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

Simultaneous assessment of the myocardial contraction and hemodynamics showed that the absence of contraction-extension anomalies is the evidence of a current functional reserve of the cardiac muscle and depends on the external and internal factors. At the same time, a volume and resistance overload of the heart and myocardial ischemia are attended with simultaneous changes in the myocardial contraction, which testifies to a unified mechanism of circulation compensation.
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PMID:[Evaluation of heart function using length-tension diagram in the clinical practice]. 229 21

Calcium antagonists have emerged as a new class of antiarrhythmic agents for the control of certain supraventricular and ventricular arrhythmias. Electrophysiologically, these agents are heterogeneous but their main action is mediated through a depressant effect on the slow calcium channel in cardiac muscle, most readily demonstrated in isolated tissue preparations. In vivo, their actions are modulated by their reflex actions and by their interaction with the autonomic nervous system due to the noncompetitive 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 electrophysiologic actions in vivo. Calcium antagonists prolong intranodal conduction time, lengthen the effective and functional refractory periods in the atrioventricular 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 the 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 long-term 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 caused by 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 ventricular premature complexes. 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 patients who develop tachycardia with a right bundle branch block and left axis deviation morphology, an arrhythmia thought to be due to triggered automaticity.
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PMID:Use of calcium antagonists for cardiac arrhythmias. 243 30

Nicardipine has high affinity for the dihydropyridine-binding site and has been shown to inhibit the influx of extracellular calcium through membrane slow channels. The calcium antagonist activity of nicardipine is greater in vascular smooth muscle than in cardiac muscle. Nicardipine has also been shown to possess greater activity in coronary than in peripheral vascular smooth muscle. This in vitro profile accounts for the decreased blood pressure and increased coronary blood flow in animal models in vivo. These pharmacologic properties are the basis for nicardipine's clinical utility in essential hypertension and acute myocardial ischemia. Nicardipine has been shown to be more vascular selective than other calcium antagonists and, therefore, possibly less inclined to produce negative inotropicity. This latter property has been confirmed in human hemodynamic studies. Nicardipine is effective in models of acute myocardial ischemia and hypertension. These results have been confirmed in antianginal and antihypertensive studies in humans. This new calcium antagonist has been shown to limit myocardial infarct size in both dogs and baboons subject to left anterior descending coronary artery ligation and to reduce the extent of ischemia-induced cerebral neuronal death in rats. Other protective effects of nicardipine have been demonstrated in paracetamol overdose in mice, chloroform-induced hepatotoxicity in rats and cerebral ischemia in gerbils and baboons. The mechanism of this cell protection of nicardipine may be related to physicochemical effects.
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PMID:Animal pharmacology of nicardipine and its clinical relevance. 244 Feb 94

To explore relationship between hypertrophy of left ventricle and its shape, blood supply and calcium turnover, the study enrolled 105 male patients with ischemic heart disease or those suspected of its presence. All patients underwent contrast coronary ventriculography, M-mode echocardiography and sectorial scanning. Moderately limited myocardial blood supply was found to be a factor, stimulating its local hypertrophy. In the event of severely impaired blood supply, no substantial myocardial hypertrophy is detectable in corresponding regions, while dynamic observation not infrequently reveals thinning of the wall. Patients with intact coronary arteries, and having more elongated shape of left ventricular cavity, demonstrate larger thickness of walls along the long axis, that is probably due to dependence of intramyocardial tension on the radius of the wall curvature. While performing ventriculography in the patients with hypertrophic myocardium, disclosed elevated level of calcium in the blood and enhanced calcium uptake by cardiac muscle versus patients without left ventricular hypertrophy.
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PMID:Significance of left ventricular shape, its blood supply and calcium turnover for evolving myocardial hypertrophy. 252 3

