Abstract
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.
Highlights
The translation of cardioprotection by ischemic conditioning to clinical practice has been largely disappointing so far (Heusch 2017; Davidson et al 2019a)
Few experimental studies have established a dose–response relationship between the conditioning stimulus and the magnitude of infarct size reduction (Skyschally et al 2009; Johnsen et al 2016). It is not even clear what exactly defines stimulus strength, to what extent stimulus strength depends on the temporal sequence of ischemia/reperfusion cycles, and for remote ischemic conditioning (RIC) to what extent it depends on a 2019 The Authors
Baseline values for coronary flow were lower in female than in male rat hearts (CFfemale: 12.4 Æ 2.2 ml/min vs. CFmale: 14.2 Æ 1.3 ml/min; P < 0.001), but not different within the female and male hearts used in the different protocols
Summary
The translation of cardioprotection by ischemic conditioning to clinical practice has been largely disappointing so far (Heusch 2017; Davidson et al 2019a). Few experimental studies have established a dose–response relationship between the conditioning stimulus and the magnitude of infarct size reduction (Skyschally et al 2009; Johnsen et al 2016). It is not even clear what exactly defines stimulus strength, to what extent stimulus strength depends on the temporal sequence of ischemia/reperfusion cycles, and for remote ischemic conditioning (RIC) to what extent it depends on a 2019 The Authors.
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