Hepatic blood flow and metabolism in severe falciparum malaria: clearance of intravenously administered galactose.

1. Hypoglycaemia and lactic acidosis are important manifestations of severe falciparum malaria. To investigate hepatic gluconeogenesis in acute falciparum malaria, liver blood flow and galactose clearance were estimated in seven adult patients with moderately severe infection and seven patients with severe infection (three of whom died later). Nine patients were restudied in convalescence. 2. Liver blood flow, determined from the plasma clearance of Indocyanine Green, was lower in acute illness than in convalescence [16.1 (7.0) versus 23.9 (7.2) ml min-1 kg-1, mean (SD)], but this difference was not statistically significant (P = 0.15). There was a significant inverse correlation between admission venous plasma lactate concentrations and the liver blood flow estimated from the clearance of Indocyanine Green (rs = 0.71, P = 0.004). 3. The plasma clearance of galactose after intravenous injection was similar in the acute [15.4 (4.90) ml min-1 kg-1] and convalescent study [12.8 (2.1) ml min-1 kg-1]. The ratio of galactose clearance to Indocyanine Green clearance was significantly higher in acute disease [1.41 (0.51)] than in convalescence [0.70 (0.34)], largely because of the elevated ratios in severely ill patients [1.48 (0.50)]. 4. The rise in blood glucose concentration after galactose administration was significantly higher during acute illness [1.48 (0.72) mmol/l] than in convalescence [0.67 (0.41) mmol/l, P = 0.022], but the insulin response was similar, indicating reduced tissue insulin sensitivity. There was no significant change in the plasma concentrations of other metabolites (lactate, pyruvate, alanine and triacylglycerol) in either study. 5. These results suggest that the segment of the glycolytic pathway between galactose and glucose is unimpaired in patients with severe falciparum malaria.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hepatic ischaemia/reperfusion injury in a rabbit model of Indocyanine Green clearance

Hepatic ischaemia/reperfusion (I/R) injury is a major cause of primary non-function of the graft after liver transplantation. The ability to assess the severity of ischaemic injury would be of prognostic value and allow the possibility of therapeutic interventions. Currently there is no reliable clinical method for assessing the severity of hepatic ischaemic injury. The hepatic handling of Indocyanine Green as a technique for monitoring the severity of I/R injury has been investigated in the present study. A rabbit model of lobar ischaemia was used. At laparotomy, left lobe hepatic ischaemia was produced for 30, 45 or 60 min, followed by 60 min of reperfusion. Liver function tests, bile excretion and flow in the hepatic microcirculation were measured in animals subjected to I/R injury and in controls. Indocyanine Green was given after reperfusion and its concentration was measured directly in the liver using near-infrared spectroscopy. Indocyanine Green hepatic uptake and excretion rates were calculated. I/R injury produced significant increases in hepatic serum enzymes and decreases in bile excretion and hepatic microcirculation in all I/R groups in comparison with controls. There was a significant reduction in Indocyanine Green uptake and excretion in the I/R groups in comparison with controls, which was correlated with the duration of ischaemia. Indocyanine Green uptake was correlated significantly with flow in the hepatic microcirculation, and its excretion was correlated significantly with the severity of liver damage, as reflected by the changes in serum enzymes and bile excretion. In conclusion, I/R injury affects the hepatic handling of Indocyanine Green, and direct quantification of the uptake and excretion of this dye by near-infrared spectroscopy may be used to objectively assess the degree of I/R injury.     

Noninvasive assessment of liver function reserve with fluorescent dosimetry of indocyanine green

Using in vivo multiphoton fluorescent dosimetry, we demonstrate that the clearance dynamics of Indocyanine Green (ICG) in the blood can quickly reveal liver function reserve. In normal rats, the ICG retention rate was below 10% at the 15-minute post-administration; While in the rat with severe hepatocellular carcinoma (HCC), the 15-minute retention rate is over 40% due to poor liver metabolism. With a 785 nm CW laser, the fluorescence dosimeter can evaluate the liver function reserve at a 1/10 clinical dosage of ICG without any blood sampling. In the future, this low-dosage ICG 15-minute retention dosimetry can be applied for the preoperative assessment of hepatectomy or timely perioperative examination.     

Extent of ischaemia caused by hepatic vascular exclusion as evaluated in a canine model.

