Triiodothyronine concomitantly inhibits calcium overload and postischemic myocardial stunning in diabetic rats

Acute effects of triiodothyronine (T-3) on postischemic myocardial stunning and intracellular Ca2+ contents were studied in the isolated working hearts of streptozotocin-induced diabetic rats and age-matched controls. After two weeks of diabetes, serum T-3 and T-4 levels were decreased to 62.5% and 33.9% of control values. Basal preischemic cardiac performance did not differ between diabetic and control rats. In contrast, during reperfusion after 20-min ischemia, diabetic rats exhibited an impaired recovery of heart rate (at 30-min reperfusion 57.5% of baseline vs. control 88.5%), left ventricular (LV) systolic pressure (44.1% vs. 89.5%), and cardiac work (23.1% vs. 66.0%). When 1 and 100 nM T-3 was added before ischemia, heart rate was recovered to 77.2% and 81.8% of baseline, LV systolic pressure to 68.3% and 81.9%, and cardiac work to 50.8% and 59.0%, respectively. Diabetic rat hearts showed a higher Ca2+ content in the basal state and a further increase after reperfusion (4.96 +/-1.17 vs. control 3.78 +/-0.48 mu mol/g, p<0.01). In diabetic hearts, H+ release was decreased after reperfusion (5.24<plus/minus>2.21 vs. 8.70 +/-1.41 mmol/min/g, p<0.05). T-3 administration caused a decrease in the postischemic Call accumulation (1nM T-3 4.66<plus/minus>0.41 and 100 nM T-3 3.58 +/-0.36) and recovered the H+ release (1nM T-3 16.2 +/-3.9 and 100 nM T-3 11.6 +/-0.9). T-3 did not alter myocardial O-2 Consumption. Results suggest that diabetic rat hearts are vulnerable to postischemic stunning, and T-3 protects the myocardial stunning possibly via inhibiting Ca2+ overload. (C) 2001 Elsevier Science Inc. All rights reserved.