Displacement of nortriptyline and uptake of 14C-lidocaine in the lung after administration of 14C-lidocaine to nortriptyline intoxicated pigs

Six anaesthetized Swedish land-race pigs were intoxicated by an intravenous infusion of notriptyline-HCl(NT) up to a concentration of 4.58+-0.58 (X+-S.E.M.)μM in arterial whole blood. A rapid injection of 2 mg/kg b.wt. lidocaine-HCl in the right atrium was followed by a rise in arterial whole blood concentration of NT up to a maximum of 7.32+-0.28μM NT. Amount displaced NT from the cardio-pulmonary circulation after the 14C-lidocaine bolus, was calculated to be 0.66+-0.03 μmol. Lung uptake of 14C-lidocaine during first-pass through the lung was not influenced to any statistically significant degree compared to a control group. Thus, first-pass uptake (FPU) was 30+-8(X+-S.E.M.)% and 39+-5%respectively. The duration of the QRS-complex of the ECG was increased (P<0.01) during the infusion of NT from 0.07+-0.01(X+-S.E.M.)sec. to 0.14+-0.02sec. when 250 mg NT-HCl had been administered. The QRS-duration was decreased (P<0.01) after the injection of the 14C-lidocaine bolus to 0.09+-0.01 sec. Mean arterial blood pressure and heartrate decreased slightly during the infusion of NT, but did not change immediately after 14C-lidocaine bolus. (author)