Estimation Of Hepatic Blood Flow Research Articles

Different methods for hepatic flow measurements: a narrative review

Hepatic blood flow measurement constitutes an essential tool for successful hepatic surgery, especially in situations where graft patency needs to be controlled, such as for instance during and after liver transplantation. In addition, because of its complex intrinsic regulation, the hepatic circulation may be seriously affected in the perioperative setting not only because of systemic hemodynamic alterations but also secondary to the administration of various drugs including anesthetic agents. Unravelling and understanding such effects implies studies involving measurement of hepatic blood flow. Therefore, knowledge and understanding of various tools for estimation of hepatic blood flow is important for correct interpretation of findings from experimental and clinical studies before potential implementation in daily clinical practice. This review summarizes the different techniques, their strengths and limitations, and potential applications in clinical practice and research.

Reliability of the estimation of total hepatic blood flow by Doppler ultrasound in patients with cirrhotic portal hypertension

Hepatic blood flow (HBF) is best estimated by the Fick's method during indocyanine green constant infusion (ICG-HBF) on hepatic vein catheterization. We investigated the consistency and agreement of HBF measured by Doppler ultrasound (US-HBF) as compared with ICG-HBF in portal hypertensive patients with cirrhosis. In 50 patients observed for HVPG measurement (56% compensated; Child score 7 ± 2; HVPG 16.6 ± 6.0 mmHg; varices in 75%) US-HBF (Sequoia-512-Acuson; 4.5-7 MHz convex probe; US-HBF = hepatic artery blood flow+portal vein blood flow) and ICG-HBF (Fick's method after an equilibration period of at least 45 min of ICG bolus of 5 mg + constant rate infusion of 0.2 mg/min). Intraclass correlation coefficient (ICC) for consistency and absolute agreement between US-HBF and ICG-HBF were calculated. Mean ICG-HBF and US-HBF were similar, being respectively 1004 ± 543 ml/min and 994 ± 494 ml/min (p = 0.661 vs. ICG-HBF). However, results in individual patients disclosed marked differences between the two methods (386 ± 415 ml/min) and showed only moderate consistency (ICC 0.456; p < 0.0001), absolute agreement (ICC 0.461; p < 0.0001) and linear correlation (R = 0.464; p < 0.0001). The discrepancy between the two methods was maximal in patients with poor liver function, high HBF by any technique and more arterialized liver circulation. Hepatic artery blood flow ≥40% of US-HBF indicated, with 90% specificity, a discrepancy ≥20% between US-HBF and ICG-HBF. HBF estimations by Doppler-ultrasound and ICG are significantly correlated, but their discrepancy in individual cases is high. Estimation of HBF by Doppler-US should be considered unreliable in patients with poor hepatic function and large liver arterialization.

Comparative study between peripherally and centrally acting sublethal and lethal doses of Leiurus quinquestriatus scorpion venom in rabbits: The usefulness of the sodium channel blocker lidocaine

