Morphological Study of the Effect of Aerobic Exercise on Organs and Arteries in Spontaneously Hypertensive Rats

Hypertension is usually accompanied by the impairment of organs and arteries, and seriously threatens human health. Aerobic exercise can effectively prevent and treat hypertension. However, the mechanism of exercise therapy in hypertension is still unclear. In this study, we explored how aerobic exercise effectively reversed the impairment of the heart, kidney, and arteries caused by hypertension through a pathomorphological perspective. Spontaneously hypertensive rats were subjected to fifteen weeks of 45 min and 90 min swimming training without weight, and we then tested the effect of exercise on the morphology and structure of the heart, kidney, iliac artery, and branch of the mesenteric artery. We found that the myocardial fibers became thinner, the cross-sectional area of myocardial cells decreased, and cardiomyocyte edema disappeared after 45 min of aerobic exercise. Additionally, the pathological microstructure of glomeruli and renal tubules were improved. At the same time, aerobic exercise could also reverse the morphology and structure of arteries and mesenteric artery branches in spontaneously hypertensive rats.

The Mechanism of Rhein Ameliorating the Survival Rate of Transplanted Mesenchymal Stem Cells by Improving Myocardial Microenvironment in Acute Myocardial Infarction

Background: The paper investigated the mechanism of Rhein improving the ischemic myocardial microenvironment, promoting the survival rate of transplanted BMSCs and functional recovery of damaged myocardium by alleviating myocardial ERS-mediated hyperinflammation and apoptosis after AMI. Material and Methods: A model of myocardial infarction was established. BLI was used to detect the survival rate of transplanted stem cells at 1, 7, 14, 21 and 28 days after surgery. TUNEL staining was used to assess apoptosis. ERS-related protein CHOP immunofluorescence staining was used to assess ERS level. The expressions of ERS-related biomarkers ATF4, CHOP, GRP78 and GRP94 were detected by Western Blot. The inflammatory factors IL-6, TNF-α and IL- 10 of myocardial tissue were detected by ELISA. CD31 immunization was performed 28 days after surgery. Fluorescence staining was used to assess tissue angiogenesis. Results: Rhein combined with BMSCs could improve cardiac function, decrease apoptosis and myocardial CHOP expression. WB showed that the expressions of ATF4, CHOP, GRP78 and GRP94 in myocardial tissue of MI rats were decreased. ELISA showed that Rhein can inhibit the expressions of pro-inflammatory factors IL-6 and TNF-α, and promote anti-inflammatory factors IL-10 expression. CD31 immunofluorescence staining showed that Rhein can promote the formation of neovascularization in infarcted myocardium. Conclusion: In AMI, myocardial ERS is activated. Rhein inhibits ERS and the mediated inflammation and oxidative stress after AMI, inhibits apoptosis, improves the survival rate of transplanted BMSCs, enhances BMSCs to promote neovascularization, inhibits myocardial fibers, and improves heart function.

Cardiotoxic Effects of Hemiscorpius Lepturus Scorpion Venom Fractions in Rats

Background: Scorpion stings are responsible for many deaths in humans; however, the toxicity mechanisms of the venoms from many species are not well studied. We investigated the cardiotoxicity of the crude venom from H. lepturus scorpion and its isolated fractions, F-I to F-VI. Methods: The scorpion’s venom was extracted into six fractions by chromotagraphy. Healthy male Wistar rats (N=72) were equally divided into eight groups of nine: G1: Controls (0.5ml. normal saline), G2: Crude venom (1000µg/kg), G3: F-I (120µg/kg), G4: F-II (430µg/kg), G5: F-III (80 µg/kg), G6: F-IV (180µg/kg), G7: F-V (60µg/kg), and G8: F-VI (130µg/kg). Blood samples were obtained by cardiac puncture at 1, 3 and 24 hours after the venom injection. The serum levels of AST, LDH, CPK, CK-MB and troponin-I were determined. Upon euthanasia, the hearts were removed from the rats and examined microscopically for histopathology. Results: In groups receiving crude venom and F-VI, we observed multifocal fragmentation of myocardial fibers, hemorrhage, degeneration and disappearance of striations in cardiac muscles as compared to the controls. The findings showed that AST and LDH activity in groups 2, 4 and 8, CPK activity in groups 2, 4, 6 and 8 and CK-MB activity and troponin-I levels in groups 2 and 8 increased significantly compared to those in the control group. Conclusion: There was evidence of significant cardiotoxicity in the group receiving crude venom and F-VI. Although alterations in the enzymatic and troponin-I levels were observed in other groups, the greatest cardiotoxicity of H. lepturus venom was caused by fraction VI.

