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.
Headrick
J P
JP
Division of Science and Technology, Griffith University, Nathan, Queensland, Australia.
Willis
R J
RJ
D000241:Adenosine / Q000037:antagonists & inhibitors* / Q000502:physiology; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013806:Theophylline / Q000031:analogs & derivatives / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine