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

Abstract

Background & AimsPortal 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.MethodsSprague-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.ResultsPortal 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.ConclusionsPortal 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.

Hypoxia sensing by hepatic stellate cells leads to VEGF-dependent angiogenesis and may contribute to accelerated liver regeneration

“…In contrast, proliferation after ALPPS may be accelerated, due to the persistently high level of hypoxia in the liver, which induces additional angiogenesis, mediated by activated HSC. The tissue hypoxia in the growing liver is either the result of the arterial buffer response due to the portal hyperflow induced in liver rerouting maneuvers and partial hepatectomy [29][30][31] or the result of a relative hypermetabolism of the hyperperfused and regenerating liver 32 . In PVL or PVE, portal hyperflow is a short-lived phenomenon of only hours, because it is counteracted by portal vein shunting across sinusoids with large collaterals developing over several days 11 .…”

Surgical preparation of rats and mice for intravital microscopic imaging of abdominal organs

“…While the horizontal approach has also been utilized by investigators outside of our group [7, 44], it is not the only approach that has been successfully utilized to image the liver. The midline vertical incision is a common approach employed by investigators [45–49], and the left subcostal incision is yet another approach that has been utilized [50, 51]. …”

“…Investigators tend to utilize inverted microscopes to study abdominal organs of interest [1, 5, 9, 32, 33, 34, 45, 46, 50, 51]. However, approaches have been developed for imaging on upright microscope stands, which may be useful to investigators without access to an inverted microscope system.…”

“Small-For-Flow” Liver Failure after Extended Hepatectomy: A Call for Update

“…Despite this, other authors, recently, have suggested that portal hyperperfusion after extended hepatectomy doesn't induce a hepatic arterial buffer response, but reduces mitochondrial redox state and hepatocellular oxygenation in rat's model. This wouldn't due to a deterioration of microvascular perfusion, but rather due to a relative hyper metabolism of the remnant liver after major resection [16].…”