Antiarrhythmic, metabolic and hemodynamic effects of Org 6001 (3alpha-amino-5alpha-androstan-2beta-ol-17-one-hydrochloride) after coronary flow reduction in pigs.
The antiarrhythmic activity of the aminosteroid Org 6001 was investigated in young pigs (20-28 kg). Ventricular arrhythmias were induced by restriction of the flow in the left anterior descending coronary artery (LAD) to 25% of its control value during a period of 30 minutes. Nine out of 30 control animals died in this period due to ventricular fibrillation. None of the 19 animals treated with Org 6001 (5-10 mg/kg) or the 12 animals treated with lidocaine (2.75-3.50 mg/kg) fibrillated. Moreover, the number of premature ventricular beats was greatly reduced in pretreated groups compared with the untreated group (P less than .001). The first derivative of left ventricular pressure decreased with 25% (P less than 0.001) after administration of Org 6001. However, during 30 minutes of LAD flow reduction to 25% of control, the adverse effects of Org 6001 were less than those of lidocaine. Myocardial lactate production indicated some delay in onset of ischemia. However, there was no indication that this beneficial effect was long-lasting. When after 30 minutes of LAD flow reduction to 25% of control, the LAD was completely occluded between its second and third branch, all untreated animals fibrillated within 120 minutes, whereas 4 of the 19 animals treated with Org 6001 and 3 of the 12 treated with lidocaine survived. It is concluded that Org 6001 has antiarrhythmic properties in the ischemic pig heart which compare favorably with those of lidocaine.
D015068:17-Ketosteroids / Q000494:pharmacology; D000731:Androstanes / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001784:Blood Gas Analysis; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D007773:Lactates / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D013552:Swine
D015068:17-Ketosteroids; D000731:Androstanes; D000889:Anti-Arrhythmia Agents; D007773:Lactates; D008012:Lidocaine; D011188:Potassium