Increased thermal response to ultrasound in the Walker carcinosarcoma treated with vasoactive drugs.
In order to evaluate the potential of a highly selective Ca2+ entry blocker (nisoldipine) and of 5-hydroxytryptamine (5-HT) as adjuvant in hyperthermia treatment, we studied the differential flow response and time-course of tumor and normal tissue temperature following the administration of the two substances and during ultrasound heating. In 12 rats bearing Walker 256 carcinomas i.p. injection of 0.2-0.4 mg/kg nisoldipine caused a reduction in the tumor-to-muscle flow relationship of 4.4 +/- 1.9 (SD) to 1.74 +/- 0.86 as determined by intraarterial 133Xe injection; i.p. injection of 2-8 mg/kg 5-HT (N = 13) caused a respective reduction from 3.9 +/- 2.67 to 1.3 +/- 1.59. During a 20-min period of 41 degrees C normal tissue temperature-controlled ultrasound heating without drugs, tumor temperature attained 40.8 +/- 0.9 degrees C (N = 16). Nisoldipine or 5-HT injection at continuing 41 degrees C normal tissue temperature controlled energy delivery produced an instantaneous further increment of tumor temperature, eventually to 44.0 +/- 1.14 degrees C or 44.2 +/- 1.26 degrees C, respectively, after a period of 20 min. Injection of 0.9% NaCl (N = 4) solution caused only insignificant changes. Blood pressure and muscle perfusion were distinctly influenced by nisoldipine, but not by 5-HT. Since both drugs instantaneously increased the temperature differential between tumor and normal tissue, though by different vasoaction, they should be considered as adjuvants in hyperthermia.
Knapp
W H
WH
Institute for Nuclear Medicine, German Cancer Research Center, Heidelberg.
Debatin
J
J
Helus
F
F
Sinn
H J
HJ
Ostertag
H
H
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D002279:Carcinoma 256, Walker / Q000098:blood supply / Q000628:therapy*; D006979:Hyperthermia, Induced; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015737:Nisoldipine; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*; D014464:Ultrasonic Therapy; D014980:Xenon Radioisotopes
D014980:Xenon Radioisotopes; D012701:Serotonin; D015737:Nisoldipine; D009543:Nifedipine