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)

Dexamethasone exerted no significant hemodynamic effect in sham-operated cats or in cats subjected to acute myocardial ischemia. However, the glucoccortcoid did normalize elevated S-T segments toward pre-ischemic values, and prevented much of the increase in plasma CPK activity following coronary artery ligation. Moreover, dexamethasone prevented loss of CPK activity and restricted the loss of lysosomal hydrolase within ischemic myocardial tissue. These data indicate that lysosomal disruption is an early consequence of myocardial ischemia and that treatment with dexamethasone prevents the loss of myocardial lysosomal and cellular enzymes as reflected in normalization of the ECG and plasma CPK activity of ischemic cats. In this way, dexamethasone may act to retard the spread of the developing infarct within the ischemic myocardium.
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PMID:Effects of dexamethasone on myocardial cells in the early phase of acute myocardial infarction. 113 39

Dexamethasone (6 mg/kg) given intravenously to anesthetized cats exerted no significant hemodynamic effect on control open-chest cats or in cats subjected to acute myocardial ischemia by coronary artery ligature. However, dexamethasone normalized elevated S-T segments toward preischemic values, and prevented much of the increase in plasma CPK activity following coronary artery ligation. Moreover, dexamethasone prevented loss of CK activity within ischemic myocardial tissue five hours after the onset of ischemia. Dexamethasone also reduced the extent of ischemic damage as assessed by a nitro-blue tetrazolium staining technique, providing anatomic verification of the reduced ischemic damage. Moreover, dexamethasone prvented the swelling and vacuolization of myocardial lysosomes in the ischemic region, indicating a stabilization of lysosomal membranes within the heart. These data indicate that lysosomal disruption is an important consequence of myocardial ischemia and that early treatment with dexamethasone prevents the loss of myocardial lysosomal and cellular enzymes as reflected in normalization of the ECG and plasma CK activity of ischemic cats. In this way, dexamethasone may act to retard the spread of the developing infarct within the ischemic myocardium.
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PMID:Mechanism of the beneficial effect of dexamethasone on myocardial cell integrity in acure myocardial ischemia. 739 11

Myocardial ischemia-reperfusion leads to significant changes in redox state, decreased postischemic functional recovery, and cardiomyocyte apoptosis, with development and progression of heart failure. Ischemia-reperfusion in the isolated perfused rat heart has been used as a model of heart failure. Clinically, mineralocorticoid receptor blockade in heart failure decreases morbidity and mortality versus standard care alone. The effects of corticosteroids on infarct area and apoptosis were determined in rat hearts subjected to 30 minutes of ischemia and 2.5 hours of reperfusion. Both aldosterone and cortisol increased infarct area and apoptotic index, an effect half-maximal between 1 and 10 nM and reversed by spironolactone. Dexamethasone and mifepristone aggravated infarct area and apoptotic index, similarly reversed by spironolactone. Spironolactone alone reduced infarct area and apoptotic index below ischemia-reperfusion alone, in hearts from both intact and adrenalectomized rats. The present study shows that cardiac damage is aggravated by activation of mineralocorticoid receptors by aldosterone or cortisol or of glucocorticoid receptors by dexamethasone. Mifepristone unexpectedly acted as a glucocorticoid receptor agonist, for which there are several precedents. Spironolactone protected cardiomyocytes via inverse agonist activity at mineralocorticoid receptors, an effect near maximal at a relatively low dose (10 nM). Spironolactone acts not merely by excluding corticosteroids from mineralocorticoid receptors but as a protective inverse agonist at low concentration. Mineralocorticoid receptor antagonists may, thus, provide an additional therapeutic advantage in unstable angina and acute myocardial infarction.
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PMID:Glucocorticoids activate cardiac mineralocorticoid receptors during experimental myocardial infarction. 1984 Dec 84