Hemoperfused isolated porcine slaughterhouse kidneys as a valid model for pharmacological studies

Mammalian models of isolated perfused kidneys provide an important tool to study pharmacological, toxicological, and physiological properties of drugs, hormones, and vasoactive substances. As organs from small laboratory animals are difficult to compare to human conditions, porcine and bovine kidneys permit better approaches to simulate human conditions. We developed an alternative model for pharmacological studies using isolated hemoperfused porcine kidneys from slaughterhouse animals to reduce laboratory animal experiments. Controlled pharmacological studies were established using furosemide (2 mg/100 g organweight) as a model drug. Kidneys were hemoperfused after a preservation period of 4.6 +/- 1.7 h. In comparison to the control period, furosemide application led to significant changes in renal parameters with urine flow: 4.2/1.7 mL/min* 100 g (furosemide/control), urine-sodium: 108/77.5 mmol/L, sodium excretion: 0.47/0.14 mmol/min* 100 g; all differences significant,p < 0.01. The parameters stabilized to normal values as found in the control period within a period of 80 min. A second group of laboratory-harvested kidneys was examined for differences and revealed limitations of the slaughterhouse organs in parameters such as oxygen consumption. In summary, the present study demonstrates the valid use of hemoperfused slaughterhouse kidneys as a pharmacological model of renal function within the limits of the use of slaughterhouse organs, and indicates that future studies using this alternative approach could reduce animal experiments. (C) 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm.