Effect of postural changes, nitroglycerin and verapamil on diastolic ventricular function as determined by radionuclide angiography in normal subjects

Whereas improvement in diastolic function indexes in response to therapeutic interventions has been attributed to a beneficial effect of the intervention, measurements of diastolic function appear to be influenced by changes in loading conditions, heart rate and sympathetic tone. Ts determine the effect of body position and short-term pharmacologic intervention on radionuclide angiographically determined left ventricular peak filling rate, high temporal resolution time-activity curves and absolute left ventricular volumes obtained by equilibrium-gated blood pool scans were evaluated in 12 normal subjects in the supine position at rest and in response to several postural and pharmacologic manipulations. This study confirmed the reproducibility of the technique and demonstrated that in normal subjects, peak filling rate varies in response to changes in body position and to short-term administration of sublingual nitroglycerin and intravenous verapamil. Peak filling rate ranged from 3.3 to 5.1 end-diastolic volumes (EDV)/s with a variability of 13.7% during five baseline supine measurements in the 12 subjects. Compared with values in the supine position (mean ± SEM = 4.38 ± 0.24 EDV/s), peak fining rate increased +16 ± 6% to 4.75 ± 0.27 EDV/s in the upright position (p < 0.05) but did not change significantly with leg elevation. Peak filling rate at baseline and during postural changes correlated significantly with ejection fraction (r = +0.49), with stroke volume (r = +0.26) and inversely with end-systolic volume (r = - 0.41), but did not correlate with heart rate or blood pressure. Short-term intravenous administration of verapamil (0.15 mg/kg) caused a further increase in peak filling rate, in both the upright (+31 ± 7%, p < 0.05) and the supine (+17 ± 9%, p < 0.05) position, whereas administration of sublingual nitroglycerin (0.4 mg) in the upright position was associated with a decrease in peak filling rate (- 26 ±5%, p < 0.01). Verapamil and nitroglycerin caused opposite effects on peak filling rate despite similar changes in heart rate and blood pressure. Ejection fraction increased (+7 ± 2%, p < 0.01) and end-diastolic and end-systolic volumes decreased (-10 ± 3%, and -21 ± 4%, respectively, p < 0.01) after sublingual nitroglycerin, whereas these variables did not change after short-term intravenous verapamil administration. The response of peak filling rate to short-term pharmacologic intervention is complex and multifactorial and interpretation must take into account changes in loading conditions.