For hypoplastic left heart syndrome (HLHS), there have been concerns regarding pulmonary artery growth and ventricular dysfunction after first stage surgery consisting of the Norwood procedure modified with a right ventricle-to-pulmonary artery conduit. We report our experience using cardiovascular magnetic resonance (CMR) to determine and follow pulmonary arterial growth and ventricular function in this cohort.Following first stage palliation, serial CMR was performed at 1 and 10 weeks post-operatively, followed by cardiac catheterization at 4 – 6 months. Thirty-four of 47 consecutive patients with HLHS (or its variations) underwent first stage palliation. Serial CMR was performed in 20 patients. Between studies, ejection fraction decreased . Pulmonary artery growth occurred on the left  but not significantly in the right. This trend continued to cardiac catheterization 4–6 months post surgery, with the left pulmonary artery of greater size than the right . By CMR, 5 had pulmonary artery stenoses initially, and at 2 months, 9 had stenoses. Three of the 9 underwent percutaneous intervention prior to the second stage procedure.In this cohort, reasonable growth of pulmonary arteries occurred following first stage palliation with this modification, although that growth was preferential to the left. Serial studies demonstrate worsening of ventricular function for the cohort. CMR was instrumental for detecting pulmonary artery stenosis and right ventricular dysfunction. Hypoplastic left heart syndrome is a congenital cardiac malformation involving hypoplasia of the ascending aorta, aortic valve atresia or stenosis, a hypoplastic left ventricle, and mitral atresia or hypoplasia. Until tAt the University of Virginia, because of these concerns it became our clinical practice to perform a cardiovascular magnetic resonance (CMR) study prior to discharge and at two months of age, followed by cardiac catheterization at 4 – 6 months of age, in children with hypoplastic left heart syndrome. The next stage of surgical palliation was usually performed after 4 – 6 months of age, and involved ligation and division of the right ventricle-to-pulmonary artery conduit, and creation of a superior vena cava-to-pulmonary artery anastomosis. If CMR defined any significant pulmonary artery stenosis or coarctation, earlier transcatheter intervention was undertaken.The intent of this study was to report on the CMR assessment of growth of the pulmonary arteries and right ventricular function after the Norwood procedure with Sano modification for hypoplastic left heart syndrome.Approval for the study was obtained from the University of Virginia Institutional Review Board Human Investigations Committee. We retrospectively reviewed the results of all children admitted following birth to the University of Virginia with the diagnosis of hypoplastic left heart syndrome (or its variations) from 2002 to the end of 2006. The time period was chosen because in mid-2002 our institution switched from the "standard" modified Norwood procedure to the SFollowing an episode of unrecognized conduit and pulmonary artery stenosis leading to cardiovascular collapse, we began a clinical program of surveillance screening by CMR for the development of significant pulmonary artery stenosis or coarctation of the aorta. CMR was performed in patients prior to discharge after first stage surgery, and again at 2 months post-operatively. By prospective protocol, CMR was also performed at 1 year of age in patients with persistent late ventricular dysfunction as defined by follow-up echocardiography.Studies were performed with general anesthesia and endotracheal intubation, which allowed the patients to remain still for the studies. Cardiac CMR was performed on a 1.5 Tesla Sonata scanner . The patient was placed supine in a two-channel head coil with monitoring of electrocardiogram, blood pressure, and oxygen saturation. Steady state free precession (SSFP) cine imaging was performed with repetition time of 2.7 ms, echo time 1.3 ms, temporal resolution 19 ms, slice thickness 4 mm, flip angle 27°, field of view 200 mm, matrix 76 × 192, and 4–5 signal averages during free breathing. Spatial resolution for SSFP was 2.6 × 1.0 × 4.0 mm. Axial and right ventricular short-axis image stacks were obtained without a gap. In addition, velocity encoded gradient echo cine imaging was obtained perpendicular to the proximal portion of the right ventricle-to-pulmonary artery conduit and in the plane of the proximal branch pulmonary arteries with repetition time of 4 ms, echo time of 3.6 ms, temporal resolution of 29 ms, slice thickness 4 mm, flip angle 30°, field of view 200 mm, matrix 93 × 256, velocity encoded at 300 cm/s, and 3 signal averages during free breathing. Spatial resolution for velocity encoded images was 2.2 × 0.8 × 4.0 mm. Finally, a 3-dimensional contrast-enhanced CMR angiogram was obtained during infusion of 0.2 mM/kg of gadolinium-DTPA. The angiogram was obtained in 1 slab with repetition time of 3.75, echo time 1.4 ms, slice thickness of 0.9 mm, flip angle 30°, field of view 200 mm, matrix 75 × 320, and 6 signal averages. Spatial resolution for CMR angiogram images was 2.7 × 0.6 × 0.9 mm.Dedicated analysis software  was utilized to calculate end-diastolic ventricular volumes and systolic function from the short axis SSFP cine images. The anterior-posterior diameter of the branch pulmonary arteries was measured from the velocity encoded cine images and confirmed by the CMR angiogram, and the point of measurement was at the hilum. SSFP cine images were not used for this measurement because of off-resonance flow effects that prevented adequate visualization of the branch pulmonary arteries. Significant pulmonary artery stenosis or coarctation were defined by CMR as an abrupt luminal narrowing > 40%. Right vAt time of CMR, all patients also had transthoracic echocardiography to compare estimates of ventricular function, and diagnoses of pulmonary artery stenoses and aortic coarctation. Figure  PulmonarAll patients underwent cardiac catheterization prior to the second stage surgery, which was intended at 4–6 months of age. Right ventricular ejection fraction was calculated by calibrated biplane Simpson's rule . Given tThe authors had full access to the data and take responsibility for its integrity. All authors have read and agree to the manuscript as written.t tests, with statistical significance defined as p < 0.05.Serial measurements for patients were compared using analysis of variance for repeated measures, and comparison between patients was analyzed using unpaired From 2002 to 2006, 47 newborns with hypoplastic left heart syndrome , and right ventricular ejection fraction decreased .  but were not different compared with body growth . . However, pulmonary artery growth occurred mainly in the left pulmonary artery , but not significantly in the right , with the left pulmonary artery larger at time of the 2By CMR, 5 patients had pulmonary artery stenoses defined at the two-week study, and at the two-month study 9/20 had pulmonary artery stenoses. Three of these underwent early percutaneous intervention for severe unilateral stenoses. On all 9 patients with CMR-defined pulmonary artery stenosis, cardiac catheterization confirmed the diagnosis. In those patients without CMR-defined pulmonary artery stenosis, no significant pulmonary artery stenosis was found at time of pre-operative cardiac catheterization.However, the ability of echocardiography to diagnose CMR-diagnosed pulmonary artery stenosis was poor, with only a 6% sensitivity (1 of 18 stenoses were diagnosed by echocardiography). There were no false positive diagnoses of pulmonary artery stenosis by echocardiography.There was no significant change in conduit regurgitant fraction (15 ± 4% vs. 16 ± 5%) between studies.st stage survivors underwent percutaneous coarctation intervention, which was judged successful in 7, and one was felt not to have clinical coarctation despite the CMR findings. This was related to an artifact caused by a metal surgical clip. Of the patients not diagnosed by CMR with a coarctation, one was found to have a coarctation at time of the pre-operative cardiac catheterization.While 9 patients were defined by CMR at the 2-week study as having a coarctation, clinically it was determined that these did not require reintervention at that time. Among these 9 patients, coarctations in 6 persisted or worsened by the 2-month study, and resolved in 3. 2 additional patients developed a significant coarctation that was defined on the 2-month study. Ten of the 26 1Echocardiography agreed with CMR-diagnosed coarctation in 7 of 10 patients who underwent cardiac catheterization. A single patient erroneously diagnosed with a coarctation by CMR was thought not to have a significant gradient by Doppler, and two unsedated patients did not have adequate arch views to determine the presence of coarctation by echocardiography.Those patients not having a diagnosis of recurrent coarctation had a right ventricular ejection fraction by CMR of 48 +/- 8% as compared to those with recurrent coarctation their ejection fraction was 41 +/- 12% (p = NS).In this cohort of patients, CMR demonstrates an important role in the detection of surgical issues complicating the Norwood procedure with Sano modification. It was able to define pulmonary artery stenosis with 100% sensitivity and specificity, and has already been proven to be instrumental in the evaluation of right ventricular function and aortic coarctation.Pulmonary artery growth in this cohort of infants with hypoplastic left heart syndrome after the Norwood procedure with Sano modification was asymmetric, with greater growth in the left pulmonary than the right. This asymmetry of growth may be related to both the direction of the flow from the right ventricle-to-pulmonary artery conduit, which is preferential to the left pulmonary artery, and that the right pulmonary artery must then pass under the reconstructed aortic arch. This is in contrast to the standard Norwood palliation, which involves a modified Blalock Taussig shunt, which frequently comes off of the right-sided innominate artery and inserts onto the right pulmonary artery. Previous work has shown asymmetric growth of the pulmonary arteries after the right-sided modified Blalock Taussig shunt, with the right pulmonary artery larger than the left . In eithFor diagnosing recurrent or persistent coarctation of the aorta, the CMR has been described as highly sensitive and specific ,20. HoweIn this cohort of patients, in which the single ventricle is of right ventricular morphology and in which a ventriculotomy was performed, there was a significant depression of systolic function, as measured by serial study. In addition, out of 26 initial hospital survivors, 2 subsequently underwent cardiac transplantation with another currently being listed. The indication in all 3 such patients was symptomatic heart failure. It is possible that the ventriculotomy plays a role in the development of late ventricular dysfunction, as has been noted in other centers . It is aBoth the survival to discharge and the interstage mortality in this cohort of patients following the Norwood procedure with Sano modification were similar to other reports in the current era,10,22,23Limitations of the present study include the different imaging modalities to evaluate right ventricular, pulmonary artery, and aortic anatomy and function. However, previous work has demonstrated excellent correlation between CMR and cardiac catheterization for right ventricular volumes and function,25, for Development of significant pulmonary artery stenosis, coarctation, and right ventricular dysfunction occurs in a portion of patients undergoing the Norwood palliation with Sano modification for hypoplastic left heart syndrome. Cardiovascular magnetic resonance is instrumental in surveillance for such complications.HLHS: Hypoplastic left heart syndrome; CMR: Cardiac magnetic resonance imaging.DSL, BBP, and GPM have no conflicts of interest to disclose. CMK has research equipment support from Siemens Medical.DSL designed the study, collected data, and drafted the manuscript. BBP performed the surgeries and drafted a portion of the manuscript. GPM participated in study design and data collection. CMK participated in study design and data collection, and drafted a portion of the manuscript. All authors read and approved the final manuscript.