1. The difference in the extent of liver ischaemia between a hepatic vascular exclusion model and an inflow occlusion model were investigated by determining Indocyanine Green retention and hepatic mitochondrial redox state during 2 h of ischaemia in 10 mongrel dogs. The splanchnic venous bed and/or the infra-hepatic inferior vena cava were decompressed by pump-driven veno-venous bypass. 2. The Indocyanine Green retention test revealed that there was no hepatic blood flow in the hepatic vascular exclusion model during ischaemia (96.8 +/- 0.73% retention of the dye after 20 min), whereas hepatic blood perfusion was still present significantly in the inflow occlusion model (78.1 +/- 1.19% retention of the dye after 20 min) (P less than 0.01). 3. The mitochondrial redox potential of the liver in the dogs with hepatic vascular exclusion decreased immediately after the induction of ischaemia and remained fixed at extremely low levels. By contrast, in the dogs with inflow occlusion the redox potential decreased gradually after induction and was maintained significantly higher than that in dogs with hepatic vascular exclusion during 2 h of ischaemia (P less than 0.01). 4. It is concluded that the extent of liver ischaemia in the hepatic vascular exclusion model with pump-driven shunt is significantly different from that in the inflow occlusion model with shunt.     

Analysis of cranial 133-Xenon clearance in the newborn infant by the two-compartment model

Cranial and chest clearance curves after intravenous administration of 133-Xenon was obtained on 112 occasions in 62 newborn infants admitted to our neonatal intensive care unit. The mean postnatal age was 5.1 days. The cranial clearance curves were submitted to two-compartment analysis. The compartmental clearance rate constants were 1.49 +/- 0.61/min and 0.099 +/- 0.033/min respectively while the fractional flow to the fast compartment was 0.51 +/- 0.14. Possible artefacts, particularly relevant to newborns, were analysed by computer simulation. It is concluded that the cranial 133-Xenon clearance curves varied considerably within the group of ill newborns and that the mean two-compartment parameter values differed considerably from those of healthy premature infants or adults, with or without cerebral illness. But the computer simulations demonstrated that the two-compartment parameters had high coefficients of variation and were significantly biased by right-to-left shunting of blood through the foramen ovale, by heterogeneity of the flow to the fastest compartment and by contamination of the cranial clearance curves by 133-Xenon in the airways. The radiation dose was 1.3 mGy to the lungs and 0.2 mGy to other tissues.     

Haemodynamic and metabolic effects of infused adenosine in man

1. Haemodynamic and metabolic effects of intravenous infusion of adenosine, an endogenous vasodilator, were studied in healthy humans. 2. Catheters were inserted into pulmonary and brachial arteries and into the hepatic and subclavian veins. Cardiac output was determined according to the Fick principle, and splanchnic blood flow was measured by using extraction of Indocyanine Green. Skin blood flow was estimated by a laser Doppler technique, calf blood flow by venous occlusion plethysmography and skeletal muscle and adipose tissue blood flow by a local isotope clearance technique. 3. Adenosine (infused in steps from 40 to 80 micrograms min-1 kg-1 into a central vein) elicited a gradual reduction in the peripheral vascular resistance to less than 50% of the basal level. There was a slight increase in the systemic blood pressure, but the pulmonary arterial and the ventricular filling pressures were unchanged. Cardiac output was doubled, accomplished by a combination of a positive chronotropic effect and an increase in stroke volume, which may be secondary to diminished peripheral resistance. 4. Skin blood flow increased by 100% at 50 micrograms of adenosine min-1 kg-1, whereas splanchnic blood flow rose significantly at 60 micrograms of adenosine min-1 kg-1. Blood flow in the calf, gastrocnemius muscle and adipose tissue did not change significantly. 5. Arterial concentrations of noradrenaline and adrenaline increased by 62 and 43%, respectively, during infusion of adenosine. Arterial levels of glycerol were depressed by more than 50%, but those of glucose and pyruvate were unchanged. 6. In conclusion, exogenous adenosine caused a marked systemic vasodilatation, with different responsiveness in the investigated vascular beds.(ABSTRACT TRUNCATED AT 250 WORDS)     