Background Scorpion envenomation is common among desert dwellers, affecting several systems and resulting in multiple organ dysfunction (MOD) or failure (MOF), mainly due to their action on Na + channels. Although scorpion venoms toxins do not pass the blood brain barrier, their CNS effects are prominent, occurring in conjunction with, or as an aftermath of peripheral actions of the venom. Objective To determine the ability of venom of the common scorpion Leiurus quinquestriatus ( LQQ) to induce MOD or MOF when injected into rabbits in micro quantities centrally (intracerebroventricularly, i.c.v.) or macro amounts peripherally (s.c. or i.v.). Also, to assess if the Na + channel blocker lidocaine can protect rabbits from the resultant manifestations. Methods Rabbits were injected with LQQ venom centrally or peripherally, in either sublethal or lethal doses, and MOD or MOF determined by assessing: cardiac output (CO), estimated hepatic blood flow (EHBF), biochemical parameters indicative of cardiac/hepatic/renal and pancreatic functions, blood pressure (BP), survival, lung/body index (LBI, indicative of pulmonary edema), and/or histological changes in hearts, lungs, livers plus kidneys. In pre-treatment experiments, lidocaine was injected 40 min before venom and protective ability examined. Results LQQ venom in sublethal doses caused comparable significant reductions (vs control) in CO and EHBF when injected i.c.v. (2 μg kg −1) or s.c. (0.2 mg kg −1). Both routes caused gradual dose-related enhanced levels of creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatinine, glucose and amylase, indicating MOD. Also, characteristic venom-induced changes in BP were evident after lethal doses of venom i.v. (0.5 mg kg −1) or i.c.v. (3 μg kg −1). Histological changes in the organs plus LBI were comparable after i.c.v. and i.v. venom injection, with animals ultimately exhibiting MOF. Lidocaine (1 mg kg −1 i.v., then infusion 50 μg kg −1 min −1, 30 min before venom), protected the animals from MOF evoked by lethal doses of the venom (whether injected centrally or peripherally), as evidenced by the amelioration of the venom’s effects on blood pressure, LBI, survival and multiple organ histopathological manifestations. Conclusion LQQ venom, whether injected centrally or peripherally caused comparable systemic dose-dependent MOD or MOF, with the latter attenuated by the Na + channel blocker lidocaine, indicating a role for Na + channels.

Hepatic Hemodynamics and Cell Functions in Human and Experimental Sepsis

Hepatic Hemodynamics and Cell Functions in Human and Experimental Sepsis

Hepatic hemodynamics and cell functions in human and experimental sepsis.

Hepatic hemodynamics and cell functions in human and experimental sepsis.

Effects of L-arginine on the systemic, mesenteric, and hepatic circulation in patients with cirrhosis.

Nitric oxide (NO) is known to play an important role in modulating both the hepatic and mesenteric circulation under physiological and pathological conditions. We investigated how L-arginine, a precursor of NO, modifies the hepatic and mesenteric circulation in patients with cirrhosis. The study design was a single-blind controlled study. We measured the systemic and portal hemodynamics before and following intravenous L-arginine and saline infusion using pulsed Doppler ultrasonography in 20 patients with cirrhosis, and then the effects were compared with those found in 20 healthy subjects. In these patients, the effects of L-arginine on hepatic circulation were investigated using hepatic catheterization. L-Arginine infusion induced systemic vasodilation in both the healthy controls and the cirrhotic patients in a similar hemodynamic manner. In these patients, the L-arginine-induced increase in the portal flow was significantly higher than that of cardiac output (CO); however, the relation was the inverse in healthy subjects. Moreover, the L-arginine-induced increase in the portal flow was greater in the cirrhotic patients than that seen in healthy subjects. As a result, L-arginine infusion was thus found to selectively augment the hepatopetal portal blood flow in the cirrhotic liver. In patients, L-arginine infusion induced marked hepatic vasodilation as demonstrated by the reduced hepatic sinusoidal resistance (HSR) and increased estimated hepatic blood flow (EHBF) associated with the ameliorated intrinsic clearance of indocyanine green. Despite the fall in HSR, the hepatic venous pressure gradient (HVPG) increased following L-arginine infusion. The mesenteric and hepatic vascular areas of cirrhosis exhibited an increased susceptibility to the dilator action of L-arginine. These findings suggest that the enhanced NO production in the splanchnic vascular area has an important role in the hepatic circulation in patients with cirrhosis.

Mild Hypothermia Alters Propofol Pharmacokinetics and Increases the Duration of Action of Atracurium

