Objective
Since hyperthermia selectively kills lung cancer cells, we developed a venovenous perfusion-induced systemic hyperthermia (vv-PISH) system for advanced lung cancer therapy. Our objective was to test the safety/accuracy of our vv-PISH system in five day sheep survival studies, following Good Laboratory Practice standards.
Methods
The vv-PISH system, which included a double lumen cannula (DLC, AvalonElite™); a centrifugal pump (Bio-Pump 560®); a heat exchanger (BIOtherm™); and a heater/cooler (modified Blanketrol III™), was tested in healthy adult sheep (n=5). The perfusion circuit was primed with pre-warmed Plasma-Lyte®A and de-aired. Calibrated temperature probes were placed in right/left nasopharynx, bladder, and blood in/out of animal. The DLC was inserted in jugular vein into the superior vena cava, with the tip in the inferior vena cava.
Results
Therapeutic core temperature (42-42.5°C), calculated from right/left nasopharnx and bladder temperatures, was achieved in all sheep. Heating time was 21±5 minutes. Therapeutic core temperature was maintained for 120 minutes followed by a cooling phase (35±6 min) to reach baseline temperature. All sheep recovered from anesthesia with spontaneous breathing within 4 hours. Arterial, pulmonary, and central venous pressures were stable. Transient increases in heart rate, cardiac output, and blood glucose occurred during hyperthermia but returned to normal range after vv-PISH termination. Electrolytes, complete blood counts, and metabolism enzymes were within normal to near normal range throughout the study. No significant vv-PISH-related hemolysis was observed. Neurological assessment showed normal brain function all 5 days.
Conclusion
Our vv-PISH system safely delivered the hyperthermia dose with no significant hyperthermia-related complications.
Summary. Syringe pumps are almost uuivt'isally n.sed for con.stant perfusion oesophagenl manonietry. despite important tccliniea! limitiition.s. A pueumatieally driveu pcrfnsion pump ha.s heen tlesijjnt-d .i^pt'ciReally for oesopliaiieal nianoluetry. This piiiiip re(iuire.'i less than one third tin-How setting of a syriii^t' pump to achieve a giveu rate of pressore rise. It is simpU-to operate and needs infrequent refillinH. Nearly two years' practical experience with this pmiip has confirmed its superiority over the syringe pump for constant perfusion manonietry.
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