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Portal Hyperperfusion after Extended Hepatectomy Does Not Induce a Hepatic Arterial Buffer Response (HABR) but Impairs Mitochondrial Redox State and Hepatocellular Oxygenation.

Dold S, Richter S, Kollmar O, von Heesen M, Scheuer C, Laschke MW, Vollmar B, Schilling MK, Menger MD - PLoS ONE (2015)

Bottom Line: This, however, did not provoke a hepatic arterial buffer response.Nonetheless, portal hyperperfusion and constant hepatic arterial blood flow were associated with a reduced mitochondrial redox state and a decreased hepatic tissue pO2 after 70% and 90% hepatectomy.This was associated with a 2-fold increase of bromosulfophthalein excretion.

View Article: PubMed Central - PubMed

Affiliation: Department of General-, Visceral-, Vascular- and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany.

ABSTRACT

Background & aims: Portal hyperperfusion after extended hepatectomy or small-for-size liver transplantation may induce organ dysfunction and failure. The underlying mechanisms, however, are still not completely understood. Herein, we analysed whether hepatectomy-associated portal hyperperfusion induces a hepatic arterial buffer response, i.e., an adaptive hepatic arterial constriction, which may cause hepatocellular hypoxia and organ dysfunction.

Methods: Sprague-Dawley rats underwent 30%, 70% and 90% hepatectomy. Baseline measurements before hepatectomy served as controls. Hepatic arterial and portal venous flows were analysed by ultrasonic flow measurement. Microvascular blood flow and mitochondrial redox state were determined by intravital fluorescence microscopy. Hepatic tissue pO2 was analysed by polarographic techniques. Hepatic function and integrity were studied by bromosulfophthalein bile excretion and liver histology.

Results: Portal blood flow was 2- to 4-fold increased after 70% and 90% hepatectomy. This, however, did not provoke a hepatic arterial buffer response. Nonetheless, portal hyperperfusion and constant hepatic arterial blood flow were associated with a reduced mitochondrial redox state and a decreased hepatic tissue pO2 after 70% and 90% hepatectomy. Microvascular blood flow increased significantly after hepatectomy and functional sinusoidal density was found only slightly reduced. Major hepatectomy further induced a 2- to 3-fold increase of bile flow. This was associated with a 2-fold increase of bromosulfophthalein excretion.

Conclusions: Portal hyperperfusion after extended hepatectomy does not induce a hepatic arterial buffer response but reduces mitochondrial redox state and hepatocellular oxygenation. This is not due to a deterioration of microvascular perfusion, but rather due to a relative hypermetabolism of the remnant liver after major resection.

No MeSH data available.


Related in: MedlinePlus

eNOS, iNOS, p-eNOS, HO-1, SOD2, HIF-1α, adenosine and A2AR expression.Representative western blot analyses of the protein expression of inducible (iNOS), endothelial (eNOS), phosphorylated endothelial nitric oxide synthase (p-eNOS), hemoxygenase-1 (HO-1), manganese superoxide dismutase 2 (SOD2), hypoxia-inducible factor-1α (HIF-1α) as well as adenosine and adenosine A2a receptor (A2AR) before (con) and 3 h after 30%, 70% and 90% hepatectomy (PHx).
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pone.0141877.g005: eNOS, iNOS, p-eNOS, HO-1, SOD2, HIF-1α, adenosine and A2AR expression.Representative western blot analyses of the protein expression of inducible (iNOS), endothelial (eNOS), phosphorylated endothelial nitric oxide synthase (p-eNOS), hemoxygenase-1 (HO-1), manganese superoxide dismutase 2 (SOD2), hypoxia-inducible factor-1α (HIF-1α) as well as adenosine and adenosine A2a receptor (A2AR) before (con) and 3 h after 30%, 70% and 90% hepatectomy (PHx).

Mentions: To study the role of nitric oxide in the regulation of liver perfusion after hepatectomy, protein expression of eNOS and iNOS was determined by Western blot analyses. Of interest, 30% as well as 70% and 90% hepatectomy resulted in a distinct increase of both eNOS and iNOS protein expression in the remnant liver tissue (Fig 4). In addition, phosphorylated eNOS was found also markedly increased after hepatectomy (Fig 5), resulting in an increase of the p-eNOS/eNOS ratio after 30% (0.52), 70% (0.95) and 90% hepatectomy (1.18) when compared to control (0.49). Of interest, this was associated with an increased expression of HIF-1α (Fig 5).