Mild intraoperative hypothermia is common.We therefore studied the effects of mild hypothermia on propofol pharmacokinetics, hepatic blood flow, and atracurium duration of action in healthy volunteers. Six young volunteers were studied on two randomly assigned days, at either 34 degrees C or 37 degrees C. Anesthesia was induced with thiopental, 3 mg/kg, and maintained with 70% N2 O and 0.6% isoflurane. Core hypothermia was induced by conductive and convective cooling. On the other study day, normothermia was maintained by a Bair Hugger Registered Trademark (Augustine Medical, Inc., Eden Prairie, MN) forced-air warmer. Propofol, 1 mg/kg lean body mass (LBM), then was given, followed by a 4-h infusion at 5 mg centered dot kg-1 centered dot h-1. After 2 h, atracurium 0.5 mg/kg was administered as an intravenous bolus. Indocyanine green was administered for estimation of hepatic blood flow. Arterial blood was assayed for propofol and indocyanine green concentration. Pharmacokinetic analysis was performed using NONMEM. Results are reported as means +/- SEM. Propofol blood concentrations averaged approximate equals 28% more at 34 degrees C than at 37 degrees C (P < 0.05). Hepatic blood flow decreased 23% +/- 11% in normothermic volunteers during the propofol infusion, and 33% +/- 11% in hypothermic volunteers (P = not significant). A three-compartment mamillary model fitted the data best. Inclusion of hepatic blood flow change from the prepropofol baseline as a covariate for total body clearance significantly improved the fit. The intercompartmental clearances were decreased in the presence of hypothermia. Core hypothermia prolonged the time to recovery of the first twitch in the train-of-four to 10% of its control value (T1 = 10%) after atracurium administration by approximate equals 60% (P < 0.05), from 44 +/- 4 min to 68 +/- 7 min. In contrast, T1 = 25%-75% remained unchanged. We conclude that 3 degrees C of core hypothermia increased propofol blood concentrations and prolonged atracurium duration of action. Hepatic blood flow was decreased during propofol administration, and this change was a significant predictor of propofol clearance, indicating that the effect of propofol on hepatic blood flow impairs the clearance of propofol itself. (Anesth Analg 1995;80:1007-14)

Circadian changes in estimated hepatic blood flow in healthy subjects.

Intravenous injections of indocyanine green (ICG) were given to 10 healthy supine subjects at 02.00, 08.00, 14.00 and 20.00 h. ICG plasma half-life, plasma clearance and estimated hepatic blood flow (EHBF), but not volume of distribution, varied significantly with time of day with EHBF being greatest at 08.00 h. This circadian rhythm in EHBF should be considered when evaluating the kinetics of high-clearance drugs at different times of day.

Alcohol infusion to measure hepatic blood flow: vanquishing the bête noire?

Experiments were carried out to determine the accuracy and validity of estimations of hepatic blood flow from systemic clearances of ethanol during very low dose (8 μmol. min.−1· kg−1) infusions of ethanol in anesthetized cats. Systemic clearances were compared with directly measured hepatic blood flow using a hepatic venous longcircuit technique. This technique 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. In 18 cats, Vmax for ethanol was 93 ± 7 μmol·min−1 per 100 g liver or 21 ± 2 μmol·min−1 · kg body weight−1 and Km was 144 ± 19 μM in terms of logarithmic mean sinusoidal concentration. At the dose of 8 μmol·min−1· kg body weight−1 used for estimation of hepatic blood flow, extraction was 0.95 ± 0.07 (mean ± SD). Systemic clearance of ethanol overestimated directly measured hepatic blood flow by 15 ± 16%. Hepatic blood flow changes expressed as percentages of the control level were accurately estimated from systemic ethanol clearance (100 ± 10%). Since 73 ± 12% of the infused ethanol was eliminated by the liver and 83 ± 11% was eliminated by the splanchnic bed, an extraslanchnic uptake of 17% accounted for the overestimation of hepatic blood flow. Estimation of hepatic blood flow from systemic clearances of ethanol during very low dose infusions may have advantages over other clearance methods. Its use in cats was illustrated in a separate series of experiments and it was shown that surgery significantly reduced hepatic blood flow. The method may merit trial for estimation of hepatic blood flow in humans.

Hepatic blood flow: estimation from clearances of very low dose infusions of ethanol in cats.

