The timing of propofol administration affects the effectiveness of remote ischemic preconditioning induced cardioprotection in rats

Abstract

The cardioprotection of remote ischemic preconditioning (RIPC) is abolished under propofol maintained anesthesia. Transient receptor potential vanilloid 1 (TRPV1) channel is present in the heart, and its activation could induce cardioprotection. Therefore, we tested whether the anesthetic propofol administration phase interfered with the RIPC‐induced cardioprotection, and RIPC‐induced cardioprotection via the cardiac TRPV1 channel. Male Sprague‐Dawley rats were subjected to myocardial 30 minutes of ischemia followed by 2 hours of reperfusion. RIPC consisted of three cycles of 5‐minute ischemia/reperfusion applied to a hindlimb. Propofol infusion at 12 mg/kg/h was commenced either at 10 minutes before the start of RIPC in the P‐pre + RIPC group, or immediately after myocardial ischemia at the onset of reperfusion (P‐post + RIPC) while performing RIPC. These two propofol infusion regimes were applied to another two grou bs without RIPC (P‐pre and P‐post groups). Infarct size (IS) was assessed by triphenyltetrazolium staining. Heart TRPV1 expression was detected by Western blot and immunofluorescence. RIPC significantly reduced myocardial IS compared with the control group (36.7 ± 3% versus 57.2 ± 4%; P < .01). When propofol was started before RIPC, the IS sparing effect of RIPC was completely abolished. However, propofol infusion starting immediately after myocardial ischemia did not affect RIPC‐induced cardioprotection. TRPV1 expression significant increase after RIPC, then propofol inhibited the TRPV1 activation of RIPC if given before RIPC but not after. Our results suggest that the timing of propofol administration is critical to preserve the cardioprotection of RIPC. Propofol might cancel RIPC‐induced cardioprotection via the cardiac TRPV1 receptor.

Remote Ischemic Preconditioning to Prevent Acute Kidney Injury After Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials

“…In fact, some recently published experimental studies suggest that the potential interaction between these factors, such as propofol, with organ protective efficacy of RIPC may be more complicated than expected. A recent study in a rat model found that the timing of propofol administration could affect RIPC-induced cardioprotection (45), and that different doses of propofol used in the studies may have also affected the results. Future studies are needed to determine the influences of patient characteristics, procedure, perioperative drugs, and RIPC protocol on the efficacy of RIPC on AKI prevention.…”

Remote Ischemic Preconditioning Improves Tissue Oxygenation in a Porcine Model of Controlled Hemorrhage Without Fluid Resuscitation

“…Of interest, Abel et al reported that extracellular microvesicles isolated from patients undergoing RIPC vs sham were associated with decreased hypoxia-evoked apoptosis of cardiomyoblasts after iso urane --but not propofol exposure [15,38]. Yu et al [39], in a rodent model, suggested that propofol blunts the cardioprotective effect of RIPC through its effect on the cardiac TRPV1 channel only if it is administered before RIPC, but not when propofol is given after RIPC [40]. Thus, the effect of propofol on RIPC remains an unresolved issue.…”

Remote ischemic preconditioning improves tissue oxygenation in a porcine model of controlled hemorrhage without fluid resuscitation

“…Of interest, Abel et al reported that extracellular microvesicles isolated from patients undergoing RIPC versus sham were associated with decreased hypoxia-evoked apoptosis of cardiomyoblasts after isoflurane – but not after propofol 15 , 38 . Yu et al 39 , in a rodent model, suggested that propofol blunts the cardioprotective effect of RIPC through its effect on the cardiac TRPV1 channel only if it is administered before RIPC, but not when propofol is given after RIPC 40 . Thus, the effect of propofol on RIPC remains an unresolved issue.…”