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

Abstract

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 less than 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 less than 0.05), without a change in Kd. In the lateral and septal zones neither the maximal number of binding sites nor Kd values differed from those of normal endocardium. In nine endocardial infarct zones, (-)-isoproterenol-stimulated adenylate cyclase activity was reduced compared with control (34,870 +/- 29,430 versus 88,660 +/- 63,640 pmol/mg DNA/30 minutes, p less than 0.01), but the ratio of (-)-isoproterenol-stimulated to maximal (sodium fluoride-stimulated) adenylate cyclase activity was unchanged between normal and infarct zones.(ABSTRACT TRUNCATED AT 250 WORDS)

The Regulation of Receptors, Ion Channels, and G Proteins in Congestive Heart Failure

“…Exercise-induced increases in lymphocyte 8-adrenoceptor density are also impaired in humans with heart failure (77,153,155). Similar observations have been made in several experimental models of heart failure induced by occlusion of the coronary vessels as in the guinea pig (4,7) and the dog (60,125). A summary of these observations is provided in Table 7.…”

“…The coronary artery occlusion model, wherein initial ischemia is induced by limiting myocardial blood suppiy usually by ligation, has been successfully employed in a wide variety of species, notably the dog (47,125,172,174,186,222), guinea pig (7,145,148), cat (42), and the rat (53,105.193,244). Alternative experimental techniques include induction of myocardial stress by rapid electrical pacing of the heart and pressure or volume overload by obstruction of arterial or venous blood flow (9 1,104,122,139,199,208,24 1,242).…”

Effects of acute ischemia in the dog on myocardial blood flow, beta receptors, and adenylate cyclase activity with and without chronic beta blockade.

“…The samples were stored at -70'C until analysis several weeks later. Previous studies showed that there is no loss of either receptor binding or adenylate cyclase activity under these circumstances compared with fresh tissue (19 (24).…”

“…The left ventricular free wall was then divided into the previously demarcated ischemic zone anteriorly and a normal posterior zone opposite to the area of ischemia. Each of these zones was then divided transmurally into two equal regions as previously described (19). These will be referred to as subendocardium and subepicardium throughout this manuscript.…”

“…Maximum adenylate cyclase activity was assessed by measuring cAMP production in the presence of 10 mM NaF; membranes were also incubated separately with 0.1 mM guanyl-5'-imidodiphosphate (GppNHp). Because canine myocardial membranes respond poorly to (-)-isoproterenol stimulation alone at 1 AM, we also measured what we have called net (-)-isoproterenol stimulation (19). This value is calculated by subtracting the GppNHp-stimulated activity from the sum of the latter plus 1 AM (-)-isoproterenol-stimulated activity.…”