Inotropic Response of the Myocardium in Rats with Postinfarction Cardiosclerosis Exposed to Extrasystolic Treatment

The inotropic response of the myocardium to extrasystolic treatment was studied on isolated perfused papillary muscles from rats with postinfarction cardiosclerosis. The development of postinfarction cardiosclerosis was accompanied by a decrease in myocardial excitability. The amplitude of extrasystolic contractions in the remodeled myocardium far surpassed the control. However, the amplitude of postextrasystolic contraction did not surpass that in normal contraction—relaxation cycle. Our results suggest that the ability of the sarcoplasmic reticulum in cardiomyocytes to accumulate Ca²⁺ is impaired during postinfarction remodeling.__________Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 139, No. 6, pp. 613–616, June, 2005     

Role of Endogenous Opioid Receptor Agonists in Regulation of Heart Resistence to the Arrhythmogenic Action of Short-Term Ischemia and Reperfusion

Preliminary selective block of -, ₁-, ₂-, and -opioid receptors had no effect on the incidence of ventricular arrhythmias during 10-min coronary occlusion-reperfusion in ketamine-narcotized rats. Repetitive short-term immobilization of rats for 2 weeks improved heart resistance to the arrhythmogenic action of coronary occlusion and reperfusion. Selective -opioid receptor antagonist CTAP completely abolished, while selective - and -opioid receptor antagonists did not modulate the antiarrhythmic effect of adaptation. Probably, endogenous agonists of -opioid receptors play an important role in the adaptive improvement of heart resistance to arrhythmogenic factors, but are insignificant for the modulation of heart resistance to the arrhythmogenic action of short-term local ischemia-reperfusion in non-adapted animals.__________Translated from Byulleten Eksperimentalnoi Biologii i Meditsiny, Vol. 139, No. 2, pp. 138–142, February, 2005     

Role of Phospholipase A2 in Activation of Isolated Cardiomyocyte Respiration in Postinfarction Cardiosclerosis

The rate of oxygen consumption by isolated cardiomyocytes was studied in rats with experimental postinfarction cardiosclerosis. The increase in oxygen consumption under these condition was comparable to that in melittin- and arachidonic acid-induced activation of phospholipase A₂ in cardiomyocytes of intact animals. Bromophenacyl bromide inhibition of phospholipase A₂ in cardiomyocytes of rats with postinfarction cardiosclerosis led to reduction of oxygen consumption rate to values characteristic of intact animal cardiomyocytes. The results confirm the hypothesis according to which high oxygen consumption in postinfarction cardiosclerosis is related to increased activity of phospholipase A₂. Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 146, No. 12, pp. 631–633, December, 2008     

Pathomorphological Criteria for Cardiosclerosis and Angioarchitectonics of the Hypertrophic Myocardium in Hypertensive Heart

We performed a pathomorphological study of 200 hearts with cicatricial changes from patients died from hypertensive disease. Most postinfarction scars in men were transmural and localized in the anterior and posterior wall of the left ventricle and in the interventricular septum. Non-transmural scars were revealed in the lateral wall (primarily in women). Pathognomonic changes in the architectonics of the heart included reduction of regional blood flow and segmentary, discontinuously extended, and diffusely extended atherosclerotic obstruction. Changes in the index of blood supply to the myocardium corresponded to pronounced decrease in vascularization of the hypertrophic left ventricle. A correlation was found between the index of blood supply to the myocardium and mean systolic and diastolic blood pressure. Therefore, the coronary bed did not satisfy the demands of hypertensive heart with cicatricial changes.     

Postinfarction Remodeling of the Heart: Types of Pathomorphological Changes in the Right Ventricle

New geometric characteristics of the right ventricle depended on the localization of macrofocal transmural scars in the left ventricle of postinfarction heart. Most pronounced changes in the right ventricle were observed during dilatational and hypertrophic remodeling of the heart. The increase and decrease in the volume were most frequently occurring and pathognomonic forms of pathomorphological changes in the right ventricle. Dilatational remodeling was accompanied by a decrease in the volume of the right ventricle. The increase in the volume of this ventricle was typical of hypertrophic remodeling. Pathological variability in the right ventricle underlies the development of severe disturbances in intracardiac hemodynamics, i.e., patho- and thanatogenesis of postinfarction heart.     

