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

In this paper, we demonstrate that ergothioneine (ES), a naturally occurring thiolhistidine, reduces ferrylmyoglobin (MbIV) to MbIII when the former (ferryl species) is produced by exposing either deoxy MbII or MbIII to H2O2. The reduction of MbIV to MbIII by ES yields the disulfide of ES which the addition of GSH promptly reduces back to ES. The addition of ES (100 microM) in the perfusion buffer of Langendorff rat heart preparations exposed to a brief period of ischemia prevents the myocardial damage (lactate dehydrogenase release) which accompanies reperfusion. The results of these experiments support a view that ES and its redox couple GSH might function in a Mb redox cycle.
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PMID:The reduction of ferryl myoglobin by ergothioneine: a novel function for ergothioneine. 238 23

The cardioprotective effects of a new antiarrhythmic drug, TYB-3823 [1-(2,6-dimethylphenyl)-dimethylaminoguanidine hydrochloride] were examined in the working hearts of rats and compared with those of lidocaine. Before ischemia, TYB-3823 at 5 x 10(-5) M produced a slight negative inotropic effect, resulting in a decrease in aortic flow and cardiac output. However, at lower concentrations (10(-6) and 10(-5) M), the drug had no significant effect on the functional cardiac parameters before ischemia. Lidocaine at such concentrations also had no effect. Global ischemia for 15 min decreased cardiac function rapidly which only recovered partially, with a delay, after reperfusion in the control hearts. Treatment with TYB-3823 accelerated the time course of recovery during reperfusion markedly, significantly improving functional cardiac parameters. However, lidocaine had little effect on recovery of function. Reperfusion-induced arrhythmia was equipotently inhibited by TYB-3823 and lidocaine. Leakage of cytosolic enzymes (lactate dehydrogenase, creatine phosphokinase and alpha-hydroxybutylic dehydrogenase) during reperfusion was inhibited more effectively by TYB-3823 than lidocaine. Light microscopic and electron microscopic examinations revealed that treatment with TYB-3823 protected against the histological damage induced by ischemia, such as hyaline degeneration of myocardium, absence of cross-striation and swelling of mitochondria. These results suggest that, unlike lidocaine, TYB-3823 causes a novel cardioprotective effect through unknown mechanisms in addition to its antiarrhythmic action.
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PMID:Novel cardioprotective effects of TYB-3823 on ischemic damage in the working hearts of rats: comparison with lidocaine. 238 91

Components of the renin-angiotensin system (RAS) have been found in heart tissue and it is likely that angiotensin II (ANG II) is generated locally in the heart as in other organs. Pharmacological interference with converting enzyme (CE) inhibitors reduced CE activity and ANG II generation in the heart. To investigate whether local inhibition of CE in the heart with the CE inhibitor ramipril might contribute to the therapeutic effects, experiments were performed in isolated perfused working rat hearts. Acute regional myocardial ischemia was induced by occlusion of the left coronary artery followed by reperfusion. In ischemic isolated rat hearts, both single oral pretreatment with ramipril (1 mg/kg) or perfusion with the active moiety, ramiprilat (10 micrograms/ml), protected against ventricular fibrillation, which invariably occurred in control hearts during reperfusion. Reperfusion arrhythmias were aggravated by perfusion with ANG I and ANG II, but prevented by bradykinin. ANG I-enhanced ventricular fibrillations were completely eliminated during local CE inhibition with ramipril. The CE inhibitor also improved cardiodynamics. Coronary flow, left ventricular pressure, dp/dtmax, and myocardial oxygen consumption were increased in comparison to controls without changes in heart rate. In the perfusate of treated hearts, lactate dehydrogenase, and creatine kinase activities and lactate production, were reduced. Myocardial tissue levels of glycogen, ATP, and creatine phosphate were increased in ramipril-pretreated hearts whereas lactate was decreased. The results of these experiments in rat hearts suggest that local inhibition of CE by ramipril exerts protective effects after ischemia and reperfusion by reducing arrhythmias and improving cardiac function and metabolism, thus probably contributing to the therapeutic effects of CE inhibitors in cardiovascular diseases.
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PMID:Beneficial effects of the converting enzyme inhibitor, ramipril, in ischemic rat hearts. 243 98

