Contractile failure in early myocardial ischemia: Models and mechanisms

Summary In early myocardial ischemia we find a number of salient electrical and ionic alterations. This article reviews action potential shortening, K accumulation, and contractile failure. Enhanced K efflux during early myocardial ischemia has been attributed to a number of mechanisms, including: the inhibition of active K uptake, osmotic changes, efflux of K ions linked to anion extrusion, cation exchange, altered cellular energy levels, in particular, the opening of ATP-dependent K channels, the involvement of other ion channels, a H/K-ion exchanger, and a catecholamine-dependent pathway. The different mechanisms are discussed. Action potential shortening was described as a salient characteristic of myocardial ischemia in 1954 by Trautwein and Dudel, and was attributed to enhanced outward current. Recently it has been shown by several authors that ATP-dependent potassium channels play a key role in this context. Contractile failure in early myocardial ischemia has been explained by shortening of the action potential duration, reduced cytoplasmic free calcium levels, intracellular acidification, and a rise in inorganic phosphate and Mg. In summary, it is concluded that ATP-dependent K channels may be involved in each of these three phenomena.     

肥厚梗阻型心肌病介入治疗方法的新改进

目的 探讨经皮“室间隔心肌隧道化学消融术（percutaneous transluminal septal tunnel myocardial ablation,PTSTMA）”治疗传统技术不适合的肥厚梗阻型心肌病（hypertrophic obstructive cardiomyopathy,HOCM）的方法及疗效.方法 选择2005年6月至2011年6月期间住院的HOCM患者中的26例为研究对象.观察经PTSTMA治疗的26例HOCM患者术后即刻左心室流出道压力阶差（left ventricular outflow tract pressure gradient,LVOTPG）变化,术后24 h磷酸肌酸激酶同工酶、心电学改变,术后3个月心脏超声指标变化以及随访临床症状的转归.结果 3例通过单支血管消融,17例通过2支血管消融,6例通过3支血管消融.LVOTG由术前（75.6±22.4）mm Hg（1 mm Hg=0.133 kPa）降至（21.4±5.84）mm Hg,差异有统计学意义（P＜0.01）.术后24 h磷酸肌酸激酶同工酶为（1 86±84）μ/L,2例发生Ⅲ＆#176;房-室传导阻滞,均于1周后恢复正常传导,10例发生室性心律失常,12例发生右束支传导阻滞.消融后室间隔厚度减少[（16.8±4.2）mm vs.（22.8±5.8）mm,P＜0.01]、左心房内径减少[（42.0±8.6）mmvs.（48.0±7.0）mm,P＜0.05],差异均有统计学意义.随访时间为（39.8±8.6）个月.与消融前比较,随访中胸痛、呼吸困难症状明显减少,纽约心脏协会心功能分级明显改善,室性心律失常明显减少,黑蒙症状也有一定改善.结论 冠状动脉造影证实冠状动脉室间隔支解剖形态不适合做传统室间隔心肌化学消融术的HOCM患者,PTSTMA能显著降低LVOTPG,改善临床症状.PTSTMA可作为HOCM心肌化学消融术的一种补充方法,其近、中期安全有效.     

Ischaemic cardiomyopathy. Pathophysiological insights,diagnostic management and the roles of revascularisation and device treatment. Gaps and dilemmas in the era of advanced technology

Ischaemic cardiomyopathy (ICM) represents an important cardiovascular condition associated with substantially increased morbidity and mortality. It is characterised from a broad spectrum of clinical manifestations and pathophysiological substrates and its diagnosis is based on the demonstration of significant left ventricular dysfunction in the context of significant epicardial coronary artery disease. Contemporary management aims at improving prognosis through evidence‐based pharmacotherapy and device therapy, where indicated. Whilst the beneficial role of revascularisation remains clear in patients with strong indications such as those with symptoms and/or acute coronary syndromes, for those patients that are asymptomatic and suffer from stable ischaemic heart disease the impact of revascularisation on hard outcomes remains less well defined and currently its adoption is hampered by the lack of robust randomised data. The aim of this review is therefore to provide a constructive appraisal on the pathophysiology of ICM, the role of the various non‐invasive imaging techniques in the diagnosis of ICM and the differentiation between viable and non‐viable myocardium and finally discourse the potential role of revascularisation and contemporary device therapy in the management of patients with ICM.     

