Abstract
BackgroundThe authors examined whether milrinone and levosimendan could exert cardiac postconditioning effects in rats under normoglycemia and hyperglycemia, and whether the effects could be mediated by mitochondrial permeability transition pore (mPTP).MethodsWistar rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received milrinone or levosimendan just before reperfusion under normoglycemic or hyperglycemic conditions with or without atractyloside, an mPTP opener.ResultsUnder normoglycemia, both 30 μg/kg milrinone (29 ± 12%) and 10 μg/kg levosimendan (33 ± 13%) reduced infarct size compared with that in the control (58 ± 7%). Under hyperglycemia, milrinone (34 ± 13%) reduced infarct size at the same dose as under normoglycemia. In contrast, neither 10 nor 30 μg/kg levosimendan protected hyperglycemic hearts, and only 100 μg/kg levosimendan (32 ± 9%) reduced infarct size compared with that in the hyperglycemic control (58 ± 13%). All of these cardioprotective effects under normoglycemia and hyperglycemia are abolished by atractyloside.ConclusionMilrinone and levosimendan exert postconditioning effects via inhibition of mPTP opening. Hyperglycemia raises the threshold of levosimendan-induced postconditioning, while milrinone-induced postconditioning is not influenced by hyperglycemia.
Highlights
Hyperglycemia (HG) is frequently observed in patients with acute myocardial ischemic events such as myocardial infarction or the usage of cardiopulmonary bypass in cardiac surgery
We hypothesized that HG would raise the threshold of levosimendan-induced PostC, which is mediated by mitochondrial KATP (m-KATP) channels, and we examined whether milrinone- and levosimendaninduced PostC could be mediated by the inhibition of mitochondrial permeability transition pore (mPTP) opening
There were no significant differences in body weight or age among the groups
Summary
Hyperglycemia (HG) is frequently observed in patients with acute myocardial ischemic events such as myocardial infarction or the usage of cardiopulmonary bypass in cardiac surgery. A phosphodiesterase 3 inhibitor (PDE-I), and levosimendan, a calcium sensitizer, are relatively new types of inotropic agent and known to facilitate functional recovery from myocardial ischemia-reperfusion injury (e.g., cardiac surgery under cardiopulmonary bypass and conditions after cardiopulmonary resuscitation), and could lead to preserved perfusion of major organs after myocardial reperfusion [7,8,9,10]. Intracellular calcium overload occurs during post-ischemic reperfusion, and could cause cardiac arrhythmias or myocardial stunning. The authors examined whether milrinone and levosimendan could exert cardiac postconditioning effects in rats under normoglycemia and hyperglycemia, and whether the effects could be mediated by mitochondrial permeability transition pore (mPTP)
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