Sex is no determinant of cardioprotection by ischemic preconditioning in rats, but ischemic/reperfused tissue mass is for remote ischemic preconditioning

We determined the impact of sex on the magnitude of cardioprotection by local and remote ischemic preconditioning (IPC and RIPC) and of ischemic/reperfused peripheral tissue mass on protection by RIPC. Hearts of female and male Lewis rats were excised, perfused with buffer, and underwent either IPC by 3 × 5/5 min global zero-flow ischemia/reperfusion (GI/R) or time-matched perfusion (TP) before 30/120 min GI/R. In a second approach, anesthetized female and male Lewis rats underwent RIPC, 3 × 5/5 min ischemia/reperfusion of one or both hindlimbs (1-RIPC or 2-RIPC), or placebo. Thirty minutes after the RIPC/placebo protocol, hearts were excised and subjected to GI/R. In female and male hearts, infarct size was less with IPC than with TP before GI/R (IPC+GI/Rfemale: 12 ± 5%; IPC+GI/Rmale: 12 ± 7% vs. TP+GI/Rfemale: 33 ± 5%; TP+GI/Rmale: 37 ± 7%, P < 0.001). With 2-RIPC, infarct size was less than with 1-RIPC in female and male rat hearts, respectively (2-RIPC+GI/Rfemale: 15 ± 5% vs. 1-RIPC+GI/Rfemale: 22 ± 7%, P = 0.026 and 2-RIPC+GI/Rmale: 16 ± 5% vs. 1-RIPC+GI/Rmale: 22 ± 8%, P = 0.016). Infarct size after the placebo protocol and GI/R was not different between female and male hearts (36 ± 8% vs. 34 ± 5%). Sex is no determinant of IPC- and RIPC-induced cardioprotection in isolated Lewis rat hearts. RIPC-induced cardioprotection is greater with greater mass of ischemic/reperfused peripheral tissue.