Propafenone, a Class IC antiarrhythmic drug, is an orally active sodium channel-blocking agent. It is effective in supraventricular tachyarrhythmias and is particularly useful in converting atrial fibrillation to sinus rhythm. In therapeutic doses, it may cause non-cardiac and cardiac toxicity, including  proarrhythmia. A 69 year-old female with hypertension and paroxysmal atrial fibrillation presented with palpitations and dyspnea. Her current medications included enalapril, atenolol and amiodarone. Physical examination showed heart rate 140 bpm and irregular. Blood pressure was 140/90 mm Hg. There was no evidence of heart failure. She was initially treated with verapamil 5 mg (IV) for rate control and propafenone 600 mg  for pharmacological cardioversion. Being admitted, the patient reported rapid palpitations, dizziness and increased dyspnea. A 12-lead electrocardiogram (ECG) showed self-limited wide QRS complex tachycardia  at a heaPropafenone is a class IC antiarrhythmic drug that is commonly used for atrial fibrillation treatment . HoweverMetabolism of propafenone is mediated by the cytochrome P-450 (CYP) isoenzyme system, including CYP2D6 (major metabolic pathway), CYP1A2 and CYP3A4. Patients should be monitored and dosage of propafenone should be reduced accordingly when the drug is used concurrently with other inhibitors of CYP2D6 (e.g.: quinidine) and CYP1A2 (e.g.: amiodarone) because plasma concentrations may increase. In therapeutic doses, propafenone may cause non-cardiac and cardiac toxicity including: agranulocytosis, reactive airway disease, hemolysis, drug fever, ataxia, hypotension, prolonged QRS duration, ventricular arrhythmias, depressed mental status, seizures and sudden death. The overall incidence of proarrhythmia with propafenone is unknown. It was reported as high as 5-10% [The ventricular response during AFL is determined by the refractory period of the AV node, the degree of concealed conduction within the node, and the status of the autonomic tone. The association of 1:1 AFL with high catecholamine levels has been previously described. Sympathetic tone might play an important role in the occurrence of 1:1 AFL . KawabatPropafenone can produce sustained monomorphic ventricular tachycardia, which is characterized by a marked increase in QRS duration and not associated with QT interval prolongation. Its heart rate is relatively slow but tends to be incessant. The mechanism of this proarrhythmic effect is likely to be due to a delay of conduction in the His-Purkinje system. This effect may encourage reentry by allowing extra time for refractory tissue to recover, thus allowing it to be reexcited  .Propafenone is a useful drug for the treatment o atrial fibrillation. It has proarrhythmic effects, such as 1:1 conducted atrial flutter and ventricular tachycardia. Rapid recognition of these complications allows discontinuing the medication and resolution of the proarrhythmia.


Mechanoelectric feedback (MEF) describes the modulation of electrical activity by mechanical activity. This may occur via the activation of mechanosensitive ion channels (MSCs). MEF has not previously been investigated in fish ventricular tissue even though fish can greatly increase ventricular end diastolic volume during exercise which should therefore provide a powerful mechanical stimulus for MEF.NSs). We then cloned the trout ortholog of TRPC1, a candidate MSCNS and confirmed its presence in the trout heart.When the ventricles of extrinsically paced, isolated working trout hearts were dilated by increasing afterload, monophasic action potential (MAP) duration was significantly shortened at 25% repolarisation, unaltered at 50% repolarisation and significantly lengthened at 90% repolarisation. This observation is consistent with the activation of cationic non-selective MSCs (MSCOur results have validated the use of MAP technology for the fish heart and suggest that, in common with amphibians and mammals, MEF operates in fish ventricular myocardium, possibly via the activation of mechanosensitive TRPC1 ion channels. MSCNS hThe influence of MSCs on the electrical activity of the intact heart has been studied by measurement of monophasic action potentials (MAPs) NS are highly implicated in the modulation of cardiac activity by stretch, their identity is still uncertain. Evidence suggests that transient receptor potential canonical (TRPC) channels are non-specific cationic ion channels that are also mechanosensitive Although MSCThe fish heart is exquisitely sensitive to stretch through the Frank-Starling response which links cardiac output to venous return . The Frais) and output pressures (Pos), we investigated the effect of myocardial stretch on the electrical activity of the isolated working fish heart to provide evidence to support the presence and physiological activity of MSCNS-like channels. Finally, we confirmed the presence of a candidate MSCNS channel, TRPC1, in the fish heart by cloning the channel and assessing its tissue distribution.We tested the hypothesis that MEF is present in fish ventricular myocardium. To do this our first aim was to validate the use of MAP technology in fish myocardium. Next, over a physiological range of input pressures (POncorhynchus mykiss) were purchased from Chirk Trout Farm . The trout were kept in re-circulated freshwater tanks at 11±1°C with a 12∶12 h light-dark photo-cycle and fed with commercial trout pellets to satiation three times a week.All procedures used in these experiments adhere to the local ethics committee and the United Kingdom Home Office Animals Scientific Procedures Act of 1986. The University of Manchester local ethics committee approved schedule 1 killing of rainbow trout with no need for a waiver of consent. Rainbow trout  was included in all solutions to preserve cardiac tonus and minimize muscle fatigue Fish  were sacrificed by concussion of the brain by striking the cranium. The heart  was excised and placed in an organ bath. The heart was then cannulated so that the inflow entered the heart through the sinus venosus and the outflow exited the heart through the bulbus arteriosus. The cannulated heart was perfused with physiological saline which contained (in mM) NaCl, 150; KCl, 5.4; MgSOi and afterload to Po by pressure transducers  attached to a ML301 bridge pod and Powerlab/4sp data acquisition system . Pressure transducers were calibrated daily using a delta-cal transducer simulator/tester . SV and cardiac outputs were calculated by collecting the solution pumped by the ventricle through the bulbus arteriosus.To dilate the ventricle and stretch the myocardium, preload and afterload on the heart could be increased by altering the heights of the reservoirs connected to the sinus venosus and bulbus arteriosus, respectively. Preload was related to Pi was sequentially raised from 0.058±0.003 kPa up to a maximum of 0.322±0.011 kPa. At a Pi of 0.322±0.011 kPa, the Po was increased from 0.5 kPa to 7.5 kPa in a stepwise manner. Because AP duration is dependent upon heart rate in the rainbow trout Initially the heart was allowed to beat spontaneously to assess the effect of stretch upon heart rate. Cardiac output, heart rate and MAPs were measured as Pet al. MAP electrodes were made to the design described and validated for use in small mammalian hearts by Knollmann MAPs were recorded from the surface of the ventricle adjacent to the bulbus arteriosus. This was achieved by placing the recording element in contact with the ventricle under slight tension so that the spring-like electrode was able to maintain contact with the ventricle during the filling and emptying stages of the cardiac cycle to eliminate motion artefacts. The reference element was in contact with solution surrounding the heart but not in direct contact with the surface of the heart. Electrodes were connected to an ml136 bio amp and Powerlab/4sp data acquisition system . Twelve individual MAPs were recorded and averaged for analysis at each condition tested (see below). MAP duration (MAPD) was assessed at 25%, 50% and 90% repolarisation  using Chart v5 . AP triangulation is a measure of the change in shape of the AP in response to an intervention Because this was the first study to measure MAPs in the fish heart, electrocardiograms (ECGs) were simultaneously measured with MAPs to match QT intervals to MAPD as a validation of the duration of ventricular repolarisation. ECGs were recorded from the surface of the heart by electrodes constructed from 2 mm Ag/AgCl pellet electrodes . ECG electrodes were placed on the base and apex of the ventricle We also recorded APs from isolated ventricular myocytes from the rainbow trout at 11°C using a whole-cell current clamp to compare the profile of the single myocyte APs with that of the MAP recordings. Myocytes were isolated as previously described NS, it has not been investigated in the trout heart. We cloned the trout variant of TRPC1 (omTRPC1), firstly to determine its tissue distribution, particularly in the heart, and secondly to compare its sequence