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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ATP-dependent, inorganic phosphate-supported 45Ca2+ uptake by digitonin-lysed adult rat ventricular cardiomyocytes was used to evaluate the effects of simulated ischemia and reperfusion on the physically intact sarcoplasmic reticulum. Mitochondrial reactions were inhibited with rotenone and oligomycin. 45Ca2+ accumulation in the presence of the calcium efflux inhibitors, procaine (10 mM) and ruthenium red (30 microM), was used to characterize unidirectional uptake kinetics. A decrease in pH from 7.2 to 6.6 increased the [Ca2+] K0.5 from 0.5 to 2.0 microM and reduced the apparent Vmax by 28%. In the absence of procaine and ruthenium red, at a free [Mg2+] of 0.5 mM, maximum net uptake occurred at pCa 6.2 when pH was 7.2 and at pCa 6.0 when pH was 6.6. At lower pCa, net Ca2+ accumulation declined. Increasing free [Mg2+] from 0.5 to 1 mM at pH 6.6 or to 2.5 mM at pH 7.2 increased net 45Ca2+ accumulation in the absence of procaine and ruthenium and shifted maximum uptake to pCa 5.6 and 6.0, respectively. Increases in cytosolic free [Mg2+] thought to occur during myocardial ischemia are therefore capable of inhibiting calcium efflux from the sarcoplasmic reticulum. Reducing [ATP] from 10 to 1 mM reduced maximum net 45Ca2+ uptake by 30% both in the presence and absence of efflux inhibitors. Preincubation of intact myocytes under conditions designed to simulate ischemia and reperfusion decreased 45Ca2+ uptake greater than or equal to 50%. The data indicate that myocardial ischemia and reperfusion can alter both Ca2+ accumulation and calcium release by the sarcoplasmic reticulum.
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PMID:Effects of simulated ischemia and reperfusion on the sarcoplasmic reticulum of digitonin-lysed cardiomyocytes. 155 Nov 98

Difficulties in studying myocardial metabolism with adequate time resolution have led to contradictory conclusions regarding the mechanisms causing contractile abnormalities during the early stages of ischemia. In acutely instrumented swine, we investigated whether abnormalities in subendocardial ATP, phosphocreatine, or lactate content develop rapidly enough during the first few heart beats after onset of partial myocardial ischemia to contribute to contractile failure. Within the first 15 beats of a 40-50% reduction in left anterior descending coronary artery blood flow, regional myocardial function was significantly reduced but continuing to deteriorate. Rapidly frozen transmural left ventricular biopsies obtained on the 15th heart beat (+/- 1.5 beats) after the onset of ischemia revealed significant decrements in subendocardial phosphocreatine and ATP levels to 77% (p less than 0.05) and 84% (p less than 0.005) of control values, respectively, but minimal change in lactate content. Metabolic effects as assessed by transmural averages took longer to become detectable; thus, there was a tendency to underestimate the importance of subendocardial metabolic effects on myocardial function. When left ventricular preload was assessed during this early time period, left ventricular end-diastolic wall thickness only decreased by 3%, and left ventricular end-diastolic pressure did not change significantly despite a large fall in coronary perfusion pressure. Thus, in an in vivo pig model with techniques optimized to detect subendocardial metabolic changes within the period of very early moderate myocardial ischemia, abnormalities in high energy phosphate compounds occurred rapidly enough to contribute to developing myocardial dysfunction, whereas preload-mediated mechanisms related to vascular distending pressure could not explain the functional deterioration under these conditions.
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PMID:Energy metabolism and contractile function after 15 beats of moderate myocardial ischemia. 157 34

The aim of this work was to ascertain whether free radicals play a causal role in the injury occurring in myocardial ischemia and reperfusion. To this purpose we observed whether spin-trapping compounds protect the heart when used at a concentration capable of reacting with free radicals. The lipophilic spin trap alpha-phenyl-t-butyl nitrone (PBN) was used because it is taken up by the myocites. Isolated Langendorff rat hearts were subjected to ischemia according to two schemes: "Model A" = 30 min zero-flow ischemia followed by 30 min reperfusion; "Model B" = 60 min of low-flow ischemia (10% of the individual value; N2 saturated) followed by 30 min reperfusion. Treated groups received in addition 5.0 mM PBN which was supplied continuously. The following parameters were measured throughout the experiment: contractile performance (RPP); coronary flow (CF); CPK; phosphocreatine (PCr), ATP, inorganic phosphate (Pi), intracellular pH (pHi). The pathology obtained by "Model A" is more severe than that of Model B, and partly irreversible. During the ischemic phase in "Model A", contractility, PCr and ATP dropped to near zero; during initial reflow CPK rose about 13-fold and Pi rose 2.5-fold, while pHi decreased to 6.1. During reperfusion, a partial recovery of PCr, Pi and pHi was observed, while RPP and ATP did not increase; PBN treatment improved significantly PCr and CPK, while the other parameters were unaffected. During ischemia, "Model B" hearts showed a drop of contractility to near zero, of PCr to 35%, of ATP to 50%; CPK rose 7-fold and Pi 1.5-fold; pHi was not modified. During reperfusion, all parameters recovered in part, with exception of Pi. PBN developed a marked protective activity on all tested parameters, which gained a nearly normal value. The results of the present investigations show that the lipophilic spin trap PBN partly protects the heart from the ischemia/reperfusion injury, thus confirming that free radicals play a causal role in this pathology; the continuous loading of the tissue with the drug can be an important factor for obtaining the protective effect.
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PMID:Protective activity of the spin trap tert-butyl-alpha-phenyl nitrone (PBN) in reperfused rat heart. 161 68

