Subacute Hemodynamic Effects of Nebivolol in Man at Rest and During Exercise

Abstract

In a subacute experiment 7 apparently healthy volunteers received a daily oral dose of 5 mg nebivolol for seven days, followed by a seven-day washout period with placebo. From the first day during treatment with nebivolol, peak exercise heart rate and systolic blood pressure, as measured during a standard ized submaximal treadmill exercise, significantly decreased by 15% and 19% respectively. A prolonged treatment for one week did not further increase the response of exercise heart rate and systolic blood pressure to nebivolol. How ever, the ratio of preejection period (PEP_c) to left ventricular ejection time (LVET_c), an indirect and valuable measure of left ventricular performance, pro gressively and significantly decreased during the seven-day treatment period with nebivolol from a mean value of 0.37±0.012 to 0.31±0.009. The improve ment of systolic time intervals resulted from a shortening of the PEP_c and a lengthening of the LVET_c. At rest, heart rate did not change significantly with nebivolol, whereas both systolic and diastolic blood pressure gradually and sig nificantly lowered. The postexercise LVET _c significantly shortened during treat ment with nebivolol, and this shortening was more pronounced after seven days of treatment. After discontinuation of treatment with nebivolol, all these effects persisted for more than thirty hours after the last intake and gradually returned to pretreatment values thereafter. From these data it appears that nebivolol effectively reduces blood pressure at rest and during exercise in healthy volun teers, beneficially influencing preload and afterload, as measured by systolic time intervals. The negative influence on myocardial contractility during the exercise test, generally observed with beta-adrenergic antagonists, does not oc cur with nebivolol. Presumably this is due to an ancillary property of nebivolol, neutralizing the negative inotropic effect due to beta blockade.