homology to mammalian TRPC1.TRPC1 is a candidate cardiac MSCThe atrium, ventricle and samples of gill, brain, kidney, intestine, gonad, liver and skeletal muscle were removed from sacrificed trout and immediately frozen in liquid nitrogen. Total RNA was extracted from these tissues with TRIzol reagent  according to the manufacturer's instructions. RNA was qualified by gel electrophoresis and quantified using an ND-1000 spectrophotometer .18 primer, as recommended by the manufacturer. cDNA corresponding to a 350 bp sequence at the 3′ end of omTRPC1 was obtained by PCR using degenerative primers designed to the homologous regions of corresponding mammalian, amphibian, avian and zebrafish genes: (FWD 5′-TGGYTBAGCTAYTTYGATGACAA-3′ and REV 5′-TGGAGGCTTTGGTGKAGAAT-3′). PCR amplification was performed using BIOTAQtm DNA Polymerase , according to manufacturer's instructions, in a 50 µl reaction mixture using a PTC-100 Peltier Thermal Cycler . Amplification was performed under PCR conditions with initial denaturation at 94°C for 2 min followed by 30 cycles at 45°C for 30 s, 56°C for 30 s, and 72°C for 2 min and final extension at 72°C for 2 min. PCR products were checked on a 0.8% agarose gel. 1∶100 dilutions of the PCR products were used in nested PCR reactions with a nested forward primer (5-AAYCATGARGAYAARGARTGGAA-3′) under similar conditions.For cDNA synthesis 1 µg total RNA was treated with DNAase I  and reverse transcribed with superscript II reverse transcriptase (Invitrogen) and an oligo(dT)5′-CAGGTCTCTCATCTCGTTGCGGAACTT-3′) and Universal Primer A Mix (UPM) which recognises the BD SMART sequence. A touchdown PCR protocol was employed following manufacturer's guidelines. A new 5′ primer was designed on the basis of the sequences obtained (5′-ACCTGGAGTGCCGTAGGCTGTCCTTCTTG-3′) and used to clone the remainder of the 5′end under the same conditions. The remaining 3′ end of OmTRPC1 was amplified using a 3′ primer (5′-CCGCTACCTGACCTCCACGCGGCAGAA-3′).The 5′ and 3′ ends of omTRPC1 were amplified using Clontech's SMART RACE cDNA Amplification Kit for rapid amplification of cDNA ends. The cDNAs for the 5′ and 3′ RACE were synthesised from total RNA, from the trout brain, using a modified lock-docking oligo (dT) primer in combination with BD SMART II A oligonucleotide. The 5′ end of the cDNA encoding omTRPC1 was amplified using the omTRPC1 5′Race primer  and sequencing reactions carried out using Applied Biosystems  BigDye sequencing kit version 1.1. Amino acid sequence comparisons were performed using DNAMAN .tm DNA Polymerase  was used in 50 µl reaction mixtures, following the PCR protocol: initial denaturation at 94°C for 2 min followed by 25 cycles for β-actin, or 30 cycles for omTRPC1, at 94°C for 30 s, 58°C for 30 s, and 72°C for 2 min and final extension at 72°C for 2 min. Gel electrophoresis on a 0.8% agarose gel was used for qualification and comparison.Gene specific primers were designed from our sequencing products and β-actin primers were designed using the NCBI nucleotide sequence for rainbow trout β-actin. Reverse transcription polymerase chain reactions (RT-PCRs) were carried out on pooled cDNA prepared from the tissue samples (n = 3). BIOTAQpost hoc test, as described in the figure legends . p<0.05 indicated a significant difference. All data are reported as means ± S.E.M.Statistical analysis was performed using one-way ANOVA or one-way RM ANOVA followed by the appropriate We were able to record trains of MAPs from the surface of beating trout hearts that displayed minimal basal line disturbance, indicating negligible motion artefacts in the recordings . The proi to a maximum (1.10±0.17 ml kg−1) at a Pi of 0.21±0.12 kPa (p<0.05). In addition, a significant elevation of heart rate from 0.36±0.02 to 0.78±0.07 Hz (p<0.05) was observed when Pi was increased . When the heart was paced at 0.8 Hz, increasing Po from 0.5 to 7.5 kPa only reduced SV slightly, by an average of 0.1 ml kg−1 , illustrating homeometric regulation of the isolated working heart In the spontaneously beating heart, raising Pi up to 0.322±0.011 kPa, followed by a stepwise increase of Po up to 7.5 kPa. i was raised to 0.322±0.011 kPa there was a significant shortening of MAPD25 to 155±53 ms (p<0.05). Raising Po to 7.5 kPa significantly shortened MAPD25 from all previous conditions  (i or Po had no significant effect on either MAPD50 or MAPD90.Stretch was applied to the heart via an increase in P p<0.05) . IncreasIncreased heart rate is known to decrease AP duration in the rainbow trout i was held at 0.322±0.011 kPa. Stretch was applied by increasing Po up to a maximum of 7.5 kPa. o was increased . MAPD50 was unaffected by changes in Po , whereas MAPD90 was significantly increased . The QT interval of the ECG also significantly increased . The effect of these changes on MAP profile can be seen in o is demonstrated by the significant change in MAP triangulation with increased Po (The hearts were paced at 0.8 Hz and Peased Po .Coding regions of the omTRPC1 gene (accession number: GQ366701) were cloned from rainbow trout cDNA. omTRPC1 is 779 amino acids in length and shares 83.8% homology with human TRPC1 . This iset al. Our MAP recordings are the first from a fish species and exhibit a time course and profile that is consistent with both the QT interval of the associated surface ECG and the intracellular APs recorded from isolated myocytes. The upstroke of the MAP was slower than that of the intracellular AP, which is consistent with previous comparisons of MAPs and intracellular APs from mammals. This is thought to be related to the fact that the MAP is recorded from a small area of tissue around the MAP electrode rather than a single myocyte and that there is a sequential alteration in current flow across this area of tissue is used in this study are similar to those used in previous work on isolated trout hearts  is equal or greater than that achieved in a similar study where the coronary system was perfused is as seen in vivo and in situThe range of Prts e.g.  and thosi and Po. We show an initial stretch-induced shortening of MAPD25 in both the spontaneously beating and externally paced isolated heart. This phenomenon was first reported in the frog ventricle NS (and possibly MSCK) driving the membrane potential to their respective equilibrium potentials We found that the electrical properties of the isolated trout ventricle were significantly altered when subjected to raised PNS is predicted to lengthen MAPD90. It was therefore possible that our observations in spontaneously beating hearts were an amalgamation of these two effects. In addition to activation of MSCs, stretch may also alter intracellular Ca2+ handling and thus Ca2+ activated membrane currents 2+ transient We saw no change in MAPD90 in the spontaneously beating heart. Stretch increased heart rate and an increase in heart rate leads to a shortening of APD in fish NSs et al.  in rainbow trout cardiac tissue. We found omTRPC1 in both the atria and ventricle of the trout heart to be similar to that of most other tissues apart from the brain, where expression was higher. Although mRNA expression does not directly relate to protein expression, the study by Ohba The fact that omTRPC1 shares 83.8% homology with mammalian TRPC1 is promising as it may have similar mechanosensitive properties. Unfortunately, it is not known which part of the protein confers mechanosensitivity and so it is impossible, at present, to asses if differences in mechanosensitivity are due to differences in the amino acid sequence.NS in fish myocardium, the Po required (5.5 kPa) to significantly alter the MAP are comparable to those measured in swimming trout NS are of physiological significance when a fish is active. As TRPC1 has been implicated in the promotion of mammalian cardiac hypertrophy In terms of the physiological importance of MEF and MSCi and Po, in a manner consistent with the activation of MSCNS, and TRPC1 (a candidate MSCNS) is present in the rainbow trout heart and is broadly similar to its mammalian ortholog. Thus our data are consistent with the idea that MEF is a common feature in the regulation of vertebrate cardiac muscle. In addition, the T-tubule network has been proffered to explain why, despite recordings of whole cell currents carried by MSCNS, no study has successfully recorded single channel activity of MSCNS from mammalian ventricular myocytes NS in adult ventricular tissue.This study provides the first MAP recordings from a fish species and is the first investigation into the effects of stretch on the electrical activity of fish ventricular myocardium. There are three principal findings: MAP recordings are a valid technique for use in fish hearts; MEF operates in trout ventricle, within physiological extremes of P


