Resuscitation of warm ischaemia predamaged porcine kidneys by fibrinolytic preflush with streptokinase: reduction of animal experiments

Abstract

In order to reduce the number of animal experiments, the use of non-heart-beating donors (NHBDs) from a commercial abattoir has been proposed. Since the use of slaughterhouse organs is legally not defined as animal experiment, this would fulfil international standards as an alternative to animal experiments. The development of intravascular thrombosis after cardiac arrest negatively impacts organ preservation and thus viability during ischaemic storage and reperfusion. A fibrinolytic preflush with streptokinase might overcome these limitations. Therefore, the functional and histomorphological integrity of kidneys preserved immediately with intact circulation (control group A) and kidneys preserved after cardiac arrest with a 30 min period of warm ischaemia (WI) (group B) was compared with kidneys preflushed with 12.5 kU/L (group C) or 50 kU/L streptokinase (group D) after 30 min WI prior to preservation. We could demonstrate that kidneys preflushed with 12.5 kU/L streptokinase (group C) performed better than those without streptokinase pretreatment after WI (group B). Parameters like oxygen consumption, perfusion pressure, laboratory values, lactate dehydrogenase level and lipidperoxidation were closer to that of the control (group A) than in groups B and D. The higher streptokinase concentration of 50 kU/L (group D) resulted histologically in a more pronounced tissue damage and an attenuated renal function, indicating toxic effects. On the basis of our results we believe streptokinase preflushed slaughterhouse kidneys to be an adequate alternative to organs from laboratory animals with the potential to further reduce the number of animal experiments.

Determination of the Preferred Conditions for the Isolated Perfusion of Porcine Kidneys

“…Szyrach et al [26] reported on flow-controlled normothermic reperfusion of porcine kidneys after cold storage in HTK for 3 h using the same flow rate (1 ml/min/g), resulting in a MAP which did not exceed 110 mm Hg. In our study, the longer but clinically more relevant cold ischemic period of 24 h could account for the increase in MAP, ultimately reaching more than 200 mm Hg.…”