CHRONIC CORTICOSTERONE TREATMENT INCREASES MYOCARDIAL INFARCT SIZE INRATS WITH ISCHEMIA-REPERFUSION INJURY

Experiments were conducted to determine the effect of chronic elevatio ns in corticosterone on myocardial infarct size. Male Sprague-Dawley r ats were treated for 7-22 days with corticosterone. Plasma corticoster one concentrations averaged 0.8 +/- 0.3 in control and 14.9 +/- 1.2 mu g/dl in corticosterone-treated conscious rats. Experiments were perfo rmed in anesthetized rats. After a 30-min control period, myocardial i schemia (30 min)-reperfusion (3 h) was performed in control and cortic osterone-treated rats. Mean arterial pressure (+/-SE) in control rats during control, ischemia, and repel fusion periods averaged 111 +/- 4, 100 +/- 5, and 94 +/- 4 mmHg (n = 6), respectively. Chronic treatment with corticosterone increased mean arterial pressure in all three per iods (128 +/- 6, 117 +/- 7, and 109 +/- 7 mmHg; n = 8; P < 0.05). Infa rct size (as % area at risk) was significantly larger in rats with chr onic elevations in corticosterone compared with control rats (77 +/- 2 vs. 51 +/- 5%; P < 0.05). Acute (2 h) blockade of the glucocorticoid type II receptors with mifepristone antagonized the increases in arter ial pressure and infarct size produced by chronic administration of co rticosterone. Neither mifepristone nor acutely administered corticoste rone affected arterial pressure or infarct size in rats without chroni c corticosterone treatment. The effect of chronic elevations in plasma corticosterone concentration to increase infarct size could contribut e to the increased risk of cardiovascular disease in clinical conditio ns associated with elevated glucocorticoid levels.