Impaired left ventricular relaxation and filling is an important pathophysiologic mechanism in hypertrophic cardiomyopathy. To determine whether isoproterenol, known to improve relaxation in isolated cardiac muscle, could favorably modify this effect, we assessed simultaneous left ventricular volume and regional systolic asynchrony (by radionuclide angiography), left ventricular pressure (by micromanometer catheters), and lactate metabolism in 12 patients with hypertrophic cardiomyopathy. Pressure-volume relations were studied during atrial pacing stress to induce myocardial ischemia and during isoproterenol infusion to similar heart rates. Angina occurred in 10 patients with pacing and in 11 patients during isoproterenol infusion; lactate consumption was reduced in nine patients during isoproterenol compared with pacing, including five patients who produced lactate with isoproterenol. During isoproterenol compared with pacing, peak left ventricular pressure was higher (205 +/- 33 vs. 142 +/- 21 mm Hg, p less than 0.001), ejection fraction was higher (77 +/- 10% vs. 71 +/- 12%, p less than 0.02), and regional systolic nonuniformity was diminished. Despite ischemia, these changes in load and nonuniformity during isoproterenol were associated with enhanced diastolic function compared with pacing tachycardia: isoproterenol reduced T 1/2, the half-time of pressure decline after peak negative dP/dt (from 46 +/- 10 to 33 +/- 6 msec, p less than 0.001), shifted the diastolic pressure-volume curve downward and rightward in 10 of 12 patients, and increased end-diastolic volume (from 77 +/- 18% to 100 +/- 11% of control values, p less than 0.001) with no change in end-diastolic pressure (19 +/- 7 to 19 +/- 5 mm Hg, p = NS). Thus, despite ischemia, isoproterenol improved left ventricular relaxation and filling compared with tachycardia in the absence of beta-adrenergic stimulation. Although isoproterenol is detrimental in hypertrophic cardiomyopathy by provoking ischemia, these data suggest that the adverse effects of ischemia on ventricular relaxation and distensibility may be alleviated by beta-adrenergic stimulation, possibly as a result of enhanced inactivation and restored load sensitivity.
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PMID:Beta-adrenergic stimulation with isoproterenol enhances left ventricular diastolic performance in hypertrophic cardiomyopathy despite potentiation of myocardial ischemia. Comparison to rapid atrial pacing. 253 98

The cardiovascular effects of levocarnitine chloride (LC-80) were investigated in in vitro and in vivo experiments, and the following results were obtained: (1) In isolated rabbit cardiac muscle preparations, LC-80 at the high concentration of 10(-2) M had little influence on the atrial rate of spontaneously beating right atria, while it caused a gradual increase in the contractile tension of both spontaneously beating right atria and electrically driven papillary muscle that reached a maximum level after 10 min of administration and lasted for 20-30 min. However, the LC-80-induced positive inotropic effect may be negligible in whole animal experiments or clinical trials, since it was elicited only after the administration of LC-80 in an extremely large dose. Furthermore, LC-80 in a high concentration (10(-2) M) had no influence on the isoproterenol-induced positive inotropic effect in electrically driven papillary muscles. (2) LC-80 in high concentrations of 10(-3)-10(-2) M did not affect the high K+-induced contraction in isolated canine left circumflex coronary artery and saphenous vein. (3) In anesthetized dogs, intraarterial injection of LC-80 in high doses of up to 10 mg did not change the blood flow of coronary, femoral, renal, mesenteric or vertebral arteries and on the adenosine-induced vasodilator action. (4) In anesthetized dogs, intravenous injection of LC-80 in doses of 100-300 mg/kg did not modify the blood pressure responses induced by norepinephrine, acetylcholine, carotid occlusion and vagal stimulation. These results suggest that the cardiovascular effects of LC-80 are extremely mild or negligible. Therefore, LC-80 may be a drug having a new pharmacological feature in its mechanism which enables it to exert a beneficial effect in the treatment of ischemic heart disease, being different from the commonly used antianginal drugs.
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PMID:[Effects of levocarnitine chloride (LC-80) on the cardiovascular system]. 273 6

Six hours of coronary occlusion has been thought to produce extensive and irreversible transmural damage and no possibility of salvage by reperfusion. This has been based on findings of adenosine triphosphate depletion and histochemical (triphenyltetrazolium chloride nonstaining) and ultrastructural changes (conventional preparatory techniques). This study tests the hypothesis that, in contrast to conventional wisdom, considerable structural and mitochondrial functional integrity remains in cardiac muscle subjected to 6 hours of regional ischemia. Twenty open-chest anesthetized dogs underwent isolation of the left anterior descending coronary artery and were observed for 6 hours. Eight of the 20 did not undergo ischemia and served as controls. Twelve underwent 6 hours of proximal ligation of the left anterior descending coronary artery (30% +/- 2% area at risk). Transmural biopsy specimens were analyzed. Coronary occlusion reduced regional blood flow (radioactive microspheres) to less than 10 ml/100 gm/min (p less than 0.05) and dyskinesia persisted in the area at risk for 6 hours. High-energy phosphates (adenosine triphosphate and creatine phosphate) declined to negligible levels and histochemical damage occurred (49% +/- 12% triphenyltetrazolium chloride non-staining). Mitochondrial ultrastructural changes (low protein denaturation embedding technique) were mild (the integrity of the inner and outer mitochondrial surface membranes and crystal membranes was maintained and myofibrillar degeneration did not occur). Mitochondrial oxidative phosphorylation rate remained at 63% of control levels, respiratory control index remained at 77%, and adenosine diphosphate/oxygen ratio was maintained at 96%. Mitochondrial Ca++ increased with lanthanum (from 26 to 46 nmol/mg protein, p less than 0.05), but irreversible calcium precipitation did not occur; calcium could be mobilized to normal levels (i.e., 13 nmol/mg protein) by ethylenediaminetetraacetic acid chelation. These data support our inference that necrosis does not occur after 6 hours of coronary occlusion and suggest that muscle salvage by reperfusion is possible after at least 6 hours of regional myocardial ischemia.
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PMID:Studies on prolonged acute regional ischemia. I. Evidence for preserved cellular viability after 6 hours of coronary occlusion. 281 16

