Abstract
Background
Rats with chronic bile duct ligation (CBDL) and portal vein ligation (PVL) are used as models of portal hypertension. CBDL rats show hypoxemia with intrapulmonary vasodilatation (IPVD), and are recognized as a model of hepatopulmonary syndrome (HPS), while PVL rats are normoxemic. We investigated the differences in arterial oxygenation between these models, and the key factors leading to HPS.
Methods
Forty-eight Sprague-Dawley rats were prepared as CBDL or PVL models, or as Sham rats. Arterial oxygenation, hemodynamics (reference sample method), and IPVD were simultaneously evaluated in conscious and unrestrained animals, using 141Ce- or 113Sn-labeled microspheres (15 µm in diameter), respectively. Endothelin-1 (ET-1) and nitrate/nitrite (end products of nitric oxide; NOx) production by the lung tissue (increment across the lungs) was also determined.
Results
The extent of IPVD was similar in both models, but hypoxemia was only observed in CBDL rats. The ET-1 level and the increment in NOx were significantly increased in CBDL rats, and the increment was directly correlated with impairment of oxygenation. Blood flow through the bronchial arteries (anatomical shunting) was increased in CBDL rats, reaching more than three times the level in PVL rats or Sham rats.
Conclusions
These results support the hypothesis that NO derived from the lung tissues contributes to hypoxemia, and IPVD appears to be a prerequisite for impaired oxygenation. The considerable increase of anatomical shunting may potentially contribute to impaired oxygenation in CBDL rats.
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References
PA Lange JK Stoller (1995) ArticleTitleThe hepatopulmonary syndrome Ann Intern Med 122 521–9 Occurrence Handle7872588
MM Hoeper MJ Krowka CP Strassburg (2004) ArticleTitlePortopulmonary hypertension and hepatopulmonary syndrome Lancet 363 1461–8 Occurrence Handle10.1016/S0140-6736(04)16107-2 Occurrence Handle15121411
MB Fallon GA Abrams (2000) ArticleTitlePulmonary dysfunction in chronic liver disease Hepatology 32 859–65 Occurrence Handle11003635
R Rodriguez-Roisin AG Agusti J Roca (1992) ArticleTitleThe hepatopulmonary syndrome: new name, old complexities Thorax 47 897–902 Occurrence Handle1465744
AG Agusti J Roca R Rodriguez-Roisin (1996) ArticleTitleMechanisms of gas exchange impairment in patients with liver cirrhosis Clin Chest Med 17 49–66 Occurrence Handle10.1016/S0272-5231(05)70298-7 Occurrence Handle8665790
Y Katsuta H Honma X-J Zhang M Ohsuga H Komeichi S Shimizu et al. (2005) ArticleTitlePulmonary blood transit time and impaired arterial oxygenation in patients with chronic liver disease J Gastroenterol 40 57–63 Occurrence Handle10.1007/s00535-004-1495-6 Occurrence Handle15692790
JB Thorens AF Junod (1992) ArticleTitleHypoxaemia and liver cirrhosis: a new argument in favour of a “diffusion-perfusion defect” Eur Respir J 5 754–6 Occurrence Handle1628734
GP Martinez JA Barbera J Visa A Rimola JC Pare J Roca et al. (2001) ArticleTitleHepatopulmonary syndrome in candidates for liver transplantation J Hepatol 34 651–7 Occurrence Handle10.1016/S0168-8278(00)00108-2 Occurrence Handle11434610
KP Mimidis C Karatza KV Spiropoulos T Toulgaridis NA Charokopos KC Thomopoulos et al. (1998) ArticleTitlePrevalence of intrapulmonary vascular dilatations in normoxaemic patients with early liver cirrhosis Scand J Gastroenterol 33 988–92 Occurrence Handle10.1080/003655298750027038 Occurrence Handle9759957
WE Hopkins AD Waggoner B Barzilai (1992) ArticleTitleFrequency and significance of intrapulmonary right-to-left shunting in end-stage hepatic disease Am J Cardiol 70 516–9 Occurrence Handle10.1016/0002-9149(92)91200-N Occurrence Handle1642191
GA Abrams CC Jaffe PB Hoffer HJ Binder MB Fallon (1995) ArticleTitleDiagnostic utility of contrast echocardiography and lung perfusion scan in patients with hepatopulmonary syndrome Gastroenterology 109 1283–8 Occurrence Handle10.1016/0016-5085(95)90589-8 Occurrence Handle7557096
BL Lima AV Franca A Pazin-Filho WM Araujo JA Martinez BC Maciel et al. (2004) ArticleTitleFrequency, clinical characteristics, and respiratory parameters of hepatopulmonary syndrome Mayo Clin Proc 79 42–8 Occurrence Handle14708947
S Kaymakoglu T Kahraman H Kudat K Demir Y Cakaloglu I Adalet et al. (2003) ArticleTitleHepatopulmonary syndrome in noncirrhotic portal hypertensive patients Dig Dis Sci 48 556–60 Occurrence Handle10.1023/A:1022549018807 Occurrence Handle12757170
