Mechanism of augmented rate of left ventricular filling during exercise

Abstract

At rest, most of left ventricular (LV) filling occurs early in diastole. This LV filling occurs in response to the pressure gradient produced as LV pressure falls below left atrial (LA) pressure. Because mitral valve flow occurs in response to an LA to LV pressure gradient, augmented diastolic mitral valve flow during exercise may be due to an increased mitral valve pressure gradient resulting from a rise in LA pressure and/or a fall in LV early diastolic pressure. Accordingly, we studied 13 conscious dogs, instrumented to measure micromanometer LV and LA pressures, and determined LV volume from three ultrasonic dimensions during exercise. The animals ran on a treadmill for 8-15 minutes at 5-8 miles/hr. With reflexes intact, during exercise, the heart rate increased from 116±20 to 189±24 beats per minute (mean ±SD, p<0.01), the maximum rate of change of LV volume (dV/dtmax) increased from 185±44 to 282±76 ml/sec (p<0.01), the ejection fraction and cardiac output increased, and the duration of diastole decreased from 296±83 to 162±71 msec (p<0.01). Mitral valve opening pressure, mean LA pressure (10.9±4.4 versus 10.2±3.9 mm Hg, p=NS), and LV end-diastolic pressure (12.8±4.8 versus 13.1±3.3 mm Hg, p=NS) were all relatively unchanged. The time constant of the fall of isovolumic LV pressure decreased from 28±3.3 to 21±4.4 msec (p<0.05). The early diastolic portion of the LV pressure-volume loop was shifted downward during exercise, with the minimum LV pressure decreasing from 3.3±2.8 to -2.8±3.4 mm Hg (p<0.05) and the maximum mitral valve pressure gradient increasing from 5.5±1.7 to 11.8±3.5 mm Hg (p<0.01). A similar downward shift of the early diastolic portion of the LV pressure-volume loop was produced by infusion of dobutamine (6 μg/kg/min i.v.) at rest, as well as by exercise when the heart rate was held constant by right ventricular pacing at 190-210 beats per minute. The downward shift during exercise was prevented by β-blockade (metoprolol, 0.5 mg/kg i.v.). We conclude that during exercise, sympathetic stimulation and tachycardia produce a downward shift of the early diastolic portion of the LV pressure-volume loop. This fall in early diastolic LV pressure augments the early diastolic mitral valve gradient without an increase in LA pressure, producing more rapid mitral valve flow in early diastole and maintaining LV filling despite the shortening of diastole during exercise.