Heart failure (HF) is a serious health and economic burden worldwide, and its prevalence is continuously increasing. Current medications effectively moderate the progression of symptoms, and there is a need for novel preventative and reparative treatments. The development of novel HF treatments requires the testing of potential therapeutic procedures in appropriate animal models of HF. During the past decades, murine models have been extensively used in fundamental and translational research studies to better understand the pathophysiological mechanisms of HF and develop more effective methods to prevent and control congestive HF. Proper surgical approaches and anesthetic protocols are the first steps in creating these models, and each successful approach requires a proper anesthetic protocol that maintains good recovery and high survival rates after surgery. However, each protocol may have shortcomings that limit the study's outcomes. In addition, the ethical regulations of animal welfare in certain countries prohibit the use of specific anesthetic agents, which are widely used to establish animal models. This review summarizes the most common and recent surgical models of HF and the anesthetic protocols used in rat models. We will highlight the surgical approach of each model, the use of anesthesia, and the limitations of the model in the study of the pathophysiology and therapeutic basis of common cardiovascular diseases. Heart failure (HF) is a leading cause of death worldwide. The mortality rate of HF is very high, with ~50% of patients dying within 5 years of their initial diagnosis, which is higher than the fatality rate of most cancers. The most recent World Health Organization estimates that cardiovascular disorders kill 17.9 million people each year, accounting for ~31% of all global deaths .The study of HF requires dependable animal models to evaluate severe changes and pharmacodynamic interactions in the structure and function of the injured myocardium and to pursue its progression to HF. In recent decades, researchers have used small animal models to better understand the pathophysiology of HF and develop more effective strategies for managing patients with congestive HF . TherefoRats are mammals belonging to the Muroidea rodent superfamily. The cardiac, pulmonary, and systemic circulatory systems, as well as their valves, are similar to those of humans. The rat heart has four chambers. On the right side of the aortic arch, the brachiocephalic trunk branches into the right common carotid artery and the right subclavian artery. The left common carotid artery is located in the anterior part of the aortic arch, while the left subclavian artery is located to its left , 5. FurtAnesthesia is an essential aspect of laboratory animal research to minimize pain and stress during experimental procedures and is also essential to ensure the reproducibility of experimental results. Appropriate anesthesia administration is crucial in achieving success in surgical experiments , 8. HereIsoflurane and sevoflurane are commonly used inhalant anesthetics in rats. They are administered through a mask or nose cone to induce and maintain anesthesia. The dose and concentration of anesthetic gas can vary based on the species, weight, and age of the rat, as well as the procedure being performed , 62.A combination of ketamine (50–100 mg/kg) and xylazine (5–10 mg/kg) is a commonly used anesthetic protocol for intraperitoneal injections in rats. This method provides a rapid onset of anesthesia and is often used in short procedures , 64.A combination of ketamine (50–100 mg/kg) and xylazine (5–10 mg/kg) is a commonly used anesthetic protocol for intramuscular injections in rats. This method also provides a rapid onset of anesthesia and is often used as a backup when inhalant anesthesia is impossible .Propofol (2–4 mg/kg) is a commonly used anesthetic for intravenous injections in rats. This method provides rapid and controlled induction of anesthesia and is often used for more invasive procedures .Unfortunately, some countries have prohibited some anesthetic drugs and classified them as narcotics; for instance, Ketamine is currently classified as a narcotic medication in Japan, and numerous other countries have reinforced limitations on its purchase, possession, and related record-keeping methods . These dIt is important to note that the correct protocol can vary greatly depending on the individual animal and the procedure being performed. Additionally, close monitoring of an animal's vital signs, such as heart rate, respiratory rate, and body temperature, is crucial during anesthetic procedures to ensure the safety and wellbeing of the animal.Coronary circulation is the main supply of blood to the cardiac tissues, and effective coronary circulation is crucial for the health of the myocardium. Constriction or blockage of one or more branches of the coronary artery is life-threatening and may cause irreversible heart damage and MI; therefore, MI is the main type of ischemic heart disease, characterized by unbalanced ischemia and myocardial necrosis , 69.Despite significant improvements in prognosis, acute myocardial infarction remains the most severe manifestation of coronary artery disease, affecting over seven million people worldwide and contributing to over four million fatalities annually in Northern Asia and Europe , 71. MI in vivo and their ability to differentiate into contractile myocytes (CAL in a rat model is a research technique commonly used to induce MI (heart attack) in rats to study the pathophysiology of the disease, test potential therapeutic interventions , 76, evamyocytes , and expmyocytes .Permanent CAL results in total blood flow blockage and irreversible hypoxia, leaving most of the area at risk of infarction and a massive and permanent scar in the myocardium. This damaged area is susceptible to pathological remodeling, which leads to the progression of HF. Furthermore, the site of the artery blockage influences the size of myocardial ischemia, with ligation closer to the heart's base causing more severe damage. The use of a well-proven procedure performed by a qualified surgeon lowered the variation in infarct size based on the ligation site .The procedure began with the injection of an anesthetic drug into the animal, followed by the use of a mechanical ventilator to secure the airway. A left thoracotomy was performed, the heart was rapidly exposed, and the initial ligation site was determined .Once the site of ligation of the left anterior descending coronary artery (LAD) was identified, a cotton earbud was gently pressed onto the artery slightly below the site of ligation, immobilizing the heart, while simultaneously making the artery noticeable and easy to recognize. A non-absorbable ligature passes below the LAD and is secured with three knots using a tapered atraumatic needle. Blanching and cyanosis of the anterior wall of the left ventricle, as well as enlargement of the left atrium, are signs of successful ligation. Due to direct vision and observation of the process and targeted area of infarction, CAL provides accurate time, location, and extent of the coronary event. The ribs and muscles were closed with dissolvable sutures, with a small gap left to aspirate any remaining air in the thorax, and air was aspirated to keep the lungs from collapsing. At the time of closure, the muscle and skin stitch sites were treated with neomycin powder and betadine, respectively. Before extubation, the lungs were deflated by submerging the exit tube connected to the endotracheal tube in an underwater seal with adequate postoperative care  9)..9).Extubation was conducted before the rats were fully awake, and a 1 mL syringe was used to carefully suction the endotracheal catheter to prevent bronchial occlusion due to heavy mucus. The rats were then placed in a recovery cage with an oxygen source for around 30 min. Analgesia (0.025 mg/kg body weight subcutaneously every 12 h) was planned for up to 72 h .These procedures are reported to have a mortality rate of more than 50% due to malignant ventricular tachycardia in the acute phase. Furthermore, infarctions are usually mild (averaging 21% of the left ventricle), which may be due to the large amount of sub-pericardial collateral circulation in this species. Consequently, only minor hemodynamic changes were observed . FurtherHowever, the MI model using the ligation technique produces a wide variation in infarct size , 86. AccCryoinjury is another technique used to create an MI rat model. It involves applying a cold probe to the surface of the heart, typically the left ventricle, to freeze and damage a small area of heart tissue. The resulting injury leads to a local inflammatory response and scar formation, mimicking the pathophysiological changes observed in human MI. This technique is commonly used to study the effects of different therapeutic interventions on cardiac repair and regeneration , as wellAccording to Van Den Bos et al. , this isThe pathophysiology of MI in the cryoinjury approach differs from that in other methods, such as LAD ligation, in that acute cell death occurs without accompanying ischemia. It is caused by mechanical stresses generated by the development of ice crystals in the intracellular and extracellular spaces, as well as in the vasculature . This teThree consecutive exposures to a liquid nitrogen-cooled cryoprobe, a 6 mm stainless steel cylinder, resulted in acute LV MI. Blanching of the wall followed by hyperemia indicated the onset of MI in the heart. In addition, the cryoinjury region of an MI heart is distinguished by its pale appearance compared with the surrounding tissue  89)..89).This method does not result in apparent HF following cryoinjury, which is most likely due to the smaller infarct size compared with coronary ligation. As a result, when an observable HF model is required, the cryo-infarction model is not a choice; in other words, cryo-infarction cannot replace the currently available HF models. Instead, it can be used as a model for evaluating medical treatments aimed at reducing cardiac remodeling and improving heart function after myocardial infarction, such as drugs that promote cardiac regeneration through progenitor cells or growth factors , and invThe IR rat model is a widely in used research to study the pathophysiology of ischemic injury and test potential therapeutic interventions. Its creation involves interrupting blood flow to a specific organ or tissue (ischemia) for a period of time and then restoring blood flow (reperfusion). In the case of the heart, a common approach is to temporarily occlude the coronary artery, induce myocardial ischemia, and then re-perfuse the tissue by removing the occlusion . This prin vivo organs before being used in dogs in 1988  is the secondary onset of reperfusion damage. This occurs as a direct result of the rapid return of blood flow to the damaged region, and is a secondary cause of cell damage and death after ischemia. In general, IR is more technically challenging than PL, resulting in smaller and more variable infarcts that frequently do not advance to other cardiovascular pathologies. However, it allows researchers to study the second wave of injury associated with blood reperfusion, which applies to clinical interventions in human acute MI patients but is not currently a therapeutic target .The same applies to the MI model, with a difference in the ligation technique. After the heart was already visible, the LAD was temporarily ligated using a piece of tubing. The suture was cut, and the tubing was removed for reperfusion once the appropriate period of ischemia had passed  39)..39).The most significant limitation of the IR model is that the majority of damage is still caused by ischemia, with reperfusion injury accounting for a considerably smaller second wave of post-MI injury. Therefore, reperfusion injury may have no apparent effect on the overall severity of MI . In addiThe AC model is a commonly used experimental model of left ventricular hypertrophy