Propofol confers postconditioning-like cardioprotection via its peroxynitrite scavenging property

Abstract

BACKGROUND: Propofol, an intravenous anesthetic that possesses antioxidant and peroxynitrite-scavenging properties, has been shown to confer cardioprotection in both experimental and clinical settings, but the precise mechanism is unclear. Reduction of peroxynitrite production (1) has been shown to play a critical role in hypoxia postconditioning mediated cardioprotection in cultured cardiomyocytes. We, therefore, hypothesize that propofol can confer postconditioning (PPC) cardioprotection via its peroxynitrite scavenging property. METHODS: With ethics approval, isolated and Langendorff-perfused hearts from male Sprague Dawley rats were exposed to 30 min of global ischemia followed by 120 min of reperfusion. During the first 15 min of reperfusion, hearts (n=6-8 per group) were either untreated (control group), or respectively treated with 50 µmol/L of propofol (PPC group), 0.1mmol/ 3-morpholino sydnonimine (SIN-1, a peroxynitrite donor which produces nitric oxide and superoxide anion simultaneously in aqueous solution, SIN group), 20 mg/L of the peroxynitrite decomposer FeTPPs (FeTPPs group), the combinations of propofol with SIN-1 (PPC+SIN) or with FeTPPs (PPC+FeTPPs groups). Myocardial infarct size (IS) was assessed by triphenyltetrazolium staining. Data are expressed as mean ± SD and were analyzed with ANOVA. RESULTS: Postischemic myocardial infarct size (IS) was 36.7±4.7% in the control group. Propofol postconditioning (PPC) significantly reduced IS (28.1±7.0%, P<0.05 vs. control). However, the infarct-sparing effect of PPC was cancelled by co-administration of SIN-1 (IS: 34.5 ±3.9% in PPC+SIN group, P>0.1 vs. control) but facilitated by co-administration of FeTPPs (IS: 15.1±3.8% in PPC+FeTPPs groups, P<0.01 vs. PPC). SIN-1 when given alone during early reperfusion exacerbated postischemic IS (50.9±1.1%, P<0.05 vs. control), while FeTPPs attenuated myocardial IS (21.5 ±8.6%, P<0.01 vs. control). CONCLUSION: It is concluded that propofol can confer postconditioning-like cardioprotection in vitro and that scavenging of peroxynitrite during early reperfusion may represent an important mechanism by which propofol postconditioning confers cardioprotection.