Remote Ischemic Perconditioning Ameliorates Myocardial Ischemia and Reperfusion-Induced Coronary Endothelial Dysfunction and Aortic Stiffness in Rats

J Cardiovasc Pharmacol Ther. 2021 Nov;26(6):702-713. doi: 10.1177/10742484211031327. Epub 2021 Aug 3.

Abstract

Background: Vascular stiffness and endothelial dysfunction are accelerated by acute myocardial infarction (AMI) and subsequently increase the risk for recurrent coronary events.

Aim: To explore whether remote ischemic perconditioning (RIPerc) protects against coronary and aorta endothelial dysfunction as well as aortic stiffness following AMI.

Methods: Male OFA-1 rats were subjected to 30 min of occlusion of the left anterior descending artery (LAD) followed by reperfusion either 3 or 28 days with or without RIPerc. Three groups: (1) sham operated (Sham, without LAD occlusion); (2) myocardial ischemia and reperfusion (MIR) and (3) MIR + RIPerc group with 3 cycles of 5 minutes of IR on hindlimb performed during myocardial ischemia were used. Assessment of vascular reactivity in isolated septal coronary arteries (non-occluded) and aortic rings as well as aortic stiffness was assessed by wire myography either 3 or 28 days after AMI, respectively. Markers of pro-inflammatory cytokines, adhesion molecules were assessed by RT-qPCR and ELISA.

Results: MIR promotes impaired endothelial-dependent relaxation in septal coronary artery segments, increased aortic stiffness and adverse left ventricular remodeling. These changes were markedly attenuated in rats treated with RIPerc and associated with a significant decline in P-selectin, IL-6 and TNF-α expression either in infarcted or non-infarcted myocardial tissue samples.

Conclusions: Our study for the first time demonstrated that RIPerc alleviates MIR-induced coronary artery endothelial dysfunction in non-occluded artery segments and attenuates aortic stiffness in rats. The vascular protective effects of RIPerc are associated with ameliorated inflammation and might therefore be caused by reduced inflammatory signaling.

Keywords: acute myocardial infarction; endothelium; heart disease; ischemia-reperfusion injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coronary Vessels / physiopathology
  • Cytokines / metabolism
  • Inflammation
  • Ischemic Preconditioning, Myocardial / methods*
  • Male
  • Myocardial Infarction / therapy*
  • Myocardial Ischemia / prevention & control*
  • Myocardial Reperfusion / methods
  • Myocardial Reperfusion Injury / prevention & control
  • Rats
  • Vascular Stiffness*

Substances

  • Cytokines