Safety evaluation of long-term temperature controlled whole-body thermal treatment in female Aachen minipig

Abstract

Objective: Thermal treatment (TT), defined as treatment using supra-physiological body temperatures (39-45 C), somewhat resembles fever in terms of temperature range, one of the first natural barriers for the body to fight exposure to external pathogens. Methods: Whole-body thermal treatment (WBTT) consists of heating up the complete body to a temperature range of 39 to 45 C. Despite the recognized therapeutic potential of hyperthermia, the broad clinical use of WBTT has been limited by safety issues related to medical devices and procedures used to achieve WBTT, in particular adequate control of the body temperature. To circumvent this, a sophisticated medical device was developed, allowing long-term temperature controlled WBTT (41.5 C for up to 8 h). Technical feasibility and tolerability of the WBTT procedure (including complete anesthesia) were tested using female Aachen minipig. Optical fiber temperature sensors inserted in multiple organs were used and demonstrated consistent monitoring and control of different organs temperature over an extended period of time. Results: Clinical evaluation of the animals before, during and after treatment revealed minor clinical parameter changes, but all of them were clinically acceptable. These changes were limited and reversible, and the animals remained healthy throughout the whole procedure and follow-up. In addition, histopathological analysis of selected key organs showed no thermal treatment-related changes. Conclusion: It was concluded that WBTT (41.5 C for up to 8 h) was well tolerated and safe in female Aachen minipigs. Altogether, data supports the safe clinical use of the WBTT medical device and protocol, enabling its implementation into human patients suffering from life-threatening diseases.

Whole-body thermal therapy as adjuvant therapy to radiation in a dog with metastasized anal sac adenocarcinoma

“…Necropsy of Aachen minipigs that underwent WBTT for safety evaluation also revealed no abnormalities within the brain (Carneiro et al, 2021). The effect of WBTT on brain tissue in dogs has been reported, both on the effect of brain hemodynamics and the bloodbrain barrier (Katsumura et al, 1995) as well as histological induced changes (Takahashi et al, 1999;Haveman et al, 2005).…”

“…The patient underwent WBTT at 41.5°C by circulating air in a dedicated treatment cabinet designed to safely induce, measure and maintain a constant elevated body temperature. The used treatment protocol was proven safe and manageable in Aachen minipigs (Carneiro et al, 2021). Reported beneficial effects of WBTT include enhancement of immunity, inhibition of DNA repair mechanisms and an increase of perfusion to tumors, making them more susceptible to adjuvant radiotherapy (Mallory et al, 2015).…”

Hyperthermia Enhances Efficacy of Chemotherapeutic Agents in Pancreatic Cancer Cell Lines

“…The thermotolerance of the liver and brain determines the maximal feasible target temperature, suited for clinical settings, to be equal to 41.8-42 • C, which may be maintained for several hours [33][34][35][36]. We have previously reported the safety and tolerability of WBTT at 41.5 • C for up to 3 consecutive exposures of 8 h in dogs and mini pigs [37,38].…”

Progress on Infrared Imaging Technology in Animal Production: A Review

“…Maintaining a relatively constant core body temperature is essential to maintaining optimal body system function and sensitive biochemical response processes [ 9 ]. Recent scientific studies have shown that a fatal brain damage might occur when the temperature is higher than 45 °C, whereas cardiac fibrillation, respiratory rate decrease, and even death might occur when temperatures are below 27–29 °C [ 10 , 11 ]. In addition, when animals are in a state of stress, estrus or pregnancy, or have infectious diseases, the autonomic sympathetic nerves in the body release catecholamines.…”