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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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)
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PMID:Sarcoplasmic reticulum dysfunction: phospholipid alterations induced by lysosomal phospholipase C. 377 91

Rates of loss of mitochondrial respiratory function were monitored during autolyses of canine myocardial samples pretreated so as to affect tissue pH and/or tissue ATP content prevailing during tissue autolysis. When autolyses occurred under conditions of differing tissue pH, but at nearly identical tissue ATP levels, the rate of loss of mitochondrial function was virtually unchanged suggesting that tissue acidosis in the absence of a concomitant tissue ATP differential had little or no effect upon the rate of progression of mitochondrial damage. In a second comparison, autolyses were carried out at constant tissue pH, but where tissue ATP content differed dramatically. Here, the rate of loss of mitochondrial function was increased markedly suggesting that tissue ATP depletion in the absence of a concomitant tissue pH differential had a major effect upon the rate of loss of mitochondrial function. Thus, of the two parameters studied, tissue ATP content alone was far more important than tissue pH alone in determining the rate of cell membrane damage during ischemia. Finally, autolyses were carried out where both tissue pH and ATP content differed. Here, an even more dramatic increase in the rate of progression of mitochondrial damage occurred suggesting the operation of synergism between tissue ATP depletion and acidosis in promoting cell injury in ischemic cardiac muscle.
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PMID:Factors affecting the loss of mitochondrial function in autolyzing cardiac muscle. 379 79

Ultrastructural changes in cardiac muscle of isolated working rabbit hearts after various periods of ischemia are described and compared with distributional changes in calcium. The effects of reperfusion on these structural parameters were also investigated. The purposes of this study were to relate the role of calcium in the degeneration of cardiac muscle; to determine whether Ca2+ localizations could serve as additional criteria to determine more closely the point of no return; and to investigate the contributory role of reoxygenation to the development of myocardial damage. This study shows the existence of topographic differences in the tolerance to ischemia in the mid area, subendocardium, and subepicardium; that the sequestration of Ca2+ by mitochondria is an energy-requiring (active) process that occurs only during reperfusion; the loss of the sarcolemma's ability to bind Ca2+ during ischemia to coincide with increased Ca2+ entry during postischemic reperfusion (this Ca2+ is scavenged by mitochondria as long as sufficient energy remains available; these changes are interpreted as being at the edge of irreversibility); and the lack of additional damage and and lack of Ca2+ accumulation in mitochondria during reperfusion in cells that are damaged to such an extent that mitochondria possess flocculent densities already at the end of the ischemic insult.
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PMID:Changes in ultrastructure and Ca2+ distribution in the isolated working rabbit heart after ischemia. A time-related study. 381 39

The physiologic results of acute dynamic exercise include complex neurologic, hormonal, pulmonary, and cardiovascular adjustments that provide an integrated response perfectly matching oxygen supply with oxygen demands. Long-term repeated bouts of dynamic exercise of sufficient intensity and duration yield predictable changes in anatomy and physiology. These changes affect active skeletal muscle and the heart. Changes in skeletal muscle include an increased capillary blood volume, increased mitochondrial density, increased oxidative pathway enzymes, and more efficient regulation of blood flow. These adaptations result in an increased oxidative capacity and more favorable fuel utilization. Oxygen extraction increases, accounting for up to 50 per cent of the increased maximal oxygen consumption, and endurance improves. Following chronic dynamic exercise the heart beats slower and has a larger stroke volume at rest and throughout a broad range of work intensities. The maximal cardiac output increases substantially, accounting for up to 50 per cent of the increased maximal oxygen consumption. The metabolic and biochemical changes found in skeletal muscle are not found in cardiac muscle. Changes found in isolated cardiac muscle do not always correlate with heart performance. The separation of central and peripheral factors in assessing heart performance is difficult because preload and afterload are major determinants of heart function and are altered by chronic dynamic exercise. Ischemia is a major stimulus for the development of coronary collateral vessel development in animals. Because dynamic exercise does not induce ischemia in normal humans, collateral vessel development may only occur in those with coronary heart disease. However, there is no convincing evidence that chronic dynamic exercise results in physiologically important coronary collateral vasculature in patients with angina. Improved work capacity is predictable following chronic dynamic exercise in patients with coronary heart disease. Although the rate pressure product that produces angina does not change following training, heart rates are lower at matched absolute workloads and the maximal consumption of oxygen increases. Changes in heart function are largely secondary to peripheral changes in these patients.
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PMID:The physiologic sequelae of chronic dynamic exercise. 388 76

