Venovenous perfusion-induced systemic hyperthermia: Five-day sheep survival studies

Abstract

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.

Thermal distribution, physiological effects and toxicities of extracorporeally induced whole‐body hyperthermia in a pig model

“…In both animal (Ballard‐Croft et al, ; Oglesbee, Diehl, Crawford, Kearns, & Krakowka, ; Vertrees et al, ) and human (Ash et al, ; Cremer et al, ; Locker et al, ; Zwischenberger et al, ) models hemodynamic changes are observed during eWBH treatment. These changes are attributable to a rapid decrease in systemic vascular resistance due to vasodilatation, resulting in a compensatory increase in heart rate and cardiac output (Faithfull et al, ; Locker et al, ).…”

“…In one of two animal studies on eWBH performed by Ballard‐Croft et al, a total of 3.070 ± 683 ml (744 ± 205 ml/hr) fluid resuscitation were reported to maintain stable hemodynamics in five sheep during eWBH (2 hr, 42–42.5°C). The second study reported fluid infusion of 100‐500 mL/hr in seven swine undergoing eWBH (2 hr, 42°C) to maintain stable hemodynamics (Ballard‐Croft et al, ). Both studies did not use corticosteroids.…”

“…6 (n = 2/2) b 7.3 ± 1.1 1.2 ± 0.5 6.0 ± 0.5 7.8 ± 1. et al, 1990) 7.47 [7.44-7.51] 7.41 [7.39-7.47] 7.42 [7.38-7.45] 7.42 [7.36-7.46] 7.43 [7.38-7.49] 7.47 [7.40-7.49] 7.42 [7.36-7.49] -7.35-7.52 Lactate (mmol/L) 0.5-1.5 maintain stable hemodynamics (Ballard-Croft et al, 2014). Both studies did not use corticosteroids.…”