Influence of Hypoxic and Hyperoxic Preconditioning on Endothelial Function in a Model of Myocardial Ischemia-Reperfusion Injury with Cardiopulmonary Bypass (Experimental Study)

Irina A Mandel,Darya A An,Irina V Suhodolo,Anna M Gusakova,Yulia S Svirko,Sergey L Mikheev,Vladimir M Shipulin,Andrey G Yavorovskiy,Andrey Yu Podoksenov,Yuri K Podoksenov

doi:10.3390/ijms21155336

Abstract

The aim of the experiment was to evaluate the effect of preconditioning based on changes in inspiratory oxygen fraction on endothelial function in the model of ischemia-reperfusion injury of the myocardium in the condition of cardiopulmonary bypass. The prospective randomized study included 32 rabbits divided into four groups: hypoxic preconditioning, hyperoxic preconditioning, hypoxic-hyperoxic preconditioning, and control group. All animals were anesthetized and mechanically ventilated. We provided preconditioning, then started cardiopulmonary bypass, followed by induced acute myocardial infarction (ischemia 45 min, reperfusion 120 min). We investigated endothelin-1, nitric oxide metabolites, asymmetric dimethylarginine during cardiopulmonary bypass: before ischemia, after ischemia, and after reperfusion. We performed light microscopy of myocardium, kidney, lungs, and gut mucosa. The endothelin-1 level was much higher in the control group than in all preconditioning groups after ischemia. The endothelin-1 even further increased after reperfusion. The total concentration of nitric oxide metabolites was significantly higher after all types of preconditioning compared with the control group. The light microscopy of the myocardium and other organs revealed a diminished damage extent in the hypoxic-hyperoxic preconditioning group as compared to the control group. Hypoxic-hyperoxic preconditioning helps to maintain the balance of nitric oxide metabolites, reduces endothelin-1 hyperproduction, and enforces organ protection.

Highlights

Coronary artery bypass grafting (CABG) with cardiopulmonary bypass is a common surgical therapy for patients suffering from coronary artery diseases
Eight percent of patients developed postoperative myocardial infarction after the CABG with cardiopulmonary bypass (CPB), 6.3% developed low cardiac output syndrome, and 3.7% patients died during the early postoperative period due to extensive postoperative myocardial infarction [4]
Aerobic cardiac function prior to ischemia was unaffected by the treatment with hypoxia and/or hyperoxia (Table 1)

Summary

Introduction

Coronary artery bypass grafting (CABG) with cardiopulmonary bypass is a common surgical therapy for patients suffering from coronary artery diseases. The heart is subjected to a long period of ischemia due to the occlusion of aortic artery. Acute cardiovascular dysfunction occurs perioperatively in more than 20% of cardiosurgical patients [2]. Twenty-five percent of patients undergoing elective CABG surgery require inotropic support for postoperative myocardial dysfunction. Acute heart failure associated with a failure to wean patients off cardiopulmonary bypass (CPB) may be surgery related, patient-specific, or both [3]. CABG surgery is associated with systemic inflammatory response, endothelial damage, and platelet activation regardless of the use of CPB. Eight percent of patients developed postoperative myocardial infarction after the CABG with CPB, 6.3% developed low cardiac output syndrome, and 3.7% patients died during the early postoperative period due to extensive postoperative myocardial infarction [4]. The preconditioning methods are able to improve or prevent the organs damage during CPB

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Discussion

Conclusion