Experiments were carried out to determine the accuracy and validity of estimations of hepatic blood flow from systemic clearances of ethanol during very low dose (8 mumol.min-1.kg-1) infusions of ethanol in anesthetized cats. Systemic clearances were compared with directly measured hepatic blood flow using a hepatic venous long-circuit technique. This technique 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. In 18 cats, Vmax for ethanol was 93 +/- 7 mumol.min-1 per 100 g liver or 21 +/- 2 mumol.min-1.kg body weight-1 and Km was 144 +/- 19 microM in terms of logarithmic mean sinusoidal concentration. At the dose of 8 mumol.min-1.kg body weight-1 used for estimation of hepatic blood flow, extraction was 0.95 +/- 0.07 (mean +/- SD). Systemic clearance of ethanol overestimated directly measured hepatic blood flow by 15 +/- 16%. Hepatic blood flow changes expressed as percentages of the control level were accurately estimated from systemic ethanol clearance (100 +/- 10%). Since 73 +/- 12% of the infused ethanol was eliminated by the liver and 83 +/- 11% was eliminated by the splanchnic bed, an extrasplanchnic uptake of 17% accounted for the overestimation of hepatic blood flow. Estimation of hepatic blood flow from systemic clearances of ethanol during very low dose infusions may have advantages over other clearance methods. Its use in cats was illustrated in a separate series of experiments and it was shown that surgery significantly reduced hepatic blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Hepatic blood flow: accuracy of estimation from infusions of indocyanine green in anaesthetized cats.

Experiments were performed to determine the accuracy of the estimation of hepatic blood flow from infusions of indocyanine green (ICG) in anaesthetized cats. 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. Mean hepatic plasma flows estimated during infusions of 3.22 and 6.44 nmol kg-1 min-1 were reliable indicators of true hepatic flow at three different flow levels, provided that a sufficiently long time (greater than 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. 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. 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. 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.

Pharmacokinetic approach to the estimation of hepatic removal of insulin.

We simultaneously measured hepatic insulin removal invasively and estimated hepatic clearance and extraction of insulin pharmacokinetically from cardiac output and peripheral plasma concentrations (relatively) noninvasively. The invasive methods involved continuous electromagnetic measurements of portal venous and hepatic arterial blood flow and simultaneous intermittent sampling of blood from the portal and hepatic veins and femoral artery for assay of insulin concentrations. The noninvasive method assumed that hepatic plasma flow is proportional to cardiac output and that hepatic clearance is a constant fraction of total body clearance of insulin. In anesthetized dogs (n = 6), endogenous insulin was suppressed with somatostatin (800 ng/kg/min) while biosynthetic human insulin (0.25, 0.50, and 1.00 mU/kg/min) was infused to steady state during three consecutive 90-min periods. Insulin concentrations were directly proportional to the infusion rate (p less than 0.01). Hepatic blood flow accounted for 20 +/- 2% of cardiac output. Measured hepatic clearance accounted for 51 +/- 5% of total body clearance of insulin and correlated with the pharmacokinetic estimates (p less than 0.01); the estimates of hepatic clearance ranged from 91 to 114% of the measured values. We conclude that this pharmacokinetic approach, which requires only samples of peripheral blood and estimates of hepatic blood flow, may be used to study the hepatic removal of insulin relatively noninvasively.

Hepatic blood flow: accuracy of estimation from galactose clearances in cats.

Experiments were carried out to determine the accuracy and validity of estimations of hepatic blood flow from clearance data during infusions of galactose in anesthetized cats. Clearance calculations were compared directly with the measured hepatic blood flows using a hepatic venous long-circuit technique. This technique allowed direct measurement and alteration of hepatic blood flow and collection of arterial and mixed hepatic venous blood samples without depletion of the animal's blood volume. It was found that infusions of galactose could not be used to estimate accurately hepatic blood flow. Infusion rate could not be used as an estimate of hepatic or splanchnic uptake owing to substantial and variable extrasplanchnic uptake. As a result, estimated hepatic flows allowing for incomplete extraction overestimated the true flow. On the other hand, extraction was less than 100%. This caused systemic galactose clearance to underestimate hepatic blood flow. These errors could cancel each other giving an apparently good estimate of hepatic flow from systemic galactose clearance. This agreement was fortuitous and occurred only at a specific dose and blood flow. We conclude that in the absence of independent measurements of both extrasplanchnic uptake and splanchnic extraction of galactose, systemic galactose clearance is not a reliable measure of hepatic blood flow in anesthetized cats. Until proved otherwise, it seems likely that this is also true in humans.

