EXPLORATORY-STUDY OF THE EFFECTS OF SINGLE DOSES OF ISOMAZOLE AN HEMODYNAMICS AND HEART-RATE-VARIABILITY PARAMETERS IN CHRONIC HEART-FAILURE

Ventricular arrhythmias and disturbed autonomic control, as reflected by abnormal heart rate variability (HRV), are related to hemodynamic i mpairment in chronic heart failure (CHF). We investigated the effects of orally (p.o.) administered isomazole, a new phosphodiesterase (PDE) inhibitor with calcium-sensitizing properties, on hemodynamics, ventr icular arrhythmias, and HRV and examined a possible interaction betwee n these parameters. Hemodynamic measurements and ambulatory ECG monito ring were performed in 12 patients with stable CHF class III-IV after single doses of isomazole 5-30 mg. Pulmonary wedge pressure decreased after 5, 10, 20, and 30 mg, but cardiac output, (CO) increased only af ter the higher doses [20 mg, +20%(p = 0.031)] of isomazole. KR did not change. Mean arterial and pulmonary artery pressure, (MAP, PAP) decre ased significantly in the 10-and 20-mg groups [10 mg, -6%(p = 0.035) a nd -14%(p < 0.001) respectively; 20 mg, -13%(p = 0.047) and -31%(p = 0 .006), respectively]. Isomazole did not exert a significant effect on ventricular arrhythmias in the subsequent 24 h after acute dosing. Ana lysis of HRV showed that rMSSD and pNN50 (parameters of vagal tone) te nded to increase after isomazole administration. Normalized high-frequ ency power during the day increased from 17.4 to 22.3 nu (p < 0.05), w hereas low frequency tended to decrease from 52.7 to 48.2 nu (p = 0.06 ). Acute isomazole administration improves hemodynamics but has no eff ect on ventricular arrhythmias. The HRV variability data suggest devel opment of an increase in vagal control of KR, parallel to the acute he modynamic improvement after isomazole. Withdrawal of vagal control of HR in CHF may be a reversible process.