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. 1991 Dec;32(6):697–704.

Assessment of hepatic blood flow in healthy subjects by continuous infusion of indocyanine green.

P A Soons 1, A De Boer 1, A F Cohen 1, D D Breimer 1
PMCID: PMC1368549  PMID: 1768562

Abstract

1. The applicability of a continuous infusion of indocyanine green (ICG) to detect changes in apparent hepatic blood flow (HBF) was investigated in six healthy subjects. 2. High-performance liquid chromatography was used to measure ICG concentrations, and the effect of intravenous propranolol (10 mg in 10 min) on HBF was investigated. 3. During 150 min infusions of ICG (1.0 mg min-1) steady-state was reached within about 30 min and thereafter the plasma dye concentration remained essentially constant until the end of infusion. 4. Blood clearance (CLb) of ICG (15.9 +/- 2.2 ml min-1 kg-1; mean +/- s.d.), calculated as infusion rate/blood dye concentration over three time periods (30-50, 80-100 and 130-150 min) during the 150 min infusion, was not different from that obtained with three 1-min infusions (0.5 mg kg-1) administered at corresponding times of the day (CLb = 14.0 +/- 2.2 ml min-1 kg-1, P = 0.06). 5. The pharmacokinetics of ICG were shown to be linear up to plasma concentrations of at least 3 micrograms ml-1 using variable infusion rates (0.5, 1.0 and 2.0 mg min-1). 6. Propranolol had little effect on ICG concentrations during continuous infusion. The AUC of ICG from the start of propranolol infusion up to 125 min thereafter was increased by 12% +/- 17% (P = 0.21) compared with placebo.