The number of cardiac myocytes in the hypertrophic and hypotrophic left ventricle of the obese and calorie-restricted mouse heart

Changes in body mass due to varying amounts of calorie intake occur frequently with obesity and anorexia/cachexia being at opposite sides of the scale. Here, we tested whether a high-fat diet or calorie restriction (CR) decreases the number of cardiac myocytes and affects their volume. Ten 6–8-week-old mice were randomly assigned to a normal (control group, n = 5) or high-fat diet (obesity group, n = 5) for 28 weeks. Ten 8-week-old mice were randomly assigned to a normal (control group, n = 5) or CR diet (CR group, n = 5) for 7 days. The left ventricles of the hearts were prepared for light and electron microscopy, and analysed by design-based stereology. In CR, neither the number of cardiac myocytes, the relationship between one- and multinucleate myocytes nor their mean volume were significantly different between the groups. In contrast, in the obese mice we observed a significant increase in cell size combined with a lower number of cardiomyocytes (P < 0.05 in the one-sided U-test) and an increase in the mean number of nuclei per myocyte. The mean volume of myofibrils and mitochondria per cardiac myocyte reflected the hypertrophic and hypotrophic remodelling in obesity and CR, respectively, but were only significant in the obese mice, indicating a more profound effect of the obesity protocol than in the CR experiments. Taken together, our data indicate that long-lasting obesity is associated with a loss of cardiomyocytes of the left ventricle, but that short-term CR does not alter the number of cardiomyocytes.     

Heart wall myofibers are arranged in minimal surfaces to optimize organ function

Heart wall myofibers wind as helices around the ventricles, strengthening them in a manner analogous to the reinforcement of concrete cylindrical columns by spiral steel cables [Richart FE, et al. (1929) Univ of Illinois, Eng Exp Stn Bull 190]. A multitude of such fibers, arranged smoothly and regularly, contract and relax as an integrated functional unit as the heart beats. To orchestrate this motion, fiber tangling must be avoided and pumping should be efficient. Current models of myofiber orientation across the heart wall suggest groupings into sheets or bands, but the precise geometry of bundles of myofibers is unknown. Here we show that this arrangement takes the form of a special minimal surface, the generalized helicoid [Blair DE, Vanstone JR (1978) Minimal Submanifolds and Geodesics 13-16], closing the gap between individual myofibers and their collective wall structure. The model holds across species, with a smooth variation in its three curvature parameters within the myocardial wall providing tight fits to diffusion magnetic resonance images from the rat, the dog, and the human. Mathematically it explains how myofibers are bundled in the heart wall while economizing fiber length and optimizing ventricular ejection volume as they contract. The generalized helicoid provides a unique foundation for analyzing the fibrous composite of the heart wall and should therefore find applications in heart tissue engineering and in the study of heart muscle diseases.     

Loss of dystrophin staining in cardiomyocytes: a novel method for detection early myocardial infarction

Myocardial infarction (MI) is the most frequent diagnosis made in majority of sudden death cases subjected to clinical and medicolegal autopsies. When sudden death occurs at a very early stage of MI, traditional macroscopic examination, or histological stains cannot easily detect the myocardial changes. For this reason we propose a new method for detecting MI at an early stage. Murine model of MI was used to induce MI through permanent ligation of left anterior descending branch of left coronary artery. Five groups of C57B6/J mice were used for inducing MI, which includes 20 minutes, 30 minutes, one hour, four hours and 24 hours post MI groups. One naïve group and sham-operated groups were used as controls. There is loss of dystrophin membranous staining in cardiac myocytes occurs as early as 20 minutes post myocardial infarction. This can be used as a novel method to diagnose early myocardial infarction in post mortem cases where diagnosis is unclear. In conclusion, evaluation of immunohistochemical expression of dystrophin represents a highly sensitive method for detecting early myocardial infarction due to the loss of staining in the infarcted areas. Dystrophin immunostaining can also be used to assess myocardial architecture.     

增龄大鼠心肌线粒体DNA损伤及DNA修复酶γ表达的变化

目的:探讨大鼠增龄过程中心肌组织DNA损伤和DNA修复酶表达的变化。方法:从不同月龄的大鼠心肌组织中提取DNA、RNA及蛋白。采用定量多聚酶链反应(Q-PCR)检测心肌DNA损伤;用RT-PCR和Western blot检测DNA修复酶γ(Polγ)表达的变化。用ELISA法检测DNA内8羟基脱氧鸟苷(8-OHdG)的水平。结果:随着鼠龄的增长,大鼠心肌组织中核DNA(nDNA)损伤不明显,线粒体DNA(mtDNA)损伤严重,DNA内8-OHdG的水平增加,Polγ的表达下降。结论:随着鼠龄的增长,大鼠心肌组织中DNA修复酶Polγ的表达下降,mtDNA损伤增加。DNA损伤与DNA修复能力下降间会引起恶性循环,最终可导致DNA损伤的增加加快心脏衰老。