EFFECTS OF SOMAN (PINACOLYL METHYLPHOSPHONOFLUORIDATE) ON CORONARY BLOOD-FLOW AND CARDIAC-FUNCTION IN SWINE

The effects of soman (pinacolyl methylphosphonofluoridate) on coronary blood flow, the electrocardiogram, and cardiac function were measured in alpha-chloralose-anesthetized swine. Coronary blood flow (CBF), me an arterial blood pressure (MAP), peak systolic left ventricular press ure (IVP), maximum rate of left ventricular pressure development (dP/d t(max)), cardiac output, and the ECG were monitored continuously. A do se of 2x LD50 of soman (1 LD50 = 4.6 mu g/kg) was given at 1 LD50/min in the femoral vein, which produced an increase in coronary sinus plas ma acetylcholine (ACh) from a control of 0.7 +/- 0.01 nmol/ml to a max imum 314% of control at 15 min and a decrease in CBF from a control of 99 +/- 13 ml/min/100 g to a minimum 55% of control at 15 min. The inc rease in ACh in the coronary sinus was significantly correlated with a decrease in CBF (r = -0.87, p < 0.001). The fall in CBF was accompani ed by concomitant decreases in IVP, MAP, and dP/dt(max), with S-T segm ent elevation and ventricular fibrillation. The increase in coronary s inus acetylcholine concentration was significantly correlated with a 1 0-fold fall in coronary sinus acetylcholinesterase levels from a contr ol of 2.47 +/- 0.97 mol acetylcholine hydrolyzed/ml blood/min and was consistent with the time course for the reduced hemodynamic measuremen ts. These studies support the hypothesis that acetylcholine increases following soman toxicity may decrease coronary blood flow, thereby ini tiating ischemic electrocardiographic changes and reducing cardiac fun ction. (C) 1996 Society of Toxicology