Disposition kinetics of propranolol isomers in the perfused rat liver

The aim of this study was to define the determinants of the linear hepatic disposition kinetics of propranolol optical isomers using a perfused rat liver. Monensin was used to abolish the lysosomal proton gradient to allow an estimation of propranolol ion trapping by hepatic acidic vesicles. In vitro studies were used for independent estimates of microsomal binding and intrinsic clearance. Hepatic extraction and mean transit time were determined from outflow-concentration profiles using a nonparametric method. Kinetic parameters were derived from a physiologically based pharmacokinetic model. Modeling showed an approximate 34-fold decrease in ion trapping following monensin treatment. The observed model-derived ion trapping was similar to estimated theoretical values. No differences in ion-trapping values was found between R(+)- and S(-)-propranolol. Hepatic propranolol extraction was sensitive to changes in liver perfusate flow, permeability-surface area product, and intrinsic clearance. Ion trapping, microsomal and nonspecific binding, and distribution of unbound propranolol accounted for 47.4, 47.1, and 5.5% of the sequestration of propranolol in the liver, respectively. It is concluded that the physiologically more active S()-propranolol differs from the R(+)-isomer in higher permeability-surface area product, intrinsic clearance, and intracellular binding site values.     

Norepinephrine: a potential modulator of the hepatic transport of taurocholate. a study in the isolated perfused rat liver

The effects of norepinephrine on portal blood flow hepatic extraction and intrinsic clearance of taurocholate were studied in the isolated perfused rat liver. Livers were perfused at a constant pressure. [14C]Taurocholate was infused continuously at a rate of 0.6 mumol/min. Then, three increasing doses of norepinephrine were added to the perfusate. Norepinephrine induced a significant dose-dependent reduction in portal blood flow. In spite of this reduction, taurocholate extraction did not increase and intrinsic clearance decreased significantly. When portal blood flow was decreased mechanically, intrinsic clearance was, as expected, flow-independent. The effects of norepinephrine on portal blood flow and intrinsic clearance were antagonised by phentolamine but not by propanolol. Norepinephrine decreases independently both portal blood flow and the vectorial transport of taurocholate. These effects are mediated by alpha adrenergic receptors.     

In vivo kinetics of microbubbles of SH U 508 A (Levovist): comparison with indocyanine green in rabbits

The aim of this study was to evaluate in vivo kinetics of microbubbles of SH U 508 A, in comparison with Indocyanine Green, a dye used as an indicator of blood flow. Microbubble kinetics were evaluated in various vessels (i.e., vena cava, aorta, renal artery, renal vein and portal vein) in rabbits after injection of SH U 508 A by measuring Doppler signals (n = 5). The kinetics of Indocyanine Green were evaluated by measuring absorbance using a photodiode (n = 5). Test substances (SH U 508 A 300 mg/mL and Indocyanine Green 1.25 mg/mL) were injected IV at a dose of 0.1 mL/kg B.W. Peak signal intensity was observed immediately after injection of SH U 508 A, followed by biphasic decay. The rates of biphasic decay were similar in all vessels. A second peak of the signal, which indicated recirculation of the microbubbles, was observed in the vena cava. The circulation and recirculation times of the microbubbles after injection of SH U 508 A were similar to that of Indocyanine Green. These findings suggest that the majority of SH U 508 A microbubbles circulate through the body similarly to blood flow, without retention, in the vasculature.     

The Influence of Dye Infusion Rate and Hepatic Plasma Flow on Indocyanine Green Clearance

The plasma clearance and extraction ratio of indocyanine green (ICG) were followed in cats anesthetized with chloralose. In one series of experiments the ICG infusion rate was raised stepwise and in another the hepatic plasma flow was changed by replacing part of the blood volume with erythrocytes, plasma, or dextran (Macrodex®). For unknown reasons blood replacement with Macrodex increased the ICG elimination. Both plasma clearance and extraction ratio were independent of ICG infusion rate but dependent on hepatic plasma flow. In contrast, a clearance calculated from the dye elimination rate and the estimated average hepatic plasma concentration of ICG was independent of changes in hepatic plasma flow. In conclusion, plasma clearance and extraction ratio of indocyanine green are not ideal for estimation of liver function. However, when clearance is calculated from the average hepatic plasma concentration of the dye, it becomes independent of hepatic plasma flow and thus a more reliable index of liver function.     

The influence of dye infusion rate and hepatic plasma flow on indocyanine green clearance.