Histamine has been proved to be released during myocardial infarction and ischemic arrhythmias in dogs. The aim of the present experiments was to evaluate if ischemia and reperfusion modify histamine and lactate dehydrogenase (LDH) release in isolated guinea-pig heart. The results obtained show a steady increase of LDH release both in the ischemic and reperfusion phases. The release of histamine was reduced during the ischemic phase and increased significantly during reperfusion. A significant diminution of mast cell granule metachromasia was observed in the right auricles at the end of the reperfusion period. D-mannitol and reduced glutathione (GSH) modified the kinetics of histamine and LDH release. Cimetidine was able to decrease significantly the release of histamine during the ischemic and reperfusion phases and also reduced the release of LDH; triprolidine was completely ineffective. The results suggest that oxygen-derived free radicals may be involved in the pathogenesis of myocardial dysfunction after ischemia and reperfusion.
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PMID:Histamine and lactate dehydrogenase (LDH) release in ischemic myocardium of the guinea-pig. 244 Feb 79

It has been shown that plasma histamine significantly increases during myocardial infarction in the dog. Histamine is also released when the isolated guinea-pig heart is reperfused after 30 minutes of low flow perfusion. The release of histamine and lactate dehydrogenase (LDH) after left anterior descending coronary artery ligation and release were investigated in the present study and related to the changes in electrocardiographic parameters and to a computer-aided analysis of left ventricular mast cell metachromasia. Spontaneous release of histamine was unchanged during ischemia and increased after the release of the ligature, while we observed a steady increase of LDH overflow. In parallel, a significant diminution of mast cell granule metachromasia was observed in left ventricular samples. The perfusion of the heart with FeCl3/ADP (10 microM/100 microM), a free radical-generating system, significantly enhanced both the basal and ischemic-reperfusion release of histamine, while perfusion with N-t-butyl-phenyl-nitrone (BPN/100 microM) a "spin-trapper" molecule, significantly decreased histamine and LDH release and the loss in metachromasia of left ventricular mast cells induced by reperfusion. Inhibitors of xanthine oxidase (allopurinol, 10 microM) and of calcium-activated proteases (leupeptin, 10 microM) modified the kinetics of histamine and LDH release.
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PMID:Histamine release in acute coronary occlusion-reperfusion in isolated guinea-pig heart. 245 99

Free radicals are produced by perfusion of isolated guinea pig heart with FeCl3/ADP (10 microM/100 microM) and/or occlusion and opening of the left anterior descending coronary artery. Cardiac histopathology was correlated with histamine and lactate dehydrogenase release and with malondialdehyde production. A differential release of histamine and lactate dehydrogenase in the perfusate was detected, showing a preferential liberation of histamine in the reperfusion phase. The increase in lipid peroxidation product in left ventricular tissues after left coronary artery occlusion was maximal at the end of ischemia.
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PMID:Free radicals induce ischemia-reperfusion injury and histamine release in the isolated guinea pig heart. 246 11

Free radicals produced by the occlusion and opening of the left anterior descending coronary artery and/or by perfusion of isolated guinea-pig heart with FeCl3/ADP (10 microM/100 microM) induce a differential release of histamine and lactate dehydrogenase (LDH) in the perfusates with a preferential liberation of histamine in the reperfusion phase, associated with an increase of ventricular arrhythmias. The release of histamine has been correlated with malonyldialdehyde (MDA) production and tissue calcium content in left ventricular tissue. MDA increased during ischemia, while the calcium content increased when the tissue was reperfused. Under these conditions, N-t-butyl-alpha-phenylnitrone (BPN), a molecule capable of forming spin adducts with free radicals, and D-mannitol are active in preventing reperfusion-induced arrhythmias.
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PMID:Ischemia-reperfusion injury and histamine release in isolated guinea-pig heart: the role of free radicals. 247 20

This study was performed to determine if cardiodepression can be dissociated from cardioprotection with calcium antagonists and which one (diltiazem, nifedipine, or verapamil) can maximally protect ischemic myocardium at a given level of cardiodepression. Isolated rat hearts were subjected to 0.1, 0.5, or 1.0 microM diltiazem, verapamil, or nifedipine 10 min before global ischemia. Ischemia was maintained for 25 min, at which time reperfusion was instituted for 30 min. Pre- and postischemia function, flow, and lactate dehydrogenase (LDH) release were measured. All three drugs reduced preischemic function and improved postischemic function and reflow in a dose-dependent fashion. LDH release and contracture were also mitigated with all drugs. When the efficacy of these drugs was expressed as the ratio of LDH release versus preischemic, postdrug function (ability of drug to reduce LDH release at a given level of cardiodepression), diltiazem had a significantly lower ratio as compared with verapamil or nifedipine. When similar experiments were performed with various concentrations of calcium in the perfusion buffer (2.50, 1.25, 0.75, 0.50, 0.41 mM CaCl2) administered 10 min before ischemia and reperfusion with normal (1.25 mM) buffer, preischemic function was reduced in a concentration-dependent fashion. Despite severe reductions in function at the concentration of 0.50 mM CaCl2, LDH release was not reduced. The concentration of 0.41 mM CaCl2, which depressed function to the same degree as 0.50 mM CaCl2, reduced LDH release. This reduction in LDH release, however, was not as great as that which occurred with the high dose of the calcium antagonists. Reperfusion with 0.41 mM calcium buffer, however, nearly abolished LDH release. Thus, although all three calcium antagonists reduced the severity of ischemia, diltiazem reduces it with the lowest cost in cardiac function. Reduction in extracellular calcium reduces cardiac function, but reductions in severity of ischemia, as measured by LDH release, do not parallel these changes.
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PMID:Dissociation of cardiodepression from cardioprotection with calcium antagonists: diltiazem protects ischemic rat myocardium with a lower functional cost as compared with verapamil or nifedipine. 247 10

