Haemodynamic dose-response effects of i.v. nicardipine in coronary artery disease

Abstract

The haemodynamic dose-response effects of the slow channel blocking agent nicardipine were evaluated in 10 male patients with angiographically confirmed coronary artery disease. At rest, following a similar control saline period, four doses of the drug (log cumulative dosage: 1.25, 2.5, 5.0 and 10.0 mg) were administered by i.v. infusion over a total duration of 40 min; haemodynamic variables were recorded in the 3-5 min following each 5 min infusion. During steady-state exercise the haemodynamic effects of the drug were evaluated by comparison of a control exercise period with observations made at the same workload (200-500 kpm) following the maximum cumulative dose (10 mg). Following the four i.v. infusions, the plasma nicardipine level increased log-linearly with the infused dose (r = 0.68). Compared with control measurements at rest after saline, these plasma concentrations (35 +/- 8 to 141 +/- 24 micrograms/l) resulted in a linear decrease in systemic blood pressure and vascular resistance with significant increase in cardiac index (maximum delta CI + 1.6 l min(-1) m(-2); P less than 0.01), stroke index (maximum delta SI + 11 ml/m2; P less than 0.01) and in pulmonary artery occluded pressure (maximum delta PAOP + 2 mm Hg; P less than 0.01). There was a significant increase in heart rate; the stroke work index was unchanged. During upright bicycle exercise the reduction in systemic blood pressure was accompanied by an increased exercise cardiac output without change in stroke index. The exercise pulmonary artery occluded pressure was unchanged compared with control observations, the stroke work index fell significantly (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)