that involves partial constriction of the aorta to increase the pressure in the left ventricle. This model is used to study the mechanisms underlying cardiac hypertrophy and HF, to test potential therapeutic interventions , and to Initially, banding had little or no effect on aortic flow, but as the animal grew, the relative severity of the constriction increased, resulting in heart hypertrophy, which has been utilized to mechanically replicate the cardiac consequences of aortic stenosis, systemic hypertension, and aortic coarctation in a variety of sites , 105.The constriction may be thoracic, near the aortic origin (ascending AC [AAC]), or in the aortic arch between the first and second trunks (transverse AC [TAC]). The constriction can also be used in the abdominal aorta, either below or above the renal arteries, with the latter inducing hypertension due to renal hypoperfusion and concurrent LV hypertrophy. The main distinction among these models is the anatomic position of the constriction .TAC and suprarenal AC cause a more gradual increase in pressure, hypertrophy, and HF, whereas AAC is frequently used to assess the effects of an early insult caused by pressure overload . The sevTAC surgery that reduces aortic diameter by 50%, causes a systolic pressure gradient of 50–60 mmHg between the aorta and the LV, resulting in clear echocardiographic evidence of LV hypertrophy and an increase in left atrial pressure around the eighth week . AccordiThe anesthetized rats were placed in the supine position for TAC. Following the skin incision, the upper half of the sternum was separated in the midline using scissors, and the thymus was removed. The aortic arch was carefully dissected from surrounding tissues. A stylet (bent and blunted) 16G intravenous catheter was tied securely to the aorta between the brachiocephalic trunk and left common carotid artery using a 4.0 silk and then removed, creating partial AC. Sutures were used to close the sternotomy and skin incisions. Rats were extubated and placed in an incubator at 28–30°C for recovery  45)..45).via drinking water for 7 days  for postoperative analgesia. In addition, the rats were administered oxytetracycline (500 mg/L of water) r 7 days .In the TAC model, although the onset of HF development differs significantly from that of patients with hypertension or aortic stenosis, the initiation of hypertension in this model is sudden and results in a 50% increase in LV mass within 2 weeks; thus, this is an ideal model to investigate intervention strategies that affect the development of cardiac hypertrophy .AC  can also produce chronic LV pressure overload, which eventually leads to cardiac hypertrophy and dysfunction. The progression of this model to HF is more gradual, making it more appropriate for hypertension-related HF. Because it does not require chest opening or artificial breathing, it is more routinely utilized in rats than TAC , 115.The 2K1C model is an experimental model of renovascular hypertension that involves placing a clip on one of the renal arteries to reduce blood flow to one of the kidneys. This reduction in blood flow stimulates the renin-angiotensin-aldosterone system, leading to increased blood pressure. This model was used to study the mechanisms of hypertension, test the efficacy of antihypertensive therapies , and stuThe physiological function of the kidney includes maintaining electrolyte and fluid balance as well as secretion of renin, a key component of the renin-angiotensin system. Thus, its role in blood pressure regulation and the development of hypertension is widely acknowledged. Since Goldblatt et al.  created According to Weber et al. , within Junhong et al. used 2K1C to simulate a rat model of diastolic dysfunction and studied its biochemical alterations using proteomic techniques. They found that diastolic dysfunction was observed in hypertensive rats 8 weeks after the operation, as evidenced by increased wall thickness, fibrosis, impaired relaxation, and increased chamber stiffness . AnotherThe anesthetized rats are subjected to a flank abdominal incision to expose the left renal hilum, and the renal artery and vein are carefully identified by blunt dissection. To prevent vessel compression during clip placement, an insulin needle tip with an outer diameter of 0.23 mm is employed in each of the rats. A titanium vascular clip is also gently placed around the left renal artery. After that, the needle tip is carefully removed, the contents of the abdomen are gently returned to their original location, the abdominal wall and skin are sutured, and the animals are allowed to recover  43, 55), 5543, 5Renovascular hypertension created by this model usually produces a complex HF model, in which myocardial hypertrophy is eccentric due to overloading and concentric due to hypertension that develops in addition to renal failure. Although this model somewhat mimics complex renal failure-induced HF to some extent, there are some issues regarding the success rate and rapid change in the geometry of the heart, which limit the study of detailed hemodynamic investigations of the heart. In a study by Ma et al. the feasibility of a novel IVPG assessment did not show significant benefits in this model within 8 weeks. However, his data revealed clear evidence of rapid changes in myocardial strain and the efficiency of a new medicine  to ameliorate the pathological consequences of the heart in this model .The 2K1C approach is not always successful in rats; for example, in the Dussaule experiment, 19 rats did not acquire hypertension, 27 had malignant hypertension, and 12 died; only 47 (45%) established stable hypertension . In addiThe AVS model is an experimental model that involves the surgical creation of a direct connection between an artery and vein, bypassing the capillary bed. This results in increased blood flow and pressure in the vein, mimicking the hemodynamic changes observed in certain pathological conditions, such as arteriovenous fistulas. The AVS model was used to study the effects of increased blood flow and pressure on vascular function and to test potential therapeutic interventions .Aortocaval fistula (ACF)-induced chronic volume overload in rats is a well-studied rodent HF model . This moAn artificial shunt between the abdominal aorta and the inferior vena cava causes a significant increase in cardiac output and venous return, which causes compensatory, initially asymptomatic ventricular hypertrophy , prolongAVS have been used to cause volume overload, dilated cardiomyopathy, and HF in rodents . DespiteThe hemodynamic data in these models suggest a persistent increase in the LV diastolic volume. The Frank–Starling mechanism is responsible for maintaining a high output status in the early stages following the development of the AV shunt. This variable represents an abrupt increase in wall stress caused by volume overload, whereas changes in LV end-diastolic pressure indicate that the development of cardiac hypertrophy and dilation of the cardiac chamber tend to regulate wall stress .Flaim et al. established a HF rat model of a chronic AVS between the abdominal aorta and the inferior vena cava, and surgical introduction of an arteriovenous fistula between the abdominal aorta and the inferior vena cava at a point ~5 mm caudal to the left renal vein was used to induce a high cardiac output state. After general anesthesia, a midline incision in the abdominal wall was made to expose the peritoneal cavity, and the abdominal aorta and vena cava were exposed and isolated for ~20 mm before all branches were occluded using bulldog clamps A 10 mm segment of the aorta and vena cava were isolated under a dissecting microscope by placing two bulldog clamps across the main vessels, and openings of approximately comparable size  were made through the medial walls at the midpoint of the isolated segments. Three interrupted microsurgical sutures (9-O Ethilon) were used to unite the opposing sides of the two apertures; the clamps were removed, and the patency of the fistula was visually confirmed by the presence of mixed arterial blood in the vena cava. After closing the abdominal incision, the animal was allowed to recover  125, 13.On the other hand, Garcia and Diebold developed a simple, rapid, and effective method for exposing the vena cava and abdominal aorta by opening the abdominal cavity with a midline incision, placing a 18-gauge needle into the abdominal aorta and progressing through the medial wall into the vena cava, constricting the aorta is momentarily below the origin of the right renal artery, and quickly repairing the aortic puncture using a cyanoacrylate glue. To confirm the patency of the shunt, a pulsatile flow of oxygenated blood into the inferior vena cava is visually observed. A standard method is used to close the abdominal cavity using an absorbable suture .In rats, an AV fistula is formed by a side-to-side anastomosis of the aorta and vena cava  or by enin vivo ..138).The following echocardiographic criteria were used to determine AR at the time of surgery: the color Doppler ratio of regurgitation jet width to left ventricular outflow tract obstruction diameter was 50–70%, and pulsed-wave Doppler proved reversed diastolic flow in the abdominal aorta . When thThis rat model has various drawbacks in terms of AR. One of the most serious complications is the extremely high mortality rate associated with acute AR secondary to HF. Multiple aortic valve leaflet perforations can cause serious valve damage, uncontrollable HF, and death. Therefore, wire perforations should be performed while echocardiography is being monitored, and repeated perforations should be avoided .Another challenge is the wire size of the perforations. Some researchers prefer thicker wires (0.9 mm), which can result in multiple leaflet injuries with severe AR, while others prefer thinner wires (0.3 mm), which result in relatively moderate AR , 141. ThPAB is a surgical model used in rats to induce right ventricular (RV) pressure overload and study the development of RV hypertrophy and HF. In this model, a band is placed around the pulmonary artery, restricting blood flow to the lungs and causing an increased RV afterload. The severity of RV pressure overload can be adjusted by varying the tightness of the band. PAB is commonly used in cardiovascular research to investigate the molecular and cellular mechanisms involved in RV hypertrophy and HF to test potential therapies for these conditions  and to ePulmonary arterial hypertension (PAH) is a chronic and frequently fatal condition . AlthougPAB involves constricting the pulmonary artery using a band or clip to increase the workload on the right ventricle and simulate the effects of pulmonary hypertension. A pre-adjusted hemostatic clip is the most widely used approach in small animal models of rats and mice , 154, orvia the PA is restricted to the inner segment of the half-closed clip  is gently torn free from the aorta using a silk thread that is threaded beneath the PA, then an 18-gauge needle is threaded alongside the PA, and the suture is securely tied around the needle and swiftly released, leaving a fixed, constricted aperture in the lumen equal to the needle's diameter. The combination of a fixed banding around the PA and the animal's growth results in dramatically elevation RV afterload over time  28, 161161, 162.sed clip . BuprenoA challenge with the banded model is to include RV failure, rather than simply a well-adapted hypertrophic RV. The difficulty is that a tight band causes abrupt RV failure and mortality in adult animals, whereas a loose band causes compensatory RV hypertrophy. To overcome this, most models begin operations with weaning. This causes stenosis to worsen as the animal develops, allowing for catastrophic RV failure over time , 163.Review design: AF, AM, and RT. Investigation: AF, AM, HH, and AElh. Data collection: AF, AElf, and HH. Writing and drafting: AF, AM, AElh, and AElf. Critical editing: AM. Supervision: RT. All authors reviewed and edited the final version.


