Influence of phenobarbital on factors responsible for hepatic clearance of indocyanine green in the rat: Relative contributions of induction and altered liver blood flow

1977 ◽  
Vol 26 (13) ◽  
pp. 1247-1250 ◽  
Author(s):  
Denis G. McDevitt ◽  
Alan S. Nies ◽  
Grant R. Wilkinson
Keyword(s):  
Blood Flow ◽  
Indocyanine Green ◽  
Liver Blood Flow ◽  
Hepatic Clearance ◽  
Altered Liver

Nicardipine increases hepatic blood flow and the hepatic clearance of indocyanine green in patients with cirrhosis

1994 ◽  
Vol 20 (6) ◽  
pp. 792-796 ◽  
Author(s):  
Juan Carlos García-Pagán ◽  
Fausto Feu ◽  
Angelo Luca ◽  
Mercedes Fernández ◽  
Pilar Pizcueta ◽  
...  
Keyword(s):  
Blood Flow ◽  
Indocyanine Green ◽  
Hepatic Blood Flow ◽  
Hepatic Clearance

Direct and indirect measurement of the hepatic extraction ratio of Indocyanine Green in the rat

1989 ◽  
Vol 76 (5) ◽  
pp. 503-508 ◽  
Author(s):  
E. Burns ◽  
C. E. Ball ◽  
J. P. Christie ◽  
G. D. Broadhead ◽  
G. T. Tucker ◽  
...  
Keyword(s):  
Blood Flow ◽  
Indocyanine Green ◽  
Liver Blood Flow ◽  
Compartment Model ◽  
Indirect Measurement ◽  
Extraction Ratio ◽  
Isolated Perfused Rat Liver ◽  
Time Data ◽  
Two Compartment Model ◽  
Liver Preparation

1. In order to estimate liver blood flow in the rat, the extraction ratio of Indocyanine Green was determined using a two-compartment model fitted to the plasma concentration time data after a single intravenous bolus dose and compared with values obtained directly by transhepatic sampling, both in the intact rat and in an isolated perfused rat liver preparation. 2. There was no agreement between estimates of the extraction ratio obtained by using the kinetic model and the directly measured values. 3. Elimination curves for Indocyanine Green were simulated to yield varied clearance values. Despite a 250% variation in clearance, extraction ratios derived using the two-compartment model were all greater than 0.9 and varied by less than 6%. 4. Estimates of liver blood flow obtained by deriving a value of the extraction ratio of Indocyanine Green using the two-compartment model are inaccurate.

Noninvasive functional liver blood flow measurement: comparison between bolus dose and steady-state clearance of sorbitol in a small-rodent model

2010 ◽  
Vol 298 (2) ◽  
pp. G177-G181 ◽  
Author(s):  
Ben van der Hoven ◽  
Hans van Pelt ◽  
Eleonore L. Swart ◽  
Fred Bonthuis ◽  
Huug W. Tilanus ◽  
...  
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Bolus Dose ◽  
Liver Blood Flow ◽  
Hepatic Clearance ◽  
Sepsis Group ◽  
Control Group ◽  
Small Rodent ◽  
Venous Flow ◽  
Sorbitol Clearance

Plasma clearance of d-sorbitol, a nontoxic polyol, occurs predominantly in the liver and has been used to measure functional liver blood flow after bolus and steady- state intravenous administration. However, it is not known which of these two administration methods is superior. Therefore, plasma d-sorbitol clearance was studied in an animal model both after a bolus dose and under steady-state (SS) conditions and compared directly with liver blood flow, under normal conditions, and after the induction of endotoxin (LPS) sepsis. Adult male Wistar rats (526 ± 38 g body wt; n = 27) were anesthetized and mechanically ventilated. Hemodynamics, hepatic arterial flow, and portal venous flow were measured. Two groups were studied, namely healthy animals that served as controls and a sepsis group that received 5 mg/kg LPS intravenously ( Escherichia coli O127:B8). Each animal received either a SS infusion (0.1 mg/100 g body wt per min) or a bolus (3 mg/100 g body wt) of a 5% d-sorbitol solution intravenously in a randomized order. After the initial measurements and a 60-min pause time in between ( T1/2,sorbitol = 9 min), a crossover was done. The hepatic clearance of d-sorbitol in the control group showed a good correlation between bolus and SS (Spearman's r = 0.7681, P = 0.0004), and both techniques correlated well with total liver blood flow (TLBF) ( r = 0.7239, P = 0.0023 and r = 0.7226, P = 0.0023, respectively). Also in the sepsis group there was a good correlation between bolus and SS sorbitol clearance ( r = 0.6655, P = 0.0182). In the sepsis group, only the SS clearance correlated with TLBF ( r = 0.6434, P = 0.024). In conclusion, in normal and under septic conditions, hepatic clearance of d-sorbitol either by bolus or a SS infusion is comparable. In healthy animals, this also correlated well with TLBF but not in septic conditions. However, this is expected because of the changes in the liver microcirculation, shunting, and decreased hepatocyte function in sepsis.

