Development of an in Situ Isolated Porcine Liver Perfusion Model for Tightly Controlled Physiologic and Pharmacologic Studies

Abstract

Several types of isolated perfused porcine liver models have been proposed for the study of hepatic assist, preservation injury, and specific physiologic or pharmacologic mechanisms. The development of a more general in situ isolated perfused model applicable to a broad range of studies is presented. This model eliminates or minimizes the shortcomings of previous models including ischemic injury prior to perfusion, limited range of vascular pressures and flows, nonphysiologic sources of portal and hepatic artery perfusion, and coupling of the liver to uncontrolled whole-body homeostatic mechanisms. Essentially the model as presented can be described as an autologous transplanted liver without preservation or ischemic injury, functioning within an adrenalectomized, cardiac output and temperature-controlled animal. Independent control of the dual hepatic vascular supply is maintained with pulsatile perfusion of the hepatic artery from the left atrium and nonpulsatile perfusion of the portal vein via the portal system. Oxygenators are not required. Hepatic vein pressure can be controlled independently of hepatic blood flow and systemic hemodynamics. Pharmacologic studies are not restricted to drugs whose termination of action is limited to hepatic metabolism because normal routes of drug redistribution, metabolism, and excretion are present. The model exhibits normal oxygen metabolism and classic control of hepatic artery resistance by portal vein blood flow. There are rather obvious significant advantages inherent in this model for tightly controlled hepatic physiologic and pharmacologic studies.

Key Words:

• age- and weight-related porcine parameters
• blood donor
• extracorporeal circuits
• isolated liver perfusion model
• porcine liver perfusion model