Download PDF
Semin intervent Radiol 2023; 40(01): 106-112
DOI: 10.1055/s-0043-1767690
Clinical Corner

Hepatic Arterial Buffer Response in Liver Transplant Recipients: Implications and Treatment Options

Mario Spaggiari
1   Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois
,
Alessandro Martinino
1   Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois
,
Charles E. Ray Jr.
2   Department of Radiology, University of Illinois College of Medicine, Chicago, Illinois
,
Giulia Bencini
1   Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois
,
Egor Petrochenkov
1   Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois
,
Pierpaolo Di Cocco
1   Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois
,
Jorge Almario-Alvarez
1   Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois
,
Ivo Tzvetanov
1   Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois
,
Enrico Benedetti
1   Division of Transplantation, Department of Surgery, University of Illinois at Chicago, Chicago, Illinois
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Physiology of Liver Blood Flow

Hepatic Blood Volume

The liver blood supply portrays one of the most sophisticated archetypes of circulation. Despite its weight (representing only 2.5% of body weight), the liver receives 25% of the cardiac output, allowing the hepatic parenchyma to be the most richly perfused of any organ. The anatomical distinctiveness of the double afferent blood supply is established between the hepatic artery and the portal vein, ensuring a total blood flow of 100 to 130 mL/min per 100 g of liver. Approximately 20 to 25% of the blood perfusing the liver is well oxygenated, and is provided by the hepatic artery. In addition to hepatic parenchymal cells, the hepatic artery provides the exclusive blood supply to the intrahepatic bile ducts. The portal vein, formed by the confluence of the splenic vein, mesenteric veins, gastric veins, and pancreatic vein, supplies around 75 to 80% of the afferent blood, which is partially deoxygenated.[1] [2] Mixing of arterial and portal blood occurs in the sinusoids, an exclusive, dynamic microvascular structure that serves as the principal site of exchange between the blood and the perisinusoidal space.[3] The hepatic veins (typically three—right, middle, and left) drain the blood from those locations into the inferior vena cava.


#

Hepatic Blood Flow Control

While the hepatic flow control mechanism has been studied extensively, some features, in particular the relationship between hepatic arterial and venous circulation, remain unclear.[4] As with other organs, the liver also strives for constant blood flow. This modulation, however, is not dependent on extrinsic innervation or vasoactive agents, but rather on a pressure-dependent autoregulation mechanism. Due to this, if the portal vein flow changes, the hepatic arterial flow is shifted in the opposite direction. This biological behavior is known as hepatic arterial buffer response (HABR).[5]

Alternate hypotheses to pressure-dependent autoregulation have been considered to account for this phenomenon, including neural and myogenic mechanisms.[1] [4] The neural mechanism has been rebuffed by observing the HABR even in denervated livers. Likewise, the myogenic mechanism, which proposed that a change in portal pressure would be somehow sensed by the hepatic artery, was excluded since changes in portal pressure are quite slight despite even major changes in portal flow.[6] [7] The most accepted theory for HABR is the adenosine washout hypothesis. In line with this theory, increased portal flow leads to a reduction of adenosine concentration and hepatic arterial constriction. Oppositely, when the portal blood flow is reduced, the amount of adenosine that accumulates in the Mall space will increase, as it will not be washed away by portal flow, leading to dilation of the hepatic artery (adenosine is a powerful vasodilator), and this effect has been studied by several investigators.[8] [9] [10] [11] As demonstrated by Lautt et al, dipyridamole, which inhibits the nucleoside transporter responsible for the cellular uptake of adenosine, potentiates the dilator response to adenosine as well as potentiating the buffer response from a 23% compensation for reduced portal flow to 34%.[8] The dilator effect of adenosine is less in the portal vein, and has approximately one-half to one-third the effect of the same dose infused directly into the hepatic artery.[1]


