Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ventricular late potentials are regarded as an expression of delayed impulse conduction in an area of myocardial ischemia and, accordingly, indicative of a preformed reentry circuit. Late potentials can be detected in chronic, stable coronary artery disease and their presence correlates closely with impairment of ventricular function and with the probability of future occurrence of tachyarrhythmic events or sudden cardiac death. While repetitive ventricular arrhythmias in the chronic stage of coronary artery disease result almost invariably from circling intraventricular wavefronts, tachyarrhythmias associated with acute myocardial infarction appear attributable to differing pathomechanisms. According to experimental studies, in acute myocardial infarction, three phases of arrhythmogenesis can be differentiated: phase 1 encompasses the first hours after vessel occlusion which generally corresponds with the prehospital phase. Due to the difference in potential of up to 25 mV between ischemic and nonischemic cardiac muscle areas, an injury current is called into existence which leads to depolarization of normal cardiac muscle tissue. The ectopic impulses so precipitated, the conduction of which is supported by the functional inhomogeneity of the infarcted region, are capable of initiating reentry tachycardia. During phase 2, a few hours to days after the ischemic event, only the subendocardial Purkinje fibers in the infarcted region exhibit focal arrhythmogenicity. In contrast to the working myocardial cells, the latter survive due to their immediate proximity to the cardiac chamber and show, ischemia-induced, a propensity to high-frequency impulse formation in terms of abnormal automaticity. Similar to the experimental findings, the cause of the frequently-observed ventricular arrhythmias in the early hospital phase appears predominantly attributable to a focal arrhythmia mechanism. During phase 3, several days to weeks after the acute myocardial ischemic event, reentry mechanisms again are in the foreground in which the electrophysiologic changes in the Purkinje fibers, in terms of increasing desynchronization, together with conduction barriers arising through the infarct scar, pave the way for reentry phenomenon. After abrupt restoration of patency of a previously occluded vessel the very frequent "reperfusion arrhythmias" are also attributable primarily to reentry mechanisms due to inhomogeneous improvement of the conduction properties in the region of the reperfused myocardium. Ventricular late potentials can be registered both invasively by means of epi- or endocardial leads as well as noninvasively from the body surface.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Ventricular late potentials in acute myocardial infarct]. 304 72

In recent years calcium channel blockers have emerged as a new class of antiarrhythmic agents for the control of certain supraventricular and ventricular arrhythmias. Electrophysiologically, they are heterogeneous but their main action is mediated through a depressant effect on the slow calcium channel in cardiac muscle. In isolated muscle, their actions are modulated by their reflex actions and by their interaction with the autonomic nervous system due to the nonocompetitive adrenergic blocking actions that some of the compounds exhibit. The major agents exerting antiarrhythmic actions are verapamil, diltiazem, gallopamil, tiapamil, and bepridil; the dihydropyridines are devoid of significant electrophysiologic actions in vivo. Calcium antagonists prolong intranodal conduction time, lengthen the effective and functional refractory periods in the AV node, but exert little or no effect on atrial, ventricular, His-Purkinje, or bypass tract conduction or refractoriness (except in the case of bepridil, which has additional electrophysiologic properties). These effects form the basis of the clinical antiarrhythmic effects of this class of agents. The most striking action is the predictable and prompt termination of reentrant supraventricular tachycardia by intravenous verapamil and diltiazem and the slowing of the ventricular response in atrial flutter and fibrillation. These agents may also be of value in the chronic control of ventricular response in atrial flutter and fibrillation; their role in multifocal atrial tachycardia and other ectopic tachycardias is less well defined. Calcium antagonists reverse ischemic ventricular arrhythmias due to coronary artery spasm but exert little or no action in the usual forms of sustained ventricular tachyarrhythmias associated with severe structural heart disease. They are poor suppressants of premature ventricular contractions. Recent data have established their role in exercise-induced tachycardia occurring in the context of ischemic heart disease; they are also of value in ventricular tachycardia occurring in young subjects developing tachycardia with a right bundle branch block with left axis deviation morphology, an arrhythmia thought to be due to triggered automaticity. The role of calcium antagonists in reducing the incidence of sudden death in the survivors of acute myocardial infarction remains uncertain.
 ...
PMID:Control of cardiac arrhythmias by calcium antagonism. 328 60

Previous work has demonstrated that myocardial ischemia results in a breakdown of the excitation-contraction coupling system of cardiac muscle associated with lysosomal activation. It has been hypothesized that lysosomal activation during the course of myocardial ischemia is mediated by the production of oxygen free radicals. We have tested the hypothesis that myocardial ischemia results in the activation of lysosomal phospholipase C and disruption of calcium transport in sarcoplasmic reticulum (SR) mediated by oxygen free radicals. Three groups of dogs were studied: sham-operated controls (n = 6); normothermic global ischemia of 30-min duration (n = 6); and 30 min of normothermic global ischemia pretreated with intracoronary superoxide dismutase (SOD, 10 micrograms/ml) plus catalase (25 micrograms/ml). In vitro, isolated SR demonstrated a significant depression of calcium uptake rates and Ca2+-stimulated, Mg2+-dependent ATPase activity at both pH 7.0 and 6.4 with the depression at pH 6.4 greater than 7.0. This depression of SR function was significantly inhibited in hearts pretreated with SOD plus catalase. In sham-operated controls, acid-induced dysfunction was associated with substantial loss of phospholipid phosphorus and major changes in phospholipid composition. SR contained an extremely active, ion-independent sphingomyelinase-phospholipase C (SM-PLC) that had maximal activity at pH 4.5-5.0. This SM-PLC was activated when control SR was incubated at acid pH and the specific activity of SM-PLC was decreased 50% in SR isolated from normothermic global ischemia. Activity remained at control levels in hearts pretreated with SOD plus catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Sarcoplasmic reticulum dysfunction: phospholipid alterations induced by lysosomal phospholipase C. 377 91

