title: Alpha-1 adrenergic receptor agonist-induced preconditioning in isolated working rat hearts.
abstract: The aim of this study was to determine whether pharmacologic preconditioning, without a short episode of myocardial hypoxia or ischemia, could improve myocardial function after a prolonged period of ischemia. Isolated rat hearts were perfused with .01, .1 or 1 mg/L of phenylephrine for 5 min followed by a 10-min washout period (preconditioning) before the induction of 30 min of normothermic global ischemia and 30 min of reperfusion. Hearts preconditioned with increasing concentrations of phenylephrine (an alpha-1 adrenergic receptor agonist) produced a reduction in the incidence of reperfusion-induced ventricular fibrillation (VF) and ventricular tachycardia (VT). Preconditioning of the hearts with the highest dose of phenylephrine (1.0 mg/L), after 30 min of ischemia, reduced the incidence of reperfusion-induced VF and VT from their nonpreconditioned control values of 87% and 100% to 33% (P < .05) and 50% (P < .05), respectively. After 30 min of ischemia, the recovery of myocardial function was significantly improved in phenylephrine-preconditioned groups. Thus, .1 and 1.0 mg/L of phenylephrine increased aortic flow from its nonpreconditioned control value of 10.8 +/- .9 ml/min to 22.4 +/- 2.4 ml/min (P < .05) and 26.5 +/- 1.5 ml/min (P < .05), respectively. Phenylephrine (1.0 mg/L) preconditioning significantly reduced ischemia/reperfusion-induced tissue Na+ and Ca2+ gains and prevented K+ and Mg2+ loss measured by an atomic absorption spectro-photometer. Our results show that alpha-1 adrenergic stimulation (preconditioning) can prevent postischemic abnormalities in intracellular ions, reperfusion arrhythmias, and contractile function without the inhibition of O2 delivery.
authors.affiliation: University of Connecticut Health Center, School of Medicine, Farmington, USA.
authors.forename: A
authors.initials: A
authors.lastname: Tosaki
authors.forename: N S
authors.initials: NS
authors.lastname: Behjet
authors.forename: D T
authors.initials: DT
authors.lastname: Engelman
authors.forename: R M
authors.initials: RM
authors.lastname: Engelman
authors.forename: D K
authors.initials: DK
authors.lastname: Das
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D017136:Ion Transport; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology* / Q000627:therapeutic use; D011292:Premedication; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D010656:Phenylephrine