Effluent from ischemic preconditioned hearts confers cardioprotection independent of the number of preconditioning cycles.

Katharina Feige,Carolin Torregroza,Jan Muehlenbernd,Markus W Hollmann,Martin Stroethoff,Annika Raupach,Ragnar Huhn,Sebastian Bunte,Anindita Das

doi:10.1371/journal.pone.0243220

Abstract

Coronary effluent collected from ischemic preconditioning (IPC) treated hearts induces myocardial protection in non-ischemic-preconditioned hearts. So far, little is known about the number of IPC cycles required for the release of cardioprotective factors into the coronary effluent to successfully induce cardioprotection. This study investigated the cardioprotective potency of effluent obtained after various IPC cycles in the rat heart. Experiments were performed on isolated hearts of male Wistar rats, mounted onto a Langendorff system and perfused with Krebs-Henseleit buffer. In a first part, effluent was taken before (Con) and after each IPC cycle (Eff 1, Eff 2, Eff 3). IPC was induced by 3 cycles of 5 min of global myocardial ischemia followed by 5 minutes of reperfusion. In a second part, hearts of male Wistar rats were randomized to four groups (each group n = 4–5) and underwent 33 min of global ischemia followed by 60 min of reperfusion. The previously obtained coronary effluent was administered for 10 minutes before ischemia as a preconditioning stimulus. Infarct size was determined at the end of reperfusion by triphenyltetrazoliumchloride (TTC) staining. Infarct size with control effluent was 54±12%. Effluent obtained after IPC confers a strong infarct size reduction independent of the number of IPC cycles (Eff 1: 27±5%; Eff 2: 35±7%; Eff 3: 35±8%, each P<0.05 vs. Con). Effluent extracted after one cycle IPC is comparably protective as after two or three cycles IPC.

Highlights

Ischemic preconditioning (IPC) still remains the strongest cardioprotective stimulus inducing significant infarct size reduction [1]
Serejo et al demonstrated that pooled effluent collected in the reperfusion phases during IPC consisting of three cycles of five minutes of myocardial ischemia and reperfusion in the isolated rat heart reduced infarct size when transferred to naive hearts [7]
The present study aims to investigate whether the number of IPC cycles influences the release of humoral cardioprotective factors into the coronary effluent

Summary

Introduction

Ischemic preconditioning (IPC) still remains the strongest cardioprotective stimulus inducing significant infarct size reduction [1]. The protective effect of IPC—regularly practiced with three cycles of five minutes of myocardial ischemia and reperfusion—is not limited to the heart and feasible at other organs [2]; a phenomenon called remote ischemic preconditioning (RIPC) [3]. This demonstrates that a release of humoral factors induced by an ischemic stimulus, transferred via the blood to distant organs is able to confer protective properties. We hypothesize that the infarct size reducing effect of the coronary effluent depends on the number of conducted IPC stimuli

Materials and methods

Results

Discussion

Conclusions