Graphene oxide (GO) was utilized as an additive to encourage the development of early strength in order to improve steel slag cement's low early strength. This work investigates the compressive strength and setting time of cement paste. The hydration process and its products were explored using hydration heat, low-field NMR, and XRD; in addition, the internal microstructure of the cement was analyzed utilizing MIP, SEM-EDS, and nanoindentation testing technologies. The results demonstrated that the inclusion of SS retarded cement's hydration, leading to a degradation of compressive strength and microstructure. However, the addition of GO was able to accelerate the hydration of steel slag cement, giving rise to a reduction in total porosity, a strengthening of the microstructure, and an improvement in compressive strength, particularly the material developing trends at the early stage. Due to its nucleation and filling capabilities, GO increases the total amount of C–S–H gels present in the matrix, specifically vast amounts of C–S–H gels with high density. It has been established that the addition of GO is capable of greatly enhancing steel slag cement's compressive strength. Graphene oxide (GO) was utilized as an additive to encourage the development of early strength in order to improve steel slag cement's low early strength. However, the utilization rate of steel slag in China is only 22%.4 Thus, how to effectively utilize steel slag is imminent.Steel slag powder (SSP) is a common industrial waste derived from iron and steel works. According to reports, the output of steel slag accounts for 15–20% of China's crude steel output, and produces about 80 million tons per year.etc. Among them, building materials are an effective way to improve steel slag utilization rate.5 Since steel slag contains dicalcium silicate (C2S), tricalcium silicate (C3S) and tetra calcium aluminoferrite (C4AF), steel slag has a cement-like hydration process and is considered a potential cementitious material.6 Using SS instead of cement to prepare green cement-based materials can improve its utilization rate, and the use of SS can reduce the amount of cement and carbon dioxide emissions.7 Costa et al. discovered that every ton of clinker saved could reduce 0.83 tons of carbon dioxide emissions and save 3.7 GJ of energy.8 Dong et al.9 discovered that using steel slag as aggregate to fabricate concrete could meet engineering requirements to some extent, However, the expansion caused by f-CaO and f-MgO in steel slag limits its engineering application. Fortunately, cement prepared with steel slag has better wear resistance, and a reasonable proportion can help reduce carbon dioxide emissions.10,11 Numerous studies have shown that,12,13 when the SS content is lower than 20%, SS concrete exhibits lower early compressive strength in comparation to the reference group. However, as further increasing SS content, the concrete compressive strength decreases significantly. Altun et al.14 found that using steel slag to replace 15% to 45% of cement reduced the compressive strength of cement slurry by 57.3% to 24.3% and 19.1% to 45.5% at 2 days and 7 days, respectively. Similar results were also obtained by Kourounis et al.,15 the 7 days compressive strengths of cement slurries containing 15%, 30% and 45% SS decreased by 18%, 37% and 54%, respectively, compared to the control sample. The mechanism of SS preventing early hydration of cement has been thoroughly investigated by Zhuang et al.16 The outcomes demonstrated that SS inhibition prevented C–S–H nucleation and development as well as the precipitation of Ca(OH)2(CH), and the SSP contains RO phase (CaO–FeO–MnO–MgO solid solution) with almost no hydration activity. The weaker interface transition zone (ITZ) formed between the RO phase and surrounding C–S–H gel, which also severely restricts the application of SS in cement-based materials.Currently, the resource utilization of steel slag mainly includes road and mine landfill, building materials, 17,18 include carbon nanotubes, nanosilica, graphene oxide (GO),19 and carbon nanofibers, among which GO is chosen because of the extremely high specific surface area, superb mechanical strength, and amazing flexibility.20,21 Active surface oxygenic functional groups, including as hydroxyl and carboxyl groups in GO increase the interlamellar distance of GO, hence enhancing its dispersion in water.22 Numerous researchers23,24 have demonstrated that theses surface oxygenic functional groups of GO will preferentially react with C3S, C2S, and C3A. Therefore, these groups will provide growth sites for cement hydration products, which will in turn promote cement hydration. Lu et al.25 discovered that the cement-based materials with 0.08% GO had 37.7%, 24.8%, and 80.6% higher tensile strength, compressive strength, and flexural strength. Peng et al.26 confirmed that the addition of GO raised the compressive and flexural strength of fly ash cement mortar, especially the early strength. It is concluded that GO provides a new insight to overcome the shortcoming of the steel slag cement low strength in the early period.Recent applications of nanomaterials in the field of civil engineeringThis research evaluated the impacts of GO on the hydration and mechanical characteristics of steel slag cement utilizing XRD, SEM/EDS, and MIP tests to improve the usage of SS as a supplemental cementing ingredient in cement-based substances. Furthermore, the impacts of GO on the composition, shape, and nanomechanical characteristics of steel slag cement hydration products were examined. The mechanism of GO in steel slag cement was then investigated, which might provide a theoretical foundation for the effect of GO on steel slag cement and the application of cement-based materials.22.1The cement applied is P.O 42.5 Portland cement, and the SS purchased from Hengduan New Material Co., Ltd. GO dispersion was provided by Shenzhen Suiheng Graphene Technology Co., Ltd. 2.2In this paper, four types of mix ratios were prepared to study the impact of GO on steel slag cement properties, and kept the water/binder ratio at 0.4. The pure cement system was used as the control group. SS cement is made by mixing 20% SS and 80% cement. The content of GO is 0%, 0.02% and 0.04% of the mass of steel slag cement, respectively, which are labeled as 20SS + 0GO, 20SS + 0.02GO and 20SS + 0.04GO. The mixing ratio of cement paste is demonstrated in After mixing GO and stirring water, then sonicated for 60 min. Mixed GO solution with cement and then poured into a 40 cm × 40 cm × 40 cm cubic mold. After 24 hours of indoor curing, the mold was removed. Then, the mechanical properties and microstructure were tested after curing under standard conditions to the corresponding age.2.32.3.1The cement paste setting time was analyzed by a Vicat apparatus in accordance with GB/T 1346-2011.2.3.21H low-field nuclear magnetic resonance (LF-NMR) produced by Suzhou Niumai Electronic Technology Co., Ltd. is applied with the magnetic field intensity of (0.30 ± 0.05) T, the main frequency of the instrument of 12 MHZ, and the probe coil diameter of 10 mm. CPMG pulse sequence test was adopted, the sampling frequency SW was 400 kHz, the half echo time τ was 90 μs, the repeat sampling delay TW was 10 000 ms, and the number of echoes NECH was 80.2.3.3The TAM Air C80 Isothermal Calorimeter (age) produced in Setaram, France, with 8 channels, can be used to determine the hydration exothermal process and age rise of each sample simultaneously.2.3.4−1, a microcomputer-controlled pressure testing machine with the model number YAW-300/20 was utilized.For the purpose of determining the compressive strength of cement paste at a loading speed of 2.4 kN s2.3.5−1.XRD analyzes cement paste phase. Anhydrous ethanol was used to dehydrate the cement paste after 3 and 28 days. Cement paste fragments were 60 °C vacuum dried for 72 h, crushed into powder, and screened at 75 μm before testing. The scanning angle range is 10°–80°, and the scanning speed is 10° min2.3.6A scanning electron microscope (SEM) and an electron energy dispersive spectrometer (EDS) were used, respectively, to observe the microstructure characteristics of cement paste and its chemical composition. Following a curing period of 28 days, the sample was cut up into smaller pieces and then immersed to prevent further hydration in anhydrous ethanol. The material was vacuum dried for three days at a temperature of forty degrees Celsius before being tested. In the course of processing, the sample was sprayed with gold.2.3.7Mercury intrusion porosimetry  is applied to analyze the pore structure and distribution of cement paste samples, which were broken and took a block about 0.5 cm inside after curing for 28 days.2.3.8et al.27The nanomechanical performances of the matrix are measured by nanoindentation apparatus. The matrix is 4 × 25, including 100 indentation points, and the point spacing is 5 μm. More preparation and testing procedures are given in the recent study of Wang 33.13.1.116 where the paste containing SS initially sets at 7–9 h. But, the initial setting time of cement paste is curtailed by adding proper amount of GO into steel slag cement. Compared with 20SS + 0GO, the initial setting time of 20SS + 0.02GO and 20SS + 0.04GO samples is shortened by 102 min and 186 min, respectively. Similar trends between the final and first setting times are evident. It is found that nano – induced nucleation can be produced in the process of hydration by mixing nano – silica into cement, to produce well-developed hydration products. In contrast, the GO used in this study possesses the nano size effect due to its tiny particles, huge specific surface area, and robust hydrophilicity enabled by oxygen-containing groups, all of which serve to enhance cement particles' ability to interact with water molecules. Additionally, it can operate as a nucleation site for cement hydration product CH and induce Ca2+ in solution to produce C–S–H gel, all of which expedite the C3S hydration reaction. To shrink cement setting time, its hydration should be sped up.An essential sign of early age hydration is the setting time. 3.1.23S and C3A is higher, and the hydration activity of SS is significantly more sluggish than that of cement stem from partially replacement of cement by SS, reducing the amount of cement needed.2,28 However, with the incorporation of GO, the cement hydration process is improved. Compared with 20SS + 0GO samples, the peak heat release value of 20SS + 0.02GO and 20SS + 0.04GO samples increased by 18.7% and 23.6%, the time of peak heat release was advanced by 33.6% and 40.7%, and the cumulative heat release value of 72 h increased by 4.2% and 13.2%, respectively. Both observations of setting time are basically consistent with the ICC results.To better reflect the reaction kinetics of paste, the heat release variation during