Identifiability analysis of an in vivo receptor-binding radiopharmacokinetic system.

A five-state, nonlinear model describing the pharmacokinetics of a receptor-binding radiopharmaceutical is presented. Local parameter identifiability analysis was performed preexperimentally to investigate the chemical and observational conditions required for adequate estimates of hepatic blood flow, receptor-ligand affinity, and receptor population. The ability to estimate the above parameters from externally observed kinetic data depended upon receptor-ligand affinity, the molar dose of the radiopharmaceutical, the number and coupling of the observers, and independent knowledge of the coupling coefficients or ligand-receptor affinity.

Effects of portacaval shunt and portacaval transposition on hepatocellular and hepatic reticuloendothelial cell activity in the dog.

Quantitative reduction of portal blood flow following a portacaval shunt (PCS) adversely affects hepatocyte function, but does not alter HRES activity [L. P. Edgcomb , J. A. Knol , and F. E. Eckhauser . J. Surg . Res. 33: 233, 1982]. To determine whether similar changes occur after qualitative alteration of portal blood flow, portacaval transpositions (PCT) were constructed in six conditioned mongrel dogs. Estimated hepatic blood flow (EHBF) was determined scintigraphically by the rate of hepatic uptake of a 500-microCi dose of 99mTc -sulfur colloid (Tsc). Hepatic reticuloendothelial cell (RES) phagocytic (PI) and degradative (DI) indices were calculated from the half-time blood disappearance of 131I-labeled RES test lipid emulsion, and the half-time urine appearance of free 131I, respectively. Opsonic activity (OI) was determined by gelatin latex particle agglutination and normalized to control values. Hepatocellular function was assessed by serial determinations of albumin (Alb), and pyruvic and glutamic oxaloacetic transaminases (SGPT and SGOT). All studies were performed prior to and at 3, 6, and 9 weeks following PCS or PCT. In the dog, neither PCS nor PCT adversely affected HRES activity. Hepatocellular function and OI remained unchanged following PCT but deteriorated significantly after PCS. Observed changes in hepatocyte function and OI following PCS suggest that hepatocellular integrity and serum opsonic activity may be interrelated.

Effects of cimetidine and ranitidine on steady-state propranolol kinetics and dynamics.

The influence of cimetidine (1000 mg daily, one day oral pretreatment) and ranitidine (300 mg daily by mouth, 1 and 6 days pretreatment) on steady-state propranolol (160 mg sustained-release capsule, once daily) plasma levels (Psss) and dynamic beta-blocker effects was assessed by bicycle ergometer exercise and isoproterenol sensitivity test in five normal subjects. During the 3 hr of the dynamic tests Psss were elevated from 25% to 67% by cimetidine, whereas Pss was unchanged by ranitidine. The estimated hepatic blood flow (EHBF) as calculated from indocyanine green (ICG) plasma clearance was only slightly reduced by 15 +/- 23% (mean +/- SD, n = 4) after one oral dose of 150 mg ranitidine and showed substantial intersubject variability. Dynamic parameters, like propranolol-induced heart rate and blood pressure changes under physical exercise or during the isoproterenol sensitivity test, were not influenced by ranitidine or cimetidine. Since our study was performed on normal subjects with relatively low propranolol doses these results do not rule out the risk of severe reinforcement of beta-adrenergic receptor blocking effects if propranolol and cimetidine are taken together by patients.

