MODULATION OF VENOUS TONE IN HEART-FAILURE

Venodilatation may be an important property in drugs used to treat heart failure. Deductions about venous tone from standard hemodynamic studies may be misleading since filling pressures may be reduced by improved left ventricular function. To study the venodilator properties of drugs, we have modified a radionuclide blood pool method and shown that venous volume is increased by 10% after glyceryl trinitrate but is unchanged after the arteriolar dilator hydralazine. In patients with congestive cardiac failure, the calcium channel blocker, felodipine, causes a marked reduction in systemic vascular resistance and left ventricular filling pressures, but venous volume remains unchanged. In a similar group of patients comparable arterial and central effects are seen after the administration of captopril, but venous volume increases by 16%, and this increased venous volume is sustained after 3 months of long-term treatment. Milrinone has been used to treat both acute and chronic heart failure. As expected of a phosphodiesterase inhibitor, it exhibits inotropic properties in animals and humans and also causes arterial vasodilatation. We have studied its effects on venous tone in 10 patients with severe heart failure (New York Heart Association classes III to IV). Milrinone was given intravenously at a loading dose of 50-mu-g/kg followed by an infusion of 0.5-mu-g/kg/min. After treatment, cardiac index, which was measured by thermodilution, increased from 1.8 +/- 0.48 to 2.3 +/- 0.65L/min/m2 (p < 0.001); pulmonary artery wedge pressure fell from 23 +/- 6 to 11 +/- 5 mm Hg (p < 0.001); and systemic vascular resistance index decreased from 4296 to 3168 dynes . sec . cm-5/m2 (p < 0.001). In each patient there was an increase in venous volume ranging from 8.7% to 43.7%, with a mean increase of 18.5%. There was no significant change in heart rate or blood pressure. Intravenous milrinone has a major effect on venous tone, and this property may be of value in the management of heart failure.