Antihypoxic, cardioprotective, and antifibrillation effects of a combined adaptogenic plant preparation

The course of treatment with combined adaptogenic plant preparation Tonizid improved mouse survival under conditions of hypobaric hypoxia and reduced the necrotic zone/risk zone ratio during ischemia and reperfusion in rats under conditions of artificial ventilation. The test preparation decreased the size of the necrotic zone, but had no effect on the size of the risk zone. Tonizid prevented ventricular fibrillation during coronary occlusion and exhibited antihypoxic, cardioprotective, and antifibrillation properties. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 8, pp. 177–180, August, 2006     

皮瓣缺血再灌注损伤治疗研究进展

在皮瓣移植术后常常会发生缺血再灌注损伤,缺血再灌注损伤是引起皮瓣部分或全部坏死的重要原因.目前对皮瓣缺血再灌注损伤的发病机制尚不清楚,大多数学者认为可能与细胞凋亡、炎性反应、组织微循环障碍、细胞氧化损伤等有关.学者们提出用缺血预处理,药物干预,减少炎性反应,移植干细胞或干细胞联合基因疗法,体外冲击波,抗氧化反应和抑制细...     

Antiarrhythmic effect of heat adaptation in ischemic and reperfusion injury to the heart

Study on a model of 6-day dosed adaptation to heat in rats showed that this adaptation decreased the severity of cardiac arrhythmias during ischemic and reperfusion injury. The duration of arrhythmias decreased not only in the ischemic period, but also under conditions of reperfusion. Adaptation delayed the development of arrhythmias during ischemia, decreased the number of animals with late reperfusion arrhythmias, and improved recovery of the heart after ischemia and reperfusion. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 1, pp. 13–16, January, 2007     

Antiarrhythmic and arrhythmogenic effects of L-carnitine in ischemia and reperfusion

Isolated rat hearts were subjected to 30-min coronary artery occlusion followed by 120-min reperfusion. The hearts (n=8–12) were perfused with Krebs-Henseleit solution enriched with L-carnitine (0.5, 2.5 and 5 mM) for 10 min before and after ischemia or reperfusion and for the whole period of ischemia and reperfusion. Two-hour perfusion with L-carnitine during ischemia/reperfusion markedly (p<0.05) and dose-dependently decreased the incidence of ventricular tachycardia (VT, maximum 65%). The incidence of reperfusion ventricular fibrillation (VF) also decreased from 63% (control) to 17% in hearts perfused with 5 mM L-carnitine, as reflected by a significant (p<0.05) decline in VF duration from 218±99 sec in control to 19±19 sec. Perfusion of etomoxir (palmitoylcarnitinetransferase-1 inhibitor) along with L-carnitine reversed the antiarrhythmogenic action of L-carnitine. Interestingly, short time preischemic administration of L-carnitine produced a concentration-dependent arrhythmogenic effects on both ischemia and reperfusion-induced arrhythmias. These results show that L-carnitine produced a protective effect against reperfusion arrhythmias only when it was perfused for the whole period of the experiment. This protective action was reversed by concomitant use of etomoxir, suggesting that the efficacy of L-carnitine is due to its mitochondrial action but cannot be solely attributed to increased fatty acid oxidation. Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 146, No. 8, pp. 175–178, August, 2008     

Rhythmoinotropic Myocardial Reactions in Rats with Postinfarction Cardiosclerosis against the Background of Streptozotocin-Induced Diabetes

We studied rhythmoinotropic reactions of the myocardium in rats with postinfarction cardiosclerosis and in rats with postinfarction cardiosclerosis against the background of streptozotocin-induced diabetes. Inotropic myocardial response in rats with postinfarction cardiosclerosis was signifi cantly inhibited after rest periods, while in streptozotocin diabetic rats the rhythmoinotropic myocardial reaction was comparable with the reaction of intact myocardium. The combination of postinfarction cardiosclerosis and diabetes paradoxically contributed to preservation of contractile function of the myocardium in rats.     

大鼠脑缺血再灌注后脑组织PAR-1表达与MDA含量的相关性研究

目的：观察脑缺血再灌注（cerebral ischemia reperfusion,CIR）后脑组织中PAR-1的表达与MDA含量变化之间的关系。方法：40只SD大鼠随机分缺血再灌注（CIR）后3h、6h、12h、1d、2d、3d、7d及假手术组8个组每组5只大鼠。于脑缺血2h后再灌注相应时间断头取脑,免疫组化法和脑组织匀浆法观察蛋白酶激活受体-1（protease—activated receptor-1,PAR-1）和丙二醛（malondialdehyde,MDA）变化情况。结果：随着CIR时间延长,PAR-1表达和MDA含量增多,呈正相关关系（r=0．844,P〈0．05）。结论：CIR后PAR-1表达增多可加重脑损伤。     

