Alpha-adrenergic receptor stimulation improves myocardial inotropy in the presence of chronic beta-adrenergic antagonists and calcium channel blockers in the isolated rat heart after cardioplegic arrest

This study was devised to evaluate the contribution of alpha(1)-adrenergic stimulation to the inotropic response of the isolated rat heart subjected to a beta-adrenergic receptor antagonist (propranolol) and calcium channel blocker (nifedipine) before 45 minutes of normothermic cardioplegic arrest and during reperfusion. Rats were chronically treated with propranolol and nifedipine. They were then anaesthetised, and the hearts were isolated and retrogradely perfused. Thereafter function was quantified, and the hearts subjected to 45 minutes of normothermic cardioplegic arrest followed by reperfusion. During reperfusion, dose-response curves were obtained for adrenaline, isoprenaline, phenylephrine and methoxamine. The alpha-adrenergic antagonist, prazosin, was also added in two series and the dose-response curves to adrenaline were repeated. The cardiac output was used as an indication of myocardial function. In the presence of propranolol and nifedipine, the dose-response curve for adrenaline was right-shifted. In the presence of prazosin, the inotropic dose-response curve also shifted to the right (compared with adrenaline only). Phenylephrine elicited a significant inotropic response, which was similar to that of adrenaline, while methoxamine was less effective. Results confirm that adrenaline stimulation results in improved inotropy (and chronotropy) of the isolated rat hearts subjected to cardioplegia and reperfusion in the presence of propranolol and nifedipine. Data further suggest that some of the improved function is due to the alpha-adrenergic receptor stimulation associated with the adrenaline infusion.