The hemodynamic profile and antiarrhythmic properties of
pirsidomine, a
nitric oxide donor, were examined in pigs.
Intravenous administration of
pirsidomine (1 mg/kg) to
chloralose-anesthetized open-chest pigs resulted in a decreased afterload, and a reduced myocardial contractility and myocardial oxygen consumption (assessed by rate-pressure product), with no alterations in heart rate. After induction of regional
myocardial ischemia by occlusion of the left anterior descending coronary artery, pigs given
pirsidomine experienced fewer
ventricular ectopic beats (119 +/- 29) than control animals did (217 +/- 53; p < 0.05), seen primarily as a reduction in the number of couplets and triplets. Although the incidence of
ventricular fibrillation was unaffected by
pirsidomine, the time to onset of this
arrhythmia was significantly prolonged by this intervention (21.3 +/- 0.9 min versus 16.1 +/- 2.5 min in controls; p < 0.05). Furthermore, the ST-segment depression seen throughout the 30-min occlusion period in controls was not sustained beyond 5 min postocclusion in
pirsidomine-treated pigs. Taken together, and in the absence of an ex vivo antiplatelet effect with this dose of
pirsidomine, these results suggest that the antiarrhythmic effect of
pirsidomine lies in its hemodynamic effects, resulting in a reduction of
ischemia. The ex vivo effect of
pirsidomine on
free radical generation from isolated leukocytes was also investigated.
Luminol-enhanced chemiluminescence produced by leukocytes in response to
phorbol myristate acetate was markedly depressed in cells isolated from blood withdrawn after administration of
pirsidomine, compared with cells tested before
drug administration.(ABSTRACT TRUNCATED AT 250 WORDS)