依达拉奉对离体大鼠心肌缺血再灌注损伤的保护作用

目的:探讨依达拉奉(ED)预先给药对大鼠离体心肌缺血再灌注(I/R)损伤的作用及其机制。方法:制作Langendorff主动脉逆行灌注心脏I/R模型。24只雄性大鼠随机分为三组(n均=8):对照组(C组)、I/R组、ED组。观察各组大鼠I/R后心功能指标:左室收缩峰压(LVSP)、左室压上升最大速率(+dp/dtmax)、左室压下降最大速率(-dp/dtmax)、冠脉流量(CF)、心肌细胞乳酸脱氢酶(LDH)及肌酸激酶同工酶(CK-MB)活性、心肌组织丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性。结果:与基础值和C组比较,I/R组再灌注时各时点的CF、LVSP、+dp/dtmax、-dp/dtmax降低(P<0.05);与I/R组比较,ED组再灌各时点的CF、LVSP、+dp/dtmax、-dp/dtmax增高(P<0.05);ED组心肌SOD活性明显高于I/R组(P<0.05),LDH及CK-MB活性、MDA含量低于I/R组(P<0.05)。结论:ED对I/R心肌有保护作用,能促进心功能恢复。其机制与清除自由基和减轻氧化应激有关。     

Opioid Receptors and Heart Resistance to Arrhythmogenic Factors

We present detailed data on the role of central and peripheral opioid receptors in the regulation of heart resistance to arrhythmogenic factors. Stimulation of peripheral delta2- and kappa1-receptors increases heart resistance to the arrhythmogenic effect of acute ischemia and reperfusion. Activation of peripheral mu- and delta1-opioid receptors improves electrical stability of the heart in animals with postinfarction cardiosclerosis. Possible mechanisms for opioidergic regulation of heart resistance to arrhythmogenic factors are discussed.     

Antiarrhythmic effect of 9-week hybrid comprehensive telerehabilitation and its influence on cardiovascular mortality in long-term follow-up – subanalysis of the TELEREHabilitation in Heart Failure Patients randomized clinical trial

IntroductionCardiac rehabilitation is a component of heart failure (HF) management, but its effect on ventricular arrhythmias is not well understood. We analyzed the antiarrhythmic effect of a 9-week hybrid comprehensive telerehabilitation (HCTR) program and its influence on long-term cardiovascular mortality in HF patients taken from the TELEREHabilitation in Heart Failure Patients (TELEREH-HF) trial.Material and methodsWe evaluated the presence of non-sustained ventricular tachycardia (nsVT) and frequent premature ventricular complexes ≥ 10 beats/hour (PVCs ≥ 10) in 24-hour ECG monitoring at baseline and after 9-week HCTR or usual care (UC) of 773 HF patients (NYHA I-III, LVEF ≤ 40%). Functional response for HCTR was assessed by changes – delta (Δ) – in peak oxygen consumption (pVO₂) as a result of comparing pVO₂ from the beginning and the end of the program.ResultsAmong 143 patients with nsVT, arrhythmia subsided in 30.8% after HCTR. Similarly, among 165 patients randomized to UC who had nsVT 34.5% did not show it after 9 weeks (p = 0.481). There was no significant difference in the decrease in PVC ≥ 10 over 9 weeks between randomization arms (14.9% vs. 17.8%, respectively p = 0.410). Functional response for HCTR in ΔpVO₂ > 2.0 ml/kg/min did not affect occurrence of arrhythmias. Multivariable analysis did not identify HCTR as an independent factor determining improvement of nsVT or PVCs ≥ 10. However, only in the HCTR group, the achievement of the antiarrhythmic effect significantly reduced the cardiovascular mortality in 2-year follow-up (p < 0.001).ConclusionsSignificant improvement in physical capacity after 9 weeks of HCTR did not correlate with the antiarrhythmic effect in terms of incidence of nsVT or PVCs ≥ 10. An antiarrhythmic effect after the 9-week HCTR affected long-term cardiovascular mortality in HF patients.     

