of changes in the S-T segment of local epicardial electrograms to quantitate myocardial infarct size has led to the need for a better understanding of this method. Accordingly, we studied the local electrographic, tension and biochemical changes that occurred after coronary occlusion and subsequent reperfusion in 44 dogs using epicardial electrograms from 10 to 12 sites, Walton-Brodie strain gauge arches and myocardial ratios of potassium ion to sodium ion (K+/Na+). After coronary occlusion for 1 hour, total S-T segment elevation increased from 10.2 +/- 2.4 to 78.3 +/- 13.7 mv (P less than 0.001) and tension development decreased to 63.6 +/- 7.0% of control value (P less than 0.001); occlusion for 3 hours resulted in a total S-T segment elevation increase from 5.8 +/- 3.4 to 56.7 +/- 8.7 mv (P less than 0.001) and a tension decrease to 61.4 +/- 5.3% (P less than 0.001) of control value. After reperfusion two types of response were observed. In nine experiments new local pathologic Q waves appeared in an average of 5.3 of 8.2 ischemic electrode sites within 5 to 10 minutes of reperfusion concomitant with a marked further decrease in total tension from 67.3 +/- 5.5% to 42.4 +/- 6.0% of control value (P less than 0.001). Simultaneously, total S-T elevation decreased from 66.1 +/- 8.2 to 25.3 +/- 3.4 mv (P less than 0.001). In seven experiments no Q waves appeared after reperfusion and there was no significant change in tension. Total S-T elevation again decreased from 58.3 +/- 12.7 to 27.1 +/- 5.7 mv (P less than 0.025). When normal saline solution was perfused distal to the coronary arterial occlusion total S-T elevation decreased from 68.0 +/- 3.6 to 36.3 +/- 5.2 mv (P less than 0.001). After 3 hours of coronary occlusion, myocardial K+ decreased and Na+ increased in the ischemic zone, resulting in a significant decrease in the K+/Na+ ratio (P less than 0.005). Reperfusion for 2 hours resulted in a further depletion of K+ and an increase in Na+ with a resultant complete reversal of the K+/Na+ ratio (P less than 0.001). In summary, after reperfusion the S-T segment abnormalities rapidly decreased in all experiments despite the appearance of new Q waves in more than half of these studies concomitant with either a decrease or no change in contractile ability and continuing myocardial K+ loss and Na+ accumulation. S-T segment mapping therefore appears to be of limited value in assessing the effect of reperfusion on infarct size. The decrease in S-T segments that occurred with perfusion of either blood or saline solution suggests a "washout" phenomenon.


Significance of S-T segment elevations in acute myocardial ischemia. Evaluation with intracoronary electrode technique. A method is described for measuring intracoronary S-T segment elevations in the closed chest, a technique that appears to provide more reliable measurements of myocardial ischemia. Electrodes were inserted through intracoronary balloon catheters that were placed within a coronary artery and its adjoining vein both proximal and at several points distal to a coronary occlusion. Intracoronary arterial and adjacent venous electrocardiograms produced equivalent tracings. The intracoronary S-T segment elevations after coronary occlusion resembled those recorded from the epicardial surface but were free of artifacts noted in open chest studies. Study of progressive alterations of the intracoronary S-T segment after proximal occlusion of the left anterior descending coronary artery in 18 closed chest dogs revealed a peak segment elevation of 3.2 +/- 0.6 mv within 5 minutes, followed within 2 to 3 hours by spontaneous reduction by more than 40% of the S-T elevation over the occluded zone. In 44% of these animals, the S-T elevation decreased spontaneously to less than 1 mv, and in 22% it decreased to the preocclusion control level within 2 hours of occlusion. This spontaneous decrease in S-T elevation was frequently followed by a secondary increase and then S-T segment fluctuations. Reperfusion of the left anterior descending coronary artery after 30 to 60 minutes of occlusion generally led to a prompt reduction in S-T elevation. In some cases S-T elevations persisted up to 14 hours of occlusion, were reduced after reperfusion and exhibited a renewed pronounced increase after subsequent reocclusion of the left anterior descending coronary artery. During the 1st hour after occlusion, the early S-T segment elevation followed by spontaneous reduction reduction generally corresponded temporally with the derangements in myocardial lactate extraction and potassium loss. However, after 1 hour of occlusion no clear-cut correlation could be established between S-T fluctuations and changes in hemodynamic or myocardial metabolic measurements. We conclude that the new closed chest intracoronary electrocardiographic S-T technique might be of use for monitoring the early ischemic myocardial derangements and to assess benefits or drawbacks of treatment in both the experimental animal and man. Correspondence of S-T segment elevation with lactate and potassium alterations in the coronary-occluded region in the 1st hour after occlusion indicates that S-T segment elevation might represent an index of early myocardial ischemia. The spontaneous S-T changes that follow coronary occlusion must be taken into consideration when investigators utilize S-T segment modification as a sign of effectiveness of treatment.