C Babbs TW Warnes NY Haboubi (1988) ArticleTitleNon-cirrhotic portal hypertension with hypoxaemia Gut 29 129–31 Occurrence Handle3343007
BK De S Sen PK Biswas SK Mandal D Das U Das et al. (2002) ArticleTitleOccurrence of hepatopulmonary syndrome in Budd-Chiari syndrome and the role of venous decompression Gastroenterology 122 897–903 Occurrence Handle10.1053/gast.2002.32419 Occurrence Handle11910341
A Regev M Yeshurun M Rodriguez A Sagie GW Neff EG Molina et al. (2001) ArticleTitleTransient hepatopulmonary syndrome in a patient with acute hepatitis A J Viral Hepat 8 83–6 Occurrence Handle10.1046/j.1365-2893.2001.00270.x Occurrence Handle11155156
A Williams P Trewby R Williams L Reid (1979) ArticleTitleStructural alterations to the pulmonary circulation in fulminant hepatic failure Thorax 34 447–53 Occurrence Handle505339
Y Ling J Zhang B Luo D Song L Liu L Tang et al. (2004) ArticleTitleThe role of endothelin-1 and the endothelin B receptor in the pathogenesis of hepatopulmonary syndrome in the rat Hepatology 39 1593–602 Occurrence Handle10.1002/hep.20244 Occurrence Handle15185300
MB Fallon GA Abrams JW McGrath Z Hou B Luo (1997) ArticleTitleCommon bile duct ligation in the rat: a model of intrapulmonary vasodilatation and hepatopulmonary syndrome Am J Physiol 272 G779–84 Occurrence Handle9142908
B Luo L Liu L Tang J Zhang CR Stockard WE Grizzle et al. (2003) ArticleTitleIncreased pulmonary vascular endothelin B receptor expression and responsiveness to endothelin-1 in cirrhotic and portal hypertensive rats: a potential mechanism in experimental hepatopulmonary syndrome J Hepatol 38 556–63 Occurrence Handle10.1016/S0168-8278(03)00012-6 Occurrence Handle12713865
XJ Zhang Y Katsuta T Akimoto M Ohsuga T Aramaki T Takano (2003) ArticleTitleIntrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with chronic bile duct ligation J Hepatol 39 724–30 Occurrence Handle10.1016/S0168-8278(03)00430-6 Occurrence Handle14568253
H Nunes D Lebrec M Mazmanian F Capron J Heller KA Tazi et al. (2001) ArticleTitleRole of nitric oxide in hepatopulmonary syndrome in cirrhotic rats Am J Respir Crit Care Med 164 879–85 Occurrence Handle11549549
B Luo L Liu L Tang J Zhang Y Ling MB Fallon (2004) ArticleTitleET-1 and TNF-alpha in HPS: analysis in prehepatic portal hypertension and biliary and nonbiliary cirrhosis in rats Am J Physiol 286 G294–303
D Lebrec L Blanchet (1985) ArticleTitleEffect of two models of portal hypertension on splanchnic organ blood flow in the rat Clin Sci 68 23–8 Occurrence Handle3964726
M Hosono K Machida N Honda T Takahashi A Kashimada H Osada et al. (2002) ArticleTitleQuantitative lung perfusion scintigraphy and detection of intrapulmonary shunt in liver cirrhosis Ann Nucl Med 16 577–81 Occurrence Handle12593425
LC Green DA Wagner J Glogowski PL Skipper JS Wishnok SR Tannenbaum (1982) ArticleTitleAnalysis of nitrate, nitrite, and [15N]nitrate in biological fluids Anal Biochem 126 131–8 Occurrence Handle10.1016/0003-2697(82)90118-X Occurrence Handle7181105
K Ando Y Hirata M Shichiri T Emori F Marumo (1989) ArticleTitlePresence of immunoreactive endothelin in human plasma FEBS Lett 245 164–6 Occurrence Handle10.1016/0014-5793(89)80213-3 Occurrence Handle2647520
G Rolla L Brussino P Colagrande L Dutto S Polizzi E Scappaticci et al. (1997) ArticleTitleExhaled nitric oxide and oxygenation abnormalities in hepatic cirrhosis Hepatology 26 842–7 Occurrence Handle9328302
G Rolla L Brussino P Colagrande E Scappaticci M Morello S Bergerone et al. (1998) ArticleTitleExhaled nitric oxide and impaired oxygenation in cirrhotic patients before and after liver transplantation Ann Intern Med 129 375–8 Occurrence Handle9735065
SA Kharitonov PJ Barnes (2000) ArticleTitleClinical aspects of exhaled nitric oxide Eur Respir J 16 781–92 Occurrence Handle10.1183/09031936.00.16478100 Occurrence Handle11106225
GA Abrams NC Nanda EV Dubovsky MJ Krowka MB Fallon (1998) ArticleTitleUse of macroaggregated albumin lung perfusion scan to diagnose hepatopulmonary syndrome: a new approach Gastroenterology 114 305–10 Occurrence Handle9453490
JF Nunn (1993) Nunn’s applied respiratory physiology EditionNumber4th ed. Butterworth Heinemann London 156–97
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Katsuta, Y., Zhang, XJ., Ohsuga, M. et al. Arterial hypoxemia and intrapulmonary vasodilatation in rat models of portal hypertension. J Gastroenterol 40, 811–819 (2005). https://doi.org/10.1007/s00535-005-1633-9
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DOI: https://doi.org/10.1007/s00535-005-1633-9