猪模型中体外诱导全身高热的热分布、生理效应和毒性。

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

机构信息

Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.

Department of Intensive Care medicine, Radboud University Medical Center, Nijmegen, The Netherlands.

出版信息

Physiol Rep. 2020 Feb;8(4):e14366. doi: 10.14814/phy2.14366.

DOI:10.14814/phy2.14366

PMID:32097540

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7058172/

Abstract

BACKGROUND

Extracorporeally induced whole-body hyperthermia (eWBH) might be a beneficial treatment in cancer patients. Objectives of this pig study were to assess thermal distribution, (patho-)physiological effects, and safety of eWBH with a new WBH device.

METHODS

Fourteen healthy adult pigs were anesthetized, mechanically ventilated, and cannulated; 12 were included in the analysis. Blood was heated in 11 pigs (one pig served as control) using a WBH device (Vithèr Hyperthermia B.V.) containing two separate fluidic circuits and a heat exchanger. Temperature was monitored on nine different sites, including the brain. Core temperature (average of 4 deep probes) was elevated to 42°C for 2 hr.

RESULTS

Elevation of core body temperature to 42°C took on average (± standard deviation) 38 ± 8 min. Initially observed temperature spikes diminished after lowering maximal blood temperature to 45°C. Hereafter, brain temperature spikes never exceeded 42.5°C, mean brain temperature was at highest 41.9°C during maintenance. WBH resulted in increased heart rates and decreased mean arterial pressures. The vast amounts of fluids required to counter hypotension tended to be smaller after corticosteroid administration. Hemodialysis was started in three animals (potassium increase prevention in two and hyperkalemia treatment in one). Severe rhabdomyolysis was observed in all pigs (including the control). All animals survived the procedure until planned euthanasia 1, 6, or 24 hr post procedure.

CONCLUSION

Fast induction of eWBH with homogenous thermal distribution is feasible in pigs using the Vithèr WBH device. Severe hemodynamic disturbances, rhabdomyolysis, and hyperkalemia were observed.

摘要

背景

体外全身热疗（eWBH）可能对癌症患者有益。本猪研究的目的是评估新型 WBH 设备的热分布、（病理）生理效应和安全性。

方法

14 头健康成年猪接受麻醉、机械通气和插管；12 头猪被纳入分析。使用包含两个独立流体回路和热交换器的 WBH 设备（Vithèr Hyperthermia B.V.）对 11 头猪（一头猪作为对照）的血液进行加热。在 9 个不同部位（包括大脑）监测温度。核心体温（4 个深部探头的平均值）升高至 42°C，持续 2 小时。

结果

核心体温升高至 42°C 平均用时（±标准差）为 38±8 分钟。最初观察到的温度峰值在将最大血液温度降低至 45°C 后减少。此后，大脑温度峰值从未超过 42.5°C，维持时大脑平均温度最高为 41.9°C。WBH 导致心率增加和平均动脉压降低。低血压时需要输入大量液体，而皮质类固醇给药后倾向于输入更小剂量的液体。3 只动物开始血液透析（2 只为预防血钾升高，1 只为高钾血症治疗）。所有猪（包括对照猪）均出现严重横纹肌溶解。所有动物均存活至计划的术后 1、6 或 24 小时安乐死。