Evaluation of 133Xe washout kinetics by controlled pig liver perfusion in vivo

The interpretation of multiexponential curves from hepatic tracer washout for estimation of hepatic blood flow (THBF) was investigated, using hepatic 133Xe washout during controlled portal and arterial perfusion of liver in anesthetized pigs. Variations of (1) THBF from 25 to 210 ml/min × 100 g, (2) the proportion of portal to arterial flow, and (3) the site of tracer application were performed. After portal injection the tracer curves were in most cases multiexponential; their analysis revealed that calculation of THBF using k values based on the monocompartmental hypothesis always grossly overestimated total flow. Estimation of THBF by height/area ( H A ), however, reflected the total flow in all cases. Only when hypoventilation or elevation of hepatic venous pressure was performed, did calculation of THBF from k values and H A values reveal similar results. THBF when estimated from H A and from indocyanine green dye extraction gave identical results, both in the controlled perfused liver and in the intact animal. Washout curve analysis after arterial Xe application showed neither a correlation with the total nor with the arterial flow, indicating incomplete mixing of both blood flow components. It is concluded that liver perfusion is multicompartmental and blood flow through the portal and arterial vascular bed is incompletely mixed. Therefore, THBF can be calculated only after portal tracer injection and when the mean transit time concept is applied.

Increase in hepatic blood flow and cardiac output during dopamine infusion in man.

The object of this paper was to evaluate the effect of a continuous dopamine infusion (10--12 micrograms/kg . min) on the estimated hepatic blood flow (EHBF) and cardiac output (CO) in man. Measurements were made in 3 periods: the initial control state, during dopamine infusion, and after the infusion. The CO (by thermodilution) and EHBF (by hepatic vein sampling after continuous indocyanine green (ICG) infusion) were measured during each phase. Ten subjects, with inapparent hepatic disease, hemorrhage, or hemodynamic anomalies, were studied. The results showed a 64% increase in the EHBF and a 49% increase in the CO. All subjects showed a return to the original baseline state after infusion. The EHBF/CO was 14% in the control period, 17.3% during infusion, and 13.4% after dopamine infusion. These changes were not statistically significant. Dopamine, therefore, increased both EHBF and CO, but the existence of intrahepatic dopaminergic receptors could not be established.

The effect of dopamine on hepatic-splanchnic blood flow after open heart surgery.

Dopamine (3,4 dihydroxyphenylethylamine) increases cardiac output and in particular the renal blood flow at the expense of other regional vascular beds not yet defined. Since the results of dopamine-induced changes in splanchnic perfusion are inconsistent, the effect of 6 mcg/kg/min dopamine was studied in 9 patients early after open heart surgery. Estimated hepatic blood flow (EHBF) was calculated from the concentration-time slopes of Indocyanine Green (ICG, Cardiogreen) in arterial and hepatic venous blood following single intravenous injection. Blood volume was measured using 51Cr tagged red cells. Cardiac output was determined according to the Fick method. 6 mcg/kg/min dopamine caused a mean EHBF-increase of 82%, from 492 +/- 64 to 824 +/- 80 ml/min/m2 (P less than 0.001). Related to the corresponding increase in cardiac index (CI) from 2.6 +/- 0.2 to 3.8 +/- 0.3 1/min/m2 (P less than 0.001), the EHBF/CI-ratio changed from 18.5 to 21.7% (P less than 0.025). The arterial-hepatic venous oxygen difference was reduced from 7.40 +/- 0.53 to 4.91 +/- 0.60 Vol% (P less than 0.001). It was concluded that splanchnic perfusion does not contribute to the preferential increase of renal blood flow under dopamine under the above mentioned conditions. Dopamine had the most beneficial effect on EHBF in two cases where the latter was severely reduced.

(+)-Propranolol clearance, an estimation of hepatic blood flow in man.

1 Hepatic blood flow was determined before and during (+)- and (+/-)-propranolol plasma concentration plateaus in 19 patients with suspected renal hypertension and normal liver function. 2 Hepatic blood flow significantly decreased (P less than 0.001) during (+/-)-propranolol administration and remained unchanged during (+)-propranolol administration. 3 Hepatic extraction ratio was 74 +/- 1% (+/-)-propranolol and 79 +/- 2% for (+)-propranolol. 4 Total propranolol clearances were determined during the steady-state achieved by a constant infusion. A highly significant positive relationship was observed (r = +0.86; P less than 0.01) between hepatic blood flow and (+)-propranolol clearance. The slope of the curve was 1.05 +/- 0.27. 5 The result implies that the total clearance of (+)-propranolol constitutes an accurate estimation of basal hepatic blood flow in subjects with normal liver function.