Influence of 1-Desamino-8-d-Vasopressin on Endogenous Fibrinolysis, Haemodynamics and Liver Blood Flow in Healthy Subjects

1994 ◽  
Vol 86 (5) ◽  
pp. 497-503 ◽  
Author(s):  
J. Burggraaf ◽  
H. C. Schoemaker ◽  
J. M. Kroon ◽  
L. Huisman ◽  
C. Kluft ◽  
...  
Keyword(s):  
Blood Flow ◽  
Confidence Interval ◽  
Indocyanine Green ◽  
Plasminogen Activator ◽  
Liver Blood Flow ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Plasminogen Activator Activity ◽  
Type Plasminogen Activator ◽  
Fibrinolytic Parameters

1. Endogenous fibrinolytic capacity increases after administration of 1-desamino-8-d-vasopressin. This increase is commonly attributed to an increase in release of tissue-type plasminogen activator from the endothelium. However, the possibility that 1-desamino-8-d-vasopressin influences liver blood flow, which is a major determinant of tissue-type plasminogen activator clearance, cannot be ruled out. 2. The influence of 1-desamino-8-d-vasopressin on haemodynamics, liver blood flow and fibrinolytic parameters was investigated in a randomized double-blind cross-over study in nine healthy male subjects (age 20–26 years). 3. 1-Desamino-8-d-vasopressin exerted significant haemodynamic effects: mean arterial pressure decreased maximally 12 (95% confidence interval 8–15) mmHg and heart rate increased maximally 21 (95% confidence interval 15–27) beats/min. 4. Endogenous fibrinolytic parameters increased after administration of 1-desamino-8-d-vasopressin. Both tissue-type plasminogen activator antigen and tissue-type plasminogen activator activity were elevated and showed the maximal response shortly after drug administration was completed. 5. 1-Desamino-8-d-vasopressin increased portal venous blood flow as measured with echo-Doppler. The maximal increase in mean blood flow of 55 (95% confidence interval 19–92)% was observed at the end of the 1-desamino-8-d-vasopressin infusion and coincided with the maximal changes in systemic haemodynamics and fibrinolytic parameters. The increase in portal blood flow was not reflected in significant changes in Indocyanine Green clearance. It appears that the Indocyanine Green method is relatively insensitive to increases in liver blood flow. 6. The observed increase in fibrinolytic activity due to tissue-type plasminogen activator activity after 1-desamino-8-d-vasopressin administration may be due to an increased release of tissue-type plasminogen activator from the endothelium and is not caused by changes in clearance.

Enhancing liver blood flow after cardiopulmonary bypass: the effects of dopamine and dopexamine

Perfusion ◽  
1999 ◽  
Vol 14 (1) ◽  
pp. 29-36 ◽  
Author(s):  
D AC Sharpe ◽  
I M Mitchel ◽  
E A Kay ◽  
J P McGoldrick ◽  
C M Munsch ◽  
...  
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cardiopulmonary Bypass ◽  
Cardiac Index ◽  
Indocyanine Green ◽  
Bypass Graft ◽  
Liver Blood Flow ◽  
Patient Specific ◽  
Disappearance Rate ◽  
Flow Measurements

