Dose-related hemodynamic and electrocardiographic effects of the calcium promoter BAY y 5959 in the presence or absence of congestive heart failure
(1997) Journal of the american college of cardiology : JACC — Vol. 30, n° 7, p. 1751-1757 (1997)
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- OBJECTIVES: The aim of this study was to assess the cardiovascular effects of BAY y 5959, a calcium promoter modulating myocardial calcium channels, in the presence or absence of congestive heart failure. BACKGROUND: There is still a clinical need for short-term administration of intravenous positive inotropes. BAY y 5959 was developed as a new approach to increase myocardial performance by selectively enhancing calcium influx in the myocytes. METHODS: Forty-one patients (21 without and 20 with congestive heart failure) were studied in an open label, dose-ranging study. Hemodynamic variables (including left ventricular [LV] angiography) and plasma samples were obtained at baseline and after 20 min of intravenous infusion of BAY y 5959 at doses ranging from 0.25 to 4.5 microg/kg body weight per min. RESULTS: In both study groups, BAY y 5959 produced dose-dependent increases in the indexes of inotropic state, without affecting isovolumetric relaxation rate. The magnitude of the response was comparable in patients with or without heart failure (average 38% increase in maximal first derivative of LV pressure [dP/dt max] at plasma levels of 100 microg/liter). BAY y 5959 also induced mild but statistically significant bradycardia and significantly decreased end-systolic volume while producing a leftward shift of the pressure-volume loop. Mean aortic pressure was unaffected at doses up to 3.0 microg/kg per min, and cardiac index improved in patients with heart failure at doses of 2.0 microg/kg per min (+23%, p < 0.05). However, at a dose of 4.5 microg/kg per min, mean aortic pressure and LV systolic wall stress increased, suggesting systemic vasoconstriction. The QT interval was also prolonged significantly at most doses. CONCLUSIONS: BAY y 5959 exhibits positive inotropic effects in patients with and without heart failure. The optimal response--combining bradycardia, reduced preload and improved cardiac output--appeared to be achieved at a dose of approximately 2.0 microg/kg per min. The impact of QT prolongation with regard to potential antiarrhythmic or proarrhythmic effects is unclear at this time.
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Rousseau, M., Massart, P.-E., van Eyll, C., Etienne, J., Ahn, S., Schaefer, H. G., Mueck, W., Bornemann, M., & Pouleur, H. (1997). Dose-related hemodynamic and electrocardiographic effects of the calcium promoter BAY y 5959 in the presence or absence of congestive heart failure. Journal of the american college of cardiology : JACC, 30(7), 1751-1757. https://doi.org/10.1016/S0735-1097(97)00368-9 (Original work published 1997)