The plasma clearance and extraction ratio of indocyanine green (ICG) were followed in cats anesthesized with chloralose. In one series of experiments the ICG infusion rate was raised stepwise and in another the hepatic plasma flow was changed by replacing part of the blood volume with erythrocytes, plasma, or dextran (Macrodex). For unknown reasons blood replacement with Macrodex increased the ICG elimination. Both plasma clearance and extraction ratio were independent of ICG infusion rate but dependent on hepatic plasma flow. In contrast, a clearance calculated from the dye elimination rate and the estimated average hepatic plasma concentration of ICG was independent of changes in hepatic plasma flow. In conclusion, plasma clearance and extraction ratio of indocyanine green are not ideal for estimation of liver function. However, when clearance is calculated from the average hepatic plasma concentration of the dye, it becomes independent of hepatic plasma flow and thus a more reliable index of liver function.     

Effect of hypoxia and pregnancy on antipyrine metabolism in isolated perfused rat livers

The effect of hypoxia on antipyrine metabolism was studied in isolated perfused livers from pregnant (19-21 days gestation) and nonpregnant female Wistar rats. Hypoxia was induced by altering the blood content and/or flow rate of the recirculating perfusion medium. Inflow and outflow pO2 values, in themselves, were not valid indicators of oxygen delivery and consumption when the liver was perfused with a blood containing medium. At a given oxygen delivery rate, oxygen consumption per gram of liver was the same in nonpregnant and pregnant rat livers. The absolute clearance of antipyrine (milliliters per hour) was significantly greater in livers from pregnant compared to nonpregnant rats, whereas antipyrine clearance, corrected for liver weight (milliliters per hour gram of liver), was significantly lower in pregnant rat livers. Antipyrine clearance (milliliters per hour) was linearly related to oxygen consumption (milliliters per minute or micromoles per minute per gram of liver) in both the nonpregnant and pregnant rat livers. As oxygen consumption decreased, livers from pregnant rats maintained a greater ability to clear antipyrine than livers from nonpregnant rats. This study emphasizes the importance of maintaining adequate oxygen delivery to isolated perfused livers during drug metabolism studies to ensure constant oxygen consumption. Otherwise, alterations in the flow rate or hematocrit of the perfusion medium may directly alter the elimination rate of the substrate.     

Liver extraction of vitamin D3 is independent of its hepatic venous or arterial route of delivery. Studies in isolated-perfused rat liver preparations

The hepatic extraction of a naturally occurring secosteroid, vitamin D3 (D3), in relation to its hepatic arterial or portal venous route of delivery has been studied in isolated rat liver preparations perfused at an arterial/venous flow ratio of 1:4. No significant difference in the fractional hepatic extraction of D3 was observed when the vitamin was administered via the portal venous route compared to when it was administered via the hepatic arterial route. Estimation of the uptake and clearance of D3 in relation to its route of delivery revealed, however, that due to the higher perfusion flow through the portal venous than through the arterial route, both the hepatic uptake and clearance of D3 were significantly higher after portal vein than after hepatic artery delivery. Moreover, calculation of the uptake of D3 after delivery through the portal venous route also revealed that it was not significantly different from that of the total hepatic uptake (uptake following portal vein + hepatic artery delivery). The data obtained during the present studies indicate, then, that the fractional hepatic extraction of D3 is not dependent on its route of entry into the liver; it also points out that, in experimental models such as in isolated-perfused liver preparations, the portal vein administration of D3 should represent adequately the total hepatic handling of the secosteroid by the normal rat liver.     

Efficient extraction by the liver governs overall elimination of hepatocyte growth factor in rats.

A steady-state pharmacokinetic analysis was performed to investigate the overall elimination and extraction of hepatocyte growth factor (HGF) by its target organs, including liver, kidney, and lung, during its constant i.v. infusion in rats. The plasma clearance of HGF became saturated as the steady-state plasma concentration (Cpss) increased, but complete saturation was not achieved, even when the Cpss ( approximately 1000 pM) was much higher than the dissociation constant for the HGF receptor (20-40 pM), which has been identified as one of the major clearance sites for HGF. This result suggests that there is a low-affinity and high-capacity clearance mechanism, other than receptor-mediated endocytosis, involved in its elimination from the body. The hepatic extraction ratio of HGF, assessed by determining the HGF concentration in both the circulating blood and hepatic vein, was 40 to 60%, whereas the HGF extraction both in kidney and lung was always less than 10%. Hepatic clearance accounted for approximately 70% of the plasma clearance at any Cpss. Thus, the present study shows that HGF in circulating plasma is efficiently extracted by the liver compared with other HGF target organs, the liver being involved in 70% of the overall elimination both under linear and nonlinear conditions. Biliary excretion of HGF was observed, but this accounted for only 0.1 to 0. 2% of the infusion rate, indicating that the nonlysosomal pathway of HGF, which avoids the lysosomal enzymes and transcytoses HGF directly into the bile, is very minor indeed.     