The use of cardiac imaging modalities has grown steadily, and cardiac nuclear studies constitute a large part of this number. Nuclear Cardiology is often mistakenly considered a synonym of myocardial perfusion imaging (MPI), but has broader applications, including metabolic imaging, innervation imaging, among other technologies. MPI has been a powerful diagnostic and prognostic tool in the assessment of patients for known or suspected CAD for decades, and is now increasingly used for the evaluation of the anti-ischemic effects of various therapies, according to changes in left ventricular perfusion defect size defined by sequential MPI. Neuronal dysfunction identified with iodine-123-metaiodobenzylguanidine may give information on prognosis in different disease conditions, such as after myocardial infarction, in diabetes and dilated cardiomyopathy. Molecular imaging may identify the predominant cellular population in the atherosclerotic plaque and help predict the likelihood of clinical events. Therefore, although its usefulness is well established, Nuclear Cardiology remains a moving science, whose roles keep in pace with evolving clinical needs and expectations. In association with the elevated prevalence, morbidity and mortality of coronary artery disease (CAD) worldwide, there has been a steady increase in the use of cardiac imaging techniques, including those based on Nuclear Medicine. In fact, cardiac studies have outgrown Nuclear Medicine and have constituted an individual subspecialty, Nuclear Cardiology. This imaging modality is often, although incorrectly, considered as a synonym for myocardial perfusion imaging (MPI), which by its turn means the evaluation of myocardial perfusion after stress versus at rest, using a variety of tracers and stressor agents in different protocols. It extends far beyond, though, including metabolic imaging, innervation imaging, among other technologies. This review will discuss current and evolving applications of Nuclear Cardiology, starting with MPI, which remains its cornerstone.For the last 2 decades, MPI has been an essential part of the diagnostic and prognostic assessment of patients for known or suspected CAD. However, as time went by and new demands and technologies have been developed, other applications of MPI have emerged, and its roles have advanced continuously. In the 1980’s, planar and then tomographic  perfusion imaging was found to reliably diagnose CAD -5. LaterMPI is a useful tool for the diagnosis of CAD ,2. It isMPI may be applied for prognostic evaluation both for patients with known or suspected CAD. It relies on 2 principles: first, a normal MPI study confers a low (<1%) short-term risk of cardiac events ; second,vs. OMT alone in stable CAD patients. A subgroup of the total population had MPI performed before and after treatment (mean 1 year after enrollment), and in this nuclear substudy, the results showed that ischemia reduction was greater with PCI+OMT than with OMT alone (33.3% versus 19.8% had ≥5% reduction of ischemia). For all patients combined, the death or myocardial infarction rate was 13.4% for patients who had ≥5% reduction of ischemia and 24.7% for those who did not have reduction at the follow-up study. This study indicated that, for stable CAD patients, having knowledge of the ischemic burden is helpful in decision-making with respect to selecting initial therapy, and regardless of the therapeutic modality used, assessment of the response to therapy, which is related to long-term outcome, is also important. Another aspect of this same application of MPI is the identification of revascularization candidates according to the amount of jeopardized myocardium and the survival benefit that a patient may obtain from a specific therapy as a function of MPI results. MPI has been able to discriminate (as a “gatekeeper”) which patients will likely benefit from invasive coronary angiography followed by coronary revascularization and who may be well suited with medical therapy [An increasingly used application of Nuclear Cardiology is to evaluate the anti-ischemic effects of various therapies by means of identifying changes in left ventricular perfusion defect size by sequential MPI and thereby track patient risk for subsequent cardiac events on the basis of the magnitude of ischemia suppression. An example is the COURAGE  trial , which eThe noninvasive detection of silent CAD is an important clinical goal in certain high-risk asymptomatic populations. Occult CAD precedes the onset of clinically manifest CAD, which too often presents as sudden death or acute myocardial infarction. Detection of occult CAD in a preclinical stage might lead to risk factor modification and institution of treatment, which would prevent or delay the onset of clinical disease, since there is now good evidence that aggressive risk factor modification can slow the progression of atherosclerosis. Bayesian analysis indicates that the detection of occult CAD by noninvasive testing should be more accurate in asymptomatic groups with high CAD prevalence, since test performance is worse in low prevalence populations . As a reNoninvasive imaging to determine the presence and extent of dysfunctional but viable myocardium has become an important component of the diagnostic assessment of patients with CAD and depressed left ventricular function. It is now well established that left ventricular dysfunction in patients with CAD is not always an irreversible process related to previous myocardial infarction because left ventricular function may improve substantially after revascularization procedures in patients with chronic CAD, and this may translate into an improvement in survival . The difIodine-123-metaiodobenzylguanidine (MIBG) was first reported as a potential neuronal imaging agent for detection of pheocromocytoma, since it has structural similarity with norepinephrine and therefore is taken up by peripheral sympathetic nerves. Further studies have shown reduced localization in denervated regions of the myocardium, after myocardial infarction, in diabetes and dilated cardiomyopathy, among other conditions , 26. MIBThe lack of widespread availability of PET cameras and radiotracers, their high costs and reimbursement issues have limited the clinical use of this technology. Recent developments are likely to change this scenario, though, since there has been a growth in the number of PET cameras and rubidium-82 generators used for perfusion imaging. This leads to real benefit, since positron emission tomography (PET) has several technical advantages over SPECT, including higher spatial resolution, accurate attenuation correction, higher temporal resolution and quantitative imaging capability that afford measurement of rapidly changing radiotracer activity concentrations in blood and myocardium. All of those determine a clinical advantage over SPECT, which often uncovers only the territory supplied by the most severe stenosis and therefore may underestimate the significance of coronary lesions; in this regard, PET has superior capability to detect multivessel CAD ,29. Computed tomography of the coronary arteries (CTA) has gained enormous popularity in a short time period, and has been taken by some as a “threat” for Nuclear Cardiology. CTA and MPI differ in what each evaluates- anatomy for one and physiology for the other. Hybrid systems are now available allowing the combined assessment of anatomy and function, linking the anatomic richness of CTA and the functional importance of perfusion either from PET or SPECT. MPI and CTA are most likely complementary imaging modalities, with the choice and sequence of testing depending on the particular clinical question and specific patient population being evaluated , 31. BMIPP is a fatty acid analog which allows metabolic imaging since most of the energy requirement of the normal myocardium under aerobic status is derived from the metabolism of fatty acids. Since under ischemia or in heart failure, beta-oxidation of fatty acids in mitochondria is reduced, early washout of BMIPP from the myocardium occurs and the uptake detected by SPECT is reduced. BMIPP imaging may be used in unstable angina, vasospastic angina and cardiomyopathies, among other indications ,33. In pin vivo is a problem and highlights the difficulty in the use of this innovative technique. In the carotids, F-18 FDG has been studied for plaque inflammation and technetium-99m-annexin SPECT has been evaluated for apoptosis within the plaque, both known markers of plaque instability [The management of CAD has almost always been based on demonstration of the severity of luminal stenosis; such an approach, however, does not characterize the plaque morphology that happens to be the major determinant of clinical outcome ,36. Apprtability ,40. Although initially applied for diagnostic purposes, Nuclear Cardiology has grown and keeps moving. Many advances have increased its applications, and many more, regarding novel instrumentation techniques and new tracers are on their way to clinical practice. Perhaps the greatest potential for the future of Nuclear Cardiology lies in molecular imaging, and Nuclear Cardiology may hopefully achieve one of the most difficult goals in Cardiology: to identify the vulnerable, rupture-prone coronary plaque.