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Selected References

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  1. Barbare J. C., Poupon R., Jaillon P., Bories P., Aussanaire M., Darnis F., Michel H., Cheymol G. The influence of vasoactive agents on metabolic activity of the liver in cirrhosis: a study of the effects of posterior pituitary extract, vasopressin, and somatostatin. Hepatology. 1984 Jan-Feb;4(1):59–62. doi: 10.1002/hep.1840040110. [DOI] [PubMed] [Google Scholar]
  2. Bauer L. A., Murray K., Horn J. R., Opheim K., Olsen J. Influence of nifedipine therapy on indocyanine green and oral propranolol pharmacokinetics. Eur J Clin Pharmacol. 1989;37(3):257–260. doi: 10.1007/BF00679780. [DOI] [PubMed] [Google Scholar]
  3. Bax N. D., Tucker G. T., Lennard M. S., Woods H. F. The impairment of lignocaine clearance by propranolol--major contribution from enzyme inhibition. Br J Clin Pharmacol. 1985 May;19(5):597–603. doi: 10.1111/j.1365-2125.1985.tb02686.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown H. S., Halliwell M., Qamar M., Read A. E., Evans J. M., Wells P. N. Measurement of normal portal venous blood flow by Doppler ultrasound. Gut. 1989 Apr;30(4):503–509. doi: 10.1136/gut.30.4.503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burns E., Triger D. R., Tucker G. T., Bax N. D. Indocyanine green elimination in patients with liver disease and in normal subjects. Clin Sci (Lond) 1991 Feb;80(2):155–160. doi: 10.1042/cs0800155. [DOI] [PubMed] [Google Scholar]
  6. CAESAR J., SHALDON S., CHIANDUSSI L., GUEVARA L., SHERLOCK S. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci. 1961 Aug;21:43–57. [PubMed] [Google Scholar]
  7. Clements D., West R., Elias E. Comparison of bolus and infusion methods for estimating hepatic blood flow in patients with liver disease using indocyanine green. J Hepatol. 1987 Dec;5(3):282–287. doi: 10.1016/s0168-8278(87)80033-8. [DOI] [PubMed] [Google Scholar]
  8. Daneshmend T. K., Jackson L., Roberts C. J. Physiological and pharmacological variability in estimated hepatic blood flow in man. Br J Clin Pharmacol. 1981 May;11(5):491–496. doi: 10.1111/j.1365-2125.1981.tb01155.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Donn K. H., Powell J. R., Rogers J. F., Plachetka J. R. Lack of effect of histamine H2-receptor antagonists on indocyanine green disposition measured by two methods. J Clin Pharmacol. 1984 Aug-Sep;24(8-9):360–370. doi: 10.1002/j.1552-4604.1984.tb02788.x. [DOI] [PubMed] [Google Scholar]
  10. Dorr M. B., Pollack G. M. Specific assay for the quantitation of indocyanine green in rat plasma using high-performance liquid chromatography with fluorescence detection. J Pharm Sci. 1989 Apr;78(4):328–333. doi: 10.1002/jps.2600780414. [DOI] [PubMed] [Google Scholar]
  11. George C. F. Drug kinetics and hepatic blood flow. Clin Pharmacokinet. 1979 Nov-Dec;4(6):433–448. doi: 10.2165/00003088-197904060-00003. [DOI] [PubMed] [Google Scholar]
  12. Grainger S. L., Keeling P. W., Brown I. M., Marigold J. H., Thompson R. P. Clearance and non-invasive determination of the hepatic extraction of indocyanine green in baboons and man. Clin Sci (Lond) 1983 Feb;64(2):207–212. doi: 10.1042/cs0640207. [DOI] [PubMed] [Google Scholar]
  13. Grasela D. M., Rocci M. L., Jr, Vlasses P. H. Experimental impact of assay-dependent differences in plasma indocyanine green concentration determinations. J Pharmacokinet Biopharm. 1987 Dec;15(6):601–613. doi: 10.1007/BF01068415. [DOI] [PubMed] [Google Scholar]
  14. Heintz R., Svensson C. K., Stoeckel K., Powers G. J., Lalka D. Indocyanine green: pharmacokinetics in the rabbit and relevant studies of its stability and purity. J Pharm Sci. 1986 Apr;75(4):398–402. doi: 10.1002/jps.2600750417. [DOI] [PubMed] [Google Scholar]
  15. Herz R., Rössle M., Bonzel T., Keller E., Gerok W. Effect of cimetidine on the hepatic extraction of indocyanine green, the portal pressure and the systemic circulation in patients with cirrhosis of the liver. Klin Wochenschr. 1984 Aug 16;62(16):759–764. doi: 10.1007/BF01721773. [DOI] [PubMed] [Google Scholar]
  16. Horn J. R., Zierler B., Bauer L. A., Reiss W., Strandness D. E., Jr Estimation of hepatic blood flow in branches of hepatic vessels utilizing a noninvasive, duplex Doppler method. J Clin Pharmacol. 1990 Oct;30(10):922–929. doi: 10.1002/j.1552-4604.1990.tb03572.x. [DOI] [PubMed] [Google Scholar]
