Limitation of Myocardial Function by Reduced Coronary Blood Flow during Isoproterenol Action

Abstract

The interpolated decrease in heart force or isometric systolic tension that occurs during isoproterenol stimulation has been examined in terms of changes in coronary flow and myocardial metabolism. In 67 open-chest dogs under pentobarbital anesthesia, determinations were made of lactate, pyruvate, Po 2 and Pco 2 in arterial and coronary sinus blood; coronary flow was measured with an electromagnetic flow transducer and ventricular force with a strain gauge arch. Although the characteristic, uncomplicated effect of isoproterenol is a marked increase in coronary flow and contractile force, this is briefly interrupted by a sharp decrease in these functions, and the decrease is associated with evidence of anaerobic metabolism. This decrease is concomitant with decreased coronary perfusion pressure and is intensified by sustained infusion of isoproterenol or by lowered oxygen concentrations in the inspired air. The stage of depressed function is counteracted by mechanical maintenance of high aortic pressure or by slow, controlled heart rate. When uncontrolled, tachycardia due to isoproterenol continues without phasic interruption. The intermediate period of depressed function is interpreted in terms of sharply decreased oxygen delivery when both cardiac rate and force are increased. The hemodynamic and metabolic values for these acutely occurring, reversible extremes have been specified.

Functional characterization of left ventricular segmental responses during the initial 24 h and 1 wk after experimental canine myocardial infarction.

“…These interventions included postextrasystolic potentiation (21)(22)(23) and infusions of dopamine (24)(25)(26)(27) and isoproterenol (28)(29)(30)(31)(32) inserted into the left atrium for pressure monitoring. The LAD was carefully dissected free of the epicardium, and a balloon occluder device placed around its proximal portion.…”

“…Infusions were intentionally limited to 2 min at each speed to avoid extreme elevations in heart rate and the secondary depression in myocardial performance known to occur in ischemic myocardium with longer infusion times (27)(28)(29)(30)(31)(32).…”

“…Functional data from this group of 20 dogs are used in the discussion of the functional alterations in dogs not receiving an intervention (Table I). 31 segments were added to the functional-histologic correlations from an additional series of dogs, instrumented, and studied in a manner identical to those dogs allowed to survive to 1 wk or beyond, but which were uniformly sacrificed at 24 h postocclusion. Thus, a total of 42 segments is correlated with respect to function and histologic necrosis (see Fig.…”

Studies in clinical shock and hypotension

“…The inotropic agents used in this study all would be expected to increase myocardial oxygen consumption (37), whether they induced peripheral vasoconstriction, like norepinephrine and metaraminol (38), or vasodilatation, like isoproterenol (39). Although the inotropic effects of these drugs could allow the ventricle to perform more work without an increase in diastolic volume, the increase in contractility would depend on adequate myocardial oxygen supply (40). CO usually rose only slightly during infusion of metaraminol or norepinephrine, but a sharp rise in ventricular work was associated in three patients with an increase in LVEDP.…”

Cardiac Pharmacology

“…In regard to the action of isoproterenol all the investigators who have used it (134,137,(143)(144)(145), with the exception of a single group (128,129), agree that it has a primary vasodilator effect. The dissenting group reported initial vasoconstriction in the isolated heart with isoproterenol as well as with epinephrine and norepinephrine; they maintain that the effect is due to activation of the [J-receptors in the coronary vessels, since it is inhibited by propranolol.…”