Perfusion induced hyperthermia for oncologic therapy with cardiac and cerebral protection

Cancer can be preferentially damaged and killed at temperatures above 41.0 degrees C. However, the heart and brain malfunction at this temperature, limiting the application of systemic hyperthermia in the treatment of metastatic cancer. We created a hyperthermic perfusion system that maximizes the temperature differential produced and extends the safe hyperthermic time. Mongrel dogs were anesthetized and mechanically ventilated. Temperature probes were placed in the rectum, bladder, peritoneal cavity, proximal aorta, pulmonary artery, and right tympanic canal. Venoarterial perfusion was instituted and the perfusate was warmed to 44 to 45 degrees C. The dogs' rectal temperature was elevated to > or = 42 degrees C for 4 hours. A small amount of venous blood was cooled to 28 to 30 degrees C and reperfused into the right atrium to maintain the pulmonary artery temperature < or = 38 degrees C. At the end of the perfusion, the dogs were decannulated, recovered, and returned to their cages for observation. Ten of 11 dogs survived the operative procedure, and no neurologic deficits were observed. The rectal temperature was successfully elevated to > or = 42 degrees C for 4 hours while maintaining the heart and brain at < or = 38 degrees C. Moderate serum biochemical changes were observed postprocedure. However, only the aspartate transaminase and alkaline phosphatase levels remained elevated above both the baseline and canine reference values by day 7. Lower abdominal and pelvic hyperthermia at 42 degrees C can be safely produced and maintained for 4 hours using an extracorporeal perfusion circuit, while protecting the heart and brain from temperature elevation.