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

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.

Effect of TLR4/MyD88/NF‐kB axis in paraventricular nucleus on ventricular arrhythmias induced by sympathetic hyperexcitation in post‐myocardial infarction rats

“…Every rat was anaesthetized and tracheally intubated, and a left‐sided thoracic incision was made between the 3rd and 4th ribs to open the muscular layer and pericardium. The anterior descending branch of the left coronary artery (LAD) was then located between the pulmonary artery cone and the left auricle and ligated 1–2 mm below the left auricle 18 . MI modelling criteria were that the rat ECG showed ST‐segment elevation, the myocardium turned grey below the ligated region, and there was reduced ventricular wall mobility.…”

“…The anterior descending branch of the left coronary artery (LAD) was then located between the pulmonary artery cone and the left auricle and ligated 1–2 mm below the left auricle. 18 MI modelling criteria were that the rat ECG showed ST‐segment elevation, the myocardium turned grey below the ligated region, and there was reduced ventricular wall mobility. In the sham‐operated group, the procedure was the same as above, but the LAD was only threaded and not ligated.…”

Specific Graft Treatment Solution Enhances Vascular Endothelial Function

“…Because preservation in the buffered solution represented by Dura-Graft© appeared to be superior to non-buffered saline in isolated rat aorta segments and relaxation in HSV, we concluded that maintenance of pH could be vital to physiologic function and cellular viability of HSV. Furthermore, a recent study by Tekin et al [20] demonstrated that SVG stored in DuraGraft© had lower oxidative level and higher antioxidant capacity, both may contribute and partially explain the preservation of endothelial function as observed in another study by Szabó et al [12]. In addition, it is important to state that SVG segments after 40-60 min (comparative time as in the Operating room) incubation with saline or DuraGraft© were transferred and then kept in KHS solution with all measurements performed under this conditions, suggesting DuraGraft© storage solution effectively alleviates endothelial dysfunction [21].…”

Sympathetic Nerve Innervation and Metabolism in Ischemic Myocardium in Response To Remote Ischemic Conditioning

“…Reperfusion was initiated following the 30 min of LAD occlusion by removal of the snare. RIPerc was induced by three cycles of 5 minutes of IR on hindlimb performed during myocardial ischemia as described previously [17] . Analgesia was initiated by intraperitoneal injection of Piritramide (0.1 ml/kg body weight) preoperatively and Piritramide in drinking water was applied as a postoperative analgesic regimen (2 ampules of Piritramide with 30 ml of Glucose 5% in 250 ml water).…”