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

Abstract

1 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).2 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 ,ug/l) resulted in a linear decrease in systemic blood pressure and vascular resistance with significant increase in cardiac index (maximum ACI + 1.6 1 min1 m-2; P < 0.01), stroke index (maximum ASI + 11 mlIm2; P < 0.01) and in pulmonary artery occluded pressure (maximum APAOP + 2 mm Hg; P < 0.01). There was a significant increase in heart rate; the stroke work index was unchanged. 3 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 < 0.05). 4 The changes in resting haemodynamic variables following nicardipine reflect the influence of a reduction in left ventricular afterload favourably modifying cardiac performance in ischaemic heart disease. During exercise, with near maximal vasodilatation, the additional reduction in systemic vascular resistance on nicardipine did not further improve exercise haemodynamics. However, nicardipine, over a wide intravenous dose-range, did not result in undue depression of cardiac function; thus it would appear to be haemodynamically safe, even in relatively severe coronary artery disease.

Haemodynamic dose‐response effects of intravenous nisoldipine in coronary artery disease.

“…Haemodynamic measurements were undertaken in the 3-5 min of each period. Finally patients were re-exercised at the previous bicycle work-load The haemodynamic measurements were obtained as previously described (Silke et al, 1984b). The radionuclide studies were undertaken using an ECG-triggered, microprocessor based, nonimaging nuclear probe (Nuclear Stethoscope, Bios Inc., Valhalla, New York), employing previously described techniques (Wagner et al, 1976;Bacharach et al, 1977;Strashun et al, 1981).…”

“…Their mechanism of action is unclear but may be attributable, at least in part, to their peripheral circulatory actions. Slow-calcium channel blockade induces a prompt reduction in systemic vascular resistance (Stone et al, 1980;Singh, 1982); this has usually been accompanied by improved indices of cardiac function in man (Kieval & Myerburg, 1982;Silke et al, 1984b). Nisoldipine is structurally related to nifedipine, and has already been demonstrated to cause arteriolar vasodilatation in man (Kazda et al, 1980;Vogt & Kreuzer, 1983).…”

Effects of nicardipine on cardiac volume at rest and during exercise‐ induced angina.

“…The pulmonary artery occluded (Campbell et al, 1984) and in coronary artery disease (Silke et al, 1984b). Blockade of the slow-calcium channels with nicardipine resulted in a dose-related reduction in systemic vascular resistance and blood pressure.…”

“…The induced vasodilatation usually has been accompanied by improved indices of cardiac function in man (Kieval & Myerburg, 1982;Silke et al, 1984a). Nicardipine is a new dihydropyridine, which already has been demonstrated to improve indices of cardiac performance in volunteers (Campbell et al, 1984), and in patients with coronary artery disease (Silke et al, 1984b). In this paper we describe the results ofthe influence of nicardipine on cardiac volume in a further 12 patients with proven obstructive coronary artery disease, at rest and during exercise-induced ischaemia.…”

Haemodynamic and radionuclide effects of amlodipine in coronary artery disease.

“…Administered acutely, they reduce systemic vascular resistance and left ventricular afterload (Singh, 1982;Stone et al, 1980). This is usually accompanied by an increased cardiac output with reduced left ventricular volume and filling pressure (Kieval et al, 1982;Silke et al, 1984aSilke et al, ,b, 1985aSilke et al, , 1986. The clinical consequences include reduction in symptomatic and objective measures of myocardial ischaemia with prolongation of exercise time (Rousseau et al, 1984a,b;Scheidt et al, 1985;Visser et al, 1985).…”