Abstract 16636: Cardiac Microstructural Associations With Metabolic Syndrome Differ by Sex

Background: Alterations in the orientation and integrity of myocardial fibers can be assessed using ultrasonic image analysis. The ability to detect such microstructural abnormalities may shed light on sex differences in the progression from metabolic risk factors to overt cardiac disease. Methods: In a community-based cohort of N=2510 adults (age 66±9 years, 56% women) without overt cardiovascular disease, we evaluated whether a novel echocardiography-based assessment of left ventricular myocardial microstructure, the signal intensity coefficient (SIC), could detect tissue-level alterations that are associated with metabolic risk factors, such as body mass index (BMI) and the metabolic syndrome. Results: In multivariable models adjusting for age and BMI, women had a significantly greater degree of cardiac microstructural alteration (coeff 0.15; s.e. 0.06, P=0.007) in the presence of metabolic syndrome, whereas this association was only borderline significant in men (coeff 0.11; s.e. 0.06, P=0.07) ( Figure ). Notably, there was no sex-specificity in the associations of either age or BMI with cardiac microstructure. Conclusion: A novel index of myocardial tissue alteration is significantly associated with presence of metabolic syndrome, even after adjusting for body size, and more prominently in women than in men. Further research is needed to examine the extent to which cardiac microstructural abnormalities may mediate the metabolic risks for cardiac disease, particularly in women.

THE FEATURES OF CENTRAL HEMODYNAMICS IN PATIENTS WITH CHRONIC CORONARY SYNDROME ON THE BACKGROUND OF GENERALIZED ATHEROSCLEROSIS UNDER THE INFLUECE OF CILOSTAZOL

The aim of the work was to study the features of central and intracardiac hemodynamics in patients with generalized atherosclerosis (GAS) and their dynamics under the influence of a selective inhibitor of phosphodiesterase 3 cilostazol. The condition of central hemodynamics was studied in patients of three study groups: 1 group consisted of 48 male GAS patients aged 65 to 83 years with clinical manifestations of lesions of four vascular territories: coronary, cerebral, mesenteric and femoral; Group 2 consisted of 23 patients with chronic coronary syndrome (CCS), postinfarction cardiosclerosis without concomitant vascular pathology, males mean age 68.5 ± 6.5 years, with clinical manifestations of atherosclerotic lesions of the coronary artery only. The control group (CG) consisted of 18 almost healthy males, the mean age in the group was 62.5 ± 5.3 years. Patients in group 1 were randomized into two subgroups. Patients of the first subgroup (GAS-C) in addition to basic therapy received cilostazol (C) at a dose of 100 mg twice a day, patients of the second subgroup - comparison subgroup (GAS-P) - received only basic therapy. The condition of central hemodynamics was assessed by echocardiography in M- and B-modes. The bioelectrical activity of the myocardium was assessed by the method of daily monitoring of the electrocardiogram. The obtained data showed significantly lower indicators of both inotropic and chronotropic myocardial function in patients of the 1st group compared to the patient with CG (p <0.05), which was significantly lower in minute volume of blood circulation (p<0.01). The comparison of central hemodynamics of patients of the 1st group with similar indicators of patients of the 2nd group revealed significantly lower values of heart rate (HR), left ventricular ejection fraction (EF), circular rate of myocardial fibers (Vcf), stroke volume (SV) and minute blood volume (MBV) in patients of the 1st group (p<0.05). After the addition of cilostazol (C) to the complex standard pharmacotherapy, an increase in inotropic and chronotropic cardiac function was observed: heart rate significantly increased by 9.1% (p<0.05), end-systolic volume decreased by 6.2%, ejection fraction increased by 5.2% (p<0.01), minute blood flow increased by 14.9% (p<0.01), and the rate of circular contraction of myocardial fibers increased by 4.7% (p<0, 05), compared with data before treatment. It is important that the increase in functional activity of the myocardium (chronotropic and inotropic), under the influence of C, was simultaneously with a decrease in the manifestations of myocardial ischemia. The number of painful (РEIM) and painless episodes of myocardial ischemia (PlEIM) probably decreased - by 24.0% and 20.6%, respectively (p<0.05). Thus, our data showed that in patients with generalized atherosclerosis with myocardial infarction, ischemic stroke with intermittent claudication and stenosis of the mesenteric arteries, the use of phosphodiesterase-3 inhibitor C as a part of complex standard pharmacotherapy and leads to increase in minute volume of blood circulation. Importantly, the increase in myocardial functional activity in patients with GAS does not increase the manifestations of myocardial ischemia, but significantly (p<0.05) reduces the number of PEIM and PlEIM.

