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)

The effect of oleanolic acid (OA) pretreatment on myocardial ischemia-reperfusion (I-R) injury was investigated using an ex vivo rat heart model. Pretreatment with OA at daily doses (0.6 and 1.2 mmol/kg) for 3 days significantly protected against I-R injury in isolated rat hearts, as evidenced by the decrease in the extent of lactate dehydrogenase (LDH) leakage and improvement in contractile force recovery. The cardioprotection was associated with a slight increase in mitochondrial reduced glutathione (GSH) level and a significant increase in mitochondrial alpha-tocopherol (alpha-TOC) level, when compared with the unpretreated I-R group. To further investigate the mechanism of myocardial protection, pretreatment with a single dose of OA (1.2 mmol/kg) produced a time-dependent protection against myocardial I-R injury as assessed by LDH leakage, with the maximum extent of protection occurring at 48 hour post-dosing. The maximum cardioprotection was associated with parallel increases in mitochondrial GSH and alpha-TOC levels in ischemic-reperfused hearts, with the stimulation of the alpha-TOC level being optimal. Furthermore, buthionine sulfoximine/phorone (BSO/PHO) treatment, while abolishing the enhancing effect of OA on mitochondrial GSH, did not completely abrogate the cardioprotection against I-R injury. The remnant cardioprotection was associated with an increase in mitochondrial alpha-TOC level, when compared with the unpretreated I-R group with BSO/PHO. The results suggest that the cardioprotection afforded by OA pretreatment against I-R injury may at least in part be attributed to the enhancement of mitochondrial antioxidant mechanism mediated by GSH and alpha-TOC, particularly under I-R conditions. Abbreviations. BSO:buthionine sulfoximine GSH:reduced glutathione I-R:ischemia-reperfusion alpha-LA:alpha-lipoic acid LDH:lactate dehydrogenase OA:oleanolic acid PHO:phorone alpha-TOC:alpha-tocopherol.
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PMID:Oleanolic acid protects against myocardial ischemia-reperfusion injury by enhancing mitochondrial antioxidant mechanism mediated by glutathione and alpha-tocopherol in rats. 1653 26

This study examined the potential deleterious effect of high-dose nitroglycerin (NTG) on cardiac function and cellular injury after ischemia (30 min) and reperfusion (120 min) in isolated perfused rat hearts. Low-dose (0.75 microg/h), medium-dose (3.75 microg/h), high-dose (15 microg/h) NTG or high-dose NTG plus glutathione (GSH, 1 mmol/L) was administrated at the time of reperfusion. Administration of high-dose NTG significantly exacerbated cardiac reperfusion injury as evidenced by increased creatine kinase and lactate dehydrogenase activity in coronary effluent, increased cardiomyocyte apoptosis and necrosis, and decreased cardiac function recovery after reperfusion. Compared with the vehicle group, formation of nitrotyrosine, a footprint for peroxynitrite (ONOO) production, was markedly increased in the hearts treated with medium-dose or high-dose NTG. Most interestingly, cotreatment with GSH blocked high-dose NTG-induced ONOO formation and attenuated myocardial ischemia/reperfusion injury. Taken together, our present results demonstrated that administration of high-dose NTG aggravated, rather than attenuated myocardial ischemia/reperfusion injury likely via increasing ONOO formation. Coadministration of GSH may reverse the advert action of high-dose NTG.
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PMID:Glutathione reverses peroxynitrite-mediated deleterious effects of nitroglycerin on ischemic rat hearts. 1663 83

