A SHEEP PREPARATION FOR STUDYING INTERACTIONS BETWEEN BLOOD FLOW AND DRUG DISPOSITION

In awake unrestrained sheep the infusions i.v. of five drugs (cefoxitin, pethidine, chlormethiazole, tocainide and lignocaine) with potentially flow-limited clearance were shown to have no significant haemodynamic effects of their own, nor to have any effects on arterial or venous oxygen tensions. Under general anaesthesia (1.5% end-tidal halothane), haemodynamic changes similar to those previously documented in man occurred. Cardiac output and hepatic blood flow were decreased to 70%, and renal blood flow to 50% of control vahies; heart rate was unchanged and mean arterial pressure decreased by an average of 10%. Hepatic and renal vein oxygen tensions were decreased significantly. Under spinal anaesthesia, apart from a 10% decrease in hepatic blood flow, there were no significant changes in any haemodynamic variables or in the arterial or in any of the venous oxygen tensions. The i.v. infusion of adequate volumes of saline at the time of blockade probably contributed to the maintenance of these indices at their baseline values