During myocardial ischemia there is a drop in high-energy phosphates in the myocardium. Cold potassium cardioplegia decreases but does not altogether prevent this reduction. Supplementation of cardioplegic solutions with the high-energy compound creatine phosphate (10 mmol/L) compared to plain cardioplegic solutions was investigated in this study. Thirty patients scheduled for aortic valve replacement were included. The patients were randomized to group I (creatine phosphate) or group II (control). Postoperative hemodynamic evaluation revealed no significant differences between the groups. However, group I exhibited a tendency toward a better stroke-work index (135 +/- 18% vs. 102 +/- 5% recovery 15 minutes after bypass and 145 +/- 16% vs. 119 +/- 11% recovery 105 min after bypass). There were fewer patients in group I (5/15) needing inotropic support compared to group II (9/14). The myocardial content of ATP and creatine phosphate showed no significant differences during ischemia and reperfusion. It is concluded that the myocardial protection during ischemia was sufficient to prevent significant reductions of myocardial ATP and creatine phosphate irrespective of supplementation with CP.
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PMID:Biochemical and functional effects of creatine phosphate in cardioplegic solution during aortic valve surgery--a clinical study. 163 61

There is evidence that the "ATP-sensitive" potassium channel opens, at least during the early stages of myocardial ischemia, despite relatively high ATP levels. Thus, channel opening may partially contribute to potassium efflux and accumulation of extracellular potassium, but probably much more profoundly to electrical abnormalities associated with ischemia, including the development of lethal arrhythmias. Several factors are discussed that may promote a significant open-channel probability of the channel, in spite of relatively high levels of ATP. It is argued that, even with a very low open probability, the magnitude of total membrane current carried by these channels may be substantial (comparable to other potassium currents) because of the high density and conductance of the ATP-sensitive potassium channel. Finally, it is shown how the ATP-sensitive potassium channel may play a role in various tissue types, ranging from the physiological to the pathophysiological. This potassium channel is therefore increasingly targeted for drug development and research.
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PMID:ATP-sensitive potassium channels and myocardial ischemia: why do they open? 163 28

The normal control of coronary blood flow is through alterations in the resistance of the intramyocardial arterioles (R2). Myocardial cellular hypoxia causes increased breakdown of ATP (or decreases synthesis) resulting in increased concentrations of the purine metabolite, adenosine. This potent endogenous, vascular smooth muscle relaxant vasodilates the R2 arterioles increasing coronary blood flow and myocardial O2 delivery. This mechanism autoregulates coronary blood flow according to myocardial O2 needs. Myocardial hypertrophy (from chronic hypertension) or coronary atherosclerosis interfere with this process and result in myocardial ischemia which may cause symptoms (angina), signs (ECG changes, regional muscle dysfunction) or tissue death (myocardial infarction). In addition, coronary atheroma disrupt endothelial function in the large R1 coronary arteries predisposing to vasoconstriction, platelet aggregation and thrombosis. Therapeutic measures for controlling ischemia may include decreasing oxygen demand (especially heart rate) and maintaining supply (R1 vasodilators and anti-thrombotic drugs such as non-steroidal anti-inflammatories). Intravenous, most inhalational and regional anesthesia appear to interfere minimally in the control of both the normal and ischemic coronary circulation. Thus optimizing myocardial oxygen balance (maintaining supply and decreasing demand) during anesthesia protects the ischemic myocardium. High doses of isoflurane, sevoflurane or desflurane are potent R2 coronary vasodilators which may cause redistribution of collateral blood flow away from ischemic regions (coronary steal). However, if tachycardia and hypotension are avoided, such an effect has not been shown experimentally or clinically. Preliminary evidence suggests that halothane may preferentially dilate R1 arteries and/or interfere with platelet aggregation. If these effects are confirmed, then halothane may prove to be the anesthetic of choice in the non-failing ischemic heart.
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PMID:Physiology, pathophysiology and pharmacology of the coronary circulation with particular emphasis on anesthetics. 164 43

