How does posture influence the haemodynamic assessment of a cardiovascular drug? Experience with nicardipine.
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.
University Department of Cardiovascular Studies, General Infirmary, Leeds, U.K.
B
B
Silke
S P
SP
Verma
A V
AV
Zezulka
S
S
Sharma
E
E
Goldhammer
N
N
Jackson
S H
SH
Taylor
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003327:Coronary Disease / Q000188:drug therapy / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D015444:Exercise; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009529:Nicardipine / Q000494:pharmacology* / Q000627:therapeutic use; D011187:Posture; D011652:Pulmonary Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D002317:Cardiovascular Agents; D009529:Nicardipine