NGS of microRNAs Involved in Cardioprotection Induced by Sevoflurane Compared to Propofol in Myocardial Revascularization Surgery: The ACDHUVV-16 Clinical Trial.

BACKGROUND: Numerous studies have demonstrated that halogenated agents elicit myocardial conditioning effects when administered perioperatively in cardiac surgery. Recent evidence has been published on the benefits of maintaining exposure to halogenated agents during the early postoperative period. The enzymatic mechanisms by which this beneficial effect is exerted were explained recently. OBJECTIVES: Our study was performed to investigate whether this phenomenon is mediated by either the activation or suppression of miRNAs targeted by halogenated anesthetics. METHODS: A double-blind, two-stage trial was conducted. The results of the first stage of the trial are presented in this paper. The sample was composed of patients undergoing off-pump myocardial revascularization surgery. Patients were randomized to receive either sevoflurane [S] or propofol [P] during the intraoperative and early postoperative period (during the first six hours after the intervention). Hemodynamics (heart rate, blood pressure, central venous pressure, cardiac index, systolic volume index, LVEF) and myocardial enzymes (troponin I) were monitored at six hour intervals during the first 48 hours. In the first stage of the trial, blood was drawn for gene sequencing from eight patients (four per group) at baseline and at 24 h. In the second stage of the study, a qPCR analysis was performed of the miRNAs identified as significant by gene sequencing. Levels of cardioprotective enzymes (serine/threonine protein kinase (Akt), tumor necrosis factor alpha (TNFα), extracellular regulated protein kinase (ERK 1/2), and caspase 3) were measured to assess their role in myocardial conditioning pathways. The purpose was to identify the miRNAs that play a major role in myocardial conditioning induced by halogenated agents. Concentrations of cardioprotective enzymes were higher in patients who received sevoflurane than the patients who were administered propofol. RESULTS: NGS differences were observed between baseline and 24-h values in the two study groups. In group P, miRNA 197-3p was overexpressed, whereas miRNAs 4443 and 1294, 708-3p were underexpressed. In group S, miRNAs 615-3p, 4466, 29, 937-3p, 636, 197-3P, 184, 4685, 296-3p, 147b, 3199, 6815, 1294 and 3176 were underexpressed; whereas 708-3p was overexpressed. qPCR showed significant variations in miRNAs 197-3p, 4443, 708-3p and 1294 in the P group, and in miRNAs 937-3p, 636, 197- 3p, 296-3p and 708-3p in the S group. CONCLUSION: In the P Group, changes in the expression of some miRNAs were associated with lower concentrations of the enzymes involved in myocardial pre- and postconditioning. In contrast, in Group S, variations in miRNAs were associated with the activation of mediators of anesthetic-induced pre- and post-conditioning, a reduction in cell apoptosis, and a decrease in caspase and TnBF alpha concentrations. Changes in these miRNAs were associated with better prognosis in patients with ischemic heart disease. The main limitation of this study will be overcome in the second stage of the trial, where the specific role of each miRNA will be determined.

Sevoflurane in intraoperative and postoperative cardiac surgery patients. Our experience in intensive care unit with sevoflurane sedation.

Recently, many studies have shown a decrease in myocardial damage in patients undergoing coronary artery bypass surgery where the anesthetic agent used was sevoflurane compared with propofol. The basis for this protective effect of the myocardium occurs through the mechanisms of preconditioning and postconditioning of halogenated agents. Both relate to the benefit of prior or subsequent administration of the drug (halogenated anesthetic agent) to the harmful stimulus for myocardial cells. The two mechanisms have similar effector mechanisms. The intraoperative administration of sevoflurane is common in anesthetic practice, but the continuation of the administration in the first postoperative hours is made possible by the AnaConDa ® device (ACD; Sedana Medical AB, Uppsala, Sweden) designed for halogenated sedation of patients admitted to intensive care units (ICU). This device has proven useful to facilitate the treatment of pathological conditions. The object of our review is to determine if there are beneficial effects to extending exposure to halogenated agents in the immediate post-operative period . In the post-operative phase, the pathological myocardium is in a reperfusion process in the coronary microcirculation and expression of certain receptors and chemical mediators can reduce potential injury secondary to reperfusion of previously hibernating and/or stunned tissue.