The three techniques allowing the noninvasive study of cardiac metabolism, namely magnetic resonance spectroscopy (MRS), positron emission tomography (PET) and single photon emission computed tomography (SPET), all use external detection with stable or radioactive isotopes. These techniques yield different information. PET is quantitative and very sensitive, and therefore only tracer amounts of molecules need to be injected. It allows neurotransmitters and receptors to be studied and a global view of metabolism (oxygen consumption, glucose and fatty acid utilization) to be obtained. SPET also has good sensitivity, but uses gamma-emitting isotopes of heteroatoms. Their longer half-lives allow follow-up for hours or days. MRS is based on stable elements with high (hydrogen 1, phosphorus 31, fluorine 19...) or low (carbon 13, Deuterium) natural abundance. It has very low sensitivity and only millimolar concentrations of substrates can be detected, but various parts of metabolism can be studied. The in vivo measurement of myocardial concentration of substances has many problems that are common to all three techniques (measurement of the volume, measurement of the quantity of each molecule, resolution, partial volume effect, improvement of the signal-to-noise ratio, movement of the organ). The complementarity of the techniques is illustrated by their applications to the study of cardiac metabolism. For instance, the energy metabolism can be studied by 31P-MRS, which detects the high-energy compounds ATP and phosphocreatine, and 13C-MRS yields information on the tricarboxylic acid cycle activity. PET and SPET allow the utilization of fatty acids, the normal fuels of the heart, to be studied. During ischaemia, PET with 18F-fluorodeoxyglucose (18FDG) can determine the glucose consumption and 1H-MRS shows the increase in lactic acid, reflecting anaerobic glycolysis. Comparison of the use of acetate labelled with 11C for PET or 13C for MRS shows the potentials and limitations of each technique. Myocardial perfusion can be evaluated directly with various PET tracers or indirectly with thallium 201 or various technetium-99m-labelled tracers by SPET. No MRS marker of perfusion is so far clinically available. Mainly SPET and PET are used clinically for the investigation of ischaemic heart disease as well as cardiomyopathies, but some initial results using 31P-MRS are being obtained.
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PMID:Complementarity of magnetic resonance spectroscopy, positron emission tomography and single photon emission tomography for the in vivo investigation of human cardiac metabolism and neurotransmission. 166 Dec 37

In cultured rat heart muscle cells, reversible long-term ATP depletion induces a decrease in beta-adrenoceptor density and a fall in isoproterenol- as well as forskolin-stimulated cAMP formation. However, isoproterenol-stimulated adenylyl cyclase activity in membrane preparations is not reduced after ATP depletion. These results suggest that the decreased responsiveness to catecholamines during myocardial ischemia cannot be explained by alterations of the beta-adrenoceptor-adenylyl cyclase system alone.
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PMID:Alterations of beta-receptor-adenylyl cyclase coupling by long-term ATP depletion in cultured rat cardiomyocytes. 166 50

Changes in tissue lactate, ATP, and cytosolic free calcium (Cai) were examined in isolated, perfused rat hearts receiving 20 min of zero-flow global ischemia (37 degrees C). Addition of diltiazem before ischemia caused a concentration-dependent decrease in lactate accumulation. This effect was not mediated by modulation of norepinephrine release since depletion of catecholamines by reserpine did not alter lactate accumulation, and diltiazem treatment reduced lactate accumulation in catecholamine-depleted hearts. Diltiazem-treated hearts showed a concentration-dependent decrease in tissue ATP utilization that was associated with the decrease in tissue lactate during ischemia. Basal time averaged Cai, determined by fluorine NMR using 5FBAPTA, was 620 nM. Diltiazem (0.9 microM) decreased this value to 489 nM and reduced heart rate and maximum pressure developed (81.3 and 53.9% of control, respectively) before ischemia. Cai increased fourfold between 9 and 15 min of ischemia in hearts receiving no drug, while there was no increase in Cai in diltiazem-treated hearts. These results show that diltiazem reduces the use of ATP and therefore production of lactate during ischemia, and indicate a relationship between preservation of ATP and maintenance of Cai that may be important in the beneficial effects of diltiazem during myocardial ischemia.
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PMID:Effects of diltiazem on lactate, ATP, and cytosolic free calcium levels in ischemic hearts. 168 81

The loss of NADH-ubiquinone oxidoreductase activity, the activity of mitochondrial electron transfer complex I, underlies the loss of mitochondrial phosphorylating respiration with NAD-linked substrates observed during myocardial ischemia. In the present study the loss of complex I activity was found to be considerably more rapid during zero-flow ischemia in rat heart, a fast heart-rate heart, than in dog heart, a slow heart-rate heart. Moreover, the greater rapidity of the loss of complex I activity in the ischemic rat heart appeared to reflect the more rapid and more severe decreases in tissue pH and in tissue ATP characteristic of the zero-flow ischemic rat heart compared to zero-flow ischemic dog heart. In vitro enzyme inactivation studies on dog heart electron transfer complex I showed that the enzyme was approximately 40% inactivated after 1 minute by incubation at pH 6.0 in the absence of added ATP. The effect of low pH upon enzyme activity was mitigated considerably by the presence of one to two mM MgATP in the incubation mixtures. Moreover, a portion of the activity-sparing effect of MgATP was still observed in the presence of the uncoupler, FCCP. This latter observation suggests that part of the function-stabilizing effect of ATP was attributable to inner membrane energization and part appeared to have been due to a direct protective effect of ATP upon the complex.
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PMID:Effects of acidosis and ATP depletion on cardiac muscle electron transfer complex I. 174 4


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