Admission hyperglycemia was defined as a glucose level ≥ 7.8 mmol/l. Contrast-enhanced CMR was performed between 3 and 7 days after reperfusion to evaluate left ventricular function and perfusion data after injection of gadolinium-DTPA. First-pass images (FP), providing assessment of microvascular obstruction and Late Gadolinium Enhanced images (DE), reflecting the extent of infarction, were investigated and the extent of transmural tissue damage was determined by visual scores.1c (p = 0.01 and 0.04), peak plasma Creatine Kinase (p < 0.001), left ventricular end-systolic volume (p = 0.005 and <0.001), and lower left ventricular ejection fraction (p = 0.001 and <0.001).Patients with a supramedian FP and DE scores more frequently had left anterior descending culprit artery (p = 0.02 and <0.001), multivessel disease (p = 0.02 for both) and hyperglycemia (p < 0.001). Moreover, they were characterized by higher levels of HbAIn a multivariate model, admission hyperglycemia remains independently associated with increased FP and DE scores.Our results show the existence of a strong relationship between glucose metabolism impairment and myocardial damage in patients with STEMI. Further studies are needed to show if aggressive glucose control improves myocardial perfusion, which could be assessed using CMR. Admission hyperglycemia is associated with increased short and long term risk of death in patients with ST-segment elevation myocardial infarction (STEMI), independently of the presence of Diabetes Mellitus -3; this Cardiac Magnetic Resonance (CMR) with a gadolinium-based contrast agent is considered to accurately assess myocardial perfusion and function abnormalities after STEMI. First pass (FP) perfusion provides a valuable assessment of the extent of microvascular obstruction (MO) , and LatThe objective of the present study was to investigate the relationship between blood glucose levels taken on admission and myocardial perfusion parameters assessed by contrast-enhanced CMR in patients after reperfusion of an acute STEMI.One hundred and thirty one consecutive patients presenting with a first acute STEMI and who underwent primary percutaneous coronary intervention  for arteries exhibiting Thrombolysis In Myocardial Infarction (TIMI) flow grade < 3, within 24 hours after symptom onset, were included in the study. Patients with TIMI flow <3 on the culprit lesion after PCI, or who were hemodynamically unstable or with a contraindication for CMR were excluded from the study. The diagnosis of STEMI was based on prolonged chest pain, ST-segment elevation ≥ 2 mm in at least two contiguous electrocardiographic (ECG) leads, and a more than three fold increase in serum creatine kinase (CK) levels ,13.Fourteen patients with a TIMI flow <3 post-PCI and 4 patients with contraindications for CMR were excluded from the studyTherefore, the study population consisted of 113 patients .All participants gave written consent before entering the study, in accordance with a protocol approved by the institutional ethics committee.2, kg/m2), clinical history of hypertension, diabetes mellitus, hypercholesterolemia, smoking, previous PCI and/or Coronary Artery Bypass Graft and peripheral arterial disease were recorded as were on-admission clinical data . Heart failure was defined by Killip class > 1. Location of MI was determined according to ECG, coronary angiographic and CMR data; no discordance was observed between the 3 methods. Current treatment before hospitalization was also recorded. Blood samples were taken at admission to measure glucose and C-Reactive Protein levels. HbA1c, HDL-Cholesterol, LDL-Cholesterol and triglyceride levels were assessed from fasting blood sample taken on the first morning after admission. Peak plasma levels of Creatine Kinase (CK) were also evaluated and dichotomized at ten times the upper normal limit for more clinical relevance. Baseline serum creatinine clearance was also evaluated by the Cockcroft-Gault formula [Demographic data, age, gender, Body Mass Index , using a phased array body coil. Left ventricular (LV) long-axis scout images were obtained to determine the orientation of the LV short axis imaging planes.For LV function evaluation, cine-CMR was performed using a breath-hold ECG-gated gradient echo sequence (FLASH 2D), with the following acquisition parameters: repetition time (TR) 9 ms, echo time (TE) 4.4 ms, pulse flip angle (α) 15°, 9 lines per segment, field of view (FOV) of 350 to 400 mm. The acquisition matrix varied from 108 × 256, (12 cardiac cycles), to 144 × 256, (16 cardiac cycles), depending on the ability of patient to hold his breath. A series of short-axis slices (thickness of 5 mm with a gap between slices of 10 mm) was defined from the base of the heart to the apex [For LV perfusion evaluation, a first-pass ECG-gated gradient echo sequence was performed (T1-weighted turboFLASH sequence) after injection of a bolus of gadolinium-diethylenetriamine pentaacetic acid  into a brachial vein at 0.1 mmol/Kg; the acquisition parameters were as follows: inversion time (TI) 400 ms, TR 3.5 ms, TE 1.7 ms, FOV 350 to 400 mm, and acquisition matrix 96 × 128, interpolated to 256 × 256. A time delay buffer at the end of the sequence was adjusted in order to acquire one image every two cardiac cycles. Three to 5 short-axis slices were obtained from the base of the heart to the apex, with the same plane as for the functional study (thickness of 12 mm with a gap between slices of 3 mm)  for 16 segments , and late images  for each of the 17 segments . Early regional hypoenhancement and late regional hyperenhancement were scored with a scheme based on the transmural extent of contrast enhanced tissue within each segment . The two scores, FP, which reflects microvascular obstruction and DE, which reflects myocardial infarct size, were determined by calculating the sum of the scores of all of the segments . Thus, the scores ranged from 0 to 64 for FP, and from 0 to 68 for DE images . Some arConcordance between expert investigators was satisfactory (interobserver variability <5%). In cases of disagreement, the final decision was taken by consensus.th percentile – 75th percentile) and dichotomous data as numbers (percentages).Continuous data were expressed as median , in accordance with the guidelines of the American Diabetes Association . Patient1c, peak CK level, ESV and LVEF. Moreover, age and sex were also included in the models.Multivariate logistic regression analysis was performed to test for independent predictors of high perfusion scores . The following variables, with a p value of less than 0.1 on univariate analysis were included in the models: left anterior descending culprit artery, multivessel disease, TIMI 0 or 1 before PCI, hyperglycemia, HbAThe Spearman rank test was performed to analyse the relationship between glycemia and perfusion scores.All the tests were two-sided and a p value <0.05 was considered as significant.Statistical analysis was performed with Sigmastat version 2.3 .1c (p = 0.01), peak CK (p < 0.001), ESV (p = 0.005) and DE score (p < 0.001) were higher in patients with a high FP score. In contrast, LVEF was lower in the group with a high FP score (p < 0.001).Characteristics of the patients according to the median value of the FP score are shown in Tables Multivariate analysis showed that peak CK  and hyperglycemia  were independent predictors of high (supra-median) FP scores. However, when DE score was included in the multivariate model, only DE remained an independent predictor of high FP score (Table 1c (p = 0.04), peak CK (p < 0.001), EDV (p = 0.01), ESV (p < 0.001) and FP score (p < 0.001) were also increased in this group. In contrast, LVEF (p < 0.001) was significantly decreased in patients with higher DE scores. Multivariate analysis showed that hyperglycemia , left anterior descending culprit artery  and peak CK  were independent predictors of high DE scores. When FP score was included in the multivariate model, hyperglycemia, left anterior descending culprit artery, peak CK, and FP score remained independent predictors of high DE score (Table Patients with high DE scores (> median) had increased risk of left anterior descending culprit artery p < 0.001), TIMI 0 or 1 before PCI in culprit artery p = 0.003) and hyperglycemia (p = <0.001) . Categorization of patients according to the presence of hyperglycemia showed that FP  or markers of myocardial infarct size . The impact of stress hyperglycemia on the extent of myocardial necrosis is not fully understood. Acute hyperglycemia may increase the inflammatory response during STEMI, and could thus influence microvascular permeability and oedema [CMR, with Late Gadolinium Enhancement is widely used to define infarct size. Extra-cellular contrast-agents accumulate in the myocardium due to increased capillary permeability oedema, increased extra-cellular space and slower kinetics in infarcted regions ,35. One d oedema . Moreoved oedema . They alFinally, admission hyperglycemia may not only be the cause of more severe myocardial damage, but also its consequence. Large myocardial infarcts are more likely to cause excessive secretion of catecholamine, which affect fatty acids and glucose homeostasis . HoweverFollow-up data were not available in this study, which attenuates the impact of the study conclusion.For evaluation of perfusion and Late Gadolinium enhancement, we did not use a real quantitative method but a semi-quantitative visual method to grade the extent of transmural myocardial damage ,22. HoweThe correlation between glycemia and perfusion scores, although significant, was weak. This relation was consolidated by the analysis of determinants of supramedian perfusion scores Table . HoweverAbnormal glucose metabolism is strongly associated with MO and the extent of myocardial infarct in successfully reperfused STEMI, as assessed by CMR. These results emphasize the interest of aggressive glucose control at the acute phase of STEMI. Moreover, CMR could play a major role in evaluating the impact of glucose control on myocardial perfusion.CK: Creatine Kinase;CMR: Cardiac Magnetic Resonance Imaging;DE: Delayed Contrast-Enhanced;EDV: Left Ventricular End Diastolic Volume;ESV: Left Ventricular End Systolic Volume;FP: First Pass;LVEF: Left Ventricular Ejection Fraction;MO: Microvascular Obstruction;PCI: Percutaneous Coronary Intervention;STEMI: ST-Segment Elevation Myocardial Infarction;TIMI: Thrombolysis in Myocardial Infarction.The author(s) declare that they have no competing interests.Each author have contributed significantly to the submitted work. Analysis and interpretation of data have been performed by AC, MZ, IL and CT; drafting of the manuscript by AC, MZ, YC, FB, and JEW; AL, PMW and BV have revised the manuscript for important intellectual content. All authors read and approved the final manuscript.


