ALPHA-ADRENERGIC RECEPTOR STIMULATION IMPROVES MYOCARDIAL INOTROPY INTHE 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)-adrene rgic stimulation to the inotropic response of the isolated rat heart s ubjected to a beta-adrenergic receptor antagonist (propranolol) and ca lcium channel blocker (nifedipine) before 45 minutes of normothermic c ardioplegic arrest and during reperfusion. Rats were chronically treat ed with propranolol and nifedipine. They were then anaesthetised, and the hearts were isolated and retrogradely perfused. Thereafter functio n was quantified, and the hearts subjected to 45 minutes of normotherm ic cardioplegic arrest followed by reperfusion. During reperfusion, do se-response curves were obtained for adrenaline, isoprenaline, phenyle phrine and methoxamine. The alpha-adrenergic antagonist, prazosin, was also added in two series and the dose-response curves to adrenaline w ere repeated. The cardiac output was used as an indication of myocardi al function. In the presence of propranolol and nifedipine, the dose-r esponse curve for adrenaline was right-shifted. In the presence of pra zosin, the inotropic dose-response curve also shifted to the right (co mpared with adrenaline only). Phenylephrine elicited a significant ino tropic response, which was similar to that of adrenaline, while methox amine was less effective. Results confirm that adrenaline stimulation results in improved inotropy (and chronotropy) of the isolated rat hea rts subjected to cardioplegia and reperfusion in the presence of propr anolol and nifedipine. Data further suggest that some of the improved function is due to the alpha-adrenergic receptor stimulation associate d with the adrenaline infusion.