Pharmacological mechanisms for left ventricular unloading in clinical congestive heart failure. Differential effects of nitroprusside, phentolamine, and nitroglycerin on cardiac function and peripheral circulation

The authors 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 < 0.05) than with NP and PH (21 to 11). Cardiac index increased (P < 0.05) during NP (2.68 to 2.93 liters/min per m ²) 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 < 0.001) during NP (1.475 to 1,200 dynes sec cm ^-5) but was unchanged (1,487) by NTG. Plethysmographically, forearm vascular resistance (FVR) decreased (P < 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 < 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.