Isoflurane inhalation significantly reduced infarct size to 26% of the risk zone compared to 60% in untreated controls (P<0.05), an effect prevented by 5-hydroxydecanoate and gadolinium.
RCT (n=52)
Randomized into one of six groups
Does isoflurane-induced preconditioning reduce infarct size in a rabbit model of ischemia-reperfusion, and is this effect blocked by 5-hydroxydecanoate or gadolinium?
Isoflurane-induced preconditioning reduces infarct size in rabbits, a protective mechanism that is likely mediated by mitochondrial ATP-sensitive potassium channels and mechanogated channels.
Tasa de eventos absoluta: 26% vs 60%
valor p: p=< 0.05
BACKGROUND: Both mitochondrial adenosine triphosphate-sensitive potassium (MKATP) channels (selectively blocked by 5-hydroxydecanoate) and stretch-activated channels (blocked by gadolinium) have been involved in the mechanism of ischemic preconditioning. Isoflurane can reproduce the protection afforded by ischemic preconditioning. We sought to determine whether isoflurane-induced preconditioning may involve MKATP and stretch-activated channels. METHODS: Anesthetized open-chest rabbits underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Before this, rabbits were randomized into one of six groups and underwent a treatment period consisting of either no intervention for 40 min (control group; n = 9) or 15 min of isoflurane inhalation (1.1% end tidal) followed by a 15-min washout period (isoflurane group; n = 9). The two groups received an intravenous bolus dose of either 5-hydroxydecanoate (5 mg/kg) or gadolinium (40 micromol/kg) before coronary occlusion and reperfusion (5-hydroxydecanoate, n = 9; gadolinium, n = 7). Two additional groups received 5-hydroxydecanoate or gadolinium before isoflurane exposure (isoflurane-5-hydroxydecanoate, n = 10; isoflurane-gadolinium, n = 8). Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. RESULTS: Area at risk was comparable among the six groups (29 +/- 7, 30 +/- 5, 27 +/- 6, 35 +/- 7, 31 +/- 7, and 27 +/- 4% of the left ventricle in the control, isoflurane, isoflurane-5-hydroxydecanoate, 5-hydroxydecanoate, isoflurane-gadolinium, and gadolinium groups, respectively). Infarct size averaged 60 +/- 20% (SD) in untreated controls versus 54 +/- 27 and 65 +/- 15% of the risk zone in 5-hydroxydecanoate- and gadolinium-treated controls (P = nonsignificant). In contrast, infarct size in the isoflurane group was significantly reduced to 26 +/- 11% of the risk zone (P < 0.05 vs.control). Both 5-hydroxydecanoate and gadolinium prevented this attenuation: infarct size averaged 68 +/- 23 and 56 +/- 21% of risk zone in the isoflurane-5-hydroxydecanoate and isoflurane-gadolinium groups, respectively (P = nonsignificant vs.control). CONCLUSION: 5-Hydroxydecanoate and gadolinium inhibited pharmacologic preconditioning by isoflurane. This result suggests that MKATP channels and mechanogated channels are probably involved in this protective mechanism.
Piriou et al. (2000) conducted an RCT in Myocardial ischemia-reperfusion injury (n=52). Isoflurane inhalation vs. No intervention (untreated control) was evaluated on Infarct size as a percentage of the risk zone (p=< 0.05). Isoflurane inhalation significantly reduced infarct size to 26% of the risk zone compared to 60% in untreated controls (P<0.05), an effect prevented by 5-hydroxydecanoate and gadolinium.