Hyperlactacidaemia in isolated hyperthermic perfusion of tumour bearing rat limbs: a study of feasibility using a novel infusion solution

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Purpose: In a methodological study the applicability of hyperlactacidaemia in isolated hyperthermic perfusion of tumour-bearing rat limbs was investigated. Methods: In 50 Sprague Dawley rats, DS-sarcoma growth was initiated on the right food dorsum by subcutaneous injection of 0.5 ml ascites cells. In the anaesthetized animals isolated limb perfusion was performed under steady state conditions for 60 min using a miniature equipment. Thereafter tumour volume was measured daily. (a) Investigation of feasability: 40 rats were allocated to four groups. Group I: Normothermic perfusion at 38oC, n=10; Group II: Hyperthermic perfusion at 40-41oC, n=10; Group III: Normothermic perfusion at 38oC and hyperlactacidaemia of 10 mmol/l, n=10; Group IV: Hyperthermic perfusion at 40-41oC and hyperlactacidaemia of 10 mmol/l, n=10. (b) Investigation of survival and histological changes: In group V hyperthermic perfusion at 40-41oC and hyperlactacidaemia of 10 mmol/l, n=10 was performed. After the animals had died, hip disarticulation of the tumour-bearing limb was performed for histological examination. Results: Normothermic and hyperthermic perfusion of tumour-bearing rat limbs using miniature equipment was feasible and tolerated by the animals. Regional hyperlactacidaemia of 10 mmol/l could be maintained throughout the perfusions. After combined treatment with hyperthermia and hyperlactacidaemia, tumour volume decreased and extensive tumour necrosis occurred, while in other animals aggressive tumour growth with bone infiltration could be observed. Conclusions: The present study demonstrates the applicability of hyperlactacidaemia in hyperthermic isolated limb perfusion in the rat and proved a tumour growth delay due to an induction of tumour necrosis thereafter. Further investigations in other tumour entities and experimental models are required to confirm this impressive therapeutic effect of hyperthermia in combination with hyperlactacidaemia.