Acute effects of triiodothyronine on glucose and fatty acid metabolism during reperfusion of ischemic rat hearts

Abstract

Clinical studies have demonstrated improved myocardial recovery after severe ischemia in response to acute triiodothyronine (T3) treatment. We determined whether T3 improves the recovery of ischemic hearts by improving energy substrate metabolism. Isolated working rat hearts were perfused with 5.5 mM glucose and 1.2 mM palmitate and were subjected to 30 min of no-flow ischemia. Glycolysis, glucose oxidation, and palmitate oxidation were measured during aerobic reperfusion by adding [5-3H]glucose, [U-14C]glucose, or [9,10-3H]palmitate to the perfusate, respectively. During reperfusion, cardiac work in untreated hearts recovered to a lesser extent than myocardial O2 consumption (MV˙o 2), resulting in a decreased recovery of cardiac efficiency, which recovered to only 25% of preischemic values. Treatment of hearts with T3 (10 nM) before ischemia increased glucose oxidation during reperfusion, which was associated with a significant increase in pyruvate dehydrogenase (PDH) activity, the rate-limiting enzyme for glucose oxidation. In contrast, T3 had no effect on MV˙o 2, glycolysis, or palmitate oxidation. This resulted in a significant decrease in H+ production from glycolysis uncoupled from glucose oxidation (2.7 ± 0.3 and 1.9 ± 0.3 μmol ⋅ g dry wt−1 ⋅ min−1in control and T3-treated hearts, respectively, P < 0.05), as well as a 3.2-fold improvement in cardiac work and a 2.3-fold increase in cardiac efficiency compared with untreated postischemic hearts ( P < 0.05). These data suggest that T3 can exert acute effects that improve the coupling of glycolysis to glucose oxidation, thereby decreasing H+ production and increasing cardiac efficiency as well as contractile function during reperfusion of the postischemic heart.