  17. Jenkins S. A., Baxter J. N., Johnson J. N., Devitt P., Shields R. Effects of propranolol on hepatic haemodynamics in the cirrhotic and non-cirrhotic rat. Br J Surg. 1985 May;72(5):354–358. doi: 10.1002/bjs.1800720508. [DOI] [PubMed] [Google Scholar]
  18. Johnson D. J., Muhlbacher F., Wilmore D. W. Measurement of hepatic blood flow. J Surg Res. 1985 Nov;39(5):470–481. doi: 10.1016/0022-4804(85)90102-7. [DOI] [PubMed] [Google Scholar]
  19. LEEVY C. M., MENDENHALL C. L., LESKO W., HOWARD M. M. Estimation of hepatic blood flow with indocyanine green. J Clin Invest. 1962 May;41:1169–1179. doi: 10.1172/JCI104570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Landaw E. M., DiStefano J. J., 3rd Multiexponential, multicompartmental, and noncompartmental modeling. II. Data analysis and statistical considerations. Am J Physiol. 1984 May;246(5 Pt 2):R665–R677. doi: 10.1152/ajpregu.1984.246.5.R665. [DOI] [PubMed] [Google Scholar]
  21. Leevy C. M., Smith F., Longueville J., Paumgartner G., Howard M. M. Indocyanine green clearance as a test for hepatic function. Evaluation by dichromatic ear densitometry. JAMA. 1967 Apr 17;200(3):236–240. [PubMed] [Google Scholar]
  22. Martin J. F., Vierling J. M., Wolkoff A. W., Scharschmidt B. F., Vergalla J., Waggoner J. G., Berk P. D. Abnormal hepatic transport of indocyanine green in Gilbert's syndrome. Gastroenterology. 1976 Mar;70(3):385–391. [PubMed] [Google Scholar]
  23. Mastai R., Bosch J., Bruix J., Navasa M., Kravetz D., Rodés J. Beta-blockade with propranolol and hepatic artery blood flow in patients with cirrhosis. Hepatology. 1989 Sep;10(3):269–272. doi: 10.1002/hep.1840100302. [DOI] [PubMed] [Google Scholar]
  24. Meijer D. K., Weert B., Vermeer G. A. Pharmacokinetics of biliary excretion in man. VI. Indocyanine green. Eur J Clin Pharmacol. 1988;35(3):295–303. doi: 10.1007/BF00558268. [DOI] [PubMed] [Google Scholar]
  25. O'Reilly T., Mac Mathúna P., Keeling P. W., Feely J. Comparison of the spectrophotometric and high-performance liquid chromatographic analysis of indocyanine green in estimating systemic clearance in patients with chronic liver disease. J Chromatogr. 1987 Jun 5;417(1):190–196. doi: 10.1016/0378-4347(87)80107-x. [DOI] [PubMed] [Google Scholar]
  26. Ohnhaus E. E. Methods of the assessment of the effect of drugs on liver blood flow in man. Br J Clin Pharmacol. 1979 Mar;7(3):223–229. doi: 10.1111/j.1365-2125.1979.tb00926.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Parker G., Ene M. D., Daneshmend T. K., Roberts C. J. Do beta blockers differ in their effects on hepatic microsomal enzymes and liver blood flow? J Clin Pharmacol. 1984 Nov-Dec;24(11-12):493–499. doi: 10.1002/j.1552-4604.1984.tb02758.x. [DOI] [PubMed] [Google Scholar]
  28. REEMSTSMA K., HOTTINGER G. C., DEGRAFF A. C., Jr, CREECH O., Jr The estimation of hepatic blood flow using indocyanine green. Surg Gynecol Obstet. 1960 Mar;110:353–356. [PubMed] [Google Scholar]
  29. Shepherd A. N., Hayes P. C., Jacyna M., Morrison L., Bouchier I. A. The influence of captopril, the nitrates and propranolol on apparent liver blood flow. Br J Clin Pharmacol. 1985 Mar;19(3):393–397. doi: 10.1111/j.1365-2125.1985.tb02659.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Skak C., Keiding S. Methodological problems in the use of indocyanine green to estimate hepatic blood flow and ICG clearance in man. Liver. 1987 Jun;7(3):155–162. doi: 10.1111/j.1600-0676.1987.tb00336.x. [DOI] [PubMed] [Google Scholar]
  31. Soons P. A., Kroon J. M., Breimer D. D. Effects of single-dose and short-term oral nifedipine on indocyanine green clearance as assessed by spectrophotometry and high performance liquid chromatography. J Clin Pharmacol. 1990 Aug;30(8):693–698. doi: 10.1002/j.1552-4604.1990.tb03628.x. [DOI] [PubMed] [Google Scholar]
  32. Villeneuve J. P., Huot R., Marleau D., Huet P. M. The estimation of hepatic blood flow with indocyanine green: comparison between the continuous infusion and single injection methods. Am J Gastroenterol. 1982 Apr;77(4):233–237. [PubMed] [Google Scholar]
  33. Wilkinson G. R. Clearance approaches in pharmacology. Pharmacol Rev. 1987 Mar;39(1):1–47. [PubMed] [Google Scholar]

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