Late cardiac perconditioning by phenylephrine in an isolated rat heart model is mediated by mitochondrial potassium channels

Abstract

The present study was designed to investigate the effect of early and late administration of phenylephrine during ischemia against regional ischemia-reperfusion injuries in an isolated rat heart model. All animals were randomly divided into experimental groups: (I) IR (Ischemic/ reperfusion): the hearts underwent 35 min of regional ischemia followed by 60 min of reperfusion; (II) 5HD-IR-0: the hearts were perfused for 5 min with 5HD (5-hydroxydecanoate, specific mKATP channel blocker, 100 µM) at the onset of regional ischemia; (III) 5HD-IR-20: the hearts were perfused for 5 min with 5HD 20 min after regional ischemia; (IV) PE-IR-10: the hearts were perfused for 5 min with phenylephrine 10 min after regional ischemia; (V) PE-IR-30: the hearts were perfused for 5 min with phenylephrine (100 µM) 30 min after regional ischemia; (VI) PE-5HD-IR-10 group: the hearts were perfused for 5 min with 5HD at the onset of regional ischemia after which phenylephrine was administrated as in group IV; and (VII) PE-5HD-IR-30: the hearts were perfused for 5 min with 5HD 20 min after the ischemia and then phenylephrine was administrated as in group V. The hemodynamic parameters were recorded throughout the experiment. Ischemia-induced arrhythmias, myocardial infarct size (IS), creatin kinase-MB isoenzyme (CK-MB), plasma lactate dehydrogenase (LDH) activities, and coronary blood flow (CBF) were measured in all animals. Perfusion of phenylephrine 30 min after the regional ischemia curtailed the myocardial infarct size, reduced CK-MB, and improved cardiac function and CBF. Administration of 5HD 30 min after the ischemia abolished cardioprotective effects of phenylephrine in the late phase. These results suggest the involvement of mK ATP in the mechanism of phenylephrine-induced late preconditioning.

Current Developments on the Role of α1-Adrenergic Receptors in Cognition, Cardioprotection, and Metabolism

“…The high metabolic rate of the heart can cause the heart to be sensitive to the lack of oxygen (i.e., ischemia) resulting in injury to the muscle. α 1 -AR have long been known to mediate protective effects against ischemia or preconditioning in ischemia in several species ( Banerjee et al, 1993 ; Kitakaze et al, 1994 ; Tsuchida et al, 1994 ; Salvi, 2001 ; Rorabaugh et al, 2005 ; Zhao et al, 2012 ; Nazari et al, 2019 ; Papay and Perez, 2020 ). In preconditioning, short periods of ischemia can stimulate signaling in the heart that protects the cardiac muscle from subsequent ischemic injury.…”

“…In preconditioning, short periods of ischemia can stimulate signaling in the heart that protects the cardiac muscle from subsequent ischemic injury. The mechanism has been multi-faceted and attributed to PKC ( Tsuchida et al, 1994 ; Mitchell et al, 1995 ; Rehring et al, 1996 ; Rorabaugh et al, 2005 ), mitochondrial potassium channels ( Nazari et al, 2019 ), mitochondrial permeability transition pore ( Naderi et al, 2010 ), 5′-nucleotidase activity ( Tsuchida et al, 1994 ) or angiogenesis ( Zhao et al, 2012 ). In recent studies, the ischemic protective effect of the α 1 -AR observed in primary cardiomyocytes was also proposed to be through the metabolic effects of glucose ( Papay and Perez, 2020 ).…”