Inotropic agents and infarct size. Theoretical and practical considerations. Recent data demonstrating the ability of interventions that alter the balance between myocardial oxygen demand and supply to affect infarct size are reviewed. The effects of inotropic agents on the determinants of myocardial oxygen consumption and coronary blood flow are discussed relative to the potential of these drugs to decrease or increase infarct size in the experimental animal and in man. The applicability of the animal data to the clinical situation is discussed and, on the basis of these considerations, guidelines are presented for the use of inotropic agents in patients with acute myocardial infarction.


Effect of hypertonic mannitol and intraaortic counterpulsation on regional myocardial blood flow and ventricular performance in dogs during myocardial ischemia. Studies were performed to determine if intervention with hypertonic mannitol and intraaortic balloon counterpulsation increases regional myocardial blood flow during acute myocardial ischemia. Anesthetized dogs on right heart bypass were studied. Heart rate was kept constant by atrial pacing. Myocardial ischemia was provided by ligating the proximal left anterior descending coronary artery for 12 minute periods. Infusion of hypertonic mannitol begun immediately after ligation increased coronary blood flow to the ischemic area by 36 +/- 9.0% (standard error) (P less than 0.01) and to the nonischemic left ventricle by 21 +/- 8.8% (P less than 0.05) as compared with flow in the same regions during the control coronary ligation. Intraaortic balloon counterpulsation begun immediately after ligation increased regional coronary flow to the ischemic region by 20 +/- 8.4% (P less than 0.05) but did not significantly alter flow to the nonischemic left ventricle as compared with levels during the control ligation. Combined intraaortic counterpulsation and hypertonic mannitol increased coronary flow to the ischemic region by 46 +/- 13% (P less than 0.02) and to the nonischemic left ventricle by 59 +/- 22% (P less than 0.05) as compared with flow during occlusion of the left anterior descending artery with mannitol alone. The data demonstrate that both hypertonic mannitol and intraaortic counterpulsation increase left ventricular ischemic regional flow and that combined hypertonic mannitol and intraaortic balloon counterpulsation provide a greater increase in regional coronary blood flow to both the ischemic and nonischemic regions of the left ventricle than mannitol alone.


