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The extent to which posture altered the haemodynamic response to slow calcium channel blocker nicardipine was evaluated in 22 male patients with angiographically confirmed coronary artery disease. Patients were randomly allocated to supine or upright posture and an otherwise identical protocol performed in each group. At rest, following a 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 period of 40 min; haemodynamic indices were recorded during the 3-5 min following each 5 min infusion. The exercise effects of the drug, in each posture, were determined by comparison of a control predrug exercise with observations at the same workload following the maximal cumulative dose. Nicardipine reduced resting mean blood pressure (MBP) and systemic vascular resistance index (SVRI) in both postures, the decrease being more pronounced when upright (MBP, -12%, -18%; p less than 0.01: SVRI, -30%, -46%; p less than 0.01). The increases in cardiac index (CI) and stroke volume index (SVI) were higher when upright (29 and 54% vs. 10 and 27%; p less than 0.01). Pulmonary artery occluded pressure (PAOP) increased by 29% when upright, without change when supine. On exercise, the effects for HR, MBP, CI, SI, and SVRI responses were independent of posture; however, a qualitative difference was apparent for PAOP (-17% vs. +14%; p less than 0.05). Thus, although the actions of nicardipine were qualitatively similar, quantitative differences related to posture were confirmed. These differences appeared to relate to posture-related baseline haemodynamic differences between the groups but with similar postnicardipine absolute values.

The haemodynamic effects of nifedipine (20 mg sublingually) were studied in 40 patients with acute myocardial infarction within 18 h of the onset of symptoms. To determine the influence of preload and afterload on the haemodynamic response to nifedipine, patients were prospectively stratified equally into four groups of 10 patients based on systemic blood pressure level (less than or greater than 160/100 mm Hg) and level of left ventricular filling pressure [pulmonary artery-occluded pressure (PAOP) less than or greater than 18 mm Hg]. In all groups, nifedipine reduced systemic arterial pressure (p less than 0.01) and vascular resistance index (p less than 0.01); heart rate (p less than 0.01) and cardiac index (p less than 0.01) were increased. PAOP was reduced by nifedipine only in those hypertensive patients in whom it was initially raised; in these patients cardiac stroke volume index also increased (p less than 0.01). In hypertensive patients with normal PAOP the cardiac stroke work index was reduced. In patients with normal systemic and pulmonary arterial pressures, nifedipine had no beneficial effects on cardiac function. These data suggested that haemodynamic criteria may allow selection of patients for nifedipine therapy following myocardial infarction; clear advantages were evident only in hypertensive patients in both the presence and the absence of left ventricular failure.

The haemodynamic dose-response effects of intravenous amrinone were measured in 16 male patients, aged 40-65 years, with radiographic and haemodynamic evidence of left ventricular failure 4-18 h after acute myocardial infarction. After a l-h control period to confirm stable haemodynamic baseline variables, patients were randomised to either low-dose (200-400-800 micrograms/kg/h) or high-dose (800-1600-3200 micrograms/kg/h) intravenous amrinone. Each of the three infusions was given consecutively over 30 min (total infusion time 90 min) in each group, and haemodynamic measurements were made at the end of each infusion step. No arrhythmias or other untoward side effects, including haematological changes, were observed during the infusions. In both groups, intravenous amrinone reduced the pulmonary artery-occluded pressure (PAOP) (p less than 0.01), increased the cardiac output (p less than 0.05), and reduced the systemic vascular resistance (p less than 0.05). The reductions in PAOP and systemic arterial diastolic pressure and the increase in heart rate were directly dose-related, but the changes in cardiac output and systemic vascular resistance were not. These results suggest that peripheral vasodilation, particularly of venous capacitance vessels, as well as positive inotropic stimulation, may play a role in the haemodynamic changes induced by intravenous amrinone in acute ischaemic left ventricular failure.