A potent phospholipid (platelet-activating factor, PAF) has been implicated in a variety of inflammatory and ischemic responses (eg, myocardial ischemia and anaphylactic shock). In isolated rat hearts perfused at constant flow, PAF produced a dose-dependent increase in coronary perfusion pressure (CPP) and a decrease in contractile force (CF). At 20 nM, PAF increased CCP by 21 +/- 1 mm Hg and decreased CF by 31 +/- 3% in nine hearts. At the peak of the PAF response, coronary effluent contained LTC4, LTD4, and LTE4 (0.22 +/- 0.05 pmol/ml) and TxB2 (0.97 +/- 0.16 pmol/ml). Addition of specific PAF receptor antagonists (eg, BN-52021 and CV-3988) inhibited peptide leukotriene and TxB2 production and blocked the coronary vasoconstriction and decrease in contractile force. Cyclooxygenase inhibitors (eg, naproxen) or specific TxA2 receptor antagonists (eg, BM-13,505) failed to prevent the increase in CPP or the decrease in CF. Furthermore, a lipoxygenase inhibitor (ie, propyl gallate) or a specific LTD4 receptor antagonist (ie, LY-171,883) prevented the increase in CPP but did not antagonize the negative inotropic response. These data indicate that the coronary constriction in the isolated perfused rat heart is a result of the PAF-induced release of endogenous peptide leukotrienes but not TxA2 production. However, the negative inotropic response appears to be partly due to a direct negative inotropic action of PAF on cardiac muscle. Thus, PAF produces a variety of direct actions and indirect effects via release of eicosanoid mediators contributing to cardiac impairment in the rat heart.
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PMID:Mechanisms of platelet-activating factor-induced cardiac depression in the isolated perfused rat heart. 282 6

The perfusion of canine cardiac muscle with 10 microM oligomycin produced a nearly 90% slowing of the net rate of tissue ATP depletion from 0.200 to 0.025 mumol X min-1 X g wet wt-1 of tissue during a subsequent myocardial autolytic interval during which tissue pH was held constant. Moreover, lowering the tissue pH during the autolytic process by 0.6 unit from approximately 6.8 to approximately 6.2 produced a nearly 60% slowing of the net rate of tissue ATP depletion from 0.200 to 0.087 mumol X min-1 X g wet wt-1. The pH dependence of the net rate of tissue ATP depletion (by an oligomycin-sensitive process) was that predicted from the mitochondrial ATPase pH-inhibition profiles reported earlier (J. Biol. Chem. 258: 9657-9661, 1983). When taken together with our observation that the mitochondrial ATPase comprises approximately 90% of the total of all of the ATP hydrolyzing activities present in cardiac muscle cells, data reported here suggest that the protonic inhibition of the mitochondrial ATPase plays a major role in regulating the rate of tissue ATP depletion during myocardial ischemia.
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PMID:Effects of oligomycin and acidosis on rates of ATP depletion in ischemic heart muscle. 293 13

During the past decade our understanding of the complex interaction between cardiac muscle and coronary vascular growth has increased substantially. Some types of cardiac hypertrophy, for example, left ventricular hypertrophy secondary to hyperthyroidism, are associated with increased coronary vascular growth. However, in most animal preparations of hypertrophy and in several clinical types of hypertrophy of the left and/or right ventricles, pathologic cardiac enlargement impairs the ability of the coronary circulation to allow normal increases and perfusion in response to intense dilator stimuli. In general, clinical studies have demonstrated far more profound abnormalities than studies in experimental animals. These observations provide a plausible explanation of why patients with hypertrophied ventricles often exhibit signs and symptoms of myocardial ischemia in the absence of coronary obstructive disease. The recent observation that experimentally produced left ventricular hypertrophy secondary to renal hypertension augments infarct size and the incidence of sudden lethal arrhythmias has additional implications relevant to the interaction between cardiac hypertrophy and myocardial perfusion. Although coronary reserve is impaired in many types of pathologic hypertrophy, the anatomic or biochemical basis for these observations remains elusive.
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PMID:Alterations in the coronary circulation in hypertrophied ventricles. 294 48


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