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EFFECTS OF ADENOSINE ANTAGONISM AND β‐BLOCKADE DURING LOW‐FLOW ISCHAEMIA IN RAT HEART
Author(s) -
Headrick J. P.,
Willis R. J.
Publication year - 1989
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1989.tb01528.x
Subject(s) - antagonism , adenosine , blockade , cardiology , medicine , ischemia , pharmacology , anesthesia , receptor
SUMMARY 1. The effects of adenosine antagonism (8‐phenyltheophylline) and β‐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 < 0.001, n = 10). Adenosine antagonism also significantly increased left ventricular developed pressure in the initial 5 min of ischaemia ( P < 0.001, n = 10). 4. β‐blockade alone was without effect in ischaemic hearts, however, β‐blockade significantly reduced the initial increases in heart rate and developed pressure observed during infusion of 8‐phenyltheophylline ( P < 0.001, n = 10). The effect of β‐blockade was transient, occurring in the initial 5–6 min of ischaemia. 5. The data indicate that endogenous adenosine directly mediates > 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.