the hydration of cement is evaluated by the ICC testing and the relevant results are shown in 3.1.329,30 Form all curves, there is a critical time point beyond which the paste enters the accelerating stage.15,31 However, this critical point is obviously advanced with the addition of 0.02% GO and 0.04% GO to the paste, compared to 20SS + 0GO, which correlates to the above setting time results.Compared with control specimens, the mixing SS cement paste showed a slow decrease process, and the end time of dormant period and acceleration period were prolonged, and the transition point of the pastes shifted towards later time , implyin3.23.2.12S and C3S existing in SS. Furthermore, the presence of SS at the early stage increased the Ca2+ concentration in pore solution, decreased the supersaturation of CH, and prevented the nucleation and development of C–S–H,16 resulting in a drop in strength. With increasing age, the gelling property of SS is encouraged, resulting in a slower rate of compressive strength degradation. The inclusion of GO, beyond that, increases the steel slag cement compressive strength. Compared with 20SS + 0GO, the compressive strength of the sample with 0.02% GO at 3 days, 7 days and 28 days increased by 18.6%, 15.9% and 13.3%, respectively, and that of the sample containing 0.04% GO increased by 25.9%, 23.7% and 22.2%, respectively. The 28 days compressive strength is marginally greater for the 20SS + 0.04GO sample than for the control group. It is clear that GO improves the early compressive strength of SS cement paste more significantly. This is mainly attributed to the fact that nano-scale GO fills the pores of the sample, raises the packing density, and improves the interfacial transition zone between particles.32 Meanwhile, GO provides additional nucleation sites for cement hydration, promoting C–S–H gel formation and cement hydration.33The cement paste compressive strength is illustrated in 3.2.23S and β-C2S) and tetracalcium aluminoferrite (C4AF) predominate in the paste, as do CH crystals. Small amount of calcite (CaCO3) is also detected and it could be on account of the occurrence of carbonation. The broad peak observed in the range between 29° ∼ 30° is associated with poorly crystallized calcium silicate hydrate phase, which tends to broaden with the addition of SS. Compared with 20SS + 0GO, the incorporation of GO improves the intensity of CH crystal's diffraction peak. Most likely, this is due to the large number of hydroxyl, carboxyl and other surface oxygenic functional groups of GO, which can react with calcium ions generated by hydration, so that the content of calcium ions in hydration products decreases, and the hydration reaction of C2S and C3S moves forward.The mineralogical compositions of the 3 days and 28 days pastes determined by XRD are presented in 3.2.32+ and Al3+ plasma generated by cement hydration will cross-link with –COOH on the GO surface, making hydration products to preferentially adhere to the GO surface, providing additional nucleation sites for cement hydration reaction and optimizing the crystal morphology and distribution of hydration products.39–41SEM photographs of the cement paste at 28 days are presented in 42 which was in line with our results that higher compressive strength obtained by 20SSP + 0.04GO paste.To explore the effect of the variation of chemical compositions on the microstructure of the pastes, the atomic ratios of the hydration products were assessed by EDS. As shown in 3.2.4et al.43 research, pores can be classified based on pore size and showed in 3.2.5E was determined using the nano-indentation test, as illustrated in 3,12,44 values of the elastic modulus for cement hydration products are distributed in five regions: 0–8 GPa, 8–20 GPa, 20–35 GPa, 35–50 GPa and >50 GPa, which represent the elastic modulus of microporous, low-density (LD) C–S–H gel, high-density (HD) C–S–H gel, CH phase and unhydrated clinker (UC), respectively.The internal relationship between microstructure and nanomechanical properties of cement-based materials can offer theoretical basis for the study of cement-based materials. The matrix's nano-indentation elastic modulus 45The frequency statistics of indentation modulus points in the matrix region were carried out, and the Gaussian function was adopted for curve fitting, as shown in 4In this study, the effect GO on the compressive strengths of SS-cement paste is investigated experimentally, and the microstructure evolution is also explained by XRD, SEM, MIP and nanoindentation techniques. The following conclusions can be drawn:(1) SS can significantly delay the setting time of cement and reduce the hydration reaction. Compared with the control sample, adding 20% SS, the cumulative heat release of cement paste for 72 hours was reduced by 33.4%. When GO was added to SS-cement, the hydration reaction of cement was enhanced, and the peak heat release value of SS-cement paste was increased by 18.7–23.6%. LF-NMR test also obtained similar results.(2) Compared with the control sample, the compressive strength of cement paste with 20% SS decreased by 25.8%, 21.1% and 17.7% at 3 days, 7 days and 28 days, respectively. However, with the incorporation of GO, the compressive strength of the SS-cement paste increased by 13.3–25.9%, especially in the early stage.(3) The analysis of microscopic results shows that with the addition of 20% SS, the cement paste has a higher total porosity and a looser microstructure. However, the incorporation of GO reduced the total porosity of the SS-cement paste by 19.1–33.5%, especially the content of harmful pores. With the increase of GO content, the microstructure of the SS-cement paste was further improved, and the C–S–H gel obtained a lower Ca/Si ratio.(4) Nanoindentation studies revealed that when 20% SS partially replaced the cement, the content of the C–S–H gel phase in the matrix decreased. With the addition of GO, the SS-cement paste obtained lower porosity, and higher C–S–H gel content. The HD C–S–H phase contents in the SS-cement matrix with the GO increased by 55.6%, further explaining the development law of the macroscopic properties of the cement-SS–GO system.There are no conflicts to declare.


This study aimed to investigate the value of tissue doppler imaging (TDI) and 4D myocardial strain parameters in evaluating left heart function of pregnant women with hypertension and the association between these parameters and relevant factors. Forty-five pregnant women with hypertensive disorder, including 20 with hypertension, 15 with mild preeclampsia, and 10 with severe preeclampsia, were recruited, and their cardiac functions were compared with those of 30 healthy pregnant women as controls. High Left ventricular end-systolic volume (LVESV), Left atrial volume index (LAVI), E/e were observed in hypertensive disorder, while Mitral peak diastolic velocity(E), Early diastolic peak velocity(e), E/A, Left ventricularglobal longitudinal strain (LVGLS), Left ventricularglobal area strain (LVGAS), and Left atrialglobal longitudinal strain (LAGLS) were decreased; for pre-eclampsia, Left ventricular end-systolic diameter (LVESD), Left atrial anteroposterior diameter (LAD-ap), LVESV, LAVI were significantly increased, LVGLS, LAGLS were significantly decreased, Left ventricular end-diastolic diameter (LVEDD), Left ventricular end-diastolic volume (LVEDV), A peak, E/e were increased, while E peak, E/A, e, Left ventricle global radial strain (LVGRS), Left ventricle global circumferential strain (LVGCS), LVGAS were decreased but not significantly; for severe preeclampsia, Left ventricular end diastolic diameter (LVEDD), LVESD, LAD-ap, Left ventricular end-diastolic volume (LVEDV), LVESV, LAVI, A, and E/e were significantly increased, while LVGLS, LVGRS, LVGCS, LVGAS, LAGLS, E peak, E/A, and e were significantly reduced. TDI combined with 4D myocardial strain parameters can detect early changes in cardiac function of hypertensive disorders in pregnancy, with LVGLS, LVGAS, and LAGLS being the most sensitive indicators for early changes. Such findings provide a basis for effective clinical treatment of these symptoms. In normal pregnancies, the effective circulating blood volume increases, leading to an increase in the cardiac workload. If sustained hypertension persists during gestation, this could lead to a decrease in cardiac pump function. The heart and kidneys are known to interact and are interdependent organs whereby damage to either can lead to the other's functional abnormalities5. Conventional evaluation techniques such as electrocardiography (ECG) and two-dimensional echocardiography (2D-echo) are often used clinically to evaluate cardiac function; however, such methods are imprecise at detecting cardiac abnormalities at an early stage and thus may result in delaying diagnosis of the condition and subsequently resulting in irrevocable damage. To address this limitation, various ultrasound techniques have been introduced recently, most notably M-mode echocardiography, tissue Doppler imaging (TDI) technology, two-dimensional speckle tracking imaging (2D-STE), three-dimensional speckle tracking imaging (3D-STI), and the most recent method, four-dimensional speckle tracking imaging (4D-STI)10. Unlike conventional methods which assume left ventricular (LV) geometry, 4D-STI technology can rapidly track echogenic speckles in three-dimensional space and thus provide more precise and reproducible measurements of myocardial motion function and three-dimensional shape of the heart without any LV geometrical assumptions. Consequently, 4D-STI can help identify cardiac abnormalities at an early stage and facilitate a timely response to any clinical deterioration. In this study, we investigated the value of TDI and 4D myocardial strain parameters in evaluating left heart function of pregnant women with hypertension and the association between these parameters and relevant factors, in order to provide a basis for effective clinical treatment of these symptoms.Hypertensive disorders in pregnancy (HDP) is a general term for a group of medical disorders clinically characterized into five diagnosable conditions, namely gestational hypertension, preeclampsia, eclampsia, chronic hypertension complicated by preeclampsia and combined chronic hypertension in pregnancy, with the two most frequently seen types being gestational hypertension and preeclampsia14. Ethical approvals were obtained from Ethics Committee of the Affiliated Hospital of Weifang Medical College (No.KY-2021-M14). Among them, the severity of preeclampsia was referred to the American College of Obstetricians and Gynecologists, which established the index of hypertensive disorders in pregnancy (2013 edition). In addition to meeting the above conditions, the following special conditions should be excluded: (1) primary hypertension, that is, hypertension that occurred before pregnancy or before 20 weeks of gestation; (2) pregnant women except for congenital heart disease, various types of cardiomyopathy, various valve diseases, various arrhythmias and other cardiac diseases; (3) pregnant women except for some endocrine diseases; (4) pregnant women except for some primary liver and kidney insufficiency; (5) Some special patients whose body size is too obese to be shown by transthoracic ultrasound. Inform the patient beforehand and obtain the patient’s informed consent.Forty-five patients, including 20 patients with gestational hypertension and 25 patients with preeclampsia, aged 20–35 years, mean age 26.60 ± 2.40 years, gestational weeks 20–40 weeks, mean gestational weeks 34.31 ± 3.20 weeks, were selected and diagnosed with hypertensive disorders in pregnancy in Our institute between March 2021 and October 2022. The criteria for diagnosing hypertensive disorders in pregnancy were in accordance with the diagnostic criteria of the eighth edition of the national undergraduate textbook of medical higher education, Obstetrics and GynecologyMeanwhile, 30 healthy pregnant women, aged 20–35 years, mean age 27.33 ± 1.71 years, gestational weeks 20–40 weeks, mean gestational weeks 34.80 ± 2.94 weeks, were selected as the control group. The healthy control group underwent a series of cardiac examinations to ensure that no signs of hypertensive disorders in pregnancy were present throughout pregnancy.A GE Vivid E95 color Doppler diagnostic echocardiograph from GE, USA was used, with a 2D M5S-D cardiac probe and a 4D 4 V cardiac probe at 3.5 MHz, equipped with a 4D imaging software package and the offline quantitative analysis software Echo PAC. Two-dimensional echocardiography was performed at a frame rate of > 28 fps. LVEDD, LVESD, Ieft ventricular septal thickness (IVST), Left ventricular posterior wall thickness (PWT), Left ventricular ejection fraction (LVEF), Left atrial end-systolic anteroposterior diameter (LAD-ap), E, Late diastolic peak velocity (A), and E/A were measured. The TDI technique was used to measured and record e at the septum of the mitral annulus and E/e at the septum of the mitral annulus. Using a 4-dimensional 4 V cardiac probe, 4-dimensional imaging was performed after the subject's heart rhythm was stabilized. A two-dimensional standard four-chamber cardiac view is selected, with the entire myocardium included, and then the 4 V-D button is clicked to select 4–6 cardiac cycles at a frame rate greater than 40% of the heart rate, and the subject is asked to hold his or her breath for 10 s. The stored data is imported into Echo PAC software for offline analysis.t test was used for two-way comparison between groups, and Pearson method was used for correlation factor analysis. P < 0.05 was considered statistically significant difference.The data were analyzed using SPSS V22.0 statistical software, and the measurement data were shown as mean ± standard deviation. one-way ANOVA was used for comparison between multiple groups, independent sample Written informed consent was obtained from all patients recruited in this study. All methods were carried out in accordance with Declaration of Helsinki and Good Clinical Practice (GCP) guidelines. Institutional Review Board of the Affiliated Hospital of Weifang Medical University have approved the study protocol (Ethics Number: KY-2021-M14).Compared with the control group, the E peak and E/A of pregnant women with gestational hypertension were lower than those of the control group, and the difference was statistically significant (P < 0.05); LVEDD, LVESD, IVST, PWT, LAD-ap, and A peak did not change significantly, and the difference was not statistically significant (P > 0.05); LVESD and LAD-ap of pregnant women with pre-eclampsia (mild) were significantly higher than those of the control group, and the difference was statistically significant P < 0.01). LVESD and LAD-ap were significantly higher than those in the control group, and the difference was statistically significant (P < 0.01), LVEDD was higher than that in the control group, peak E and E/A were lower than those in the control group, peak A was higher than that in the control group, and the difference was statistically significant (P < 0.05), and IVST and PWT had slight changes compared with those in the control group, but the difference was not statistically significant (P > 0.05); LVEDD, LVESD, LAD-ap, and LAD-ap in pregnant women with preeclampsia (severe) were not statistically significant (P > 0.05), LVESD and LAD-ap were significantly higher than those in the control group, and the difference was statistically significant (P < 0.01), the E peak and E/A were significantly lower than those in the control group, the A peak was significantly higher than those in the control group, and the difference was statistically significant (P < 0.01), and the IVST and PWT were slightly increased than those in the control group, but the difference was not statistically significant (P > 0.05) ; e was decreased in pregnant women with pre-eclampsia (mild) compared with the control group, and E/e was increased compared with the control group, and the difference was statistically significant (P < 0.05); e was significantly decreased in pregnant women with pre-eclampsia (severe) compared with the control group, and E/e was significantly increased compared with the control group, and the difference was statistically significant (P < 0.01) Table .Table 3CIn comparison with the control group, LVESV and LAVI were higher, LVGLS, LVGAS and LAGLS were lower in pregnant women with gestational hypertension compared with the control group, and the difference was statistically significant P < 0.05). Although LVGRS and LVGCS had slight changes compared with the control group, However, there was no statistical significance (P > 0.05), and LVEDV and LVEF had no significant changes compared with the control group (P > 0.05). LVESV and LAVI in pregnant women with preeclampsia (mild) were significantly higher than those in the control group, LVGLS and LAGLS were significantly lower than those in the control group, the difference was statistically significant (P < 0.01), LVEDV was higher than that in the control group, LVGRS, LVGCS and LVGAS were all lower than those in the control group. The difference was statistically significant (P < 0.05), although LVEF was slightly changed compared with the control group, the difference was not statistically significant (P > 0.05); LVEDV, LVESV and LAVI in preeclampsia (severe) pregnant women were significantly higher than those in the control group, while LVGLS, LVGRS, LVGCS, LVGAS and LAGLS were significantly lower than those in the control group, and the difference was statistically significant (P < 0.01). Although LVEF showed a downward trend, However, the difference was not statistically significant (P > 0.05)  are a serious threat to both maternal and fetal health. The rise in prevalence of this disorder and associated health risks have made it one of the most common maternal disorders in recent times21. Furthermore, 4-D speckle tracking (4D-ST) is an attractive technique due to its lack of dependence on heart stereometry, cardiac cycle bias, and single-plane constraints compared to 2-D ST. Moreover, supplementing this non-invasive technique with unique calculation of area strain can help to detect earlier signs of myocardial morphological and functional changes22. Our results indicate that LV global longitudinal strain (LVGLS), LV global radial strain (LVGRS), and LV global circumferential strain (LVGCS) were reduced in pregnant women with gestational and pre-eclampsia (mild and severe) compared to a control group, as were LV global area strain (LVGAS) and left atrial global longitudinal strain (LAGLS). Moreover, in both gestational and pre-eclampsia cohorts, a statistically significant reduction was found for LVGLS, LVGRS, LVGCS, LVGAS, and LAGLS. This decrease in strain parameters may be attributed to the decrease of myofilaments in cardiac myocytes, partial loss of myogenic fibronectin, ischemia, and hypoxia in hyperemesis gravidarum, which leads to a relative increase in cardiac stiffness and hence, weakening of myocardial wall motion and smaller amplitude of movements24. Moreover, in earlier stages of hypertension, namely, gestational hypertension, LVGLS, LVGAS and LAGLS were reduced compared to healthy controls26. The left atrium, an important indicator for cardiovascular prognosis, was also found to be enlarged and had decreased function with lower LAGLS that decreased further for more severe hypertension cohorts. These findings suggest that changes in systolic function and myocardial injury are occurring during the period of gestational hypertension29. 4D-ST has enabled early detection of cardiac dysfunctions in hyperemesis and a more accurate non-invasive assessment of cardiac damage before clinical symptoms manifest. This technique is important for identifying and mitigating further cardiac complications.The results of this study show that measurements can be made using conventional echocardiography and tissue Doppler imaging (TDI) techniques, suggesting that short-term left ventricular (LV) pressure and volume overload may also lead to diastolic dysfunctionIn clinical practice, a careful integration and analysis of all parameters of echocardiography should be conducted in patients with hyperemesis gravidarum in order to provide early and accurate assessment of cardiac function. Early and rapid diagnosis is of paramount importance, as it can help clinicians to timely take relevant treatment measures according to the severity of the condition and significantly improve the survival rate of both pregnant women and perinatal infants.30. In addition, Speckle-tracking analysis suffers from some limitations, such as intervendor variability, dependence on good image quality and temporal stability of tracking pat-terns.Several limitations to this study need to be acknowledged. Most recent literature data suggest that both the physiological rise in the diaphragm and a narrow antero-posterior chest diameter may contribute to a significant reversible reduction in all the main myocardial strain parameters, assessed by strain echocardiographic imaging in healthy pregnant women. As a consequence the impairment in myocardial strain parameters detected in pregnant women with hypertensive disorders may not be interely ascribed to intrinsic myocardial dysfunction, particularly in those women with anterior chest wall deformity and/or pectus excavatumIn conclusion, in this study, we reported that TDI combined with 4D myocardial strain parameters can detect early changes in cardiac function of hypertensive disorders in pregnancy, with peak, e, E/A, E/e, LVGLS, LVGAS, and LAGLS being the most sensitive indicators for early changes. Such findings provide a basis for effective clinical treatment of these symptoms.


