Prostacyclin production by the heart: Effect of nicotine and carbon monoxide

Smoking has been linked to the development and progression of atherosclerosis but the mechanism by which smoking exerts its deleterious effects remains unknown. This study was designed to examine in a systematic way the effects of nicotine and carbon monoxide on platelets, arterial walls, and the heart. Results of experiments designed to assess the effect of nicotine and carbon monoxide on the production of prostacyclin (PGI2) by the rabbit heart are reported. Animals exposed to carbon monoxide had the carboxyhemoglobin raised to at least 12% by breathing an atmosphere enriched with carbon monoxide. Nicotine was infused at 50 μg/kg/hr for 1 week. Nicotine was measured by gas/liquid chromatography. PGI2 was measured by radioimmunoassay of 6-keto-PGF1α, and its biologic activity was assessed by inhibition of platelet aggregation. Nicotine is concentrated in the heart and blood vessel wall and causes a statistically significant reduction in PGI2 production. Carbon monoxide raised PGI2 production significantly in all chambers, and the combination of nicotine and carbon monoxide further raised PGI2 production. The difference between the effects of nitrogen and carbon monoxide alone and nitrogen and a combination of nitrogen and carbon monoxide was significant in all chambers. It is hypothesized that nicotine exerts a direct metabolic effect in lowering PGI2 production. Carbon monoxide may make the endothelial cell relatively hypoxic, a powerful stimulus of PGI2 production, or less likely exert a direct toxic effect on the endothelial cell

A model to study intestinal and hepatic metabolism of propranolol in the dog

A model to investigate hepatic drug uptake and metabolism in the dog was developed for this study. Catheters were placed in the portal and hepatic veins during exploratory laparotomy to collect pre- and posthepatic blood samples at defined intervals. Drug concentrations in the portal vein were taken to reflect intestinal uptake and metabolism of an p.o. administered drug (propranolol), while differences in drug and metabolite concentrations between portal and hepatic veins reflected hepatic uptake and metabolism. A significant difference in propranolol concentration between hepatic and portal veins confirmed a high hepatic extraction of this therapeutic agent in the dog. This technically uncomplicated model may be used experimentally or clinically to determine hepatic function and metabolism of drugs that may be administered during anaesthesia and surgery