Controversy exists in the literature concerning the effects of insulin and glucagon on cardiac muscle contractility, in particular during anoxia, ischemia or sepsis. The purpose of the present study was to determine the effects of insulin and glucagon on the systolic function of the normal and the dysfunctioning septic rat myocardium in the Langendorff preparation. In the normal isolated rat heart, neither insulin nor glucagon exhibited any lasting inotropic effect on systolic function or coronary flow. Sepsis (cecal ligation and puncture) resulted in a dramatic reduction of systolic function to 44% of control animals. All insulin-containing formulations tested improved systolic function in septic hearts by a mean of 85% compared to Krebs and glucose only. However, this improvement did not reach statistical significance compared to the use of Krebs and glucose only. Glucagon at 100 micrograms/l was doing as well as Krebs and glucose alone while at 1 mg/l glucagon was only able to maintain pre-perfusion contractility. Our results suggest that neither insulin nor glucagon seem to possess special inotropic properties for the isolated perfused normal or septic rat heart.
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PMID:The effect of insulin and glucagon on systolic properties of the normal and septic isolated rat heart. 390 99

The course of recovery of heart activity [assessed by heart rate, atrioventricular (AV) conduction time, monophasic action potentials, contractile force, and perfusion rate] from hypothermic ischemic arrest was studied on isolated perfused rat hearts. The effect of control ischemic arrest was compared with various cardioplegic protective formulations based on high K+ content. During control hypothermic ischemia (20 degrees C), the heart activity extinguished only gradually, action potentials were biphasic, AV conduction was extremely prolonged, and contractions were slow and relatively strong. On reperfusion (37 degrees C), the recovery of electrical activity was almost instantaneous and normalized within 2 min, whereas the contractile force remained substantially depressed. In contrast, K+-containing cardioplegic solutions stopped the heart within several cycles. Postarrest recovery was delayed and transitorily associated with severe arrhythmias (AV block, repetitive afterdepolarizations and oscillations during elevated plateau, and ventricular fibrillation). Nevertheless, the action potentials as well as the contractile force virtually normalized in 10-15 min. Procaine-containing cardioplegic solutions were ineffective in preventing the onset of postarrest reperfusion arrhythmias, whereas addition of nifedipine to the K+-containing cardioplegic solutions largely prevented these arrhythmias, and contractile force was further improved by high concentrations of glucose. The data indicate that postarrest electrical and mechanical recovery do not recover in parallel. Furthermore, high concentrations of calcium antagonist and glucose preserve the electrical and mechanical properties of the cardiac muscle during periods of cardiac arrest.
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PMID:Differences in electrical and mechanical recovery from ischemic heart arrest and cardioplegia. 399 47

Free fatty acids are the major energy source for cardiac muscle. Oxidation of fatty acid decreases or even ceases during ischemia. Its recovery after transient ischemia remains largely unexplored. Using intracoronary carbon-11 palmitic acid as a tracer of myocardial fatty acid metabolism in an open chest dog model, retention and clearance of tracer in myocardium were evaluated at control, during ischemia and after reperfusion following a 20 minute occlusion of the left anterior descending coronary artery. Myocardial C-11 time-activity curves were analyzed with biexponential curve-fitting routines yielding fractional distribution and clearance half-times of C-11 palmitic acid in myocardial tissue. In animals with permanent occlusion and intracoronary injection of C-11 palmitic acid distal to the occlusion site, the relative size and half-time of the early clearance curve component differed markedly from control values and did not change with ongoing ischemia. Conversely, in animals with only 20 minutes of coronary occlusion, the relative size of the early C-11 clearance phase was still significantly depressed at 20 and 90 minutes of reperfusion but returned to control level at 180 minutes. Tissue C-11 clearance half-times remained significantly prolonged throughout the reperfusion period. Regional function in reperfused myocardium monitored with ultrasonic crystals recovered slowly and was still less than control after 3 hours of reperfusion. The data indicate that after transient ischemia, myocardial fatty acid metabolism fails to recover immediately. Because the metabolic recovery occurs in parallel with recovery of regional function, C-11 palmitic acid in conjunction with positron tomography may be useful for studying regional fatty acid metabolism noninvasively after an ischemic injury, and may be helpful in identifying reversible tissue injury.
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PMID:Retention and clearance of C-11 palmitic acid in ischemic and reperfused canine myocardium. 401 19

Recovery from hypoxia has been shown to prolong cardiac muscle contraction, particularly the relaxation phase. The present studies were designed to examine whether incomplete relaxation between beats can result from this prolongation of contraction and relaxation in isolated muscle after hypoxia and in the canine heart after both hypoxia and acute ischemia. The relationship between heart rate and the extent of incomplete relaxation is emphasized in view of the known enhancement of the velocity of contraction caused by increasing heart rate. The extent of incomplete relaxation during 10-s periods of pacing at increasing rates was examined before and after hypoxia in isometric cat right ventricular papillary muscle (12-120 beats/min) and in the canine isovolumic left ventricle (120-180 beats/min). Incomplete relaxation was quantified by measuring the difference between the lowest diastolic tension or pressure during pacing and the true resting tension or pressure determined by interruption of pacing at each rate. In eight cat papillary muscles (29 degrees C), there was significantly greater incomplete relaxation 5 min after hypoxia at rates of 96 and 120 beats/min (P < 0.02 vs. before hypoxia). In seven canine isovolumic left ventricles, recovery from hypoxia and higher heart rates also resulted in incomplete relaxation. Incomplete relaxation before hypoxia at a rate of 180 beats/min was 0.8+/-0.5 cm H(2)O and at 5 min of recovery from hypoxia was 12.6+/-3.5 cm H(2)O (P < 0.01). 12 hearts were subjected to a 1.5-3-min period of acute ischemia and fibrillation. There was significant incomplete relaxation at a rate of 140 beats/min for 5 min after defibrillation and reperfusion. These data indicate that incomplete relaxation is an important determinant of diastolic hemodynamics during recovery from ischemia or hypoxia. The extent of incomplete relaxation appears to be a function of the rate of normalization of the velocity of relaxation and tension development after ischemia or hypoxia, the heart rate, and the magnitude of developed tension or pressure.
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PMID:Incomplete relaxation between beats after myocardial hypoxia and ischemia. 483 Feb 27

