CYCLOSPORINE-A DECREASES CORONARY BLOOD-F LOW IN THE DOG

The objective of the present study was to determine the effect of cycl osporine (CSA) on coronary artery reactivity. Six mongrel dogs, weighi ng 20 to 30kg were anesthetized with sodium pentobarbital and were art ificially ventilated. A median sternotomy was performed to expose the heart. Left anterior and circumflex coronary flows were measured with an electromagnetic flowmeter. Heart rate, mean arterial pressure, coro nary sinus pressure and dP/dt were monitored during all experiments. B lood samples were withdrawn from the coronary sinus to measure CSA. In jections of 5 and 10mg of CSA in the left anterior descending coronary artery were administered to all animals and the measure of the circum flex coronary blood flow was used as control during the experiments. T he decrease in left anterior descending coronary artery blood flow ave raged 24 +/- 9% tp = 0.002, and 18 +/- 11% (p = 0.009), and the increa se in coronary vascular resistance averaged 31 +/- 12% (p = 0.005) and 16 +/- 24% (p = 0.1) after 5 and 10mg of CSA, respectively. There wer e no significant changes in circumflex coronary artery blood flow and in dP/dt during the experiments. Cyclosporine blood levels averaged 45 3 +/- 226 nmol/l and 1087 +/- 199 nmol/l after injections of 5 and 10m g of CSA, respectively. In conclusion, this study suggests that CSA ca n cause acute vasoconstriction of the arterial coronary vasculature.