The effects of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker with alpha-/beta-adrenoceptor blocking activities, on myocardial infarct size, apoptosis and necrosis in the rat after myocardial ischemia/reperfusion (45 min/120 min) were investigated. Ten minutes prior to left coronary artery occlusion, rats were treated with vehicle or labedipinedilol-A (0.25 or 0.5 mg/kg, i.v.). In the vehicle group, myocardial ischemia-reperfusion induced creatine kinase (CK) release and caused cardiomyocyte apoptosis, as evidenced by DNA ladder formation and terminal dUTP deoxynucleotidyltransferase nick end-labeling (TUNEL) staining. Treatment with labedipinedilol-A (0.25 or 0.5 mg/kg) reduced infarct size significantly compared to vehicle group (18.75+/-0.65% and 8.27+/-0.29% vs. 41.72+/-0.73%, P<0.01). Labedipinedilol-A also reduced the CK, CK-MB, lactate dehydrogenase (LDH) and troponin T levels in blood. In addition, labedipinedilol-A (0.5 mg/kg) significantly decreased TUNEL positive cells from 19.21+/-0.52% to 9.73+/-0.81% (P<0.01), which is consistent with absence of DNA ladders in the labedipinedilol-A group. Moreover, labedipinedilol-A pretreatment also decreased calcium content in ischemic-reperfused myocardial tissue. In conclusion, these results demonstrate that labedipindielol-A, through reduction of calcium overload and apoptosis, exerts anti-infarct effect during myocardial ischemia-reperfusion and would be useful clinically in the prevention of acute myocardial infarction.
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PMID:Protective effect of labedipinedilol-A, a novel dihydropyridine-type calcium channel blocker, on myocardial apoptosis in ischemia-reperfusion injury. 1664 91

Ping-Lv-Mixture (PLM) is a Chinese medicinal formula. The present study aimed to determine the effects of PLM on myocardial ischemia-reperfusion (MI/R) induced arrhythmias in rats. Arrhythmia model was established by occlusion of the left arterial descending coronary artery and thereafter reperfusion. A lead II electrocardiogram was monitored throughout the experiment. The results showed that pretreatment of PLM to MI/R rats significantly reduced the incidence and duration of ventricular tachycardia and ventricular fibrillation. On induction of MI/R, the activities of creatine kinase and lactate dehydrogenase were increased in vehicle group. PLM (0.04-1.00 g/kg) administration prevented the increase of these enzymes. Moreover, a significant increase of myocardium superoxide dismutase and decrease of malondialdehyde contents were observed in rats of PLM groups. On the other hand, the expressions of platelet activating factor (PAF) receptor mRNA was down-regulated in a dose-dependent manner in the PLM-treated groups by RT-PCR. Thus, it can be concluded that pretreatment with PLM inhibited lipid peroxidation in rats through suppressing the expression of PAF receptor, which may contribute to its preventive effect on myocardial ischemia-reperfusion induced arrhythmias.
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PMID:Protective effects of Ping-Lv-Mixture (PLM), a medicinal formula on arrhythmias induced by myocardial ischemia-reperfusion. 1673 89

Improved preservation of the harvested heart with attenuation of the reperfusion injury is important for successful outcomes of cardiac transplantations. The most commonly used cardioplegic solution, to prevent ischemic changes has been St Thomas' Hospital cardioplegic solution (STHCS). However, it is neither ideal nor sufficient to prevent myocardial ischemia and reperfusion injury. Phosphodiesterase inhibitors can attenuate the damage due to the injuries of ischemia and reperfusion. In this study we sought to enrich STHCS with a phosphodiesterase inhibitor to improve preservation of cardiac functions. The harvested hearts of 24 rats were divided into four groups. All hearts were mounted on a Langendorff perfusion system. After a stabilization period, cardiac arrest was maintained by STHCS. The hearts were stored in STHCS alone or with milrinone, amrinone, or enoximone for 6 hours. The reperfusion was maintained using a modified Tyrode's solution. All hearts were compared for their preischemic and postischemic left ventricular developed pressure, +dp/dtmax, -dp/dtmax, duration of systole, ejection time, and time to reach peak systolic pressure. Coronary effluent was collected for lactate dehydrogenase (LDH) measurements. The initial values for all metrics were comparable between the groups. During the postreperfusion period, all hearts showed lower peak systolic pressures than the initial values. Although the amrinone group seemed to have higher values, the 25-minute result was at the border of significance and the 30-minute value, significantly higher. All hearts showed far lower results of maximum changes in contractility during the time period (+dp/dtmax) versus the initial values; comparisons between groups were not significant. For the parameter of maximum changes in relaxation during the time period (-dp/dtmax), while other hearts showed lower results, the amrinone group displayed values comparable to the initial ones after 20 minutes. Comparisons between groups were insignificant. While other hearts had comparable values for time of systole, the hearts applied with milrinone reached these values after 15 minutes. Group comparison for time of ejection revealed that the results at 5-minute postreperfusion were higher in the enoximone and the amrinone groups than the milrinone group. Postreperfusion 5-minute results were higher in the enoximone and the amrinone groups than the milrinone group for time to reach peak systolic pressure. LDH levels were lowest in the amrinone group. In conclusion, our study revealed that adding phosphodiesterase inhibitors to STHCS improved peak systolic pressure and maximum changes in relaxation during the time period (-dp/dtmax, mm Hg/s). It also decreased the LDH leakage, which corresponded to the degree of ischemic tissue damage. Amrinone seemed to result in more favorable results, which may be attributed to its additional effects on inflammation, including those on cytokines and leukocyte aggregation.
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PMID:Effect of combining phosphodiesterase III inhibitors with St Thomas Hospital's solution used as transplantation preservative solution in isolated rat hearts. 1679 75

