Experiments were performed to determine the validity of the indocyanine green (ICG) clearance technique, with and without allowances for incomplete hepatic extraction, as an estimate of hepatic plasma flow. This technique was compared with that of directly measured hepatic blood flow using a hepatic venous long-circuit preparation in the anesthetized cat. This preparation allowed direct measurement and alteration of hepatic blood flow and collection of arterial, portal, and hepatic venous blood samples without depletion of the animal's blood volume. Measurements of ICG by spectrophotometry and high-pressure liquid chromatography (HPLC) were equally accurate, but the HPLC was 100 times more sensitive and allowed smaller sample volumes. It was determined that systemic clearance of ICG after a bolus dose (1.3 mumol/kg) was much smaller than hepatic blood flow. Allowance must be made for the incomplete extraction. When the clearance was multiplied by extraction, mean estimated hepatic plasma flow exceeded the measured flow values by 20-30%, and this difference was attributed to temporary extrahepatic distribution. In all experiments estimated hepatic plasma flows were highly variable, and reasons for this are discussed. In hepatectomized cats ICG was found to be distributed into extrahepatic tissues.

1 -* After a 300 mg i.v. bolus dose, blood pressure is maximally reduced in 2 minutes, then rises rapidly over the next 10 to 40 minutes to a plateau level that is maintained for a variable length of time.*-* This same dose of diazoxide administered over a longer period has been observed to have a plateau effect of less magnitude and shorter duration.4 ' ' It was postulated that, because diazoxide is highly protein-bound, the high plasma-free diazoxide

1 Experiments were performed to determine the accuracy of the estimation of hepatic blood flow from infusions of indocyanine green (ICG) in anaesthetized cats. 2 The estimated flows were compared to hepatic blood flows measured directly in a hepatic venous long-circuit preparation. This preparation allowed direct measurement and alteration of hepatic blood flows, and collection of arterial and mixed hepatic venous blood samples without depletion of blood volume in the animal. 3 Mean hepatic plasma flows estimated during infusions of 3.22 and 6.44 nmol kg-'min-' were reliable indicators of true hepatic flow at three different flow levels, provided that a sufficiently long time (> 30 min) was allowed for distribution equilibrium and that data from several animals were pooled to reduce random variability. Variability arose through subtraction of plasma arterial and hepatic venous levels to obtain the arteriovenous difference. 4 Estimations of hepatic plasma flow by intravenous infusions of ICG were more accurate and reliable than estimations from bolus injections of ICG, or intravenous infusions of galactose studied previously. 5 The kinetics of hepatic uptake of ICG are complex. Extraction and clearance of ICG fell steadily with time during the infusions and constant plasma ICG levels were not attained during 150 min infusions. This is attributed to the effects of accumulation of ICG within the liver cells since hepatic uptake substantially exceeded biliary excretion rate. 6 Total ICG concentrations in sinusoid and liver cells increased in parallel. The concentration in the liver cell was 88 (60-115) times the concentration in the sinusoid but we have no data on whether or not the free concentrations in plasma and cell were in equilibrium.

We describe a 38 year-old female who ingested 900 mg of diltiazem. She experienced hypotension, bradycardia and heart block but responded well to supportive care that included normal saline infusion and vasopressors. Calcium administration was not beneficial. Serial plasma concentrations of diltiazem, N-demethyldiltiazem and desacetyldiltiazem were quantified. By comparing the elimination half-life for diltiazem with historical controls, it is concluded that multiple dose charcoal therapy was not beneficial for our patient.

No abstract