The hepatic circulation in health and disease: Report of a single-topic symposium

Blood flow and vascular resistance in the hepatic vasculature are closely regulated through a balance of vasoactive molecules including nitric oxide (NO), carbon monoxide (CO), endothelin (ET), and prostanoids such as prostacyclin. These vasoregulatory agents interact with unique nonparenchymal cells in the hepatic sinusoid through autocrine and paracrine mechanisms. These cells, which include sinusoidal endothelial cells (SEC), hepatic stellate cells (HSC), and Kupffer cells (KC), each have the molecular machinery to synthesize and/or respond to these vasoactive molecules. This complex interaction of cells and molecules, although not well understood, appears to involve vasoregulatory mechanisms that are unique to the hepatic vascular bed. Alterations in the function of the cells lining the sinusoids and in the activity of vasoactive mediators in the hepatic circulation play a role in mediating vascular disturbances which may arise in the liver secondary to cirrhosis, sepsis, and liver transplantation. Thus, understanding the mechanisms which regulate blood flow in the hepatic circulation are of vital importance. On June 21-22, 1996, the American Association for the Study of Liver Diseases sponsored a symposium entitled ''Liver Microcirculation in Health and Diseases.'' The purpose of this conference was to review current basic research endeavors pertaining to the hepatic circulation. The conference was organized into four sessions, with each session composed of several lectures. This article will summarize the salient aspects of each lecture based on summaries submitted by the speaker and modified based on dictations of the lecture. The first section, entitled ''Endothelial and Smooth Muscle Regulation of Vascular Function,'' chaired by William C. Sessa and Roberto J. Groszmann, examined basic mechanisms of vascular regulation, with particular emphasis on the physiology and biology of the endothelial cell and its modulation by other cell types, vasoactive mediators, and biomechanical forces. The second section, entitled ''The Liver Microcirculation,'' chaired by Robert S. McCuskey and Jurg Reichen, addressed anatomic and physiological studies in the hepatic circulation and novel characteristics of HSC. The third section, entitled ''Pathogenesis of Portal Hypertension,'' chaired by Jaime Bosch and Didier LeBrec, examined mechanisms that may account for the hemodynamic disturbances in the liver and other regional beds that are characteristic of chronic liver disease. The fourth section, entitled ''Sepsis and Transplantation,'' chaired by Ian R. Wanless and Andres T. Blei, discussed the mechanisms that mediate the microvascular injury often observed after liver transplantation and during sepsis.