Neil C. Moran

444 Dissociation of the augmentation of cardiac contractile force from the activation of myocardial phosphorylase by catecholamines

The correlation between the inotropic action of catecholamines on the dog heart in situ and their effect on myocardial glycogen phosphorylase has been examined. Sensitivity in the detection of small changes in the percent of the enzyme in the a form was heightened by serial biopsy of the heart and by the use of an analytical procedure which resulted in constant and very low activity of phosphorylase a in control samples. Small doses of epinephrine, administered either by i.v. infusion or by rapid injection, which were sufficient to increase left ventricular contractile force, did not elicit a significant augmentation in phosphorylase a. The infusion of larger doses resulted in an increase in enzyme activity, but this declined at a time when contractile force was still maintained at a constant level. In dogs whose body temperature had been lowered to 28-30°, phasic alterations in contractile force in response to norepinephrine also did not correlate with phosphorylase activation. The negative inotropic action of catecholamines which occurred in hypothermia after the administration of ouabain was associated with an increase in enzyme activity. It was concluded from these studies, that while augmentation of phosphorylase activity in the dog heart in situ may be an important factor in the action of catecholamines on myocardial contractility, it is not possible to state whether or not there is a necessary relation between the two.