Portal Hyperperfusion after Extended Hepatectomy Does Not Induce a Hepatic Arterial Buffer Response (HABR) but Impairs Mitochondrial Redox State and Hepatocellular Oxygenation.

Dold S, Richter S, Kollmar O, von Heesen M, Scheuer C, Laschke MW, Vollmar B, Schilling MK, Menger MD - PLoS ONE (2015)

eNOS, iNOS, p-eNOS, HO-1, SOD2, HIF-1α, adenosine and A2AR expression.Representative western blot analyses of the protein expression of inducible (iNOS), endothelial (eNOS), phosphorylated endothelial nitric oxide synthase (p-eNOS), hemoxygenase-1 (HO-1), manganese superoxide dismutase 2 (SOD2), hypoxia-inducible factor-1α (HIF-1α) as well as adenosine and adenosine A2a receptor (A2AR) before (con) and 3 h after 30%, 70% and 90% hepatectomy (PHx).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4629903&req=5

pone.0141877.g005: eNOS, iNOS, p-eNOS, HO-1, SOD2, HIF-1α, adenosine and A2AR expression.Representative western blot analyses of the protein expression of inducible (iNOS), endothelial (eNOS), phosphorylated endothelial nitric oxide synthase (p-eNOS), hemoxygenase-1 (HO-1), manganese superoxide dismutase 2 (SOD2), hypoxia-inducible factor-1α (HIF-1α) as well as adenosine and adenosine A2a receptor (A2AR) before (con) and 3 h after 30%, 70% and 90% hepatectomy (PHx).
Mentions: To study the role of nitric oxide in the regulation of liver perfusion after hepatectomy, protein expression of eNOS and iNOS was determined by Western blot analyses. Of interest, 30% as well as 70% and 90% hepatectomy resulted in a distinct increase of both eNOS and iNOS protein expression in the remnant liver tissue (Fig 4). In addition, phosphorylated eNOS was found also markedly increased after hepatectomy (Fig 5), resulting in an increase of the p-eNOS/eNOS ratio after 30% (0.52), 70% (0.95) and 90% hepatectomy (1.18) when compared to control (0.49). Of interest, this was associated with an increased expression of HIF-1α (Fig 5).

Bottom Line: This, however, did not provoke a hepatic arterial buffer response.Nonetheless, portal hyperperfusion and constant hepatic arterial blood flow were associated with a reduced mitochondrial redox state and a decreased hepatic tissue pO2 after 70% and 90% hepatectomy.This was associated with a 2-fold increase of bromosulfophthalein excretion.

View Article: PubMed Central - PubMed

Affiliation: Department of General-, Visceral-, Vascular- and Pediatric Surgery, University of Saarland, Homburg/Saar, Germany.

ABSTRACT

Background & aims: Portal hyperperfusion after extended hepatectomy or small-for-size liver transplantation may induce organ dysfunction and failure. The underlying mechanisms, however, are still not completely understood. Herein, we analysed whether hepatectomy-associated portal hyperperfusion induces a hepatic arterial buffer response, i.e., an adaptive hepatic arterial constriction, which may cause hepatocellular hypoxia and organ dysfunction.

Methods: Sprague-Dawley rats underwent 30%, 70% and 90% hepatectomy. Baseline measurements before hepatectomy served as controls. Hepatic arterial and portal venous flows were analysed by ultrasonic flow measurement. Microvascular blood flow and mitochondrial redox state were determined by intravital fluorescence microscopy. Hepatic tissue pO2 was analysed by polarographic techniques. Hepatic function and integrity were studied by bromosulfophthalein bile excretion and liver histology.

Results: Portal blood flow was 2- to 4-fold increased after 70% and 90% hepatectomy. This, however, did not provoke a hepatic arterial buffer response. Nonetheless, portal hyperperfusion and constant hepatic arterial blood flow were associated with a reduced mitochondrial redox state and a decreased hepatic tissue pO2 after 70% and 90% hepatectomy. Microvascular blood flow increased significantly after hepatectomy and functional sinusoidal density was found only slightly reduced. Major hepatectomy further induced a 2- to 3-fold increase of bile flow. This was associated with a 2-fold increase of bromosulfophthalein excretion.

Conclusions: Portal hyperperfusion after extended hepatectomy does not induce a hepatic arterial buffer response but reduces mitochondrial redox state and hepatocellular oxygenation. This is not due to a deterioration of microvascular perfusion, but rather due to a relative hypermetabolism of the remnant liver after major resection.

No MeSH data available.


Related in: MedlinePlus