Economic/decision study, level III.

To elucidate the hemodynamic effects of prazosin, an antihypertensive agent, in congestive heart failure, we studied 10 patients with ischemic cardiomyopathy and severe ventricular dysfunction. After an oral dose of 2 to 7 mg, heart rate was unchanged (P greater than 0.05). One hour after prazosin administration, mean arterial pressure declined from 95 to 78 mm Hg (P less than 0.001); left ventricular filling pressure declined from 30 to 18 mm Hg (P less than 0.001), cardiac index increased from 2.1 to 2.9 liters per minutes per square meter (P less than 0.001), and systemic vascular resistance fell from 2074 to 1156 dynes sec cm-5 (P less than 0.001). In both forearms vascular resistance and venous tone were reduced (86 to 48 mm Hg per ml per 100 g per minute, and 59 to 18 mm Hg per ml, respectively [P less than 0.001]). All responses persisted for a least six hours (P less than 0.01). Prazosin benefits severe congestive heart failure by inducing a sustained fall of both cardiac preload and impedance.

We compared cardiocirculatory actions of the commonly employed systemic vasodilators, intravenous (iv) nitroprusside (NP), iv phentolamine (PH), and sublingual nitroglycerin (NTG), causing left ventricular (LV) unloading in 29 chronic coronary subjects with congestive failure to determine whether they produce disparate responses in LV function by different relaxing actions on systemic resistance and capacitance beds. Each drug equally lowered systemic arterial pressures to a small extent, whereas heart rate rose slightly with NTG. Cardiac catheterization showed a decline in end-diastolic pressure with NTG (19 to 8 mm Hg) which was greater (P less than 0.05) than with NP and PH (21 to 11). Cardiac index increased (P less than 0.05) during NP (2.68 to 2.93 liters/min per m2) and PH (2.60 to 3.02) but was unchanged (2.83) by NTG. Stroke work increased with PH, ejection fraction rose with NP and PH, and mean ejection rate increased with each, whereas pressure-time per minute fell and end-diastolic volume decreased with each agent. Total systemic vascular resistance declined (P less than 0.001) during NP and PH (1,475 to 1,200 dynes sec cm-5) but was unchanged (1,487) by NTG. Plethysmographically, forearm vascular resistance (FVR) decreased (P less than 0.01) with NP and PH (61.6 to 39.1 mm Hg/ml per 100 g/min) but not (52.4) by NTG. The decreases in venous tone (VT) with NTG (18.2 to 9.3 mm Hg/ml) and NP (18.5 to 9.8) were greater (P less than 0.05) than with PH (18.8 to 13.1) FVR/VT percent changes of 0.96, 1.62, and 0.53 with NP, PH, and NTG indicated balanced systemic arteriolovenous relaxation by iv NP, greater arteriolar dilation with iv PH, and predominant venous dilation by sublingual NTG. Thus, vasodilators produce disparate modifications of LV function by their differing alterations of preload and impedance, which are dependent upon relative extents of relaxation of systemic resistance and capacitance vessels characteristic of each agent as used clinically.

SUMMARY We used first-pass radionuclide angiocardiography to assess filling fraction during the first third of diastole, peak filling rate and peak filling rate during the first third of diastole as indexes of left ventricular diastolic performance at rest and after upright bicycle exercise in 32 normal patients and 68 patients with coronary artery disease. The mean filling fraction was unchanged from rest to exercise in normal patients (47 ± 15% vs 46 ± 13%; NS). Even in 49 coronary patients with normal (. 50%) ejection fraction at rest, filling fraction was less than that in normal patients at rest (35 ± 11% vs 47 ± 15%,p < 0.001). Despite similar resting heart rates, patients with coronary disease had lower (p < 0.001) peak filling rate and peak filling rate during the first third of diastole than normal patients. With exercise, filling fraction decreased (p < 0.001) from the resting value in coronary patients. These data suggest that (1) indexes of diastolic performance can be noninvasively assessed at rest and during exercise using first-pass radionuclide angiocardiography, (2) abnormalities in early diastolic performance are often present at rest in patients with coronary artery disease despite normal systolic performance, and (3) exercise-induced ischemia results in increased early diastolic dysfunction in patients with coronary disease.ABNORMALITIES in left ventricular diastolic performance are common in patients with coronary artery disease.1 2 Myocardial relaxation during early diastole is an active, energy-dependent process and previous investigations have shown that hypoxia may impair the rate of myocardial relaxation.3 Abnormalities in diastolic performance during ischemia may occur in the absence of impaired systolic performance.4' The noninvasive assessment of left ventricular diastolic performance in the patient with coronary artery disease either at rest or during physiologic stress such as exercise has been difficult by traditional techniques.Use of first-pass angiocardiography and gated cardiac blood pool imaging have shown that the response of left ventricular systolic performance to exercise is a sensitive marker of left ventricular ischemia.6 8 Few