Spasticity is a complex neurological disorder, causing significant physical disabilities and affecting patients' independence and quality of daily lives. Current spasticity assessment methods are questioned for their non-standardized measurement protocols, limited reliabilities, and capabilities in distinguishing neuron or non-neuron factors in upper motor neuron lesion. A series of new approaches are developed for improving the effectiveness of current clinical used spasticity assessment methods with the developing technology in biosensors, robotics, medical imaging, biomechanics, telemedicine, and artificial intelligence. We investigated the reliabilities and effectiveness of current spasticity measures employed in clinical environments and the newly developed approaches, published from 2016 to date, which have the potential to be used in clinical environments. The new spasticity scales, taking advantage of quantified information such as torque, or echo intensity, the velocity-dependent feature and patients' self-reported information, grade spasticity semi-quantitatively, have competitive or better reliability than previous spasticity scales. Medical imaging technologies, including near-infrared spectroscopy, magnetic resonance imaging, ultrasound and thermography, can measure muscle hemodynamics and metabolism, muscle tissue properties, or temperature of tissue. Medical imaging-based methods are feasible to provide quantitative information in assessing and monitoring muscle spasticity. Portable devices, robotic based equipment or myotonometry, using information from angular, inertial, torque or surface EMG sensors, can quantify spasticity with the help of machine learning algorithms. However, spasticity measures using those devices are normally not physiological sound. Repetitive peripheral magnetic stimulation can assess patients with severe spasticity, which lost voluntary contractions. Neuromusculoskeletal modeling evaluates the neural and non-neural properties and may gain insights into the underlying pathology of spasticity muscles. Telemedicine technology enables outpatient spasticity assessment. The newly developed spasticity methods aim to standardize experimental protocols and outcome measures and enable quantified, accurate, and intelligent assessment. However, more work is needed to investigate and improve the effectiveness and accuracy of spasticity assessment. Spasticity is one of many sensory-motor signs and symptoms that may be present following an upper motor neuron (UMN) lesion, causing significant clinical problems such as physical disabilities, abnormal gait or motor disorders , 2. SpasIn clinical practice, spasticity is defined as a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks resulting from hyper-excitability . AccordiThere is no consensus on valid and reliable clinical spasticity measures, due to the patient's neurophysiological complexity and peripheral changes . MeasureObjective assessment of spasticity using biomechanical techniques such as isokinetic dynamometer or pendulum test is considered a valid measurement in multiple joints and makes it possible for standardization of assessment protocols –17. BiomThe mechanisms of spasticity are investigated mostly from neurophysiological studies . ResearcBalci and Luo et al. reviewed previously used methods for spasticity assessment, such as clinical scales, gait analysis and neural and non-neural contribution measurements , 10. How*, (2) hyperton*, (3) measur* or assess* or evaluation (4) cerebral palsy or stroke or spinal cord injury or multiple sclerosis. The formal logical query was (1 OR 2) AND 3 AND 4. The search was conducted up until December 4th, 2022.We conducted a web-based search for relevant literature using the following electronic databases: Scopus, PubMed and Web of Science. We employed a query based on the following keywords (‘All fields' and MeSH): (1) spasTo be included, the screened papers had to satisfy the following criteria: (A) inclusion of the specified query in the abstract and/or title and/or in the keywords, (B) full-paper articles published in in peer-reviewed journals between 2016 and 2022, (C) availability in English, and (D) recruitment of human participants affected by spasticity conditions such as stroke, cerebral palsy, spinal cord injury and multiple sclerosis.After removing duplicate articles, one author screened the remaining articles based on their titles and abstracts. Subsequently, two authors conducted a full-text screening to determine the eligibility of the remaining articles. In cases where the two authors disagreed on the results for the same article, a third author was involved in the evaluation process.A flow chart depicting the selection process is presented in Most clinical spastic evaluations depend on changes in resistance during passive motions at constant such as Ashworth Scale (AS) , Modifiep = 0.41) in elbow flexors (An examiner moves patient's joint quickly to rate the level of resistance and then spasticity level for the target muscle group using AS and MAS . The AS  flexors . It is n flexors . MAS sho flexors . The relTS and MTS take into account passive range of motion (PROM) and muscle responses to passive stretch at the possible fastest stretching rate . TS and r > 0.89) with stretch reflex, M-response areas, and EMG co-contraction ratios during ankle dorsiflexion  was found between elbow flexors spasticity and stretch reflex threshold using CSS measurements , evaluates spasticity by observing a muscle's response to a rapid stretch imposed by gravity and the resulting oscillations between flexion and extension . The penScales are preferred methods in clinical spasticity assessment, even though the reliability of scales has been questioned by researchers . A seriePatients may use different terms than clinicians to describe spasticity in clinical practice . CliniciThe SPAsticity Scale (SPAS) is developed based on torque measurements during pendulum test . The datr = 0.840~0.946, p = 0.000) in upper limb spasticity when evaluating different body positions such as sitting and standing in patients with post-stroke hemiplegic (P < 0.05)  takes into account movement speeds, clonus states and dynamic muscle length to capture mild change in spastic limbs . TSS incmiplegic . TSS is  < 0.05) .Australian Spasticity Assessment Scale (ASAS) takes into account the velocity –dependent features of TS and MTS and uses the similar scoring framework to MAS for clinical compliance . ASAS onClinical scales are the preferred method of spasticity assessment in a simple and convenient manner, especially MAS and MTS are used more frequently in the clinical evaluation of spasticity than spasticity scales. It is now widely used in different settings such as outpatient and scientific research. Although these clinical scales have reported good reliability in the assessment of spasticity, a combination of objective methods such as instrumentation is necessary.Medical imaging technologies, such as near-infrared spectroscopy (NIRS) , magneti2Hb) concentration, deoxygenated hemoglobin (HHb) concentration, total hemoglobin (tHb) concentration, and the tissue oxygenation index (TOI%),   . In addiand HHb) . NIRS isand HHb) . Althougand HHb) . Howeverand HHb) , 76. TheMRI can provide information on muscles' elastic parameters and changes in muscle tissue properties before and after an exercise . A standp = 0.95)  of grayscale image , ultraso = 0.95) .Quantitative echogenicity alone cannot assess the mechanical properties of the spastic muscles, muscle's architectural parameters, such as muscle thickness, fascicle length and pennation angle, have a closer relation to spasticity , 81. USIP < 0.001 and R2 = 0.536, P = 0.002), and also found that SWV increases with the increased level of spasticity   visually evaluates spasticity by echo intensity (EI) of the spastic muscles in the transverse view using a B-type real-time ultrasonography with a linear probe , 88. The< 0.001) . HoweverMedical imaging techniques enable physicians to rely less on subjective tests such as MAS and MTS when managing spasticity. Medical imaging is feasible to provide quantitative information in the assessment and monitor the treatment effects of muscle spasticity . It is nDeveloping tools suitable for spasticity evaluation is a goal that clinicians or researchers are committed to. Many spasticity evaluation devices are developed such as portable-sensor based devices , robots-Portable-sensor based spasticity assessment devices are generally developed based on angular , inertiap ≤ 0.01). It has been suggested that automatically robot-assisted devices could be alternatives for clinical spasticity evaluation.Robot-aided spastic devices may improve the accuracy of spasticity assessment and also can be used in clinical settings for patient-specific rehabilitation . Robot-aP < 0.02) than in healthy individuals   based on spasticity assessment have shown reliability. However, they are not as widely used as clinical scales. The main limitation is the lack of well-equipped laboratories and experienced practitioners. In addition, these devices may not be as suitable for clinical settings. For example, this may increase the burden on clinical physiotherapists learning to operate spasticity assessment equipment and may be more suitable for scientific studies to explore the pathological mechanism of spasticity rather than for outpatient spasticity assessment.Electrical stimulation is often used to stimulate muscles and nerves. Motion can be stimulated by providing enhanced sensory input to the paretic limb . High frrPMS is an effective approach since some patients with severe spasticity are unable to perform sustained voluntary-contraction movements . rPMS caNumerous studies have also explored the effect of rPMS on rehabilitation, in which rPMS can significantly reduce spasticity in patients with central nervous injuries regardless of single or multiple stimulations , 117. CoIt is should be noted that current studies using rPMS in the assessment of spasticity are limited to the upper extremities, and rPMS may not be appropriate for the assessment of patients with lower limb spasticity. Although current studies have demonstrated its reliability in the assessment of upper extremity spasticity, validation in the assessment of lower extremity spasticity is also needed.Neuromusculoskeletal models could gain insights into the underlying pathology of spastic muscles  see Tab. Analyzivan der Krogt et al. conducted spasticity and contracture assessment of the hamstring muscles in children with CP using a neuromusculoskeletal model . The modA recent study simulated actual spasticity responses in patients with stroke based on a haptic model of MAS . This reThe COVID-19 pandemic has impacted the field of physical medicine, especially in the spasticity outpatient evaluation, making the diagnosis more difficult. The emergence of telemedicine may be one of the solutions to solve this dilemma see . A recenA number of studies have focused on and investigated the reliability of tele-evaluation of spasticity. Harper et al.  used telKim et al. discovered that the agreements for the strength and the spasticity of elbow flexor between in-person and remote assessments were substantial (kappa = 0.643) and fair (kappa = 0.308), respectively . De DonnA recent study summarized the potential, challenges and recommendations for telemedicine in long-term neurological diseases and investigated how telemedicine can be used effectively . PatientThis review article has presented an overview the methods developed for the assessment of spasticity from 2016 to 2022 and explores their feasibility. The newly developed spasticity methods aim to standardize experimental protocols and outcome measures, enabling quantified, accurate, and intelligent assessment. However, it is important to note that spasticity patients often exhibit more pronounced pathological during active movements rather than passive movements. The current evaluation methods tend to prioritize passive evaluation while overlooking assessment during active motion. Therefore, future research should focus on combining active and passive motor assessments and incorporating patient self-reports to provide a comprehensive evaluation of spasticity. By considering both active and passive aspects, we can obtain a more holistic understanding of spasticity and improve the accuracy of assessment. Further exploration in this direction will contribute to advancing the field of spasticity assessment.Conceptualization: YM and MH. Methodology: YM and DL. Formal analysis: JH, AL, JY, and CQ. Writing: JH and YM. Review and editing and funding acquisition: YM, MH, and DL. All authors have read and agreed to the published version of the manuscript. All authors contributed to the article and approved the submitted version.