Intermedin is a novel member of the calcitonin/calcitonin gene-related peptide (CGRP) family peptide, which has vasodilatory and hypotensive actions identical to those of adrenomedullin and CGRP. Cleavage sites located between 2 basic amino acids at Arg93-Arg94 result in the production of prepro-intermedin95-147, namely intermedin1-53. The bioactive action of intermedin1-53 and its physiological significance are unclear. In this work, we aimed to explore the effects of intermedin1-53 on acute myocardial injury induced by isoproterenol. Myocardial ischemia injury in rats was induced by subcutaneous injection of a high dose of isoproterenol, and the therapeutic effect of intermedin1-53 was observed. Plasma lactate dehydrogenase activity, myocardial and plasma malondialdehyde content were higher in the isoproterenol group than that in controls. Isoproterenol-treated rats showed lower maximal rate of increase and decrease of left-ventricle pressure development (+/-left-ventricle dp/dtmax) and higher left-ventricle end-diastolic pressure (all P<0.01), which suggested severe heart failure and myocardial injury. Semi-quantitative RT-PCR analysis showed that the gene expression of calcitonin receptor-like receptor and receptor-activity-modifying protein (RAMP)1, RAMP2 and RAMP3 in ventricular myocardia were up-regulated by 79% (P<0.01), 48% (P<0.01), 31% (P<0.05) and 130% (P<0.01), respectively, compared with controls. In myocardial sarcolemmal membranes, the maximum binding capacity for [125I]-intermedin1-53 was increased by 118% (P<0.01) in the isoproterenol group compared with controls. Rats treated with low dosage intermedin1-53 (5 nmol/kg/day, 2 days) showed 21% (P<0.05) higher myocardial cAMP content, 18% and 31% higher+left-ventricle dp/dtmax and -left-ventricle dp/dtmax respectively, 288% lower left-ventricle end-diastolic pressure (all P<0.01), and attenuated myocardial lactate dehydrogenase leakage and malondialdehyde formation (all P<0.01). Treatment with high dosage intermedin1-53 (20 nmol/kg/day, 2 days) gave better results than that with low dosage intermedin1-53. These results suggest that the intermedin receptor system was up-regulated in isoproterenol-induced myocardial ischemic injury and intermedin1-53 might play a pivotal cardioprotective role in such injury.
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PMID:Intermedin1-53 protects the heart against isoproterenol-induced ischemic injury in rats. 1698 13

In this report, we describe a simple and fast method for creating a murine myocardial infarction model and providing a useful and convenient tool for the research in ischemic heart disease. We established acute myocardial infarction in the Kunming-strain mouse within 2 minutes by ligating the left anterior descending coronary artery. The model was evaluated by observing the changes in histology and in the serum levels of aspartate aminotransferase and lactate dehydrogenase. Obvious myocardial necrosis was found in the 24-hr experimental (ligation) group. The average size of the infarction was 44.3% +/- 2.9% of the left ventricle. Serum levels of aspartate aminotransferase and lactate dehydrogenase reached their peak in the 24-hr experimental group and were normal in the 72-hr experimental group. We set forth a simple and quick method for producing acute myocardial infarction experimentally in the mouse. The model can be reproduced in a stable manner, under experimental conditions that are easy to duplicate.
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PMID:A simple and fast experimental model of myocardial infarction in the mouse. 1704 83

