Potent hemodynamic effects of bimakalim, a new potassium channel opener, in humans.
The cardiac hemodynamic effects of bimakalim, a new potassium channel opener, were evaluated in 12 normal volunteers by echocardiography (ECHO)/Doppler in a placebo-controlled, randomized double-blind, cross-over, dose-ranging study. A single oral dose (0.25-1 mg) was given at weekly intervals. Hemodynamic measurements were made at 0, 90, 120, and 240 min after drug intake and ECHO/Doppler was performed at 0 and 90 min. Reproducibility of the ECHO/Doppler study was assessed by comparing predose baseline values of the four different phases of treatment (placebo and 0.25, 0.5, and 1 mg) by analysis of variance (ANOVA), which showed no significant differences for left ventricular ejection fraction (LVEF). Doppler-derived stroke volume (SV), total peripheral resistance (TPR), and peak mitral early to late velocity ratio (PEV/PAV). ANOVA showed significant increases in LVEF (p = 0.0003) and SV (p = 0.03), however, and decreases in TPR (p = 0.002) and PEV/PAV (p = 0.005) after bimakalim treatment. Heart rate (HR) showed a dose-dependent increase, but systolic and diastolic blood pressure (SBP, DBP) did not change with bimakalim. Despite vasodilatory headaches, none of the volunteers discontinued the study. Bimakalim appears to be a potent vasodilating drug that may have an important role in management of patients with compromised LV function.
Senior
R
R
Department of Cardiology, Northwick Park Hospital and Clinical Research Centre, Harrow, England.
Buchner-Moell
D
D
Raftery
E
E
Lahiri
A
A
D000284:Administration, Oral; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001578:Benzopyrans / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004095:Dihydropyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D004452:Echocardiography; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D000959:Antihypertensive Agents; D001578:Benzopyrans; D004095:Dihydropyridines; D014665:Vasodilator Agents; C061050:bimakalim