Cholinergic induced coronary vasospasm: Treatment of organophosphate toxicity. Final report, 1 May 1988-31 October 1991
To evaluate the mechanism of organophosphate's possible acetylcholine (ACh) mediated vasospasm, studies were conducted on sixteen, Yorkshire swine. In one group of eight pigs, a dose of two LD-50s of soman (4.6 Kg/kg 205 JIG) was given at 102.5 microgram/second in the femoral vein. These experiments demonstrated that following soman injection coronary blood flow decreased, with an increase in acetylcholine levels and coronary vascular resistance. The fall in coronary blood flow was accompanied by concomitant decreases in acetyl-cholinesterase levels, hemodynamic function, S-T segment elevation and ventricular fibrillation. In eight additional pigs intracoronary saline or ACh (1.05 + or - 0.39 micrometers) infusions tested coronary vasoactivity in the resting condition. Following the sedentary experiments the same pigs underwent six treadmill exercise studies:(1) Exer. Cont., 1 ml/min saline, i.c.;(2) Exer.+ 0.10 + or - 0.02 micrometers ACh, i.c.; (3) Exer. + 0.52 + or - 0.20 micrometers ACh, i.c.; (4) Exer. + 1.05 + or - 0.39 micrometers ACh, i.c.; (5) Exer.+ ACh-atropine, 1.05 + or - 0.39 micrometers ACh, i.c., atropine 28 microgram/kg, i.v.; or (6) Atropine, 1 ml/min saline, i.c., atropine 28 microgram/kg i.v. At rest ACh decreased coronary blood flow by 28%. Exercise increased coronary blood flow by 77% while exercise plus ACh infusions reduced coronary blood flow by 19%, 261/, and 31% for Exer.+0.10, Exer.+0.5, and Ex+1.05 JIM ACh, respectively. In addition, ACh infusion during exercise decreased the lactate consumption and at Exer.+1.05 micrometer ACh there was a lactate production with a reduction in Mv02. These data support ACh mediated coronary vasospasm in the swine.
- Research Organization:
- Uniformed Services Univ. of the Health Sciences, Bethesda, MD (United States)
- OSTI ID:
- 6374181
- Report Number(s):
- AD-A-262873/3/XAB
- Country of Publication:
- United States
- Language:
- English
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560300* - Chemicals Metabolism & Toxicology