The mechanical property of the cardiac muscle has been classically analyzed in two ways; shortening of muscle fiber, and the development of tension within the muscle. In the ejecting ventricle, left ventricular (LV) function can be analyzed by the analogous two-dimensional framework of pressure-volume loops, which are provided by plotting the instantaneous volume against corresponding LV pressure. The integral pressure with respect to volume allows to assess a total external ventricular work during ejection. The diastolic pressure-volume relations reflect a chamber stiffness of the ventricle. Force-velocity relations also provide an useful conceptual framework for understanding how the ventricle contracts under given afterload, with modification of preload. In the presence of coronary artery disease, the regional nature of left ventricular contractile function should be defined as well as the global ventricular function as described above, because the latter is determined by the complex interaction of dysfunction of the ischemic myocardium and of compensatory augmentation of shortening of the normally perfused myocardium. We utilized a computer technique to analyze the local wall motion of the ischemic heart by cineventriculography. The boundaries of serial ventricular images are automatically traced and superimposed using the external reference system. Radial grids are drawn from the center of gravity of the end-diastolic image. Measurement of length of each radial grid throughout cardiac cycle provides the analysis of movement of the ventricle at a particular point on the circumference. Using phasic pressure obtained simultaneously with opacification as the common parameter, segmental pressure-length loops are constructed simultaneously at various segments. The loops are similar over the entire circumference in the normal heart, being rectangular in morphology and with synchronous behavior during contraction and relaxation. However, the marked distortion of pressure-length loops with clockwise rotation or figure of eight inscription is observed in the ischemic segments. Systolic work of the ischemic segment diminishes dramatically, and the loops exhibit varying degrees of inclination. The control segment loops also show an inclination to the opposite direction of the ischemic loops. These differences are presumably related to the local redistribution of the myocardial tension during systole in the ischemic ventricle. Thus, the method described should be of particular value in assessing the regional myocardial function in the ischemic ventricle and effects of various interventions which modify ischemia.
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PMID:[Assessment of cardiac function by left heart catheterization: an analysis of left ventricular pressure-volume (length) loops]. 639 55

From the literature which has appeared over the last decade a selection was made of the three major calcium antagonists: nifedipine, verapamil and diltiazem. In the clinical situation, the net hemodynamic and electrophysiological effect of these drugs is the result of complex interactions between their peripheral and their central effects. The degree of baroceptor stimulation and reflex mediated beta-adrenergic activity, which counteracts and influences the intrinsic negative dromotopic, chronotopic and inotropic effects of calcium antagonists, are related to the degree of peripheral dilation. Nifedipine is the most potent arterial vasodilator and is consequently associated with the most intense reflex adrenergenic activity. Although their effects on vascular and cardiac muscle are similar but not identical, there exist major differences in their antiarrhythmic properties. All act as an antiarrhythmic agent when ischemia or reperfusion cause the arrhythmias, while verapamil selectively blocks the A-V node conduction. All three discussed calcium antagonists are effective in treating patients with coronary spasm, variant angina and unstable angina. In our personal experience with 73 patients with unstable angina with prolonged severe pain at rest with transient ST-segments and T-wavechanges without elevated enzyme levels, 21 became asymptomatic within 8 hours of treatment with conventional therapy, which included nitrates and betablockers. Of 52 who remained refractory to such therapy, the addition of 10 mg of nifedipine orally every two hours to a maximum of 60 mg rendered 42 of the 52 asymptomatic within 8 hours. Arguments why we believe that the timely administration of nifedipine to these and similar patients will reduce or delay the incidence of arrhythmias and myocardial infarction are given on the basis of experimental data. Nifedipine greatly dilates coronary arteries, an effect which persists even after the drug's general hemodynamic effects disappear. It is shown that antagonists have anti-ischemic properties which are primarily related to the persistent reduction of the basic coronary vascular tone which increases oxygen supply whilst reduced myocardial contractility leads to decreased oxygen consumption. Furthermore, preservation of cellular integrity is achieved via protection against intracellular Ca2+ excess, as demonstrated by preserved intracellular high energy phosphate. A randomized multicenter trial in the Netherlands is now in progress to clarify the definitive role of beta blockade versus calcium antagonists therapy of their combination in this syndrome.
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PMID:Treatment of unstable angina with emphasis on calcium antagonists. 644 34


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