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

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.

Endothelial Function and Hypoxic-Hyperoxic Preconditioning in Coronary Surgery with a Cardiopulmonary Bypass: Randomized Clinical Trial

“…A few changes were in conjunction with preconditioning: less reduction of nitrate concentration at the end of the surgery, and stabilization of NO metabolites at 24 h after surgery as compared to the control group. Contrary to our recent experimental study, where we have found that HHP had an infarctlimiting effect, balanced NO metabolites, and reduced ET-1 hyperproduction in the simulation of IRI under the conditions of CPB [47]. Besides, we observed statistically significant differences in ET-1 production and NO metabolites imbalance in patients with postoperative complications compared with noncomplicated patients.…”

“…Sample size calculation was carried out for the study with 130 patients randomized in the proportion of 1:1. Due to the lack of a unified protocol, we developed our protocol of preconditioning, which allows us to simulate the phenomenon of hypoxic-hyperoxic preconditioning in animals and humans [46,47]. The sample size calculation was based on our previous results [46].…”

Endothelial Function and Hypoxic–Hyperoxic Preconditioning in Coronary Surgery with a Cardiopulmonary Bypass: Randomized Clinical Trial

“…A few changes were in conjunction with preconditioning: Less reduction in nitrate concentration at the end of the surgery and stabilization of NO metabolites at 24 h after surgery as compared to the control group. This is contrary to our recent experimental study where we have found that HHP had an infarct-limiting effect, balanced NO metabolites, and reduced ET-1 hyperproduction in the simulation of IRI under the conditions of CPB [ 25 ]. Additionally, we observed statistically significant differences in ET-1 production and a NO metabolites imbalance in patients with postoperative complications compared with noncomplicated patients.…”

“…Sample size calculation was provided for the study with 130 patients randomized into the two equal groups. Due to the lack of a unified protocol, we developed our protocol of preconditioning, which allows us to simulate the phenomenon of hypoxic–hyperoxic preconditioning in animals and humans [ 24 , 25 ]. The sample size calculation was based on our previous results [ 24 ].…”