Reduction of Experimental Myocardial Infarct Size by Corticosteroid Administration

Abstract

A B S T R A C T The influence of the administration of pharmacologic doses of hydrocortisone on the extent and severity of acute myocardial ischemic injury and on subsequent necrosis after acute coronary occlusion was investigated in 28 dogs. In order to study acute myocardial injury, repeated epicardial electrocardiograms were recorded from 10 to 15 sites on the anterior surface of the left ventricle. Average ST segment elevation (ST) and the number of sites in which ST segment elevation exceeded 2 mV (NST), indices of the magnitude and extent of myocardial injury, respectively, were analyzed at 30 and 60 min after coronarv occlusion. In the control g,-oup ST and NST did not change significantly in this time interval while in the treated group, which received 50 mg/kg hydrocortisone just after the 30 min recording, ST fell from 3.5±0.8 to 1.1+0.4 mV (P<0.01) and NST was reduced from 6.7±1.1 to 1.4±0.8 (P < 0.01).In order to study the influence of hydrocortisone on r. crosis, epicardial ST segment elevation 15 min after coronary occlusion was compared to myocardial creatine phosphokinase activity (CPK) and histologic appearance 24 h later in each site. In a control group (14 dogs) a relationship was established between ST segment elevation at 15 min (in millivolts) and CPK activity (in international units per milligram of protein) 24 h later: log CPK = -0.0611ST + 1.26 (N:= 102 specimens, r =-0.79). In the treated groups, hydrocortisone (50 mg/kg i.v.) was given either at 30 min after occlusion (seven dogs) or at 6 h after occlusion (six dogs).Both groups received supplementary doses of hydrocortisone (25 mg/kg) 12 h after occlusion. The two treated groups exhibited less CPK depression than that expected A preliminary report Of this investigation appeared in Clin. Res. 1972. 20: 207. from ST segment elevation at each site, with slopes of the regression lines which were significantly less steep: log CPK =-0.0288ST + 1.26 (N = 48, r = -0.71) and log CPK = -0.0321ST + 1.31 (N = 48, r = -0.76) in the i h and 6 h groups, respectively. Histologically, sites with ST segment elevations of less than 2 mV at 15 min after occlusion exhibited normal appearance 24 h later. Sites with ST segment elevations (> 2 mV) in the control group showed histologic changes compatible with early myocardial infarction in 96% of specimens, while this occurred only in 61% and 63% of specimens, respectively, in the treated groups, showing that over one third of the sites were protected from undergoing necrosis due to the intervening hydrocortisone treatment. Thus pharmacological doses of hydrocortisone prevent myocardial cells from progressing to ischemic necrosis even when administration is initiated 6 h after coronary occlusion. INTRODUCTIONRecent investigations in our laboratory have begun to delineate factors determining the extent and severity of myocardial ischemic injury and subsequent necrosis after acute coronary occlusion. The possibility of modi-

Glucocorticoids Activate Cardiac Mineralocorticoid Receptors During Experimental Myocardial Infarction

“…29 In previous studies, the effect of glucocorticoids during experimental myocardial infarction has not been uniformly consistent. In early studies, 30,31 protective effects were reported, as well as in more recent studies, 32 in which glucocorticoids were shown to attenuate myocardial apoptosis in neonatal pigs. Similar attenuation of apoptosis by glucocorticoids has been shown in neonatal rat cardiomyocytes.…”

Nontranscriptional actions of the glucocorticoid receptor

“…Corticosteroids inhibit endothelial cell activation and leukocyte-endothelial interaction, thereby exerting prominent, and very rapid, anti-inflammatory effects on the vasculature [12]. Steroid treatment improves survival of patients with acute myocardial infarction and protects the myocardium from experimental ischemic injury [13,14,15]. In ischemic stroke steroids can improve clinical outcome in a subset of patients with severe stroke and administration of high doses of corticosteroids substantially reduces tissue damage in experimental focal cerebral ischemia [16,17,18,19].…”

“…Furthermore, in patients with active rheumatoid arthritis steroids rapidly inhibit leukocyte recruitment into inflamed joints [56]. In myocardial infarction and ischemic stroke, high-dose steroids cause a transient decrease in blood pressure and systemic vascular resistance accompanied by an increase in coronary and cerebral blood flow within minutes of administration [10,14,57].…”

“…A consistent feature of the beneficial actions of corticosteroids is the requirement for highdose steroids [9,10,14,19,57]. Ischemia protection usually requires acute treatment (e.g., less than 6 h after the onset of ischemia).…”

Estudo da ação da estreptoquinase e do alopurinol em retalhos cutâneos em ilha submetidos à isquemia prolongada: estudo experimental em ratos

“…9 Secondary ischemia in transplant organs or tissues often goes undetected in the initial stages, and becomes clinically apparent only when the chance of recovering the tissue is gone, despite review of anastomoses and monitoring vascular permeability. Tissue is then not perfused, leading to necrosis.…”