Haemodynamic effects of intravenous quinacainol with and without autonomic nervous system blockade.
Normal subjects are able to compensate negative inotropic drug effects by adrenergic stimulation. This may limit the relevance of hemodynamic investigations with new drugs. Therefore, the haemodynamic effects of a new class 1 antiarrhythmic drug, quinacainol, were evaluated in 16 patients with normal left ventricular function 5 and 25 minutes after intravenous administration in 2 settings: 12 patients were untreated, and 4 patients were pretreated with beta-blockers and atropine to block a reflex adrenergic discharge and vagolytic reaction. Cardiac contractility decreased in all patients: in the untreated group, the heart rate increased from 74 +/- 10 beats per minute to 80 +/- 9 and Vmax decreased from 1.56 +/- 0.56 circ/sec to 1.36 +/- 0.45 at 5 minutes and 1.36 +/- 0.61 at 25 minutes; in the pretreated group, the heart rate did not change. Vmax decreased from 1.61 +/- 0.19 circ/sec to 1.33 +/- 0.08 at 5 minutes and to 1.09 +/- 0.13 at 25 minutes. Autonomic nervous system blockade unmasked a significant persistent negative inotropic effect of the drug in this series of patients with normal left ventricular function. This method may be useful for evaluating the haemodynamic effects of antiarrhythmic drugs in preliminary studies before administration to patients with impaired left ventricular function.
Service de Cardiologie, CHU Pitié-Salpétrière, Paris, France.
G
G
Drobinski
G
G
Montalescot
M
M
Krumenacker
N
N
Moussallem
Y
Y
Grosgogeat
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects; D004347:Drug Interactions; D005260:Female; D006334:Heart Function Tests; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D011804:Quinolines / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D011804:Quinolines; C037907:quinacainol; D001285:Atropine