#

Publication History

Article published online:
04 May 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Lautt WW. Hepatic Circulation: Physiology and Pathophysiology [Internet]. San Rafael, CA: Morgan & Claypool Life Sciences; 2009. [cited November 30, 2022]. (Colloquium Series on Integrated Systems Physiology: From Molecule to Function to Disease). Accessed March 5, 2023 at: http://www.ncbi.nlm.nih.gov/books/NBK53073/
    CrossrefGoogle Scholar
  • 2 Sacks D, Baxter B, Campbell BCV. et al; From the American Association of Neurological Surgeons (AANS), American Society of Neuroradiology (ASNR), Cardiovascular and Interventional Radiology Society of Europe (CIRSE), Canadian Interventional Radiology Association (CIRA), Congress of Neurological Surgeons (CNS), European Society of Minimally Invasive Neurological Therapy (ESMINT), European Society of Neuroradiology (ESNR), European Stroke Organization (ESO), Society for Cardiovascular Angiography and Interventions (SCAI), Society of Interventional Radiology (SIR), Society of NeuroInterventional Surgery (SNIS), and World Stroke Organization (WSO). Multisociety Consensus Quality Improvement Revised Consensus Statement for endovascular therapy of acute ischemic stroke. Int J Stroke 2018; 13 (06) 612-632
    PubMedGoogle Scholar
  • 3 Adams DH. Hepatology: a textbook of liver disease. Gut 2003; 52 (08) 1230-1231
    PubMedGoogle Scholar
  • 4 Eipel C, Abshagen K, Vollmar B. Regulation of hepatic blood flow: the hepatic arterial buffer response revisited. World J Gastroenterol 2010; 16 (48) 6046-6057
    CrossrefPubMedGoogle Scholar
  • 5 Quintini C, Hirose K, Hashimoto K. et al. “Splenic artery steal syndrome” is a misnomer: the cause is portal hyperperfusion, not arterial siphon. Liver Transpl 2008; 14 (03) 374-379
    CrossrefPubMedGoogle Scholar
  • 6 Sancetta SM. Dynamic and neurogenic factors determining the hepatic arterial flow after portal occlusion. Circ Res 1953; 1 (05) 414-418
    CrossrefPubMedGoogle Scholar
  • 7 Mathie RT, Lam PH, Harper AM, Blumgart LH. The hepatic arterial blood flow response to portal vein occlusion in the dog: the effect of hepatic denervation. Pflugers Arch 1980; 386 (01) 77-83
    CrossrefPubMedGoogle Scholar
  • 8 Lautt WW, Legare DJ, d'Almeida MS. Adenosine as putative regulator of hepatic arterial flow (the buffer response). Am J Physiol 1985; 248 (3, Pt 2): H331-H338
    PubMedGoogle Scholar
  • 9 Lautt WW, Legare DJ. The use of 8-phenyltheophylline as a competitive antagonist of adenosine and an inhibitor of the intrinsic regulatory mechanism of the hepatic artery. Can J Physiol Pharmacol 1985; 63 (06) 717-722
    CrossrefPubMedGoogle Scholar
  • 10 Ezzat WR, Lautt WW. Hepatic arterial pressure-flow autoregulation is adenosine mediated. Am J Physiol 1987; 252 (4, Pt 2): H836-H845
    PubMedGoogle Scholar
  • 11 Legare DJ, Lautt WW. Hepatic venous resistance site in the dog: localization and validation of intrahepatic pressure measurements. Can J Physiol Pharmacol 1987; 65 (03) 352-359
    CrossrefPubMedGoogle Scholar
  • 12 Kiuchi T, Kasahara M, Uryuhara K. et al. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors. Transplantation 1999; 67 (02) 321-327
    CrossrefPubMedGoogle Scholar
  • 13 Dahm F, Georgiev P, Clavien PA. Small-for-size syndrome after partial liver transplantation: definition, mechanisms of disease and clinical implications. Am J Transplant 2005; 5 (11) 2605-2610
    CrossrefPubMedGoogle Scholar
  • 14 Troisi R, Ricciardi S, Smeets P. et al. Effects of hemi-portocaval shunts for inflow modulation on the outcome of small-for-size grafts in living donor liver transplantation. Am J Transplant 2005; 5 (06) 1397-1404
    CrossrefPubMedGoogle Scholar
  • 15 Masuda Y, Yoshizawa K, Ohno Y, Mita A, Shimizu A, Soejima Y. Small-for-size syndrome in liver transplantation: definition, pathophysiology and management. Hepatobiliary Pancreat Dis Int 2020; 19 (04) 334-341
    CrossrefPubMedGoogle Scholar
