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

Abstract

A hypoxic-hyperoxic preconditioning (HHP) may be associated with cardioprotection by reducing endothelial damage and a beneficial effect on postoperative outcome in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Patients (n = 120) were randomly assigned to an HHP and a control group. A safe, inhaled oxygen fraction for the hypoxic preconditioning phase (10-14% oxygen for 10 min) was determined by measuring the anaerobic threshold. At the hyperoxic phase, a 75-80% oxygen fraction was used for 30 min. The cumulative frequency of postoperative complications was 14 (23.3%) in the HHP vs. 23 (41.1%), p = 0.041. The nitrate decreased after surgery by up to 20% in the HHP group and up to 38% in the control group. Endothelin-1 and nitric oxide metabolites were stable in HHP but remained low for more than 24 h in the control group. The endothelial damage markers appeared to be predictors of postoperative complications. The HHP with individual parameters based on the anaerobic threshold is a safe procedure, and it can reduce the frequency of postoperative complications. The endothelial damage markers appeared to be predictors of postoperative complications.

Keywords: cardioprotection; cardiopulmonary bypass; endothelial damage markers; hypoxic–hyperoxic preconditioning; ischemia-reperfusion injury; oxygen transport.

Figure 1

Flowchart of patient enrollment. HHP—hypoxic–hyperoxic preconditioning; CPB—cardiopulmonary bypass.

Figure 2

The dynamics of oxygen consumption (a) and oxygen delivery (b) indices during the hypoxic–hyperoxic preconditioning. *—p < 0.05 comparing to the baseline.

Figure 3

Receiver operating characteristic curves for endothelin-1 and nitric oxide metabolites for the prediction of postoperative complications. (a) AUC for ET-1 before surgery (blue line) is 0.70 (95% confidence interval (CI) 0.543; 0.856), p = 0.020. The cutoff is 0.759 fmol/mL, sensitivity—78%, specificity—53%; AUC for ET-1 at the end of surgery (green line) is 0.67 (95% CI 0.499; 0.832), p = 0.054. The cutoff is 0.710 fmol/mL, sensitivity—78%, specificity—66%. (b) AUC for NO₂.total 24 h after surgery (green line) is 0.71 (95% CI 0.540; 0.872), p = 0.023. The cutoff is 8.166 µmol/L, sensitivity—82%, specificity—52%; AUC for NO₃.endo 24 h after surgery (blue line) is 0.73 (95% CI 0.579; 0.883), p = 0.007. The cutoff is 7.322 µmol/L, sensitivity—83%, specificity—52%. (c) AUC for NO₂.endo at the end of surgery is 0.77 (95% CI 0.625; 0.920), p = 0.002. The cutoff is 0.768 µmol/L, sensitivity—81%, specificity—66%.

Figure 4

Heart rhythm recovery. The HHP group (a) and the control group (b) in the postperfusion period. Types of rhythm recovery: (Blue) spontaneous sinus rhythm recovery; (Green) ventricular fibrillation (VF) after aorta declamping, sinus rhythm recovery after defibrillation; (Red) ventricular fibrillation after aorta declamping, atrioventricular blockade after defibrillation, the need for temporary pacing. *—p = 0.008 between groups.

Figure 5

Prediction of complications after surgery by ΔPCO2 and C(a-v)O2 monitoring (ROC curves): (a) ΔPCO₂ after 30 min of hyperoxia for the prediction of ventricular fibrillation after CPB; AUC is 0.69 (95% confidence interval (CI) 0.543; 0.833), p = 0.019. The cutoff is less than 6.35 µmol/mL, sensitivity—82%, specificity—52%; (b) ΔPCO2/C(a-v)O2 after 10 min of hyperoxia for prediction of postoperative complications in chronic heart failure patients. AUC is 0.85 (95% confidence interval (CI) 0.682; 1.000), p = 0.010. The cutoff is more than 0.90, sensitivity—88%, specificity—64%.