Remote intermittent ischemia before coronary artery bypass graft surgery: a strategy to reduce injury and inflammation?

Abstract

Perioperative myocardial ischemia contributes to postoperative morbidity and mortality. Remote intermittent ischemia (RI) has been shown to benefit patients undergoing coronary artery bypass graft (CABG) surgery by decreasing postoperative cardiac troponin levels. In addition, there is evidence that volatile anesthetics may provide myocardial protection. In this prospective randomized controlled trial we tested the hypothesis that RI is cardioprotective under a strict anesthetic regime with volatile anesthesia until cardiopulmonary bypass (CPB). We also assessed whether RI modulates postoperative cytokine and growth factor concentrations. Fifty-four patients referred for elective CABG surgery without concomitant valve or aortic surgery were randomized to three 5-min cycles of left upper limb ischemia by cuff inflation (RI) or placebo without cuff inflation (Plac). All patients received the volatile anesthetic isoflurane (1.15-1.5 vol%) before CPB and the intravenous anesthetic propofol (3-4 mg/kg/h) thereafter until the end of surgery. Cardiac arrest during CPB was induced by intermittent cross-clamp fibrillation, or by blood cardioplegia. We excluded patients older than 85 years, with unstable angina, significant renal disease, and those taking sulfonylureas. Troponin I (cTnI) was measured preoperatively and after 6, 12, 24 and 48 h. In addition, brain natriuretic peptide (BNP), creatine kinase (CKMB) and a panel of cytokines and growth factors were analyzed perioperatively. Although cTnI, BNP and CKMB all increased post-CABG, there were no significant differences between RI and Plac groups; area under the curve for cTnI 189.4 (183.6) ng/mL/48 h and 183.0 (155.2) ng/mL/48 h mean (SD), p = 0.90, respectively, despite a tendency to a shorter (p < 0.07) cross-clamp time in the treatment group. Similarly, there were no differences between groups in the central venous concentrations of numerous cytokines and growth factors. In patients undergoing CABG surgery RI does not provide myocardial protection under a strict anesthetic regime with volatile anesthesia until CPB, and RI was not associated with changes in cytokines.

Experimental cardiovascular and lung research Remote ischemic preconditioning versus standard myocardial protection in cardiac surgery: ten years of clinical trials. A systematic review and meta-analysis

“…Subgroup analysis of the studies reporting outcomes of CABG with or without AVR showed results consistent with the general trend (SMD -0.42; 95% CI: -0.70 to -0.13, p = 0.005) and I 2 = 67% [9,[20][21][22][23][24][25][26][27]. Studies concerning isolated valvular surgery did not confirm the protective result of rIPC; however, heterogeneity (I 2 = 94%) was essentially influencing the outcome effect under the random [28][29][30].…”

“…Finally, fifteen papers were found to present the best available evidence. These studies pertained to: adult coronary bypass grafting surgery with or without AVR [9,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27], adult valvular surgery [28][29][30], and pediatric cardiac surgery [31][32][33]. All the available papers were designed as prospective randomized controlled trials.…”

“…Male gender proportion ranged from 35% to 100% in the rIPC group and from 28% to 100% among the controls. The majority of patients were operated on due to coronary artery disease (335 in the rIPC group and 340 in the control group) [9,[20][21][22][23][24][25][26][27]. The analysis of rIPC in pediatric patients undergoing cardiac surgery included 67 patients in the rIPC study groups and 70 in the control groups [31][32][33], whereas 89 and 90 patients were submitted to isolated valvular surgery with or without rIPC, respectively [28][29][30].…”

“…All studies were proof-of-concept trials with small sample sizes, and only three included more than 100 patients [20][21][22]. Diabetic subjects were partially included in six trials [9,[21][22][23][24]30]. Time from rIPC to global ischemia (e.g.…”

“…Secondly, this meta-analysis gathered its evidence from proofof-concept trials, which are, by definition, limited in terms of the number of participants. Funnel plot analysis was employed to find evidence of asymmetry, and four studies were indeed found to lie outside the 95% confidence interval, with one additional study located on its border [20,21,24,28,31] (Fig. 3).…”