Risk stratification for sudden cardiac death in post‐myocardial infarction (post‐MI) patients remains a challenging task. Several electrocardiographic noninvasive risk factors (NIRFs) have been associated with adverse outcomes and were used to refine risk assessment. This study aimed to evaluate the performance of NIRFs extracted from 45‐min short resting Holter ECG recordings (SHR), in predicting ventricular tachycardia inducibility with programmed ventricular stimulation (PVS) in post‐MI patients with preserved left ventricular ejection fraction (LVEF).We studied 99 post‐MI ischemia‐free patients  with LVEF ≥40%, at least 40 days after revascularization. All the patients underwent PVS and a high‐resolution SHR. The following parameters were evaluated: mean heart rate, ventricular arrhythmias , QTc duration, heart rate variability (HRV), deceleration capacity, heart rate turbulence, late potentials, and T‐wave alternans.p = .039). SDNN values <50 ms were also associated with PVS inducibility . No significant differences were identified for the other NIRFs. The presence of diabetes, history of ST‐elevation MI (STEMI) and LVEF <50% were also important predictors of positive PVS.PVS was positive in 24 patients (24.2%). HRV, assessed by the standard deviation of normal‐to‐normal R–R intervals (SDNN), was significantly decreased in the positive PVS group , can provide an initial, practical, and rapid screening tool for arrhythmic risk assessment in post‐MI patients with preserved LVEF. This study evaluates the performance of various clinical parameters and NIRFs extracted from short‐duration ECG recordings, in predicting ventricular tachycardia inducibility with PVS, in post‐MI patients with preserved LVEF. We found that reduced HRV, presence of diabetes, history of STEMI and LVEF <50% were significant predictors of positive PVS. The indication for implantable cardioverter‐defibrillator (ICD) implantation for primary prevention is currently solely based on left ventricular ejection fraction (LVEF) ≤ 35%  parameters, such as heart rate (HR), QRS duration, ectopic ventricular activity, late potentials (LPs), repolarization abnormalities and indices of the cardiac autonomic nervous system, have been studied as potentially useful tools to identify high‐risk asymptomatic post‐MI patients with preserved left ventricular systolic function. These parameters may indicate an arrhythmic substrate, reflecting different patterns of arrhythmogenicity, i.e., the presence of fibrotic, arrhythmogenic areas , abnormal ventricular repolarization  and autonomic nervous system dysfunction   for the assessment of noninvasive ECG risk parameters, and consequently SCD risk stratification, appears attractive. The development of a fast, practical, and effective risk evaluation method, which could be applied even during a single outpatient clinic visit, would be beneficial for both patients and physicians. This study aims to assess the performance of noninvasive ECG parameters, extracted from 45‐min resting SHR, in distinguishing the subset of post‐MI patients who are potentially at high risk of SCD as guided by a positive PVS.2The study protocol was approved by the Institutional Ethics Committees and all patients provided written informed consent. The study population consisted of post‐MI patients, enrolled in the PRESERVE‐EF study, a multicentre, prospective, observational cohort study, in 4 tertiary cardiology departments . Correction of automatic measurements and exclusion of artifacts was performed after a careful review of each recording. We studied the following parameters: mean HR, PVCs, ventricular couplets, VT, HRV, DC, HRT onset and slope, TWA, LPs, and mean QTc duration. Each parameter was analyzed as a numeric variable, as well as a dichotomous variable, using normal cut‐off points suggested by relevant previous publications , with three Clinical evaluation included medical history, demographic parameters, and laboratory blood tests. A resting 12‐lead surface ECG in the supine position and sinus rhythm was obtained at a paper speed of 25 mm/s (sensitivity 10 mV/cm). We evaluated the P wave, PR interval, QRS complex, QT interval, and RR duration. Fridericia formula was used for the correction of the QT interval measurements. The echocardiographic examination included LVEF estimation using Simpson's biplane method, left ventricular end‐diastolic diameter, left ventricular wall thickness of the interventricular septum, and the posterior wall and left atrial diameters using the M‐mode technique in the parasternal long‐axis view.2.1t‐test or the non‐parametric Mood's median test and Mann–Whitney U‐test, as appropriate. The categorical variables are expressed as absolute numbers and frequencies and were compared using Pearson's chi‐squared test or 2‐tail Fisher's exact test. Binary logistic regression analysis was conducted to estimate the odds ratio (OR) for the measured variables between groups regarding inducibility in PVS. We calculated the sensitivity, specificity, and predictive values of variables that were different between PVS positive and PVS negative groups. Moreover, receiver operating characteristic (ROC) analysis was conducted and the area under the ROC curve (AUC) was interpreted as the probability of a positive PVS. A level of significance of <0.05 was used in all instances.Data were analyzed using the SPSS Statistics version 27 software (IBM Corp.). Continuous variables are presented as mean ± standard deviation or median [interquartile range] if their values were not normally distributed. The examination of normality was performed by the Kolmogorov–Smirnov test. Comparisons of the continuous variables were performed using the Student's 3p = .008), as well as the history of ST‐elevation MI (STEMI) . In univariate analysis, the OR was estimated 3.750  and 3.929  for positive PVS, for the above variables, respectively.The study population consisted of 99 patients. Of these, 24.2% had positive PVS and 75.8% had negative PVS. Table p = .028) and reduced LVEF , compared with the PVS negative group. Importantly, LVEF less than 50% yielded an OR of 4.759  for PVS inducibility.The echocardiographic and baseline 12‐lead electrocardiographic parameters are demonstrated in Table p = .028). The estimated sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of abnormal HRV in predicting a positive PVS were 75%, 50.7%, 65.5%, 61.9%, and 56.6%, respectively, and the AUC was 0.625 .Data extracted from SHR are summarized in Table p = .013), comparable to LVEF.Based on the previous findings, the presence of diabetes, history of STEMI, LVEF, and SDNN were considered for multivariate logistic regression analysis Table . The est4The purpose of this study was to investigate the value of NIRFs, extracted from SHR, in predicting the outcome of PVS in patients with post‐MI with preserved LVEF. The main finding of the study is that reduced HRV is a significant, independent risk marker of positive PVS, which may have important clinical implications. The other NIRFs were not different between the compared groups.The selected ECG NIRFs have been extensively studied as indices of post‐infarction fibrosis , cardiac repolarization abnormalities , and impaired autonomic nervous system function   , echocardiography (LVEF), and SHR for the estimation of HRV and LPs. This initial screening tool should be combined with invasive PVS, as an integral second step, for the final decision on ICD implantation in high‐risk patients. The incorporation of advanced imaging modalities, such as cardiac magnetic resonance, may further improve the accuracy of this risk stratification strategy and is a subject of ongoing research , can form a useful, practical, and rapid screening risk assessment tool for general cardiologists. This approach can be widely implemented in everyday clinical practice since it can be performed even during a single outpatient clinic visit.7Konstantinos Triantafyllou contributed to the conceptualization, formal analysis, methodology, investigation, visualization, writing—original draft preparation, and writing—review and editing. Nikolaos Fragakis and Vassilios Vassilikos contributed to the conceptualization, formal analysis, methodology, supervision, visualization, writing–original draft preparation, and writing—review and editing. Konstantinos A. Gatzoulis contributed to the conceptualization, methodology, supervision, writing—original draft preparation, and writing—review and editing. Antonios Antoniadis and Georgios Giannopoulos contributed to the formal analysis, visualization, writing—original draft preparation, and writing—review and editing. Petros Arsenos contributed to the methodology, visualization, writing—original draft preparation, and writing—review and editing. Dimitrios Tsiachris contributed to the methodology, writing—original draft preparation, and writing—review and editing. Christos‐Konstantinos Antoniou, Konstantinos Trachanas, and Konstantinos Tsimos contributed to the investigation, writing—original draft preparation, and writing—review and editing.None.This study was approved by the Ethical Committee of the Aristotle University of Thessaloniki, Greece, and followed the ethical Declaration of Helsinki. Patients gave informed consent for their participation.


