Nitric oxide provides myocardial protection when added to the cardiopulmonary bypass circuit during cardiac surgery: Randomized trial

Abstract

Objectives: The aim of this pilot study was to elucidate the effects of exogenous nitric oxide (NO) supply to the extracorporeal circulation circuit for cardioprotection against ischemia-reperfusion injury during coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB).Methods: A total of 60 patients with coronary artery disease scheduled for CABG with CPB were enrolled in a prospective randomized study. Patients were allocated randomly to receive treatment according to standard or modified CPB protocol where 40-ppm NO was added to the CPB circuit during cardiac surgery. The primary endpoint was the measurement of cardiac troponin I (cTnI). The secondary end points consisted in the measurements of creatine kinase-muscle/brain fraction (CK-MB) and vasoactive inotropic score (VIS).Results: NO delivered into the CPB circuit had a cardioprotective effect. The level of cTnI was significantly lower in NO-treated group compared with the control group 6 hours after surgery: 1.79 AE 0.39 ng/mL versus 2.41 AE 0.55 ng/mL, respectively (P ¼ .001). The CK-MB value was significantly lower in NOtreated group compared with the control group 24 hours after surgery: 47.

Effect of nitric oxide on postoperative acute kidney injury in patients who underwent cardiopulmonary bypass: a systematic review and meta-analysis with trial sequential analysis

“…Forty-eight studies were excluded due to lack of full text, not randomized for NO therapy or crossover studies, not reporting renal outcomes, and using peritoneal dialysis as readily therapy. Finally, six studies were eligible for systematic review [18, 19, 21, 22, 31, 32]. Among the six included studies, one study was ultimately excluded, because not all the patients in NO and control groups underwent CPB [32].…”

“…Two studies started NO therapy immediately before CPB weaning [21, 22] and defined renal dysfunction as urine output less than 0.3 ml/h [21] or need for renal replacement treatment (RRT) [22], respectively. Three studies delivered NO from the beginning of CPB and defined AKI by the KDIGO criteria [18, 19, 31]. Detailed information of all included studies is shown in Table 1, and quality evaluation is shown in Fig.…”

“…First, to evaluate the potential impact of the sparse data and imbalance of sample size, we pooled the effect sizes by the Peto method and found that it was similar to that obtained by the primary analysis (Table 2, Additional file 4, data not shown). Second, the three studies that had low risk of bias and reported AKI using KDIGO criteria [18, 19, 31] were included in a sensitivity analysis. Data also corroborated the beneficial effect of NO on renal function (RR, 0.71, 95% CI 0.54–0.94, p = 0.02, I 2 = 10%, Additional file 5, data not shown).…”

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

“…Previous studies clearly demonstrated that the deficiency of endothelial NO-synthase exacerbates myocardial IRI, whereas its overexpression, the administration of NO donors, and the inhaled NO, all protect the myocardium [ 27 , 28 , 29 ]. NO is an important key mediator and trigger in cardio protection afforded by both early and late ischemic preconditioning [ 29 ].…”

Commentary: Just say NO? Does nitric oxide improve myocardial protection during cardiac surgery?

“…Ischemia-reperfusion injury during cardiopulmonary bypass (CPB) is inevitable, and the quest to ameliorate this injury has been pursued for decades. In their study in this issue of the Journal, Kamenshcikov and colleagues 1 have taken on this challenge, hypothesizing that nitric oxide (NO) in the cardiopulmonary bypass circuit will reduce myocardial injury during coronary artery bypass grafting (CABG) surgery. The salutary effects of NO have been the subject of intense investigation, which indeed culminated with the Nobel Prize in Medicine in 1998.…”