Effect of H2-receptor antagonists on steady-state extraction of indocyanine green and lidocaine by the perfused rat liver

Variable effects of cimetidine on the clearance in humans of the high-clearance compounds lidocaine and indocyanine green have been reported, some investigators finding a reduction and others no change. We measured the extraction of indocyanine green, which is not metabolized and of lidocaine, which is metabolized by the perfused rat liver, in an open system with a fixed flow rate. The extraction ratios of both indocyanine green (ERICG) and lidocaine (ERL) were determined under control conditions and during continuous infusion of cimetidine and other H2-receptor antagonists (ranitidine, nizatidine, and ICI 125,211) on separate occasions. The effects of increasing concentrations of cimetidine and ranitidine were measured, and single concentrations of nizatidine and ICI 125,211 were used. Indocyanine green was measured spectrophotometrically or by high-performance liquid chromatography (HPLC). Lidocaine concentrations in perfusate were measured by gas chromatography, and H2-receptor antagonist levels in perfusate and in liver by HPLC. The perfused rat liver extracted indocyanine green (ERICG = 0.43 +/- 0.04) and lidocaine (ERL = 0.78 +/- 0.01) with steady state being reached within 5 minutes. Neither cimetidine nor ranitidine altered steady-state indocyanine green extraction. In contrast, ERL was decreased by all four H2-receptor antagonists but with differing potencies. In this system, cimetidine was the most potent agent, reducing ERL by 28.5% at a cimetidine concentration of 56 mumol/L. The other H2-receptor antagonists also decreased ERL:ICI 125,211 by 20% (49 mumol/L), ranitidine by 13% (38 mumol/L), and nizatidine by 9% (43 mumol/L). A dose-response relationship for cimetidine and ranitidine was developed, confirming the greater potency of cimetidine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alterations in tissue oxygen consumption and extraction after trauma and hemorrhagic shock

OBJECTIVES: Although trauma and hemorrhage are associated with tissue hypoperfusion and hypoxemia, changes in oxygen delivery (DO2), oxygen consumption VO2), and oxygen extraction at the organ level in a small animal (such as the rat) model of trauma and hemorrhage have not been examined. Therefore, the objectives of this study were to determine whether blood flow, DO2, VO2, and oxygen extraction ratio in various organs are differentially altered after trauma-hemorrhagic shock and acute resuscitation in the rat. DESIGN: Prospective, randomized animal study. SETTING: A university research laboratory. SUBJECTS: Male Sprague-Dawley rats (n = 6-7 animals/group) weighing 275-325 g. INTERVENTIONS: Male rats underwent laparotomy (i.e., soft tissue trauma) and were bled to and maintained at a blood pressure of 40 mm Hg until 40% of shed blood volume was returned in the form of lactated Ringer's solution. They were then resuscitated with four times the volume of shed blood with lactated Ringer's solution for 60 mins. At 1.5 hrs postresuscitation, cardiac output and blood flow were determined by using strontium-85 microspheres. Blood samples (0.15 mL each) were collected from the femoral artery and vein and the hepatic, portal, and renal veins to determine total hemoglobin and oxygen content. Systemic and regional DO2, VO2, and oxygen extraction ratio were then calculated. MEASUREMENTS AND MAIN RESULTS: Both the systemic hemoglobin and systemic arterial oxygen content in hemorrhaged animals at 1.5 hrs postresuscitation were >50% lower as compared with sham-operated controls. Cardiac output and blood flow in the liver, small intestine, and kidneys decreased significantly, but blood flow in the brain and heart remained unaltered after hemorrhage and resuscitation. Systemic DO2 and VO2 were 73% and 54% lower, respectively, than controls at 1.5 hrs after resuscitation. Similarly, regional DO2 and VO2 in the liver, small intestine, and kidneys decreased significantly under such conditions. In addition, the liver had the most severe reduction in VO2 (76%) among the tested organs. However, the oxygen extraction ratio in the liver of sham animals was the highest (72%) and remained unchanged after hemorrhage and resuscitation. CONCLUSION: Because the liver experienced the most severe reduction in VO2 associated with an unchanged oxygen extraction capacity, this organ appears to be more vulnerable to hypoxic insult after hemorrhagic shock.     