Heart failure with preserved left ventricular ejection fraction and abnormal diastolic function is commonly observed after recovery from an acute myocardial infarction. The aim of this study was to investigate the physiopathology of heart failure with preserved ejection fraction in a model of healed myocardial infarction in dogs.Echocardiography, levels of neurohormones and conductance catheter measurements of left ventricular pressure-volume relationships were obtained in 17 beagle dogs 2 months after a coronary artery ligation, and in 6 controls.Healed myocardial infarction was associated with preserved echocardiographic left ventricular ejection fraction  and altered Doppler mitral indices of diastolic function. NT-proBNP was increased, aldosterone was decreased, and norepinephrine was unchanged. Invasive measurements showed a markedly decreased end-systolic elastance  and end-systolic elastance to effective arterial elastance ratio , with altered active relaxation  but preserved left ventricular capacitance  and stiffness constant. Among echocardiographic variables, the wall motion score index was the most reliable indicator of cardiac contractility while E', E/A and E'/A' were correlated to dP/dtmin.In the canine model of healed myocardial infarction induced by coronary ligation, heart failure is essentially characterized by an altered contractility with left ventricular-arterial uncoupling despite vascular compensation rather than by abnormal diastolic function Heart failure with preserved left ventricular (LV) systolic function as assessed by echocardiographic measurement of an ejection fraction (EF) higher than 50%, together with altered indices of diastolic function , is obseIn order to explain the pathophysiological mechanism (diastolic versus systolic heart failure) of elevated diastolic pressures, we investigated systolic and diastolic function by invasive studies of LV pressure-volume relationships in dogs, two months after recovery from myocardial infarction induced by a coronary ligation. We also recorded indices of systolic and diastolic function by Doppler echocardiography and tissue Doppler imaging, and measured circulating neurohormones N-terminal B-type natriuretic propeptide (NT-proBNP), aldosterone and norepinephrine, to investigate their potential value in predicting systolic and diastolic alterations in LV function.2 of 1, a respiratory rate of 12 cycles/min and a tidal volume of 12 - 15 ml/kg. Lactate-Ringer was infused at 10 ml/kg/hour and sufentanyl at 1 μg/kg/hour. During anesthesia, care was taken to maintain body temperature above 36°C. A left thoracotomy was performed, the pericardium opened, and the left circumflex artery and/or its marginales dissected and permanently ligated with special care to obtain the same infarction extent despite individual anatomical variations. This procedure was realized under constant ECG monitoring, and ventricular arrhythmias were treated with lidocaïne (2 to 4 mg/kg IV over a period of 2 minutes followed by an infusion of 75 μg/kg/min). After surgery, buprenorphine  and cefalexin  were administered during 48 hours.The protocol was approved by the Animal Care and Use Committee of the ULB, and conformed to the "Guide for the Care and Use of Laboratory Animals published by The US National Institutes of Health .Twenty-three beagles , weighing 13.7 ± 0.4 kg and aged 12 ± 2 months, were included in the study. Myocardial infarction was induced in 17 dogs, 6 were used as controls. After premedication with midazolam (0.1 mg/kg IV) and sufentanyl (0.1 μg/kg IV), anesthesia was induced with propofol (3 - 4 mg/kg IV) and maintained with isoflurane (1.5 - 2%). Animals were ventilated with a FiOA clinical examination including cardiac auscultation and a Doppler-echocardiography was performed before inclusion of the dogs in the study. Blood for electrolytes and neurohormones measurements and echocardiography were performed in the conscious state 1 week before coronary ligation (baseline) and repeated 2 months after recovery from myocardial infarction. A cardiac magnetic resonance imaging (MRI) and a left heart catheterization for the measurement of pressure-volume loops were performed 2 months after myocardial infarction. We also realized pressure-volume loops in 6 weight- and age-matched control dogs.Infarct size was assessed by using the 1.5 Tesla clinical MRI scanner  with a 2-element phased array coil placed over the chest . Gadodiamide (0.2 mmol/kg) was manually injected intravenously in 3 seconds. Following a delay of 10 to 15 minutes, contrast-enhanced images were acquired and raw images processed by manual outlining of the endocardial, epicardial and infarct borders. Total infarct volume was calculated as the summation of the contrast-enhanced volumes from the entire left ventricular myocardial volume. Relative infarction size was determined as the ratio of infarct volume to LV wall volume times 100.echo, LVESVecho) and ejection fraction (LVEFecho) by the single plane Simpson's rule. Fractional shortening (FS) was calculated from M-mode derived linear dimensions and LV mass was derived from the truncated ellipsoid model. Relative wall thickness (RWT) was calculated in diastole as /. Early diastolic myocardial velocity (E'), late  diastolic myocardial velocity (A'), and systolic myocardial velocity (S') of the septal annulus movement were measured and the E'/A' ratio calculated. Additional Doppler assessment included the peak velocities of the mitral flow E and A waves (E and A), mitral flow deceleration time (DT) and the derived E/A and E/E'ratios. All images were recorded and analyzed off line according to specific guidelines [In order to obtain high quality Doppler-echocardiographic images in an unstressed state, the dogs had been acclimatized to the laboratory and trained to lay in lateral recumbency on a table. Doppler echocardiography  was carried out under continuous ECG monitoring with a 5 MHz electronic probe, the dog, in conscious state, lying in lateral recumbency, scanning through the dependent chest wall through an contrived hole in the table. A right parasternal window was used to record bidimensional and M-mode images in the long and short axes. A left parasternal window was used to record the bidimensional apical four chambers view, pulsed-wave Doppler of mitral flow and tissue Doppler of mitral septal annulus movement. The LV length and endocardial borders were traced at end-diastole and end-systole, using the bidimensional right long axis view which best shows the LV cavity, in order to calculate end-systolic and end-diastolic LV volumes  and care was taken to maintain end-expiratory CO2 between 30 and 35 mmHg and body temperature above 36°C. Under fluoroscopic control, a 6F pigtail combined conductance-pressure catheter  was advanced through the carotid into the LV apex and connected to a Leycom Sigma-5 signal processor  for instantaneous LV volume signal and to a Millar pressure monitor  for instantaneous LV pressure signal. A 5F Swan-Ganz thermodilution catheter  was advanced through the jugular vein and positioned in a main branch of the pulmonary artery for cardiac output (CO) measurements. A 7F transluminal valvuloplasty catheter  was advanced through the jugular vein and positioned in the posterior vena cava just below the junction with the right atrium for transient preload reductions. Blood conductivity was determined using the Rho cuvette. Parallel conductance was measured in duplicate by the hypertonic saline method (7.5 ml NaCl 10%) [βLVEDV) to the end-diastolic pressure-volume points. The chamber stiffness constant (β) and capacitances (LV volumes) at pressures of 15 and 20 mmHg were derived from the EDPVR of each dog [Anesthesia was induced by intravenous injection of midazolam 1 mg/kg  and sufentanyl 3 μg/kg and maintained by continuous infusion (midazolam 0.750-1.125 mg/kg/hour + sufentanyl 2.5-3.75 μg/kg/hour). The dogs were mechanically ventilated (FiOaCl 10%) . Active Commercially available radioimmunoassay kits were used to assess NT-proBNP , aldosterone  and norepinephrine . Serum sodium, potassium and osmolality levels were measured .All results are expressed as mean ± SEM and statistical significance is determined at p < 0.05. Distribution normality was tested with a Kolmogorov-Smirnov test. Normally distributed data were tested by paired or unpaired Student's t-tests. Other data were analyzed by a Mann and Whithney test. Forward stepwise regressions were used to investigate the correlations between echocardiographic variables, neurohormones and invasive measurements .The MRI performed 2 months after myocardial infarction revealed that we were in presence of a moderate latero-posterior infarct with a myocardial infarction size of 13 ± 0.74% of the LV wall.Left ventricular remodeling - As compared to baseline, the infarcted dogs showed increased LVEDVecho and LVmass and a decreased RWT.Left ventricular systolic function - The LVEFecho was decreased but its mean value remained above 50%. The LVEFecho stayed higher than 50% in all infarcted dogs except 3 and higher than 45% in all dogs 2 months after myocardial infarction. The FS was mildly reduced but remained above 25%, mitral S' was reduced, while LVESVecho and WMSI were increased.Left ventricular diastolic function - E', E/A and E'/A' were decreased, E, A' and DT stayed unchanged and A and E/E' were increased.Left ventricular global and systolic function - In infarcted dogs as compared to controls, LVEDP, LVEDV, and LVESV were increased, while LVEF, dP/dtmax, mean arterial pressure, Ees and Ea were decreased, whereas, heart rate and CO stayed unchanged. It is of interest that Ees decreased proportionally more than Ea, resulting in a decrease in Ees/Ea. Representative pressure-volume loops during transient vena cava occlusion, Ees and Ea in a control dog and in a dog 2 months after myocardial infarction are shown in figure Left ventricular diastolic function - The infarcted dogs had a reduced dP/dtmin and Tau tended to increase (p = 0.057). Capacitances at 15 mmHg and 20 mmHg and the chamber stiffness constant β remained unchanged in infarcted dogs compared to controls.Compared to baseline, NT-proBNP was increased, aldosterone was decreased, and norepinephrine was unchanged after recovery from myocardial infarction. Serum electrolytes and osmolality stayed unchanged after myocardial infarction.The echocardiographic indices of systolic function WMSI, LVEF, S' and LVESV were correlated to Ees  and to Ees/Ea  while FS was not correlated to Ees r = 0.25, p = NS) and FS and LVESV were not correlated to Ees/Ea . Forward stepwise regression analyses showed that the best predictors of Ees and Ees/Ea were respectively WMSI  and S'   but not to Tau. Forward stepwise regression analysis showed that E/A and E' were the best predictors of active relaxation determined by dP/dtmin  Figure .echo stayed above 50%. Therefore the heart failure qualified for a diagnosis of "heart failure with preserved ejection fraction".In the present study, the dogs with healed myocardial infarction presented with a stage B heart failure, defined as a structural disease strongly associated with the development of heart failure but without signs or symptoms at rest . The echA decreased end-systolic elastance (Ees) and/or a rightward shift of the end-systolic pressure-volume relationship (ESPVR) are characteristics of decreased inotropism. Acute regional left ventricular ischemia has been shown to induce a rightward shift of the ESPVR without any change