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.

An Improved Model of Isolated Hemoperfused Porcine Livers Using Pneumatically Driven Pulsating Blood Pumps

“…A comparison of the data published by Gibelin et al and Eisele et al for the hepatic artery resistance with the data obtained in our model, however, is difficult since the authors worked with different species and/or considerably longer preservation periods. Nevertheless, the data obtained in this model for the hepatic artery resistance are in accordance with the values described for pigs (Travis et al, 1996). In comparison with the previous model developed in our laboratory (Grosse-Siestrup et al, 2001) no relevant differences between the values for hepatic artery resistance in both models were detected, but a steady state of this parameter was only achieved with the present model.…”

“…The values for this parameter were than stable through the entire perfusion period. Moreover, comparing the values obtained in this study with the values published for pigs (Travis et al, 1996) no differences were observed. In contrast to our data, in another study performed with an isolated pig liver (using roller pumps), where organs were preserved in different manners, but also perfused with blood, oxygen consumption decreased during the first 3 hours of perfusion (Adham et al, 1997).…”

“…An increase on the glucose concentration in plasma was observed in the first hour of perfusion. This was also described by Travis et al (1996), as possibly, due to high levels of glucose in the dialysate or a changed glycogen metabolism (Travis et al, 1996). Histological investigation of tissue samples in the future might contribute in understanding this phenomenon.…”

“…Potassium levels that are influenced by the organ preservation solution were initially low and only slightly increased during perfusion. An increase on potassium in the perfusate is usually referred to cell damage (Travis et al, 1996). At least 2 ways of cell damage were possible in our system: hepatocellular injury and hemolysis.…”

Clinical Management and Current Research in Isolated Limb Perfusion for Sarcoma and Melanoma

“…Preliminary data suggest a shorter time to reach physiological oxygen saturation, less fluctuation in levels of oxygen tension and less fluid shift in the circuit compared to a nonpulsatile group [105]. As is known from cardiac surgery [106,107] and in situ liver perfusion in porcines [108], pulsatile flow may result in a decreased peripheral vascular resistance, reduced sympathetic nerve activity and thus may improve both microcirculation and tissue function while lactate levels remain unchanged [109]. However, no difference could be observed in ET or prostacyclin levels after extracorporeal circulation during aortocoronary bypass operation whether or not pulsatile flow was used [110].…”