Studies in animal models of myocardial ischemia-reperfusion revealed that the administration of insulin-like growth factor (IGF-1) can provide substantial cardioprotective effect. However, the mechanisms by which IGF-1 prevents myocardial ischemia-reperfusion injury are not fully understood. This study addresses whether mitochondrial bioenergetic pathways are involved in the cardioprotective effects of IGF-1. Single cardiomyocytes from adult rats were incubated in the absence or presence of IGF-1 for 60 min and subjected to 60 min hypoxia followed by 30 min reoxygenation at 37 degrees C. Mitochondrial function was evaluated by assessment of enzyme activities of oxidative phosphorylation and Krebs cycle pathways. Hypoxia/reoxygenation (HR) caused significant inhibition of mitochondrial respiratory complex IV and V activities and of the Krebs cycle enzyme citrate synthase, whereas pretreatment with IGF-1 maintained enzyme activities in myocytes at or near control levels. Mitochondrial membrane potential, evaluated with JC-1 staining, was significantly higher in IGF-1 + HR- treated myocytes than in HR alone, with levels similar to those found in normal control cardiomyocytes. In addition, IGF-1 reduced both HR-induced lactate dehydrogenase (LDH) release and malondialdehyde production (an indicator of lipid peroxidation) in cardiomyocytes. These results suggest that IGF-1 protects cardiomyocytes from HR injury via stabilizing mitochondria and reducing reactive oxidative species (ROS) damage.
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PMID:Mitochondrial involvement in IGF-1 induced protection of cardiomyocytes against hypoxia/reoxygenation injury. 1726 81

Hyperlipidemia is a major risk factor for the premature development of coronary heart disease and it has been shown to increase the incidence of myocardial ischemia and cardiac events. Pentacyclic triterpenes possess antiatherosclerotic, antioxidant, anti-inflammatory and cytoprotective effects. To study the effect of plant derived triterpene, lupeol and its ester lupeol linoleate, on lipid status and biochemical changes on heart tissue, male albino Wistar rats were fed high-cholesterol diet (normal rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days. There was a significant (p<0.001) increase in the levels of total cholesterol, triglycerides and phospholipids along with augmented activities of lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in the heart tissue. Triterpenes treatment reduced the above alterations produced in hypercholesterolemic rats. The transmembrane enzymes, namely Na(+), K(+)-ATPase, Ca(2+)-ATPase and Mg(2+)-ATPase showed a decrease in their activities. Triterpenes treatment reversed these levels, prevented the hypertrophic cardiac histology and restored the normal ultrastructural architecture. In conclusion, lupeol and lupeol linoleate intervention minimized the lipid abnormalities and abnormal biochemical changes induced by HCD fed rats. This shows that triterpenes possess cardioprotective effects which will be beneficial in hypercholesterolemic condition. Out of these two triterpenes tested, lupeol linoleate appeared to be even more effective than lupeol.
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PMID:Protective effect of lupeol and its ester on cardiac abnormalities in experimental hypercholesterolemia. 1733 64

We have previously found that, following myocardial ischemia/reperfusion injury, isolated hearts from bax gene knockout mice [Bax(-/-)] exhibited higher cardioprotection than the wild-type. We here explore the effect of Bax(-/-), following myocardial infarction (MI) in vivo. Homozygotic Bax(-/-) and matched wild-type were studied. Mice underwent surgical ligation of the left anterior descending coronary artery (LAD). The progressive increase in left-ventricular end diastolic diameter, end systolic diameter, in Bax(-/-) was significantly smaller than in Bax(+/+) at 28 d following MI (p < 0.03) as seen by echocardiography. Concomitantly, fractional shortening was higher (35 +/- 4.1% and 27 +/- 2.5%, p < 0.001) and infarct size was smaller in Bax(-/-) compared to the wild-type at 28 days following MI (24 +/- 3.7 % and 37 +/- 3.3%, p < 0.001). Creatine kinase and lactate dehydrogenase release in serum were lower in Bax(-/-) than in Bax(+/+) 24 h following MI. Caspase 3 activity was elevated at 2 h after MI only in the wild-type, but reduced to baseline values at 1 and 28 d post-MI. Bax knockout mice hearts demonstrated reduced infarct size and improved myocardial function following permanent coronary artery occlusion. The Bax gene appears to play a significant role in the post-MI response that should be further investigated.
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PMID:Bax deficiency reduces infarct size and improves long-term function after myocardial infarction. 1740 56


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