  • 16 Lo CM, Liu CL, Fan ST. Portal hyperperfusion injury as the cause of primary nonfunction in a small-for-size liver graft-successful treatment with splenic artery ligation. Liver Transpl 2003; 9 (06) 626-628
    CrossrefPubMedGoogle Scholar
  • 17 Hernandez-Alejandro R, Sharma H. Small-for-size syndrome in liver transplantation: new horizons to cover with a good launchpad. Liver Transpl 2016; 22 (S1): 33-36
    CrossrefPubMedGoogle Scholar
  • 18 Troisi R, Praet M, de Hemptinne B. Small-for-size syndrome: what is the problem?. Liver Transpl 2003; 9 (09) S1
    CrossrefPubMedGoogle Scholar
  • 19 Soejima Y, Shirabe K, Taketomi A. et al. Left lobe living donor liver transplantation in adults. Am J Transplant 2012; 12 (07) 1877-1885
    CrossrefPubMedGoogle Scholar
  • 20 Marcos A, Olzinski AT, Ham JM, Fisher RA, Posner MP. The interrelationship between portal and arterial blood flow after adult to adult living donor liver transplantation. Transplantation 2000; 70 (12) 1697-1703
    CrossrefPubMedGoogle Scholar
  • 21 Glanemann M, Eipel C, Nussler AK, Vollmar B, Neuhaus P. Hyperperfusion syndrome in small-for-size livers. Eur Surg Res 2005; 37 (06) 335-341
    CrossrefPubMedGoogle Scholar
  • 22 Manner M, Otto G, Senninger N, Kraus T, Goerich J, Herfarth C. Arterial steal: an unusual cause for hepatic hypoperfusion after liver transplantation. Transpl Int 1991; 4 (02) 122-124
    CrossrefPubMedGoogle Scholar
  • 23 Presser N, Quintini C, Tom C. et al. Safety and efficacy of splenic artery embolization for portal hyperperfusion in liver transplant recipients: a 5-year experience. Liver Transpl 2015; 21 (04) 435-441
    CrossrefPubMedGoogle Scholar
  • 24 Demetris AJ, Kelly DM, Eghtesad B. et al. Pathophysiologic observations and histopathologic recognition of the portal hyperperfusion or small-for-size syndrome. Am J Surg Pathol 2006; 30 (08) 986-993
    CrossrefPubMedGoogle Scholar
  • 25 Emond JC, Renz JF, Ferrell LD. et al. Functional analysis of grafts from living donors. Implications for the treatment of older recipients. Ann Surg 1996; 224 (04) 544-552 , discussion 552–554
    CrossrefPubMedGoogle Scholar
  • 26 García-Criado A, Gilabert R, Bargalló X, Brú C. Radiology in liver transplantation. Semin Ultrasound CT MR 2002; 23 (01) 114-129
    CrossrefPubMedGoogle Scholar
  • 27 Crossin JD, Muradali D, Wilson SR. US of liver transplants: normal and abnormal. Radiographics 2003; 23 (05) 1093-1114
    CrossrefPubMedGoogle Scholar
  • 28 Hashimoto K, Miller CM. The concept of functional graft size: an eternal theme of maximizing donor safety and recipient survival in living donor liver transplantation. Transplantation 2022; 106 (04) 696-697
    CrossrefPubMedGoogle Scholar
  • 29 Troisi R, de Hemptinne B. Clinical relevance of adapting portal vein flow in living donor liver transplantation in adult patients. Liver Transpl 2003; 9 (09) S36-S41
    CrossrefPubMedGoogle Scholar
  • 30 Ito T, Kiuchi T, Yamamoto H. et al. Changes in portal venous pressure in the early phase after living donor liver transplantation: pathogenesis and clinical implications. Transplantation 2003; 75 (08) 1313-1317
    CrossrefPubMedGoogle Scholar
  • 31 Troisi R, Cammu G, Militerno G. et al. Modulation of portal graft inflow: a necessity in adult living-donor liver transplantation?. Ann Surg 2003; 237 (03) 429-436
    CrossrefPubMedGoogle Scholar
  • 32 Sato Y, Yamamoto S, Oya H. et al. Splenectomy for reduction of excessive portal hypertension after adult living-related donor liver transplantation. Hepatogastroenterology 2002; 49 (48) 1652-1655
    PubMedGoogle Scholar
  • 33 Ikegami T, Toshima T, Takeishi K. et al. Bloodless splenectomy during liver transplantation for terminal liver diseases with portal hypertension. J Am Coll Surg 2009; 208 (02) e1-e4
    CrossrefPubMedGoogle Scholar
  • 34 Mohkam K, Darnis B, Schmitt Z, Duperret S, Ducerf C, Mabrut JY. Successful modulation of portal inflow by somatostatin in a porcine model of small-for-size syndrome. Am J Surg 2016; 212 (02) 321-326
    CrossrefPubMedGoogle Scholar
