Dissociation between reperfusion induced arrhythmias and increases in ventricular alpha 1 receptor density in the anaesthetised rat.
Using anaesthetised rats we have assessed (1) whether the density of alpha 1 adrenergic receptors increases during coronary artery occlusion, (2) whether any change in density can be associated with the onset of reperfusion induced ventricular fibrillation, and (3) whether alpha 1 blockade with prazosin modifies the incidence of reperfusion induced ventricular fibrillation. The incidence of fibrillation upon reperfusion after 3, 5, 10, 20 and 30 min occlusion was 20, 75, 50, 16 and 10% (n = 10-12 in each group) respectively. alpha 1 Receptor density was measured using [3H]-prazosin in non-ischaemic and ischaemic tissue obtained after 0, 5 and 30 min ischaemia. Receptor density was not significantly altered at the time of maximum incidence of reperfusion induced ventricular fibrillation (5 min occlusion) but did significantly increase in both non-ischaemic and ischaemic tissue after 30 min occlusion, when the incidence of fibrillation upon reperfusion was very low (8%). At this time the values were 17.0(SEM 2.3) and 18.4(0.6)fmol.mg-1 protein in non-ischaemic and ischaemic zones as compared to 10.7(0.6) and 12.8(1.0)fmol.mg-1 protein in sham operated control animals (p less than 0.05 in both cases). Prazosin (0.1 or 1.0 mg.kg-1 body wt intravenously, 5 min prior to coronary occlusion) did not alter the incidence of ventricular fibrillation, ventricular tachycardia or total number of premature ventricular complexes upon reperfusion. We conclude that ischaemia induced changes in alpha 1 receptor density do not parallel changes in vulnerability to reperfusion induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
Manning
A S
AS
Cardiovascular Research, Rayne Institute, St Thomas's Hospital, London.
Crome
R
R
Klein
N
N
Hearse
D J
DJ
Maguire
M E
ME
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D003327:Coronary Disease / Q000150:complications* / Q000378:metabolism; D006352:Heart Ventricles / Q000032:analysis; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000209:etiology*; D009206:Myocardium / Q000032:analysis*; D010424:Pentobarbital; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D010424:Pentobarbital; D011224:Prazosin