Beta-adrenergic receptor properties of canine myocardium: Effects of chronic myocardial infarction

To determine the effects of chronic myocardial infarction on beta-adrenergic properties of canine myocardium, the hearts of nine mongrel dogs were studied 3 weeks after acute myocardial infarction. Infarction was produced by ligating the left anterior descending coronary artery in five dogs and the circumflex artery in four dogs. The heart was divided into normal and infarct zones (either anterior or posterior, depending on the vessel ligated) and marginal zones (septal and lateral), each zone being subdivided into epicardial and endocardial portions. Myocardial blood flow (microsphere technique) was markedly reduced in the infarct zone. In eight endocardial infarct samples after left anterior descending ligation, the maximal number (± SD) of binding sites assessed by 125I-iodocyanopindolol was 3.9 ± 1.9 pmol/mg deoxyribonucleic acid (DNA) and was reduced from normal endocardial values (9.7 ± 9.4 pmol/mg DNA, p < 0.05). The dissociation constant (Kd), which is a measure of the affinity of the iodinated antagonist for the receptor, did not differ (304 ± 222 versus 338 ± 219 pM, p = NS). In the epicardium, the maximal number of beta-adrenergic receptors was also reduced (p < 0.05), without a change in Kd. In the lateral and septal zones neither the maximal number of binding sites nor Kdvalues differed from those of normal endocardium. In nine endocardial infarct zones, (−)-iso-proterenol-stimulated adenylate cyclase activity was reduced compared with control (34,870 ± 29,430 versus 88,660 ± 63,640 pmol/mg DNA/30 minutes, p < 0.01), but the ratio of (−)-isoproterenol-stimulated to maximal (sodium fluoride-stimulated) adenylate cyclase activity was unchanged between normal and infarct zones. No other changes from normal were found in any of the other zones. Three weeks after circumflex artery ligation, there were no significant differences in beta-adrenergic receptor density or affinity or in (−)-isopro-terenol-stimulated or maximal adenylate cyclase activity when normal and infarct zones were compared. It is concluded that after chronic canine myocardial infarction there is no evidence of increased beta-adrenergic receptor density or augmented (−)-isoproterenol-stimulated adenylate cyclase activity. Therefore, any alterations in beta-adrenergic receptor properties after myocardial infarction must occur rapidly or be mediated by a pathway other than direct alteration of the beta-adrenergic receptor or coupling between the receptor and adenylate cyclase.