Relationship of Arrhythmogenic Substrate and Frequent Ventricular Extrasystoles in Patients with Nonischemic Cardiomyopathy

Cardiomyopathies (CMP) are related with scarring tissue due to fibrotic and disarrangement of myocardial fibers that promote an slowed conduction and substrate for sustained reentrant ventricular arrhythmias. Sometimes, CMP can be associated with ventricular extrasystoles but uncommonly originated from scarring tissue. The case report show a patient with nonischemic CMP, frequents premature ventricular contractions and sustained ventricular tachycardia submitted to catheter ablation.

Behavior of fetal longitudinal myocardial fibers assessed by speckle tracking to obtain strain and strain rate values for low-risk pregnancies

ObjectiveTo analyze the behavior of fetal longitudinal myocardial fibers assessed by speckle tracking (STE) after fetal viability.MethodsA cross-sectional study was performed in 156 women with normal singleton pregnancies from 22 to 31 weeks of gestation. Strain (S) and strain rate (SR) values were measured in both ventricles during the fetal cardiac cycle. The population was divided into five gestational age groups based on 2-week intervals. The correlations of maternal variables with the S and SR variables and intra-observer analysis were performed.ResultsThere was a significant difference in the S and SR values of the left ventricle (LV) among the gestational age groups (P = 0.007). Significantly higher S and SR values were observed in early age groups demonstrating reductions in LV S and SR values at 26 weeks, followed by stabilization. For the right ventricle (RV), there was no significant difference between gestational age groups. Significant intra-observer agreement was observed for S values of the RV (P = 0.008) and LV (P = 0.0004) and SR values of the RV (P = 0.0001) and LV (P = 0.015).ConclusionDecreases in the S and SR values of the LV occurred after 26 weeks, followed by stabilization. No significant difference was observed in the S or SR value of the RV among the gestational age groups, and no significant association of any maternal variable evaluated with S and SR values was observed. Significant intra-observer agreement was obtained among the results.

Investigating the Histological Changes in Heart, Lung, Liver and Kidney of Male Albino Mice Treated with Ivabradine