Liver blood flow is reduced after cardiopulmonary bypass (CPB) and both dopamine and dopexamine are used to overcome this. This study compares the effects of these agents on liver blood flow. Thirty patients undergoing elective coronary artery bypass graft surgery were randomized into three groups ( n = 10 per group). Six hours after surgery baseline liver blood flow was determined by the percentage disappearance rate of indocyanine green measured by dichromatic auricular densitometery. Patients then received infusions of either: (1) placebo (dextrose 5%); (2) dopamine (4 μg/kg/min); (3) dopexamine (1 μg/kg/min increasing to 2 μg/kg/min). One hour after infusion, liver blood flow measurements were repeated. In the dopexamine group the infusion was increased and the measurements repeated another hour later. We found that patient-specific variables and operative details were similar for all groups. Postoperative cardiac index and heart rate were increased significantly by dopamine (cardiac index 2.82 ± 0.46 l/m/m2 vs 3.28 ± 0.67 l/m/m2: p < 0.001 and heart rate 87.5 ± 13.2 vs 96 ± 16: p < 0.05) and dopexamine at 2 μg/kg/min (cardiac index 2.71 ± 0.53 l/m/m2 vs 3.45 ± 0.67 l/m/m2: p < 0.05 and heart rate 89.0 ± 18.9 vs 107.4 ± 13.6: p < 0.001) compared to placebo (cardiac index 2.97 ± 0.8 l/m/m2 vs 3.18 ± 0.9 l/m/m2: p > 0.05 and heart rate 77.2 ± 7.4 vs 77.3 ± 8: p > 0.05) despite similar atrial and systemic arterial pressures. The disappearance rate of indocyanine green was not altered during infusion of placebo group (9.0 ± 3.2%/min vs 7.9 ± 3.0%/min: p > 0.05) or dopexamine at 1 μg/kg/min (9.7 ± 3.1%/min vs 11.2 ± 4.1%/min: p > 0.05). The disappearance rate was increased with dopamine (6.7 ± 3.7%/min vs 11.8 ± 3.0%/min: p < 0.05) and dopexamine 2 μg/kg/min (9.7 ± 3.1%/min vs 13.5 ± 3.2%/min: p < 0.05). This indicates a 76% increase in liver blood flow with dopamine and a 38% increase with dopexamine. We conclude that dopamine 4 μg/kg/min and dopexamine 2 μg/kg/min increase liver blood flow, although this may, in part, be related to an increase in cardiac output. Dopexamine shows no advantage over dopamine in enhancing liver blood flow after CPB.

Effect of Changes in Liver Blood Flow on the Pharmacokinetics of Saruplase in Patients with Acute Myocardial Infarction

1997 ◽  
Vol 78 (03) ◽  
pp. 1015-1020 ◽  
Author(s):  
Jean M T van Griensven ◽  
Rudolph W Koster ◽  
Gwynn R Hopkins ◽  
Horst Beier ◽  
Wolfgang A Günzler ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Blood Flow ◽  
Indocyanine Green ◽  
Plasminogen Activator ◽  
Hepatic Blood Flow ◽  
Plasma Concentrations ◽  
Liver Blood Flow ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator

SummaryBackground: The recombinant unglycosylated single chain urokinase-type plasminogen activator saruplase is cleared for a large part by the liver. A large interindividual variation in saruplase concentration is found in acute myocardial infarction (AMI) patients. The variable cardiac performance after an infarct may induce differences in liver blood flow that could explain the concentration diversity. This study was performed to investigate the relation between hepatic blood flow and the pharmacokinetic and pharmacodynamic properties of saruplase.Methods and Results: Thirteen AMI patients were enroled in this open label study. Patients received a bolus injection of 20 mg saruplase followed by a one-hour infusion of 60 mg saruplase. Concurrently 36 mg intravenous indocyanine green (ICG) was given over 1 h to measure hepatic blood flow. Blood samples were taken at regular time intervals to measure plasma levels of urokinase-type plasminogen activator (u-PA) antigen and activity, the two-chain form (tcu-PA) activity, indocyanine green, fibrinogen, fibrin and fibrin degradation products, α2-antiplasmin and thrombin antithrombin III complex. A correlation was seen between the clearance of ICG and both those of u-PA antigen (r = 0.62; p <0.05) and u-PA activity (r = 0.57; p <0.05). A negative correlation was seen between the area under the curve of tcu-PA activity and the areas under the effect curves of both fibrinogen and α2-antiplas-min (r = -0.84; p <0.01 and r = -0.65; p <0.05).Conclusions: Liver blood flow is an important determinant of the clearance of u-PA antigen and activity and reduction of flow in patients with heart failure will lead to an increase in plasma concentrations. High plasma concentrations of tcu-PA activity lead to increased systemic fibrinogenolysis. These results may be used to optimize saruplase treatment in patients with impaired cardiac function or after co-medication with drugs that affect liver blood flow.

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