Abstract
Minimization of irreversible myocardial damage after ischemia-reperfusion episode remains valid and unsolved problem. Among of many pharmacological agents have been effective in experimental studies, only a few of them are evidence of its efficacy in clinical trials. This is largely explained by the mechanism of action of these compounds, aimed primarily at preventing reperfusion injury, and do not affect myocardial cells subjected to prolonged ischemia without reperfusion. In recent years, the interest of researchers confined to the mechanisms of programmed necrosis or necroptosis, which morphologically has no different to necrosis, but has molecular targets for suppression. In this paper, on the model of global ischemia-reperfusion in rats we have studied cardioprotective effects of high-activity and low-toxicity necroptosis inhibitors - necrosulfonamide and necrostatin-1s. We demonstrated the infarct-limiting effect of these compounds, as well as the best parameters of intracardiac hemodynamics after an episode of global ischemia-reperfusion. We believe these compounds are interesting for further preclinical studies.
Highlights
Among of many pharmacological agents have been effective in experimental studies, only a few of them are evidence of its efficacy in clinical trials. This is largely explained by the mechanism of action of these compounds, aimed primarily at preventing reperfusion injury, and do not affect myocardial cells subjected to prolonged ischemia without reperfusion
The interest of researchers confined to the mechanisms of programmed necrosis or necroptosis, which morphologically has no different to necrosis, but has molecular targets for suppression
On the model of global ischemia-reperfusion in rats we have studied cardioprotective effects of high-activity and low-toxicity necroptosis inhibitors — necrosulfonamide and necrostatin-1s
Summary
Zhaoa J, Jitkaewa S, Caia Z. et al Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis // PNAS. The investigation of cardioprotective effects of novel necroptosis inhibitors – necrosulfonamide and necrostatin-1s in the rat model of isolated perfused rat heart
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