Abstract
Reverse-mode activation of the Na+-Ca2+ exchanger (NCX) at the time of reperfusion following ischemia contributes to Ca2+ overload and cardiomyocyte injury, KB-R7943, as a selective reverse-mode NCX inhibitor, reduces lethal reperfusion injury under normal conditions, but its effectiveness under certain pathological states is in dispute. In the present study, we sought to determine the effect of KB-R7943 in hyperlipidemic animals and assess if the K+ ATP are involved in the protective mechanisms. Anesthetized rats were randomized into five groups, as follows, and were subjected to 25min global ischemia (GI) followed by 120 min reperfusion (R). Normally fed animals: a Control group (NC) with no additional intervention. Cholesterol fed (6weeks) animals: a Chol group (HC) with no additional interventions, a KB-R7943 group (HKB) treated with KB-R7943, a KB-R7943 and glybenclamide group (HGKB) treated with KB-R7943 and glybenclamide (K+ ATP, blocker, 0.3μM), a glybenclamide group (HGLY) treated with glybenclamide The infarct size was measured by triphenyltetrazolium. The infarct size was 35±5.0% in NC, 46±8.7% in HC and 47±8.5% in HGLY (NC vs. HC, P 0.05). KB-R7943 reduced the infarct size (28.6±3.3% in HKB vs. HC, P<0.05), In addition, KB-R7943 attenuated apoptotic cell (HKB vs. HC, p<0.05), glybenclamide abolished the effect reached by KB-R7943. Thus, diet-induced hypercholesterolemia enhances myocardial injury; KB-R7943 reduces infarct size and apoptosis in hyperlipidemic animals through the activation of K+ ATP channels.
Highlights
Anesthetized rats were randomized into five groups, as follows, and were subjected to 25min global ischemia (GI) followed by 120 min reperfusion (R)
Patients with Ischemic heart disease (IHD) are likely to have a number of co-morbid conditions at the time of presentation, many of which can influence the sensitivity of the myocardium to certain cardioprotective strategies [1]
We investigated the effects of hypercholesterolemia alone on the ischemic myocardium in an isolated rat model of acute ischemiareperfusion (IR)
Summary
Anesthetized rats were randomized into five groups, as follows, and were subjected to 25min global ischemia (GI) followed by 120 min reperfusion (R). Fed animals: a Control group (NC) with no additional intervention. Diet-induced hypercholesterolemia enhances myocardial injury; KB-R7943 reduces infarct size and apoptosis in hyperlipidemic animals through the activation of channels. We investigated the effects of hypercholesterolemia alone on the ischemic myocardium in an isolated rat model of acute ischemiareperfusion (IR). Some investigators reported that diet-induced hypercholesterolemia enhances myocardial injury by increasing oxidative stress [3], upregulation of inflammation [4], inhibition of nitric oxide synthesis [5], vascular obstruction [6], and increased cardiomyocyte apoptosis [7], while others have found no additional harm after reperfusion injury [2,7], or have shown that hypercholesterolemia improves myocardial function and may even be cardioprotective [8]
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