The influence of hyperthermia on the uptake of cisplatin in the rat cervical spinal cord.
The influence of local hyperthermia on the uptake of cisplatin in the rat cervical spinal cord was investigated. After single intraperitoneal or intravenous injection of cisplatin (5 mg/kg body weight), the spinal cord region cervical 5-thoracic 2 was heated for 60 min at mean (S.D.) 41.2 (0.4) degrees C or 40 min 42.4 (0.3) degrees C using a 434 MHz microwave heating device. One day after treatment with either hyperthermia alone, cisplatin alone or the combination, none of the animals expressed neurological symptoms. The spinal cord was dissected and platinum levels were measured by flameless atomic absorption spectroscopy. No difference was found in uptake of platinum in the spinal cord between control- and heat treated animals. In a second series of experiments, the spinal cord was heated for 30-60 min. during a 2 h infusion of cisplatin. One day after treatment at 42.3 degrees C for 60 min, neither motor nor sensory functions were affected and platinum levels did not differ significantly between control and treated animals. Also, platinum levels measured in the spinal cord immediately after cisplatin infusion were not influenced by heat treatment at 42.1 or 43.0 degrees C for 30 min. However, after a heat dose of 60 min 43 degrees C, cisplatin uptake was significantly increased (P less than 0.001) by a factor of 2.8 (1.3). The data demonstrate that mild hyperthermia has no effect on the uptake of cisplatin in the spinal cord, while an injurious heat dose leads to a significant increase in cisplatin uptake. The present findings indicate that, in case of treatment of tumours of the central nervous system with hyperthermia and cisplatin, a treatment which might be toxic for the tumour is well tolerated by the normal nervous tissue.
Sminia
P
P
Department of Radiotherapy, Academisch Medisch Centrum, University of Amsterdam, The Netherlands.
Los
G
G
Hendriks
J J
JJ
van Vugt
M J
MJ
Haveman
J
J
González González
D
D
D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D006979:Hyperthermia, Induced; D010984:Platinum / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000378:metabolism*
D010984:Platinum; D002945:Cisplatin