The direct cardioprotective efficacy of the potassium channel activators pinacidil and cromakalim was determined in isolated globally ischemic rat hearts. Isolated buffer-perfused rat hearts were subjected to 25 min of ischemia followed by 30 min of reperfusion. These hearts were pretreated with 1 to 100 microM pinacidil, 1 to 7 microM cromakalim or vehicle. Pinacidil resulted in significant improvements in reperfusion function and cardiac compliance, though it did not significantly reduce lactate dehydrogenase release at any concentration. The protective effects of pinacidil were greatest at a 10 microns concentration and were slightly diminished at higher concentrations (30 and 100 microns). Although not affecting the severity of ischemia alone, 10 microM glyburide (potassium channel blocker) completely reversed the protective effects of pinacidil on reperfusion function and compliance. Cromakalim (7 microM) resulted in a greater than 50% improvement in reperfusion function and compliance and unlike pinacidil significantly reduced lactate dehydrogenase release by approximately 50%. At 1 microM, glyburide alone did not significantly affect the severity of ischemia but reversed the protective effects of cromakalim. Not only did glyburide reverse the protective effects of cromakalim, it resulted in a worsening of ischemia compared to vehicle, an effect not seen with glyburide alone. Thus, both pinacidil and cromakalim appear to have direct cardioprotective efficacy, though some differences between them may be possible. The mechanism of their protective effects appears to be via potassium channel opening as the potassium channel blocker glyburide reverses the protective effect of these compounds. Intracellular electrophysiological studies showed that ischemia-induced depolarization was reversed with cromakalim, which increased the resting potential nearly back to preischemic levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anti-ischemic effects of the potassium channel activators pinacidil and cromakalim and the reversal of these effects with the potassium channel blocker glyburide. 250 75

The ability to resist transient ischemia was studied in isolated hearts of 18 months old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Both types of hearts showed optimal performance during the preischemic period when perfused at a diastolic perfusion pressure of 8.0 (WKY) and 13.3 (SHR) kPa. Hemodynamic recovery of WKY hearts during reperfusion at 8.0 kPa, following 45 min global ischemia, was satisfactory. coronary perfusion completely normalized, contractility (dPlv/dtmax) was slightly depressed and cardiac output returned, on the average, to 40% of the preischemic values. In contrast, hemodynamic function of SHR hearts reperfused at 13.3 kPa was greatly depressed, as evidenced by almost complete abolition of cardiac output, severe reduction of dPlv/dtmax and persistent underperfusion of the endocardial layers. In addition, the postischemic release of lactate dehydrogenase was retarded and enhanced. The release patterns of degradation products of adenine nucleotides showed a shift to the endstage products xanthine and uric acid. The enhanced vulnerability of the hypertrophied heart to ischemia was even more expressed when the SHR hearts were reperfused at 8.0 kPa. Postischemic function was characterized by electrical instability, loss of contractility and cardiac output, and noreflow in the endocardial layers. Persistent accumulation of lactate and degradation products of adenine nucleotides in the postischemic hearts are in line with the lack of reperfusion. The present results indicate that a detailed mechanistic explanation for the reduced ability to withstand ischemia of SHR cannot be based on differences in ATP content or an altered anaerobic glycolitic activity prior and during ischemia. It is suggested that a defect on the circulatory level, probably caused by enhanced reactivity of the coronary vessels towards ischemia-elicited factors, is responsible for the higher vulnerability of hypertrophied heart to an ischemia insult.
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PMID:Recovery of hypertrophied rat hearts after global ischemia and reperfusion at different perfusion pressures. 252 32


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