Myocardial Ischemic Injury and β-Adrenergic Receptors in Perfused Working Rabbit Hearts

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

“…Recently, Thandroyen et al have shown in a cardiac myocyte cell culture system derived from neonatal rat ventricle that 2 h of hypoxia is associated with an increase of f3-adrenergic receptor number and a decrease in isoproterenol-stimulated adenylate cyclase activity (14). By contrast, in the isolated nonblood-perfused working rabbit heart, 1 h of ischemia was associated with a decline in the maximal number of f-adrenergic binding sites (15). Similar results have been reported in the rabbit after 30 min of ischemia (16), and in embryonic chick and neonatal rat ventricular myocytes after 2 h of hypoxia ( 17,18).…”

“…The lack of change in adrenergic receptor density and affinity that we observed thus may actually represent relative upregulation in the face of well-documented increases in the local release of catecholamines in ischemic myocardium (34-36). Indeed, a number of reports have suggested that there is either no change or a decrease in 1-receptor density when normal and ischemic or hypoxic tissues are compared in crude membrane preparations from the dog (32), guinea pig (37), and rabbit (15,16) or in intact embryonic chick or neonatal rat ventricular myocytes (17,18). The preservation of adrenergic receptor density and loss of isoproterenol-stimulated activity that we observed argue either for defective coupling between the ,B-adrenergic receptor and the adenylate cyclase complex, or a decrease or alteration in the number of functionally active stimulatory guanine nucleotide regulatory (Gs) units because both GppNHp-and NaF-stimulated activities were also reduced.…”

Ischemic preconditioning is associated with a delay in ischemia-induced reduction of beta-adrenergic signal transduction in rabbit hearts.

“…[30][31][32][33] Using rabbit hearts, we observed that the p-adrenergic receptor number decreased rapidly after 10 minutes of ischemia and persisted after 20 to 60 minutes of sustained ischemia. The reason for the discrepancy in the response of /8-adrenergic receptor regulation to sustained ischemia between some previous studies and ours is not clear.…”

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

“…Such considerations suggest that the conclusions drawn from such studies may be highly dependent upon the experimental methods employed to determine receptor changes. Accordingly, no changes in P-adrenoceptor density were observed when normal and ischemic myocardium were compared in crude membrane preparations from the cat (42), dog (76,126), guinea pig (148), and rabbit (197,253). In fact, Corr et al (42) observed a decrease in P-adrenoceptor density during a 2-min reperfusion period following ischemia in cats.…”

“…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). The isolated perfused heart preparation has been a useful model for investigating biochemical and metabolic changes during myocardial ischemia and hypoxia in vitro (50,177,197). In this model, the isolated heart is perfused with a well-oxygenated physiologic medium, the rate of flow or the composition of which can be modified to elicit globally ischemic or hypoxic conditions.…”