ENHANCEMENT OF THE FORCE FREQUENCY EFFECT ON MYOCARDIAL-CONTRACTILITY BY ADRENERGIC-STIMULATION IN CONSCIOUS DOGS

Background. The influence of changes in heart rate on myocardial contractility (the force-frequency effect) differs under various experimental conditions, including the anesthetized versus the conscious state. Methods and Results. To assess the influence of beta-adrenergic stimulation on force-frequency effects on myocardial contraction and relaxation, seven instrumented conscious dogs were studied in which heart rate could be controlled by atrial pacing after the intrinsic rate was slowed with a bradycardiac agent (UL-FS 49 0.5-0.75 mg/kg). Left ventricular (LV) pressure was measured with a micromanometer under resting conditions and during dobutamine infusion at low, intermediate, and high doses (2.7, 5.4, and 10.7-mu-g/kg/min). At each dose, heart rate was progressively increased from 100 to 210 beats per minute. In the absence of dobutamine (control), no significant positive force-frequency effect was detected on LV dP/dt(max); this was probably due to the known effect of the observed decrease in preload to reduce LV dP/dt(max), thereby offsetting an effect of the force-frequency response to increased dP/dt. However, during dobutamine infusions, the force-frequency effect was observed to increase significantly in a dose-dependent manner with increases in heart rate. An increase in heart rate from 100 to 210 beats per minute increased LV dP/dt(max) by 12.4+/-12.5% with low-dose, 22.7+/-13.1% with intermediate-dose, and 27.5+/-8.9% with high-dose dobutamine. Changes in preload and aortic pressure were within the same ranges under control conditions and at each of the three dobutamine doses. The time constant of LV pressure fall (tau) was significantly shorter with increases in heart rate during control, but only the highest dobutamine dose caused further significant shortening in tau with increased heart rate. Conclusions. These data indicate that there is a pronounced dose-dependent action of beta-adrenergic stimulation to enhance force-frequency-induced contractile responses in normal conscious dogs.