Effects of adenosine antagonism and beta-blockade during low-flow ischaemia in rat heart.

1. The effects of adenosine antagonism (8-phenyltheophylline) and beta-blockade (1-propranolol) were examined during low-flow ischaemia (0.5 mL/min per g for 20 min) in rat heart. 2. Myocardial adenosine release, heart rate, and left ventricular developed pressure were monitored to determine whether endogenous adenosine affected ischaemic function directly, and/or via interaction with endogenous catecholamines. 3. Adenosine release increased more than 10-fold during low-flow ischaemia. Release displayed a phasic pattern, with maximal release occurring at 10 min. Ischaemia produced bradycardia (-180 beats/min) which was reduced by 8-phenyltheophylline infusion (P less than 0.001, n = 10). Adenosine antagonism also significantly increased left ventricular developed pressure in the initial 5 min of ischaemia (P less than 0.001, n = 10). 4. beta-blockade alone was without effect in ischaemic hearts, however, beta-blockade significantly reduced the initial increases in heart rate and developed pressure observed during infusion of 8-phenyltheophylline (P less than 0.001, n = 10). The effect of beta-blockade was transient, occurring in the initial 5-6 min of ischaemia. 5. The data indicate that endogenous adenosine directly mediates greater than 30% of the bradycardia associated with low-flow ischaemia, and that endogenous adenosine inhibits the release and/or the effects of endogenous catecholamines produced during the initial 5-6 min of ischaemia.