Liver blood flow measured by indocyanine green in conscious unrestrained miniature pigs

For studies in physiology and biochemistry of the liver the measurement of hepatic blood flow is a fundamental precondition. Therefore, the least invasive method, the measurement of liver blood flow by indocyanine green (ICG) dye elimination, was re-evaluated for the miniature pig, an animal model of increasing interest. The accuracy of spectrophotometric determination of ICG was enhanced by addition of 5% of desoxycholic acid. It was shown that ICG was eliminated exclusively by the liver. An extraction rate of 30%-50% was found in mini-pigs, but an insufficient rate of 5%-10% in pigs of German landrace. A liver blood flow ranging from 70 to 160 ml/100 g X min-1 was measured. These values are in good accordance with datas from simultaneous estimation of blood flow by 133Xenon washout. As shown for a starvation/refeeding cycle, liver blood flow measurement by ICG combined with permanently implanted catheters is a practicable tool for studies of the metabolic and pharmacologic fate of substances resorbed from the gut.     

In vivo mechanisms for the enhanced acetylation of sulfamethazine in the rabbit after hydrocortisone treatment

The administration of hydrocortisone (HC; 75 mg/kg i.v. daily for 10 days) to rabbits significantly increased the metabolic clearance (Clm) of sulfamethazine (SMZ) from 1.92 +/- 0.05 to 2.85 +/- 0.06 liters/hr/kg (P less than 0.01). However, p.o. availability of SMZ was similar before (0.42 +/- 0.06) and after (0.39 +/- 0.03) steroid treatment. Furthermore, total liver blood flow as measured by the radioactive microsphere technique was increased (P less than 0.01) from 3.64 +/- 0.15 to 5.12 +/- 0.54 liters/hr/kg by HC treatment. Estimates of presystemic intestinal extraction and hepatic extraction were derived. These data predicted that intestinal extraction ranged from 0.11 to 0.15 in untreated rabbits and from 0.11 to 0.16 in HC-treated rabbits. Moreover, intestinal clearance was shown to contribute less than 4% to Clm of SMZ on both study days. By comparison, estimates of hepatic extraction ranged from 0.51 to 0.53, and from 0.54 to 0.56 in untreated and HC-treated rabbits, respectively. Based on the concept of a well-stirred, perfusion-limited model of hepatic elimination, the HC-induced increases in hepatic enzyme activity and blood flow were shown to make comparable contributions to the increase in hepatic clearance. It is concluded that the liver is the major site of SMZ acetylation in untreated and HC-treated, rapid acetylator rabbits. Furthermore, the increase in Clm of SMZ observed in vivo after HC treatment is attributable primarily to increases in hepatic N-acetyltransferase activity and liver blood flow.     

Clinical pharmacology of nicardipine in liver transplant patients

Summary— Slow calcium channel antagonists are widely used among transplanted patients suffering from hypertension, although some of them tend to reduce hepatic blood flow. The aim of our study was to determine the pharmacological properties of nicardipine in transplanted patients with hypertension. Ten hours after liver transplantation, six patients (three men, three women) received 5 mg of intravenous nicardipine to prevent high blood pressure during intensive care. Prior to the administration and during the study (at the completion of the infusion, 3, 5, 10, 15, 20, 30, 45, and 60 min after infusion), the systemic and splanchnic parameters were measured (Swan Ganz catheter). Blood samples were drawn simultaneously from radial artery and free hepatic veins, in order to obtain the hepatic extraction of nicardipine. The hepatic extraction ratio was around 70% for the first 3 min, then decreased and remained stable thereafter, around 45%, showing a non linear first-pass metabolism pattern. Plasma hepatic clearance of nicardipine (699–850 ml/min) was close to total plasma clearance throughout the study (978 ± 222 ml/min, from 71 to 87%) and half of the estimated hepatic plasma flow values at the same times (1467–1770 ml/min, from 44 to 51%). No statistically significant changes were observed in cardiac output and hepatic blood flow during the study, although there was a decrease in mean arterial blood pressure from 87 ± 6 mm Hg baseline level to 76 ± 3 mmHg, 60 min after administration. Nicardipine chlorhydrate seems to be appropriate in post operative liver transplant patients when blood pressure must be decreased. Nicardipine safely lowers peripheral resistance, and does not induce changes in hepatic blood flow. Its extraction remains stable, after a hepatic saturation phenomenon.