On the nature of protection by propranolol against myocardial necrosis after temporary coronary occlusion in dogs. Propranolol has been shown to reduce the extent of necrosis that develops after temporary coronary occlusion in dogs. To determine whether this protective action was related to beta adrenergic blockade or to direct effects, necrosis was quantitated in the posterior papillary muscle 2 to 4 days after 40 minute periods of coronary occlusion in anesthetized open chest dogs. Groups of dogs either were untreated or were pretreated with doses of d,l-propranolol, 0.005 to 5 mg/kg body weight, or doses of d-propranolol 2.5 or 5 mg/kg. Necrosis was greatly reduced in dogs treated with 5 mg/kg of d, l-propranolol. This protective effect was significant but quantitatively less with 0.5 and 0.05 mg/kg of d, l-propranolol. A dose of 0.005 mg/kg d, l-propranolol and d-propranolol failed to alter myocardial necrosis significantly. The dose-related reduction of necrosis with d, l-propranolol correlated with a similar dose relation for beta adrenergic blockade and suggested that a protective effect was related to beta blockade. The reduction of necrosis with 0.05 and 0.5 mg/kg of d, l-propranolol (a level at which direct "membrane stabilizing" effects are insignificant) suggested that direct effects were not essential for protection. The negative results with d-propranolol further support our conclusion that propranolol reduces myocardial ischemic injury through beta adrenergic blockade rather than through direct myocardial actions.


Metabolic evaluation of agents designed to protect the ischemic myocardium and to reduce infarct size. There is as yet no adequate animal mode for human myocardial ischemia. The commonly utilized technique of coronary arterial ligation in large animals may induce regional ischemia but introduces variables that make it difficult to compare studies in different laboratories. A model of global ischemia in an isolated perfused rat heart that offers a rapid, inexpensive means for producing graded, controlled, stable state and reproducible ischemia is described. The technique has been utilized with success to study the hemodynamic and metabolic effects of ischemia and to evaluate pharmacologic interventions designed to protect the ischemic myocardium. Propranolol has been shown to improve bioenergetics and reduce anaerobic glycolysis by a depression of the hemodynamic response of ischemic myocardium. Methylprednisolone appears to exert its primary effect by direct coronary vasodilation, increasing resting or control flow and providing an enhanced reserve when ischemia is imposed. Mannitol improves cardiac performance by reducing the increased myocardial cell water content induced by hypoxia or anoxia.


Effect of nitroprusside on local contractile performance after coronary ligation and reperfusion. To study the effects of nitroprusside infusion on the regional contractile performance of the left ventricle after coronary occlusion, local tension and segment length of the ischemic, border and nonischemic zones were studied using Walton-Brodie strain gauge arches and mercury-in-Silastic tubing segment length gauges in open chest dogs. The effect of this intervention on the time period for functional reversibility of the affected areas after revascularization was also examined. Fifteen minutes after occlusion of the left anterior descending coronary artery, nitroprusside (4 to 11 mug/kg per min) was infused to keep systolic pressure 20 to 25% below control levels for 2 hours after occlusion and then 1 hour after reperfusion. The ischemic zone showed no change in either tension or length although there was a gradual continuing decrease in tension. However, in the border zone total tension which had decreased to 81.4 +/- 9.6 (standard error of the mean) percent of control level 15 minutes after coronary occlusion, increased to 87.5 +/- 11.3% immediately after nitroprusside infusion and continued at that level for 2 hours. Preejection tension rate of tension rise and ejection tension demonstrated parallel increases. Segment length, which had increased to 144.1 +/- 4.5% of control level after coronary occlusion, declined to 115 +/- 10.7% (P less than 0.02) immediately after the onset of infusion. The nonischemic zone showed a sustained increase in all tension variables (P less than 0.01) and a decrease in segment length during the period of nitroprusside infusion with a return to control value after discontinuation of the infusion. The immediate deterioration in tension in the ischemic zone caused by reperfusion after 2 hours of occlusion was prevented by nitroprusside. The border zone continued to maintain improved tension after reperfusion but exhibited an immediate decrease from 84.1 +/- 7.8% to 69.1 +/- 11.7% (P less than 0.05) after discontinuation of nitroprusside. In summary, nitroprusside infusion provides a sustained increase in tension and decrease in length of the border and the nonischemic zones after acute coronary occlusion whereas the ischemic zone remains unaffected. Although administration of nitroprusside fails to prolong the time period for functional reversibility of the affected zones with reperfusion, it appears to prevent further deterioration.