KB—R7943改善大鼠心肌缺血—再灌注损伤室性心律失常的作用

目的：研究Na^ -Ca^ 交换抑制剂KB－R7943（2－[2-4(4-Nitrobenzyloxy)phenyl]cthyl]isothiourea methanesulphonate)对大鼠心肌缺血－再灌注损伤致室性心律失常的抑制作用。方法：制备大鼠离体左右心房,研究KB－R7943对其心肌及心率的影响,采用离体血管平滑肌张力记录不研究KB－R7943对大鼠胸主动脉血管平滑肌张力作用的影响,利用大鼠离体和在体心肌缺血－再灌注损伤（ischemia/reperfusion,I/R)致心律失常模型研究KB－R7943的抗心律失常。结果：KB－R7943对大鼠心肌收缩力、心率及血管平滑张力作用的影响均较弱,但它可有效地降低大鼠离体和在体心肌I／R后室早、室速、室颤的发生率和持续时间。结论：KB－R7943有较强的抗I／R性心律失常作用,但对大鼠正常心血管功能活动无明显影响。     

Improvement of Cardiac Contractile Function in Rats with Postinfarction Cardiosclerosis after Transplantation of Mononuclear and Multipotent Stroma Bone Marrow Cells

We compared the efficiency of autologous mononuclear cells and multipotent stromal cells of the bone marrow after their non-selective intracoronary transplantation on day 30 after acute coronary infarction in rats. Improvement of hemodynamic parameters of myocardial contractility (rates of left ventricular pressure rise and drop) in comparison with the initial values and deceleration of postinfarction prolongation of QRS and QT intervals were observed in rats of the experimental group in contrast to controls in 4 weeks after transplantation. These functional changes were more intensive after transplantation of multipotent stromal cells and were accompanied by more pronounced morphological signs of reverse myocardial remodeling: thickening of the scarred left ventricular wall, shrinkage of the scar, and decrease in left ventricular dilatation index.     

局灶性脑缺血再灌注损伤对成年大鼠脑内源性神经干细胞的影响

目的：研究局灶性脑缺血再灌注损伤（focal cerebral ischemic and reperfusion injury，fCIRI）对成年大鼠脑内源性神经干细胞（endogenetic neural stern cells，eNSCs）的影响。方法：采用线栓法模拟局灶性大脑中动脉阻塞（middle cerebreal artery occlusion，MCAO）制造成年大鼠fCIRI，持续脑缺血2h后再灌注。将动物随机分组为fCIRI组和假手术对照组。腹腔注射5溴脱氧尿嘧啶（5-bromo-2-deoxyuridine，BrdU）标记具有增殖活性的细胞。在不同时间点取脑，应用免疫组化（免疫荧光法）观察eNSCs的表达。结果：与假手术对照组比较，fCIRI组缺血损伤同侧的侧脑室下区（subventricular zone，SVZ）eNSCs数量明显增多（P〈0．01）。fCIRI后eNSCs的数量变化与时间呈正相关性（P〈0．01）。结论：fCIRI能促进激活成年大鼠脑eNSCs使其进行增殖。     

以短时心率变异性反映充血性心力衰竭患者自主神经活动的改变

基于短时心率变异性（HRV）分析,探讨充血性心力衰竭（CHF）患者自主神经活动的变化和影响。选用THEW数据库中正常人子数据库作为正常对照组（n=189）,对于PhysioNet中两个CHF子数据库的样本（n=44）,按照NYHA等级,将NYHA I-II级划分轻度CHF 组（n=12）,NYHA III-IV级为重度CHF组（n=32）。对每一个Holter记录选取日间和夜间安静态各5 min的RR间期（RRI）序列,分别进行时域、基于AR模型的频域和去趋势波动（DFA）分析。在正常组、轻度CHF组和重度CHF组等三组中,CHF患者日间的短时分形尺度指数（(α₁)_d）两两比较均有显著性差异,并存在下降趋势（依次分别为1.35±0.21、1.03±0.29和0.81±0.29）,反映心率动力学从分形特性转向更随机化的结构。同时,日间HFn((HFn)_d)在三组间的两两比较中均存在显著性差异,并存在上升趋势（依次分别为23.89%±12.78%、37.22%±11.24%和56.30%±15.28%）, 表明CHF导致交感神经和迷走神经交互作用趋于消失。利用夜间RRI（RRI_n）,(HFn)_d 和 (α₁)_d等3个指标进行Fisher线性判别,区分正常人和CHF患者的灵敏性和特异性分别为90.91%和92.06%,而区分轻度和重度CHF患者的灵敏性和特异性分别为84.38%和100%。所进行的研究将HRV非线性方法与传统方法相结合评估自主神经状态, 为监测CHF病情或观察治疗效果等潜在的临床应用提供了依据。