Effects of hyperthermia on the rat bladder: a pre-clinical study on thermometry and functional damage after treatment.
The rat bladder was heated using a microwave applicator which was equipped with a system of circulating deionized water. The applicator was operated at 434 MHz and was placed at the ventral side with the rats in supine position. Temperatures in the bladder and adjacent were monitored using thermocouples with single or multiple sensors. One thermocouple located most centrally in the bladder served as reference. The rats were treated at intravesical reference temperature of 41, 42, 43, 44 and 45 degrees C for 1 h. The heating time to reach the reference temperature was approximately 5 min. Temperatures inside the bladder varied within 0.5 degrees C from the reference value, while the temperatures in the urethra were approximately 1.0 degrees C lower. At the left and the right side of the outer bladder wall, temperatures were approximately 0.5 degrees C lower than the reference value, while the temperature on the dorsal and ventral sides of the bladder wall were 1.0-1.5 degrees C lower. In the rectum, located in the treatment field, the temperature reached 39.1, 40.5, 42.4 and 42.5 degrees C after 1 h of hyperthermia at intravesical reference temperatures of 41, 42, 43, 44 and 45 degrees C, respectively. Body core temperature measured in the esophagus behind the pericardium never exceeded 40.0 degrees C. The capacity of the bladder was assessed after 1 h at 43, 44 and 45 degrees C at various intervals after heat treatment. In the sham treated control group and in the animals treated at 43 degrees C, no reduction in bladder capacity was observed. The treatment group where the bladder was kept at 44 degrees C for 1 h showed a clear reduction in bladder capacity at days 1 and 3 after hyperthermia. In the 45 degrees C treatment group, four out of seven rats died, this within a few days after treatment. The three surviving rats were tested for bladder capacity and all had a reduced capacity at days 3 and 7 post-treatment. Four weeks after 44 degrees C hyperthermia, all rats had recovered. After hyperthermia, depending on the heat-dose, an increase in blood urea nitrogen (BUN) was observed. After treatment at 42, 43 and 44 degrees C, peak values were observed after approximately 1 day (16 or 24 h) followed by recovery; after 42 degrees C, BUN levels were almost back to normal after 1 week; after 43 degrees C, the level was still twice as high as control levels; and after 44 degrees C, recovery of BUN levels to normal seemed slow, 1 week after treatment it was still five times as high as control. From these results, it is concluded that temperatures in the bladder below 44 degrees C are well tolerated. After 1 h at 44 degrees C, a transient decrease in bladder capacity was observed, as well as a high level of azotemia. After 1 h at 45 degrees C, a high mortality rate was observed. These observations agree with early clinical observations and may be used as guidelines for further clinical work.
Haveman
J
J
Department of Radiotherapy, Academic Medical Centre, PO Box 22700, 1100 DE Amsterdam, The Netherlands. j.harveman@amc.uva.nl
Smals
O A G
OA
Rodermond
H M
HM
D000818:Animals; D001806:Blood Urea Nitrogen; D001831:Body Temperature; D003556:Cystitis / Q000209:etiology; D005260:Female; D006979:Hyperthermia, Induced / Q000009:adverse effects*; D008872:Microwaves / Q000009:adverse effects; D051381:Rats; D011914:Rats, Inbred BN; D013817:Thermography; D001743:Urinary Bladder / Q000503:physiopathology* / Q000528:radiation effects*; D014554:Urination