Potent Hemodynamic Effects of Bimakalim, a New Potassium Channel Opener, in Humans

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Abstract

Summary

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.

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