Abstract

The effects of remote ischemic preconditioning (RIPC) in cardiac surgery have been inconsistent. We investigated whether anesthesia or beta-blockers interfere with RIPC cardioprotection. Fifty patients undergoing cardiac surgery were randomized to receive limb RIPC (four cycles of 5-min of upper arm cuff inflation/deflation) in the awake state (no-anesthesia; n = 17), or under sevoflurane (n = 17) or propofol (n = 16) anesthesia. In a separate crossover study, 11 healthy volunteers received either carvedilol or no medication prior to RIPC. Plasma dialysates were obtained and perfused through an isolated male Sprague–Dawley rat heart subjected to 30-min ischemia/60-min reperfusion, following which myocardial infarct (MI) size was determined. In the cardiac surgery study, pre-RIPC MI sizes were similar among the groups (39.7 ± 4.5% no-anesthesia, 38.9 ± 5.3% sevoflurane, and 38.6 ± 3.6% propofol). However, post-RIPC MI size was reduced in the no-anesthesia group (27.5 ± 8.0%; p < 0.001), but not in the anesthesia groups (35.7 ± 6.9% sevoflurane and 35.8 ± 5.8% propofol). In the healthy volunteer study, there was a reduction in MI size with RIPC in the no-carvedilol group (41.7 ± 4.3% to 30.6 ± 8.5%; p < 0.0001), but not in the carvedilol group (41.0 ± 4.0% to 39.6 ± 5.6%; p = 0.452). We found that the cardioprotective effects of limb RIPC were abolished under propofol or sevoflurane anesthesia and in the presence of carvedilol therapy.

Highlights

  • New treatment strategies are required to improve clinical outcomes in patients with ischemic heart disease, the leading cause of death and disability worldwide

  • Remote ischemic preconditioning (RIPC), in which brief cycles of non-lethal ischemia and reperfusion are applied to an organ or tissue away from the heart, has been shown to protect the myocardium against lethal acute ischemia/reperfusion (IR) injury [1]

  • We found that RIPC did not protect myocardium against IR injury in isolated rat heart under either sevoflurane or propofol anesthesia

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Summary

Introduction

New treatment strategies are required to improve clinical outcomes in patients with ischemic heart disease, the leading cause of death and disability worldwide. Remote ischemic preconditioning (RIPC), in which brief cycles of non-lethal ischemia and reperfusion are applied to an organ or tissue away from the heart, has been shown to protect the myocardium against lethal acute ischemia/reperfusion (IR) injury [1]. This strategy, which can be non-invasively applied by inflating and deflating a pneumatic cuff placed on the upper arm to induce cycles of brief IR (termed limb RIPC), has been shown to reduce procedure-related myocardial injury in patients undergoing elective percutaneous coronary intervention [2] as well as myocardial infarct (MI) size in ST-segment elevation myocardial infarction patients [3,4,5]. It has been suggested that beta-blockers (BBs) may interfere with RIPC by attenuating organ protection or altering RIPC-related signaling pathways [14]

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