Ten fresh hearts were tested ex-vivo under steady and pulsatile flow in typical right-heart loading conditions. Hemodynamics and 3D echocardiographic imaging of TV and right ventricle (RV) were acquired. Hearts were then kept frozen for 14 days, defrosted, and tested again with the same protocol. Morphometric parameters of TV and RV were derived from 3D reconstructions based on echo data. Fresh samples showed a slightly dilated TV morphology, with coaptation gaps among the leaflets. Sample freezing induced worsening of TV insufficiency, with significant (p < 0.05) increases in annulus size (annulus area and perimeter 7.7–3.1% respectively) and dilation of RV (9.5%), which led to an increase in tenting volume (123.7%). These morphologic alterations reflected into a significant increment of regurgitation fraction (27%). Together, such results suggest that fresh porcine heart samples may be a reliable ex-vivo model of mild FTR condition, which can be enhanced through freezing/thawing treatment to model a severe pathological condition.Emerging treatments for tricuspid valve (TV) regurgitation require realistic TV pathological models for preclinical testing. The aim of this work was to investigate structural features of fresh and defrosted porcine right-heart samples as models of mild and severe functional tricuspid regurgitation (FTR) condition in The online version contains supplementary material available at 10.1007/s10439-022-03080-2. Severe FTR was found to be a predictor of long-term survival and was associated with 36% 1-year mortality.1 Surgical open-heart TV repair is performed only in carefully selected patients. The procedure is indeed challenging and was associated with high in-hospital mortality rates (9–18%).12 Thus, the majority of the patients is left untreated. A potential solution to these vulnerable patients can be represented by transcatheter devices. Recent advancements in the field of transcatheter technologies led to the development of novel TV transcatheter therapies.22 The initial clinical experiences showed safety in patients with high surgical risk2 and many devices are in preclinical development phase. Nevertheless, these procedures are extremely challenging for the clinicians, as the devices interact with cardiac structures and complex anatomy in beating heart conditions and the operator is guided by medical imaging only. This poses challenges not only for the final users to gain proficiency, but also for the innovators of medical industry during device development. Hence the need for platforms capable to accurately simulate the pathology in terms of hemodynamics and anatomical realism, both to provide adequate test benches for the development of novel implantable devices, and procedure simulation environments for operator training.Functional tricuspid regurgitation (FTR) is caused by tricuspid annulus (TA) and/or papillary muscles (PM) displacement due to right ventricle (RV) dilation. This condition leads to tricuspid valve (TV) leaflets malcoaptation and tethering, and in turn to blood leakage across the valve.in-vivo animal models. These models provide important insights into the pathophysiology and allow evaluating the preclinical safety and efficacy of the therapies, yet they can only replicate a limited number of pathologies. Laboratory experimental cardiovascular models and numerical modelling are an alternative to in-vivo testing and can limit the number of animal tests. Experimental models can feature artificial polymeric26 or biological16 cardiac structures. Polymeric models offer the possibility to reproduce patient specific anatomy derived from medical imaging but the reproduction of functional atrioventricular valves is quite challenging, due to their complex anatomy.29 On the other hand, models exploiting biological structures provide realism in terms of anatomical features and biomechanical properties yet in some cases introduce availability and management issue. Moreover, the numerical models can provide complementary data to the experimental analysis.23A key-feature of such platforms is the ability to replicate FTR main determinants. In this perspective, the most realistic approach is represented by the 9 using defrosted porcine whole right hearts, and was successfully exploited for the ex-vivo hemodynamic assessment of FTR transcatheter therapies.27 Indeed, it was observed that defrosted porcine hearts, once internally pressurized to obtain pulsatile flow conditions, display TV leaflets tethering and malcoaptation, which enabled us to replicate the fluid dynamic indexes of the FTR-affected right heart with a certain realism. However, there is still a need for a detailed characterization of the structural features of the TV and RV before and after the freezing–thawing process, in order to obtain a widely usable FTR model by this methodology. Undoubtedly, with a completely characterized ex-vivo pathological model, the assessment of anatomical alterations secondary to the implant of a medical device can provide relevant information both in designing and in training activities. For example, the dimensioning of a novel implantable device must be based on the anatomy of the target and of the surrounding structures as well as on their alterations following the implant. These alterations, if realistically replicated in the platform, can provide insights on the execution of the devices implant procedure, enhancing the training experience.In our laboratory, a pulsatile-flow mock loop of the pulmonary circulation with modelled FTR was developedex-vivo models of FTR in porcine right hearts.In this work, we systematically characterized the fluid-dynamic and morphometric features of the TV-RV complex before and after the freezing/thawing process, in view of making this methodology a reliable approach to obtain well-controllable Ten fresh whole porcine hearts were collected from a local abattoir (weight: 581 ± 61 g). The left ventricles were dissected, and the inferior vena cava and coronary sinus were closed with a suture. Hydraulic connectors were secured to the right heart at the level of superior vena cava , pulmonary artery (pulmonary connector) and through an opening created on the septal wall . The connectors were used to integrate the heart samples with the experimental platforms. Samples were tested first in steady flow and then in pulsatile flow experimental platforms according to a testing protocol described below. After the test, samples were disconnected from the platform and frozen for 14 days at − 18 °C keeping the hydraulic connectors in place. Samples were then defrosted at room temperature, connected to the experimental platforms, and tests were repeated.Figure TV backflow was measured at ventricular pressure of 15 and 30 mmHg to represent normotensive and hypertensive systolic conditions.9 The right heart was connected to the setup as shown in Fig. The setup used was described in details elsewhere.−1), a compliance (16.5 mL × mmHg−1) and an adjustable peripheral resistance (0.22–1.18 mmHg × s × mL−1) which allowed for pressure regulation within a range of typical pulmonary pressure values. The outflow of the impedance simulator was connected to a reservoir  was pushed from the pump into the ventricle and through the pulmonary valve into the pulmonary impedance simulator 3, Fig. . The pulTricuspid Regurgitant fraction (TRF) [%] calculated as the ratio between the TV backflow volume and the ventricular systolic stroke volume;Cardiac Output (CO) [L/min], expressed as mean value of the pulmonary flow rate;Pulmonary regurgitant volume (PRV) [mL], calculated as the time integral of the negative pulmonary flow rate.After averaging the raw data over 10 cardiac cycles, the following indexes were calculated:15 At first, the TV long axis was defined at the end-systole phase, defined as the time instant prior to valve opening. Subsequently, 18 planes evenly rotated (20degrees) around the TV axis were automatically defined by interpolating the volumetric data. On each plane, the atrial contour of the TV leaflets was manually traced  was used to assess TV morphology from the 3D acquisitions, following an approach that was initially adopted for 4 dimensional multidetector computed tomography data.Bidimensional and tridimensional perimeter : perimeters defined on the bidimensional (projection of the annulus on the best-fit plane) and three-dimensional TV profile. Fig. aBidimensional and three-dimensional area : areas enclosed in the bi- and three- dimensional TV profiles. Fig. aDmax, Dmin): the longest and shortest chord, respectively, connecting two annular points and crossing the centroid of the TA points : the volume included between the three-dimensional plane of the valve anulus and the surface of the valve leaflets  was manually defined . This software enabled the evaluation of the RV intracavitary volume recreating the 3D anatomy through a four-step semi-automatic segmentation process:t-test.The data were expressed as mean ± standard deviation after confirming their normal distribution (Shapiro–Wilk test). Statistical differences between parameters of fresh and defrosted samples were assessed using a paired The freezing and defrosting treatment of porcine heart samples yielded TV and RV morphological and hemodynamic alterations with respect to fresh heart samples. Qualitatively, the effects of the freezing process on TV configuration in end systole can be appreciated from the videos enclosed as supplementary materials containing exemplary fiberscopic images, 2D echocardiographic planes and TV 3D reconstructions  and 30 mmHg (p < 0.001), respectively. Pulsatile flow tests reported statistically significant variations in the TRF value which increased by 27% after freezing treatment (p = 0.01). This indicates alterations in RV and TV functioning as also qualitatively noticeable by the tricuspid valve flow reported in Fig. p = 0.54) as confirmed by the unvaried negative portion of the curve  increase in annulus size: annulus area and perimeter increased by 6.7–2.9% and 7.7–3.1% in 3D and 2D reconstructions, respectively. Similarly, Dmax and Dmin values increased by 3.3% and 4.9%, respectively. The reported annular dilation, together with RV volume increase by 9.5% (p = 0.05), accounted for a 124% (p = 0.001) increase in TV tenting volume.The quantitative investigation of TV and RV morphology suggests a high impact of the freezing process on the geometry of the valve at end systole as annular and ventricular dilation were observed. Quantitatively, sample freezing induced significant  and on the stage of the pathology.13 The proposed model could be used as a tool to match the suitable therapeutic strategy to the underlying mechanism. In particular, it could be used to evaluate the efficacy of a device in case of mild RV dilation (exploiting fresh samples) or severe RV dilation (exploiting defrosted samples). Furthermore, post-operative RV dilation was observed as a determinant of pathology recurrence.5 Our model can simulate long-term dilation of the RV. The device or surgical technique can be tested in the mild-FTR experimental model (i.e. in fresh samples) and then in the severe-FTR experimental model (i.e. in frozen/defrosted samples). This could provide an insight on the treatment efficacy in the setting of progressive RV dilation.Bench models able to reproduce the complexity of the TV apparatus constitute an important asset as they can assist, facilitate, and speed up the development of novel transcatheter techniques. Different strategies are adopted to model the FTR condition in preclinical experimental platforms. Considering ex-vivo and in-vivo porcine studies to human data.Additionally, this work provides 3D anatomical data of porcine TV which could be a reference to the scientific community in the context of translating the ex-vivo passive beating heart platform. The heart lacked the natural heart muscle contraction and the pumping system induced paradoxical motion of the ventricle resulting in ventricle volume increase during systole and decrease in diastole. Similar issues were also present in left ventricle mock loop10 and the possible influence of this paradoxical ventricular behaviour was compensated by the lack of papillary muscles contraction. This preserved an efficient functional morphology of the mitral valve preventing leaflet bulging towards the left atrium.28 In TV case, the same principles apply, however due to RV properties the systolic volume increase leads to exaggerated PM displacement, leaflets tethering and thus regurgitation. The transvalvular pressure drop recordings were omitted in this work. The pressure ports connected to the heart chambers would have introduced shadows in the echocardiographic images, which are the focus of this work. Previous works from our group27 already assessed the transvalvular pressure drop, showing that our experimental platform allows to obtain realistic and repeatable values. The transvalvular pressure drop is an important parameter to be considered during evaluation of the heart valve therapies and therefore in the future it would be of interest to adapt the platform to perform simultaneous acquisitions of ultrasound and pressure data.The study carries intrinsic limitations of Moreover, morphological evaluation was performed by semi-automatic 3D echocardiographic data segmentation which is an operator dependent process. To limit operator-dependency of the collected data, the segmentations were performed independently by two operators and the averaged values were reported.ex-vivo passive beating right heart platform and presented a methodology to model different grades of FTR severity exploiting fresh and defrosted porcine hearts. The adopted strategy allowed selective replication of mild or severe morphological and hemodynamic features of FTR, making the porcine heart model a reliable tool to increase efficacy and efficiency of FTR treatment strategies.In conclusion, we quantitatively characterized the 3D morphological features of TV and RV in the Supplementary file1 (MP4 9921 kb).Below is the link to the electronic supplementary material.