Increased heart rate accelerates norepinephrine washout from normal myocardium

Abstract

We determined whether a change in heart rate affected the decay of the ventricular inotropic response to sympathetic stimulation in an experimental group and in a control group of anesthetized dogs. We induced complete heart block in each animal and paced the ventricles at rates of 90, 120, and 150 min-1 during two observation periods. In the experimental group, desipramine hydrochloride was given during the second period to block the neuronal uptake mechanism. The control animals did not receive desipramine during either period. The time required for the ventricular inotropic response to decay by 50% after cessation of a 2-min train of sympathetic stimulation was used as an index of the rate of norepinephrine washout from the myocardial interstitium. As we increased the pacing rate over the range of 90-150 min-1 in the experimental group, the mean decay half times (+/- SE) decreased by 36 +/- 4% (P less than 0.001) before desipramine and by 26 +/- 6% (P less than 0.001) in the presence of desipramine. These decrements in the decay half times were not significantly different from each other. The mean decay half times decreased by 36 +/- 4% (P less than 0.001) in the control dogs; the effects did not change appreciably from the first to the second observation period. We conclude that an increase in pacing frequency facilitates the washout of norepinephrine from the ventricular myocardium; this facilitation is equally pronounced regardless of whether the neuronal uptake mechanism is intact or suppressed.