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 system for advanced lung cancer therapy. Our objective was to test the safety and accuracy of our venovenous perfusion-induced systemic hyperthermia system in 5-day sheep survival studies, following Good Laboratory Practice standards.

METHODS:

Our venovenous perfusion-induced systemic hyperthermia system, which included a double-lumen cannula (Avalon Elite, Rancho Dominguez, Calif), a centrifugal pump (Bio-Pump 560; Medtronic Inc, Minneapolis, Minn), a heat exchanger (BIOtherm; Medtronic Perfusion Systems, Brooklyn Park, Minn), and a heater/cooler (modified Blanketrol IIIl Cincinnati Subzero, Cincinnati, Ohio), was tested in healthy adult sheep (n=5). The perfusion circuit was primed with prewarmed Plasma-Lyte A (Baxter Healthcare Corp, Deerfield, Ill) and de-aired. Calibrated temperature probes were placed in the right and left sides of the nasopharynx, bladder, and blood in/out tubing in the animal. The double-lumen cannula was inserted through the jugular vein into the superior vena cava, with the tip in the inferior vena cava.

RESULTS:

Therapeutic core temperature (42°C-42.5°C), calculated from the right and left sides of the nasopharynx 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 minutes) 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 venovenous perfusion-induced systemic hyperthermia termination. Electrolytes, complete blood counts, and metabolism enzymes were within normal to near normal range throughout the study. No significant venovenous perfusion-induced systemic hyperthermia-related hemolysis was observed. Neurologic assessment showed normal brain function all 5 days.

CONCLUSIONS:

Our venovenous perfusion-induced systemic hyperthermia system safely delivered the hyperthermia dose with no significant hyperthermia-related complications.

• Authors: Cherry Ballard-Croft, Dongfang Wang, Kyle Rosenstein, Jingkun Wang, Robert Pollock, J Ann Morris, Joseph B Zwischenberger
• Journal: The Journal of thoracic and cardiovascular surgery (J Thorac Cardiovasc Surg) Vol. 148 Issue 5 Pg. 2360-6 (Nov 2014) ISSN: 1097-685X [Electronic] United States
• PMID: 24908352 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers

Topics

• Animals
• Biomarkers (blood)
• Body Temperature Regulation
• Equipment Design
• Extracorporeal Circulation (adverse effects, instrumentation, methods)
• Female
• Hemodynamics
• Hemolysis
• Hyperthermia, Induced (adverse effects, instrumentation, methods)
• Lung Neoplasms (therapy)
• Materials Testing
• Models, Animal
• Perfusion (adverse effects, instrumentation, methods)
• Sheep, Domestic
• Time Factors