Cardioprotective effects of triiodothyronine supplementation against ischemia reperfusion injury by preserving calcium cycling proteins in isolated rat hearts.

Hypothyroidism is associated with profound left ventricular dysfunction. Triiodothyronine (T3) supplementation may improve cardiac function after ischemic reperfusion (I/R) injury. In the present study, the effect of T3 on major calcium cycling proteins and high-energy phosphate content during I/R was evaluated. Isolated perfused rat hearts were divided into 5 groups: Sham Control (Sham, n=10), Control (n=8), T3 10 nM (T3-10, n=10), T3 25 nM (T3-25, n=10) and T3 50 nM (T3-50, n=10). T3 was administrated for 60 min before 30 min of ischemia and 120 min of reperfusion. The protein contents of Ca2+-release channels (RyR2), Ca2+-adenosine triphosphatase (SERCA2a), phospholamban (PLB), sarcolemmal Ca2+-adenosine triphosphatase (PMCA) and sodium-calcium exchanger (NCX), as well as the high-energy phosphate content in heart tissues were measured by western blot analysis. The results revealed that T3 improved the contractile recovery (left ventricular developed pressure; +dP/dt, -dP/dt) after I/R. Western blotting assays demonstrated that I/R depressed the contents of RYR2, SERCA2a and phosphorylated RYR2 and PLB; there were no effects on the contents of PLB, PMCA and NCX. T3 reversed I/R-induced degradation of RyR2 and SERCA2a, restored the phosphorylation of RyR2 and PLB, and preserved the high-energy phosphate contents of ATP and creatine phosphate. T3 supplementation protected the heart against I/R injury via the preservation of Ca2+-cycling proteins and high-energy phosphate content.