The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair
- 1 October 2009
- journal article
- review article
- Published by American Physiological Society in Physiological Reviews
- Vol. 89 (4), 1269-1339
- https://doi.org/10.1152/physrev.00027.2008
Abstract
The complex functions of the liver in biosynthesis, metabolism, clearance, and host defense are tightly dependent on an adequate microcirculation. To guarantee hepatic homeostasis, this requires not only a sufficient nutritive perfusion and oxygen supply, but also a balanced vasomotor control and an appropriate cell-cell communication. Deteriorations of the hepatic homeostasis, as observed in ischemia/reperfusion, cold preservation and transplantation, septic organ failure, and hepatic resection-induced hyperperfusion, are associated with a high morbidity and mortality. During the last two decades, experimental studies have demonstrated that microcirculatory disorders are determinants for organ failure in these disease states. Disorders include 1) a dysregulation of the vasomotor control with a deterioration of the endothelin-nitric oxide balance, an arterial and sinusoidal constriction, and a shutdown of the microcirculation as well as 2) an overwhelming inflammatory response with microvascular leukocyte accumulation, platelet adherence, and Kupffer cell activation. Within the sequelae of events, proinflammatory mediators, such as reactive oxygen species and tumor necrosis factor-α, are the key players, causing the microvascular dysfunction and perfusion failure. This review covers the morphological and functional characterization of the hepatic microcirculation, the mechanistic contributions in surgical disease states, and the therapeutic targets to attenuate tissue injury and organ dysfunction. It also indicates future directions to translate the knowledge achieved from experimental studies into clinical practice. By this, the use of the recently introduced techniques to monitor the hepatic microcirculation in humans, such as near-infrared spectroscopy or orthogonal polarized spectral imaging, may allow an early initiation of treatment, which should benefit the final outcome of these critically ill patients.This publication has 916 references indexed in Scilit:
- Adenosine induces loss of actin stress fibers and inhibits contraction in hepatic stellate cells via Rho inhibitionJournal of Hepatology, 2008
- Hepatic Microcirculation in Fatty Liver DiseaseThe Anatomical Record, 2008
- Taurine improves graft survival after experimental liver transplantationLiver Transplantation, 2005
- Continuous infusion ofN-acetylcysteine reduces liver warm ischaemia–reperfusion injuryBritish Journal of Surgery, 2004
- Improvement of rat liver graft quality by pifithrin-?-mediated inhibition of hepatocyte necrapoptosisJournal of Hepatology, 2004
- Sinusoidal endothelial cell and hepatocyte death following cold ischemia-warm reperfusion of the rat liverJournal of Hepatology, 2004
- Role of endothelins and nitric oxide in hepatic reperfusion injury in the ratJournal of Hepatology, 1998
- Adenovirus-mediated expression of cytokine-induced neutrophil chemoattractant in rat liver induces a neutrophilic hepatitisJournal of Hepatology, 1997
- Characterization of signaling pathways to na+/H+ exchanger activation with epidermal growth factor in hepatocytesJournal of Hepatology, 1994
- Termination of endothelin signaling: Role of nitric oxideJournal of Cellular Physiology, 1994