in Ees ,16 or a The adequacy of systolic function adaptation to afterload can be evaluated by a ratio of end-systolic ventricular and arterial elastances, Ees/Ea . ExtensiWe wondered if general anesthesia applied during the invasive measurements could have accounted for an overestimation of systolic failure and ventricular-arterial uncoupling in the present experiments. Both midazolam and sufentanyl have cardiodepressant and hypotensive effects ,25. BothMeasurements of Ees and Ees/Ea and associated diastolic function changes in heart failure with preserved LVEF have been reported variably according to underlying physiopathology. In patients with various non ischemic cardiac diseases, Ees and Ea tend to be preserved, but diastolic stiffening is a constant finding ,5,22. SyWhile in our experiments Ees was decreased as expected, there was also a decrease in Ea suggesting an adaptative decrease in arterial stiffness, albeit insufficient to prevent uncoupling. This decrease in Ea, also observed in heart failure after coronary microembolism in dogs  could beIn the present study, most of the echocardiographic indices of systolic function predicted Ees or Ees/Ea, but the most performant of them appeared to be WMSI for Ees and mitral septal annulus S' wave for Ees/Ea. The WMSI reflects healed infarction-related wall motion asynchrony, and its sensitivity in the alteration of systolic function in postmyocardial infarction . It has In conclusion, heart failure with preserved LVEF observed in dogs 2 months after an acute myocardial infarction relates to decreased contractility leading to ventricular-arterial uncoupling despite vascular compensation while LV compliance at rest is preserved. In these circumstances the WMSI is the most performant echocardiographic index to predict cardiac contractility while E/A and E'/A' are correlated to LV active relaxation but not to LV compliance.The pericardium was opened during thoracotomy to ligate the circumflex artery and left opened to avoid any increase in intrapericardial pressure due to postoperative bleeding or exsudation. PV loops mainly depend on ventricular preload, afterload, contractility, relaxation and compliance but may be affected by intrapericardial pressure. In normal hearts, the pericardium is minimally stressed and its effect on LV pressure is small. In acute cardiac dilation, the stress is increased and intrapericardial pressure may substantially contribute to LV diastolic pressure . Over tiThe authors declare that they have no competing interests.MM carried out the coronary ligations, the pressure-volume loops  and the magnetic resonance imaging , performed the statistical analysis and drafted the manuscript. BE carried out the coronary ligations. KT anesthetized the dogs for the coronary ligations, the pressure-volume loops and the magnetic resonance imaging. IH and MM participated in the serum BNP dosages. PT and TM carried out the resonance imaging recording and analysis. JB and GH participated in the coordination of the study and helped to draft the manuscript. SB and RN participated in the analysis of the pressure-volume loops results and helped to draft the manuscript. KME conceived the study, participated in its design, coordinated the study, carried out the echocardiography, and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/10/32/prepub


There are several stigmas on the resting surface electrocardiogram that are indicators of past myocardial injury. Broad QRS pattern with bundle branch block, Q waves, persistent ST elevation are some of those facsimiles which may at times even be considered as definitive signs of left ventricular impairment.We would like to focus here on a lesser known entity of the surface electrocardiogram - the fragmented QRS complex. This marker of myocardial injury may often be the only electrocardiographic marker in patients with non-Q myocardial infarction and in patients with resolved Q wave. It can also be a reliable pointer to left ventricular functional compromise.Fragmented QRS electrocardiograms were for the first time recorded from canine hearts with experimentally induced acute ischemia and healing. It was found that fragmented electrocardiograms were more frequently observed in healed myocardial infarctions more than 2 weeks old, than in preparations from 5 day old infarcts .The asynchronous excitation of muscle fibers causing fragmentation of electrocardiogram may be due to the poorly inter-connected muscle bundles; separated by high resistance intercellular connective tissue caused by the healing process. This effect is most pronounced at the bordering areas of necrosis where the connective tissue invades the surviving 'islands' of muscle, hence causing separation and distorted orientation of muscle fibers. Any form of gross structural abnormality, like large chamber dilatation, may also cause a similar picture. Flowers et al   have eveIt has been observed in various studies  ,4 that fDas MK et al   using myBroad premature ventricular complexes (≥160 ms) with notched QRS (notch separation >40 ms) was found to be a reliable marker of a global form of ventricular dysfunction involving ventricular mass, chamber size or function   . It may Flowers et al    found a Fragmented QRS electrocardiogram is an independent predictor of left ventricular function. It is a marker of higher stress myocardial perfusion abnormalities and functional deterioration   . This waQRS fragmentation with or without Q waves was found to predict a higher mortality and recurrent cardiac events than either Q wave  alone or resolved Q wave without QRS fragmentation   ,11. HencFragmented QRS on the resting surface electrocardiogram is a simple, fast and inexpensive modality of non invasive investigation that can be of great value in predicting the cardiac status and prognosis of an individual being evaluated for coronary artery disease.


Left ventricular hypertrophy can be due to various reasons including hypertension. It constitutes an increased cardiovascular risk. Various left ventricular geometric patterns occur in hypertension and may affect the cardiovascular risk profile of hypertensive subjects.One hundred and eighty eight hypertensive participated in this study. Left ventricular hypertrophy was diagnosed by echocardiography. Relative wall thickness was derived by 2 × PWT/LVIDd. Subjects were arbitrarily categorized according to the duration of hypertension. Statistical analysis was done using SPSS 15.0.The mean age of the study population was 55.95±10.71 years. Subjects who had hypertension for >5 years were more likely to be older and had a lower ejection fraction, larger left ventricular diastolic internal dimension than those with duration of hypertension <5 years. Concentric remodeling was the commonest left ventricular geometric pattern among the hypertensive subjects closely followed by normal left ventricular geometry. Concentric hypertrophy and eccentric hypertrophy were rare among the study population.Left ventricular geometry was associated mainly with left ventricular chamber and wall dimensions.Concentric remodeling is the commonest pattern of left ventricular geometric pattern of the left ventricle among hypertensive subjects. Left ventricular geometry is associated with the chamber and wall dimensions. Eccentric hypertrophy is associated with the lowest left ventricular systolic function and therefore possibly an herald to progressive systolic impairment. Left venticular hypertrophy (LVH) and abnormal LV geometry are both important markers of cardiovascular risk among hypertensive subjects. They are associated with increased cardiovascular morbidity due to progressive ischaemic compromise, systolic and /or diastolic dysfunction, arryhthmias and sudden cardiac death –5. LVH i2 or standard deviation increase of left ventricular mass [2 in men and women respectively, although there is a relatively wide range of published cutoff values [LVH can be diagnosed by electrocardiography or echocardiography . Though lar mass . Left velar mass –15. Leftf values , 17. Finf values . Other sf values .Various left ventricular geometrical pattern occurs as a result of adaptation of the left ventricle to increasing wall tension, pressure and volume changes in hypertension. The geometric patterns have significant impact on systolic and diastolic function of the left ventricle . The geoOne hundred and eighty-eight consecutive hypertensive subjects on treatment for hypertension who had echocardiography seen at the LAUTECH Teaching Hospital, Osogbo, Nigeria were recruited for this study. Blood pressure was measured with Accosson sphygmomanometer and hypertension was diagnosed when systolic and/or diastolic blood pressure remained persistently over 140/90 mmHg respectively on more than two occasions after at least five minutes rest and/or the use of antihypertensive therapy.All of them were receiving antihypertensive therapy consisting of at least two of a combination of diuretics, calcium channel blocker, Angiotensin converting enzyme inhibitors or beta blockers. Subjects with diabetes mellitus and chronic kidney disease were also excluded. Appropriate history taking, urinalysis and fasting blood sugar were used to exclude diabetes and chronic renal disease which are the commonest cause of secondary hypertension in our environment. The weight was taken using a standard weighing scale to the nearest 0.5kg while the height was taken with a stadiometer. The body mass index was derived by dividing the weight (in kilograms) by the square of the height (in meters). General physical examination was conducted on each participant. The duration of the hypertension was taken as the duration from the time a subject was told that he/she had elevated blood pressure to the time of the procedure. Subjects were categorized as “early” hypertensives if the duration of illness is less than one year. Those with duration more than 5 years were categorized as “long term” hypertensive subjects and those in between categorized as “intermediate”.Echocardiography was done according to the recommendations of the American Society of Echocardiography (ASE) with the patient in the left lateral decubitus position . Two dim2 and 110g/m2 for males and females respectively. Relative wall thickness was derived by 2 × PWT/LVIDd . Normal relative wall thickness was defined as < 0.45. Normal geometry was defined as normal left ventricular mass and normal relative wall thickness. Concentric remodeling was defined as increased relative wall thickness with normal left ventricular mass while concentric hypertrophy was defined as increased relative wall thickness and increased leftventricular mass. Eccentric hypertrophy was defined as increased left ventricular mass with normal relative wall thickness. Ethical approval was obtained for the study.Left ventricular hypertrophy was considered present if the left ventricular mass index is ≥ 134g/mStatistical analysis was done using the Statistical Package for Social Sciences (SPSS) 15.0 (Chicago Ill.) Categorical variables were expressed as proportions and percentages while continuous variables were expressed as means ± standard deviation. Comparison between categorical variables were done by the use of chi square test, while that of numerical variables were done with the use of analysis of variance (MANOVA) test. A probability of p< 0.05 was taken as statistically significant.One hundred and eighty-eight hypertensive Nigerians were recruited consecutively for this study. They were aged between 32 