  • 35 Shimazu M, Kitajima M. Living donor liver transplantation with special reference to ABO-incompatible grafts and small-for-size grafts. World J Surg 2004; 28 (01) 2-7
    CrossrefPubMedGoogle Scholar
  • 36 Palmes D, Minin E, Budny T. et al. The endothelin/nitric oxide balance determines small-for-size liver injury after reduced-size rat liver transplantation. Virchows Arch 2005; 447 (04) 731-741
    CrossrefPubMedGoogle Scholar
  • 37 Man K, Lee TK, Liang TB. et al. FK 409 ameliorates small-for-size liver graft injury by attenuation of portal hypertension and down-regulation of Egr-1 pathway. Ann Surg 2004; 240 (01) 159-168
    CrossrefPubMedGoogle Scholar
  • 38 He C, Liu X, Peng W, Li C, Wen TF. Evaluation the efficacy and safety of simultaneous splenectomy in liver transplantation patients: a meta-analysis. Medicine (Baltimore) 2018; 97 (10) e0087
    CrossrefPubMedGoogle Scholar
  • 39 Yoshizumi T, Itoh S, Shimokawa M. et al. Simultaneous splenectomy improves outcomes after adult living donor liver transplantation. J Hepatol 2021; 74 (02) 372-379
    CrossrefPubMedGoogle Scholar
  • 40 Umeda Y, Yagi T, Sadamori H. et al. Preoperative proximal splenic artery embolization: a safe and efficacious portal decompression technique that improves the outcome of live donor liver transplantation. Transpl Int 2007; 20 (11) 947-955
    CrossrefPubMedGoogle Scholar
  • 41 Su CM, Chou TC, Yang TH, Lin YJ. Graft inflow modulation in living-donor liver transplantation: hepatic hemodynamic changes in splenic artery ligation and splenectomy. Ann Transplant 2022; 27: e936609
    PubMedGoogle Scholar
  • 42 Pravisani R, Baccarani U, Adani G. et al. Splenic artery syndrome as a possible cause of late onset refractory ascites after liver transplantation: management with proximal splenic artery embolization. Transplant Proc 2016; 48 (02) 377-379
    CrossrefPubMedGoogle Scholar
  • 43 Fleckenstein FN, Luedemann WM, Kücükkaya A. et al. Splenic artery steal syndrome in patients with orthotopic liver transplant: Where to embolize the splenic artery?. PLoS One 2022; 17 (03) e0263832 DOI: 10.1371/journal.pone.0263832.
    CrossrefPubMedGoogle Scholar
  • 44 Taniguchi M, Shimamura T, Suzuki T. et al. Transient portacaval shunt for a small-for-size graft in living donor liver transplantation. Liver Transpl 2007; 13 (06) 932-934
    CrossrefPubMedGoogle Scholar
  • 45 Boillot O, Delafosse B, Méchet I, Boucaud C, Pouyet M. Small-for-size partial liver graft in an adult recipient; a new transplant technique. Lancet 2002; 359 (9304): 406-407
    CrossrefPubMedGoogle Scholar
  • 46 Botha JF, Campos BD, Johanning J, Mercer D, Grant W, Langnas A. Endovascular closure of a hemiportocaval shunt after small-for-size adult-to-adult left lobe living donor liver transplantation. Liver Transpl 2009; 15 (12) 1671-1675
    CrossrefPubMedGoogle Scholar
  • 47 Takada Y, Ueda M, Ishikawa Y. et al. End-to-side portocaval shunting for a small-for-size graft in living donor liver transplantation. Liver Transpl 2004; 10 (06) 807-810
    CrossrefPubMedGoogle Scholar
  • 48 Sánchez-Cabús S, Fondevila C, Calatayud D. et al. Importance of the temporary portocaval shunt during adult living donor liver transplantation. Liver Transpl 2013; 19 (02) 174-183
    CrossrefPubMedGoogle Scholar
  • 49 Sato Y, Yamamoto S, Takeishi T. et al. Management of major portosystemic shunting in small-for-size adult living-related donor liver transplantation with a left-sided graft liver. Surg Today 2006; 36 (04) 354-360
    CrossrefPubMedGoogle Scholar
  • 50 Troisi RI, Berardi G, Tomassini F, Sainz-Barriga M. Graft inflow modulation in adult-to-adult living donor liver transplantation: a systematic review. Transplant Rev (Orlando) 2017; 31 (02) 127-135
    CrossrefPubMedGoogle Scholar
  • 51 Sato Y, Oya H, Yamamoto S. et al. Method for spontaneous constriction and closure of portocaval shunt using a ligamentum teres hepatis in small-for-size graft liver transplantation. Transplantation 2010; 90 (11) 1200-1203
    CrossrefPubMedGoogle Scholar