An improved model of isolated hemoperfused porcine livers using pneumatically driven pulsating blood pumps.
Existing liver perfusion models are largely limited by high degrees of ischemic and reperfusion injury and the lack of standardization. To establish a highly standardized perfusion model and minimize reperfusion injury, a porcine liver perfusion model was developed using an artificial heart pump (Buecherl Artificial Heart). This model is characterized by pneumatically driven and pressure controlled blood pumps with pulsating flow characteristics. The perfusion parameters and the integrity of the perfused organ were assessed using hemodynamic and hepatic function tests. In eight porcine liver perfusion experiments the system allowed maintaining stable and physiologic organ function over 3 hours by bile production (5.5 +/- 3.1 ml/30 minutes, resp. 22.9 +/- 8.4 ml cumulative at 180 minutes), oxygen consumption (2.2 +/- 0.2 ml/min/100 g overall mean) and significantly better liver enzyme levels (AST 19.5 +/- 10.1 U/l/100 g, ALT 2.1 +/- 0.8 U/l/min, LDH 57.8 +/- 24.2 U/l/100 g) compared to previous studies. It was also possible to reduce the circulating blood volume to 1,000 ml and to create a compact perfusion system that is adoptable to other organ systems such as the kidneys. The compact size and the absence of magnetic components also allow a use for advanced imaging techniques. In conclusion this optimized perfusion system provides a sound basis for future studies in the area of hepatotoxicity and pharmacology.
Nagel
Stefan
S
Department of Comparative Medicine and Experimental Animal Science, Charité-University Medicine Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany. stefan.nagel@charite.de
Hegemann
Olaf
O
Groneberg
David A
DA
Grosse-Siestrup
Christian
C
D000818:Animals; D001775:Blood Circulation / Q000502:physiology*; D001784:Blood Gas Analysis; D004867:Equipment Design; D005260:Female; D006354:Heart, Artificial; D006439:Hemodynamics; D006464:Hemoperfusion / Q000295:instrumentation* / Q000379:methods; D066298:In Vitro Techniques; D007260:Infusion Pumps; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D023421:Models, Animal; D009926:Organ Preservation; D009929:Organ Size; D011673:Pulsatile Flow / Q000502:physiology*; D013552:Swine / Q000502:physiology*