and 86 years old with mean age 55.95 ± 10.71 years. The study population consisted of 113 males (60.11%)and 75 females (39.89%). Long-term hypertensive subjects were older, and also had a statistically significantly lower ejection fraction and a larger left ventricular internal dimension in systole than those with duration of hypertension < 5 years. Compared with early hypertensive subjects, intermediate and long term hypertensive subjects had a higher relative wall thickness and posterior wall thickness. Left ventricular mass and left ventricular mass index was higher among those whose hypertension is > 1 year. About 36% of those with “early” hypertension had normal geometry compared to about 23.6% of those with hypertension >1 year. A large part of those subjects with intermediate and long term duration of hypertension had concentric remodeling. (63.3% of intermediate duration and 64.1% of long term hypertensives) as compared to 52.46% of those who are recently diagnosed with hypertension. Abnormal left ventricular geometries are commoner among intermediate and long term hypertensive subjects than those recently diagnosed with hypertension. Concentric remodelling was the commonest pattern of left ventricular geometry among these cohort and seem to be more commoner among male hypertensive subjects.LVM, LVMI, and RWT was highest among hypertensive subjects with concentric hypertrophy followed by those with eccentric hypertrophy as shown in Left ventricular geometry and structural alterations occurs in response to systemic hypertension in various pattern. This is determined to a large extent by whether pressure or volume overload is predominating –23. ConcThis study shows that the majority of the hypertensive subjects in this study had concentric remodeling. About three-fifths (60.1%)of the hypertensive subjects had concentric remodeling as against 27.7% with normal left ventricular geometry. A study of the pattern of left ventricular geometry among newly diagnosed essential hypertensives also documented that 28% of newly diagnosed subjects had normal geometry . The simEffective and tight blood pressure control may retard or even reverse the adverse changes in cardiovascular geometry and dysfunction. Angiotensin converting enzyme inhibitors (ACE-I) and Angiotensin receptor blockers (ARBs) are particularly useful in this case as they have been shown to produce neurohormonal regulation, cardiovascular and renal remodeling than other groups of antihypertensive drugs. Although, other antihypertensive drugs also have influence on cardiac remodeling, control of blood pressure, and reversal of cardiac remodeling associated with pressure and volume overload in hypertensive subjects, ACE-I and ARBs are particularly useful . Many ofProgressive alteration in geometric pattern of the left ventricle also influence left ventricular systolic function parameters . As the Systolic blood pressure was associated with abnormal LV geometry and LVH in this study. Hypertensive subjects with concentric hypertrophy and concentric remodeling had the highest mean systolic blood pressure while those with eccentric hypertrophy had a similar mean blood pressure as those with normal left ventricular geometry . This waAmong these cohort, eccentric hypertrophy and concentric hypertrophy were equally common in agreement with other studies . Left veThis study showed that concentric remodeling is the commonest type of geometric pattern present among treated hypertensive subjects. The presentation is associated with clinical parameters such as age, gender and duration of hypertension. Longitudinal studies are necessary to delineate the possible role of these findings in the adaptive mechanism of Left ventricular structure and on the cardiovascular morbidity pattern in hypertensive subjects.The authors declared no conflicts of interests whatsoever.AA: study concept, design, data collection, statistical analysis, manuscript writing, and review. AO: study design, data collection, manuscript writing and review. OG: study design, manuscript writing, editing, review


To compare gender-related normal limits for left ventricular (LV) ejection fraction (EF), end-diastolic and end-systolic volumes (EDV and ESV), obtained using two myocardial perfusion-gated single photon emission computed tomography (SPECT) quantification methods. A total of 185 patients were retrospectively selected from a consecutive series of patients examined for coronary artery disease (CAD) or for management of known CAD. Patients were included in the study group if they had normal or probably normal results with stress and rest perfusion imaging and if the combined interpretation of perfusion studies and gated rest studies showed no signs or suspicion of myocardial infarction. The gated SPECT studies were performed using a 2-day stress/gated rest Tc-99m sestamibi protocol. All patient studies were processed using CAFU and quantitative-gated SPECT (QGS), the two software packages for quantification of gated SPECT images. The lower normal limits for EF were higher for CAFU compared with QGS for both women (59% versus 53%) and men (54% versus 47%). The upper normal limits for EDV were also higher for CAFU compared with QGS for both women (133 versus 107 ml) and men (182 versus 161 ml). The differences between the software packages were small for ESV . Gender-specific normal limits need to be applied for LV EF and volumes determined by gated SPECT. Separate criteria for abnormal LV EF and EDV need to be used for women and men depending on the software package used. We recently presented CAFU, a new method for quantification of left ventricular (LV) volumes and ejection fraction (EF) from myocardial perfusion, gated single photon emission computed tomography (SPECT) images  m2. The study was approved by the Research Ethics Committee at Gothenburg University.A total of 185 patients, 122 women and 63 men, were retrospectively selected from a consecutive series of patients examined between 15 September 2004 and 14 September 2006 at Sahlgrenska University Hospital in Gothenburg for coronary artery disease (CAD) or for the management of known CAD. Patients were included in the study group if they had normal or probably normal results with stress and rest perfusion imaging and if the combined evaluation of stress/rest non-gated images and gated rest images was normal or probably normal with regard to occurrence of myocardial infarction (MI). One experienced physician interpreted all examination results during the study period. The interpretations were done at the time of clinical reporting, and clinical information and the results of the stress test were available to the physician. The QGS and Cequal software packages were used to aid visual interpretation  equipped with a low-energy high-resolution collimator.−1 and order 5. The reconstruction of gated data was done using filtered back-projection with a Butterworth filter with a critical frequency of 0·40 cycles cm−1 and order 10. No attenuation or scatter correction was used.Acquisition, with the patient in the supine position, was done in step-and-shoot mode using circular acquisition and a 64 × 64 matrix, zoom factor 1·28, pixel size 6·9 mm, with 60 projections over 180°, 40 s per projection. In patients weighing >90 kg the acquisition time per projection was increased to 55 s. During the rest acquisition the patient was monitored with a three-lead ECG. The acceptance window was opened to ±20% of the predefined R–R interval. Other beats were rejected. Each R–R interval was divided into eight equal time intervals. Gated SPECT acquisition was performed at the same time as ungated routine SPECT acquisition. An automatic motion-correction program was applied in studies showing patient motion during acquisition. Tomographic reconstruction of non-gated data was performed using filtered back-projection with a Butterworth filter with a critical frequency of 0·52 cycles cmThe short-axis images from all patient studies were processed using the two software packages for quantification of gated SPECT images, CAFU  using the QGS program. This program automatically identifies the epi- and endocardial contours for each of the sets of short-axis slices in the cardiac cycle to calculate volume changes.P < 0·05 as statistically significant. In the comparisons of mean values, we used paired t-test to compare the two different methods and unpaired t-test with heterogeneous variances to compare male and female patients. The LV volumes and EF were approximately normally distributed, and consequently, normal limits were defined as the mean values +2 SDs for the volumes and the mean values - 2 SDs for EF. We calculated 95% CIs for the normal limits. We regarded CIs for the two methods that did not overlap as significantly different. Note that this is a conservative approach for paired data.All statistical analyses were conducted using Microsoft Office Excel 2003. We considered Normal gated SPECT values for LV volumes and EF, calculated using CAFU and QGS, are summarized in The normal limits and corresponding 95% CIs are presented in Gender-related normal limits for LV volumes and EF from gated SPECT were established for the CAFU method. The differences between these normal limits and the corresponding limits for QGS are slightly higher for EF  compared with the previously presented EF difference between the two methods in a mixed patient population (4%)  were close to those presented by A large group of randomly selected healthy volunteers would probably be a better study group for establishing normal limits. This type of reference population is rarely available in nuclear medicine and ‘healthy’ patients are often used instead. This approach can be criticized, since subjects referred to myocardial perfusion imaging may have some reasons for the referral, which may not be found at the examination, e.g. microvascular disease or non-cardiac disease, indicating that they may not be representative of a healthy reference population. In this study we excluded patients with documented hypertension, diabetes, CAD, MI, heart failure, previous revascularization, cardiomyopathy, ECG signs or suspicion of MI, LBBB, and pre-excitation abnormal ECG at rest. The patients with diabetes, hypertension and prior revascularization are likely to represent a ‘less well’ part of the reference population, leading to excessively broad normal limits. On the other hand, applying very rigorous exclusion criteria may lead to a reference population that represents a ‘too healthy’ part of the population. We believe that the inclusion and exclusion criteria in this study represent a reasonable balance in order to have a relevant reference population for establishing normal limits.The number of women was nearly twice as many as the number of men in this study. This is a somewhat surprising finding, since the study group was selected from a consecutive series of patients examined for CAD or for the management of known CAD and the numbers of women and men were about the same in the total group. There could be a selection bias in that more women with low likelihood of CAD, but with unspecific ECG changes at a preceding exercise test, were referred to myocardial perfusion scintigraphy in order to rule out significant CAD.In conclusion, gender-specific normal limits need to be applied for LV EF and volumes determined by gated SPECT. Separate criteria for abnormal LV EF and EDV need to be used for both women and men, depending on the software package used.