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

1992 ◽  
Vol 82 (1) ◽  
pp. 63-70 ◽  
Author(s):  
S. Pukrittayakamee ◽  
N.J. White ◽  
T. M. E. Davis ◽  
S. Looareesuwan ◽  
W. Supanaranond ◽  
...  
Keyword(s):  
Blood Flow ◽  
Indocyanine Green ◽  
Falciparum Malaria ◽  
Plasma Clearance ◽  
Plasma Concentrations ◽  
Liver Blood Flow ◽  
Severe Infection ◽  
Acute Illness ◽  
Plasma Lactate ◽  
Severe Falciparum Malaria

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. Since galactose does not stimulate insulin secretion directly and does not appear to increase plasma lactate concentrations, this simple sugar may be an alternative to glucose in the treatment of malaria-associated hypoglycaemia.

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.

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.

Reduced Hepatic Blood Flow and Intestinal Malabsorption in Severe Falciparum Malaria

1989 ◽  
Vol 40 (5) ◽  
pp. 470-476 ◽  
Author(s):  
Malcolm E. Molyneux ◽  
Rodney E. Phillips ◽  
Ian S. Menzies ◽  
Richard P. H. Thompson ◽  
David A. Warrell ◽  
...  
Keyword(s):  
Blood Flow ◽  
Falciparum Malaria ◽  
Hepatic Blood Flow ◽  
Intestinal Malabsorption ◽  
Severe Falciparum Malaria

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.

Effects of a Meal on Plasma Clearance of [14C]Glycocholic Acid and Indocyanine Green in Man

1981 ◽  
Vol 61 (3) ◽  
pp. 325-330 ◽  
Author(s):  
J. H. Marigold ◽  
I. T. Gilmore ◽  
R. P. H. Thompson
Keyword(s):  
Indocyanine Green ◽  
Plasma Clearance ◽  
Enterohepatic Circulation ◽  
Liver Blood Flow ◽  
Normal Subjects ◽  
Volume Of Distribution ◽  
Blue Dye ◽  
Glycocholic Acid ◽  
Disappearance Curve ◽  
Plasma Disappearance Curve

1. The fasting plasma disappearance curve of [14C]glycocholic acid after intravenous injection was compared in nine normal subjects with that obtained 100 min after a standard liquid test meal. 2. Plasma disappearance curves of indocyanine green were determined in 13 normal subjects under the same conditions. 3. Plasma clearances were significantly increased after the meal for both [14C]glycocholic acid (median 455 ml min−1 m−2, range 376–672 increased to 704, 528–1968; P < 0.01) and indocyanine green (359, 227–473 increased to 435, 358–985; P < 0.01). 4. Median initial volume of distribution was unaltered, but in four subjects it was greatly increased after the meal, although no alteration in plasma volume, measured with Evans blue dye, was observed. 5. The increased postprandial plasma clearance of glycocholic acid is probably due to an increase in liver blood flow, and suggests that in health this part of the enterohepatic circulation of bile acids also varies with meals.

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.

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