The present study aimed to investigate the histological changes of heart, lung, liver and kidney which caused by different concentrations (10, 20 and 40 mg/kg) of Ivabradine. Results of the study revealed some histological changes represented by aggregation of the lymphocytes around respiratory bronchioles of the lung. In the liver, the drug caused hepatocyte necrosis and infiltration of the lymphocytes. In Kidney, there are no histopathological modifications in the tissue after the animals treated with 10 mg\kg of Ivabradine. When the animals treated with Ivabradine drug at 20mg/kg of bw, dose showed vascular congestion between myocardial fibers of heart. Emphysematous changes of the alveoli and infiltration of lymphocytes around respiratory bronchioles of lung. In the liver there were dilated blood sinusoids. Also, there are vascular congestion and congestion of capillaries in the glomerular of kidney. Male mice treated with Ivabradine drug at 40 mg/kg of bw cause increase spaces between myocardial fibers, cardiac atrophy and myocardial degeneration in the heart. In addition, there are infiltration of lymphocytes around respiratory bronchioles, pulmonary congestion and emphysematous changes of the alveoli in lung. In the liver, the drug cause amyloid deposition and degeneration of hepatocytes. Furthermore, the drug caused vascular congestion in the kidney. Conclusion: From the current study, we conclude that the different concentrations of Ivabradine caused tissue changes in the heart, lung, liver and kidneys. The study should continue using different drugs and concentrations.

Structural and Biomechanical Adaptations of Right Ventricular Remodeling—In Pulmonary Arterial Hypertension—Reduces Left Ventricular Rotation During Contraction: A Computational Study

Pulmonary hypertension (PH) is a degenerative disease characterized by progressively increased right ventricular (RV) afterload that leads to ultimate functional decline. Recent observational studies have documented a decrease in left ventricular (LV) torsion during ejection, with preserved LV ejection fraction (EF) in pediatric and adult PH patients. The objective of this study was to develop a computational model of the biventricular heart and use it to evaluate changes in LV torsion mechanics in response to mechanical, structural, and hemodynamic changes in the RV free wall. The heart model revealed that LV torsion and apical rotation were decreased when increasing RV mechanical rigidity and during re-orientation of RV myocardial fibers, both of which have been demonstrated in PH. Furthermore, structural changes to the RV appear to have a notable impact on RV EF, but little influence on LV EF. Finally, RV pressure overload exponentially increased LV myocardial stress. The computational results found in this study are consistent with clinical observations in adult and pediatric PH patients, which reveal a decrease in LV torsion with preserved LV EF. Furthermore, discovered causes of decreased LV torsion are consistent with RV structural adaptations seen in PH rodent studies, which might also explain suspected stress-induced changes in LV myocardial gene and protein expression.

Sarcomere length–dependent effects on Ca2+-troponin regulation in myocardium expressing compliant titin

Cardiac performance is tightly regulated at the cardiomyocyte level by sarcomere length, such that increases in sarcomere length lead to sharply enhanced force generation at the same Ca2+ concentration. Length-dependent activation of myofilaments involves dynamic and complex interactions between a multitude of thick- and thin-filament components. Among these components, troponin, myosin, and the giant protein titin are likely to be key players, but the mechanism by which these proteins are functionally linked has been elusive. Here, we investigate this link in the mouse myocardium using in situ FRET techniques. Our objective was to monitor how length-dependent Ca2+-induced conformational changes in the N domain of cardiac troponin C (cTnC) are modulated by myosin–actin cross-bridge (XB) interactions and increased titin compliance. We reconstitute FRET donor- and acceptor-modified cTnC(13C/51C)AEDANS-DDPM into chemically skinned myocardial fibers from wild-type and RBM20-deletion mice. The Ca2+-induced conformational changes in cTnC are quantified and characterized using time-resolved FRET measurements as XB state and sarcomere length are varied. The RBM20-deficient mouse expresses a more compliant N2BA titin isoform, leading to reduced passive tension in the myocardium. This provides a molecular tool to investigate how altered titin-based passive tension affects Ca2+-troponin regulation in response to mechanical stretch. In wild-type myocardium, we observe a direct association of sarcomere length–dependent enhancement of troponin regulation with both Ca2+ activation and strongly bound XB states. In comparison, measurements from titin RBM20-deficient animals show blunted sarcomere length–dependent effects. These results suggest that titin-based passive tension contributes to sarcomere length–dependent Ca2+-troponin regulation. We also conclude that strong XB binding plays an important role in linking the modulatory effect of titin compliance to Ca2+-troponin regulation of the myocardium.