A model of different degree left coronary artery (LCA) occlusion in rats has been developed. The activity of creatine kinase and its cardiospecific MB isoenzyme was determined both in the cardiac muscle and blood plasma of 62 animals at different time after complete or partial LCA occlusion. A direct dependence of the decrease in the enzyme activity in the heart and hyperfermentemia on the degree of LCA occlusion has been established. It is concluded that the model of LCA occlusion in rats could be useful for the study of different forms and stages of myocardial ischemia.
 ...
PMID:[Change in the activity of creatine kinase and its MB isoenzyme as affected by partial and complete occlusion of the coronary artery in rats]. 377 79

Verapamil has a negative inotropic action in isolated cardiac muscle. Its effects on left ventricular function were tested in 25 patients with suspected coronary artery disease. A double-blind, randomized, placebo-controlled study design was used. Verapamil (0.2 mg/kg over 10 minutes) significantly lowered mean arterial pressure (from 105 to 89 mm Hg) while increasing the cardiac index (from 2.8 to 3.1 liters/min/m2). No statistically significant effect was seen on heart rate, left ventricular end-diastolic pressure or end-systolic volume index, ejection fraction, peak rates of systolic wall thickening or diastolic wall thinning, or percentage of hemiaxial shortening. However, there was a small increase in the left ventricular end-diastolic volume index (from 94 to 102 ml/m2). Important findings were a reduction in systemic vascular resistance (from 39 to 30 U . m2), an increase in left ventricular end-diastolic volume index consistent with a negative inotropic effect, and no evidence of improved regional wall dynamics in portions of the left ventricular wall considered hypokinetic because of myocardial ischemia.
 ...
PMID:Effect of verapamil on left ventricular function: a randomized, placebo-controlled study. 634 Apr 53

Although vasodilators are used with increasing frequency for the treatment of heart failure and myocardial ischemia, their direct effects on cardiac muscle have not been completely characterized. To delineate the action of vasodilators on mammalian myocardium, the chronotropic and inotropic effects of vasodilators on isolated guinea-pig atria (n = 163) have been determined. The spontaneous frequency and the peak rate of isometric force development at a fixed frequency of 200/min were used as indexes of chronotropy and inotropy. The potency series for negative chronotropy was diltiazem greater than D600 greater than verapamil greater than lidoflazine greater than bepridil greater than prenylamine greater than perhexiline greater than nifedipine. The potency series for negative inotropy differed substantially, exhibiting the sequence nifedipine greater than D600 greater than verapamil greater than bepridil greater than lidoflazine greater than prenylamine greater than perhexiline greater than diltiazem. Therefore, nifedipine acted as an "inoselective" and diltiazem as a "chrono-selective" depressant. Other vasodilators, including papaverine, nitroglycerin, nitroprusside, adenosine, dipyridamole, diazoxide and hydralazine exerted no or negligible negative chronotropic or inotropic effects even at high concentration (10(-5) M). Therefore, only vasodilators classified among the calcium antagonists proved to have appreciable direct myocardial effects. This supports the view that these drugs constitute a category of agents distinct from classical vasodilators.
 ...
PMID:Inotropic and chronotropic effects of vasodilators. 680 62

Electrical coupling between cardiac muscle cells is mediated by specialized sites of plasma membrane interaction termed gap junctions. These junctions consist of clusters of membrane channels that directly link the cytoplasmic compartments of neighboring cells. Each gap-junctional channel consists of two connexons, one from each of the interacting plasma membranes, extending across the narrow extracellular gap. Connexons are constructed from connexins, a multigene family of conserved proteins. Different connexins confer specific electrophysiologic characteristics on the assembled channel protein. The major connexin of the mammalian heart is connexin43, although other types of connexins are also expressed, notably connexin40 in myocytes of the atrioventricular conduction system. Confocal laser scanning microscopy of anti-connexin43 immunolabeled samples reveals two major abnormalities in myocardial gap junctions in ischemic heart disease: loss of the usual ordered distribution of gap junctions at border zones adjacent to infarct scars, and reduction in the quantity of connexin43 gap junctions in myocardium distant from the infarct. These and other changes reported in myocardial gap-junctional communication pathways following infarction may result in heterogeneous anisotropic conduction and reduced conduction velocity, thereby forming a proarrhythmic substrate. Current evidence suggests that reduction in connexin43 content is a general pathogenetic feature of cardiac disease, and that changes in the expression levels of other connexin types may contribute to altered electrophysiologic function in the diseased heart.
 ...
PMID:Pathophysiology of gap junctions in heart disease. 751 52

