Intravenous KR-31372 significantly reduced infarct size in anesthetized dogs from 57.0% to 28.0% (p < 0.05) and dose-dependently reduced infarct size in rats following ischemia/reperfusion.
Does KR-31372 reduce infarct size and improve contractile function following ischemia/reperfusion injury in rat and dog models?
KR-31372 provides significant cardioprotection against ischemia/reperfusion injury in animal models, likely via activation of mitochondrial K(ATP) channels.
Tasa de eventos absoluta: 28% vs 57%
valor p: p=< 0.05
The cardioprotective effects of (2S,3R,4S)-N'-benzyl- N"-cyano-N-(3,4-dihydro-2-dimethoxymethyl-3-hydro- xy-2-methyl-6-nitro-2H-benzopyran-4-yl)-guanidine (KR-31372) were evaluated against ischemic/reperfusion injury in isolated rat hearts in vitro and in anesthetized rats and dogs in vivo. In isolated perfused rat hearts subjected to a 30-min global ischemia/30-min reperfusion, KR-31372 (1-10 microM) significantly improved severe contracture (end-diastolic pressure and time to contracture), markedly reduced reperfusion lactate dehydrogenase release, and enhanced the recovery of reperfusion contractile function (left ventricular developed pressure and double product) in a concentration-dependent manner compared with the vehicle-treated group. In anesthetized rats subjected to a 45-min coronary occlusion and a 90-min reperfusion, intravenous KR-31372 dose-dependently reduced infarct size from 58.6% to 48.5, 48.1 and 39.6% at 0.3, 1.0 and 3.0 mg/kg, respectively (p < 0.05). In anesthetized beagle dogs that underwent a 1.5-hour occlusion followed by a 5-hour reperfusion, KR-31372 (2 mg/kg, i.v.) markedly reduced infarct size from 57.0% in controls to 28.0% (p < 0.05). The cardioprotective effects of KR-31372 on contractile function in globally ischemic rat hearts and on reperfusion injury in anesthetized rats were significantly reversed by pretreatment with selective adenosine triphosphate-sensitive potassium (K(ATP)) channel blockers, sodium 5-hydroxydecanoate and glibenclamide. Taken together, these results indicate that KR-31372 possesses potent cardioprotective effects in rats and dogs and its effects may be mediated by activation of mitochondrial K(ATP) channels.
Lee et al. (Fri,) conducted a other in Ischemic/reperfusion injury. KR-31372 vs. Vehicle/controls was evaluated on Infarct size (p=< 0.05). Intravenous KR-31372 significantly reduced infarct size in anesthetized dogs from 57.0% to 28.0% (p < 0.05) and dose-dependently reduced infarct size in rats following ischemia/reperfusion.