Electrical coupling between cardiac muscle cells is mediated by specialised sites of plasma membrane interaction termed gap junctions, one of three types of intercellular junction of the cardiac intercalated disk. Gap junctions consist of clusters of plasma membrane channels directly linking the cytoplasmic compartments of neighbouring cells. Gap-junctional channels are constructed from connexins, a multigene family of conserved proteins. The principal connexin isoform of the mammalian heart is connexin43; other connexins, notably connexin40, connexin45 and connexin37, are also expressed but in smaller quantities. Antibodies directed against unique sequences of these molecules allow investigation of the role of gap junctions and their component connexins in relation to the electrophysiological properties of the healthy and diseased heart. Confocal laser scanning microscopy of working ventricular myocytes immunolabelled with anticonnexin43 antibodies permits highly sensitive detection of gap junctions, allowing detailed analysis of the spatial distribution of the conduction pathways from the level of the cell to that of the tissue as a whole. Gap junction distribution, number and regional variations in the type of connexin expressed all contribute to the uniform anisotropic pattern of impulse spread characteristic of normal myocardium and the orderly, sequential contraction of the cardiac chambers. Connexin40 is preferentially expressed by myocytes of the atrioventricular conduction system and represents a specialisation facilitating fast conduction, allowing rapid distribution of the impulse throughout the working ventricle. Two major abnormalities in connexin43 gap junctions are detected in human ischaemic heart disease. First, at border zones adjacent to infarct scars, zones which are particularly prone to re-entry arrhythmia, there is marked disruption of the usual ordered distribution pattern of gap junctions. Second, a widespread downregulation of connexin43 gap junctions occurs in myocardium distant from the infarct, a change that is also found in the hypertrophic (non-ischaemic) heart. Consequent localised heterogeneous conduction and reduced conduction velocity provide an explanation for the genesis of re-entry arrhythmias. A current working hypothesis is that reduction in connexin43 gap junctions is a general pathogenetic feature of cardiac disease which predisposes the heart to arrhythmia, and that this reduction may form part of a wider pattern of alteration in the levels of other connexin isoforms.
 ...
PMID:Cardiac muscle cell interaction: from microanatomy to the molecular make-up of the gap junction. 759 43

We hypothesized that the slowly inactivating component of Na+ current, which is an integral part of the Na+ window current, is a major pathway for Na+ loading during myocardial ischemia. The putative protective effects of tetrodotoxin (TTX) and R-56865, at concentrations that selectively blocked the Na+ window current, as assessed by action potential plateau shortening without affecting maximum upstroke velocity (Vmax), were examined in isolated Langendorff-perfused guinea pig hearts subjected to 50 min of normothermic global ischemia and 60 min of reperfusion. In papillary muscles, TTX reduced action potential duration at > or = 10 nM but reduced Vmax only at > or = 1 microM. R-56865 (10 nM-10 microM) failed to affect Vmax but concentration dependently reduced action potential duration. Ischemia-induced cardiac dysfunction, including increases in left ventricular end-diastolic pressure and lactate dehydrogenase and creatine phosphokinase release at reperfusion, was attenuated by TTX and R-56865 (0.1-320 nM). Ischemic contracture (increase in left ventricular end-diastolic pressure) was abolished by drug concentrations as low as 1 nM, whereas higher concentrations (> 10 nM) of TTX and R-56865 were required to restore systolic function at reperfusion. TTX and R-56865 had little or no effect on hemodynamic variables. Evidence is provided of pronounced and direct cardioprotective effects of low concentrations of R-56865 and TTX in cardiac muscle during ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Alleviation of contractile dysfunction in ischemic hearts by slowly inactivating Na+ current blockers. 765 17

Post-systolic shortening is a wall motion abnormality defined as shortening of cardiac muscle after the end of ejection and usually regarded as a manifestation of ischaemia. This study was designed to determine whether changes in preload may alter the magnitude of ischaemia-induced post-systolic shortening. Eleven beagles were anaesthetized (halothane 0.8%) and instrumented for measurement of pressures, flows and dimensions in the apical subendocardium supplied by the left anterior descending coronary artery. Myocardial ischaemia was obtained by tightening a micrometer-controlled snare around the left anterior descending coronary artery. Post-systolic shortening, calculated as end-systolic length minus minimum length divided by end-systolic length, was measured at different levels of preload. Increasing the preload from 4 to 17 mmHg caused a significant reduction in post-systolic shortening (8.9% vs. 12.9%, P < 0.05, Student's paired t-test); post-systolic shortening was negatively correlated with coronary perfusion pressure (r = 0.35, P < 0.01) and positively correlated with systolic bulging. This study demonstrates that the amount of post-systolic shortening depends on the volume status, which therefore has to be taken into account in interpreting regional wall motion abnormalities, such as those detected by echocardiography.
 ...
PMID:The influence of preload on post-systolic shortening in ischaemic myocardium. 778 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>