Mild Hypothermia via External Cooling Improves Lung Function and Alleviates Pulmonary Inflammatory Response and Damage in Two-Hit Rabbit Model of Acute Lung Injury

Abstract

Objectives

Targeted temperature management (TTM) with therapeutic hypothermia (TH) has an organ-protective effect by mainly reducing inflammatory response. Here, our objective was to determine, for the first time, whether mild TH with external cooling, a simple and inexpensive method, could be safe or even beneficial in two-hit rabbit model of acute lung injury/acute respiratory distress syndrome (ALI/ARDS).

Methods

Twenty-two New Zealand rabbits (6-month-old) were randomly divided into healthy control (HC) with conventional ventilation, but without injury, model group (ALI), and hypothermia group with external cooling (ALI-HT). After induction of ALI/ARDS through mild lung-lavages followed by non-protective ventilation, mild hypothermia was started in ALI-HT group (body temperature of 33–34 °C). All rabbits were conventionally ventilated for an additional 6-h by recording respiratory parameters. Finally, lung histopathology and inflammatory response were evaluated.

Results

Hypothermia was associated with higher oxygen saturation, resulting in partial improvement in the P/F ratio (PaO₂/FiO₂), oxygenation index, mean airway pressure, and PaCO₂, but did not affect lactate levels. The ALI-HT group had lower histopathological injury scores (hyperemia, edema, emphysema, atelectasis, and PMN infiltration). Further, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and −8 levels in lung tissue and serum samples markedly reduced due to hypothermia.

Conclusion

Mild TH with external cooling reduced lung inflammation and damage, whereas it resulted in partial improvement in gas exchanges. Our findings highlight that body temperature control may be a potentially supportive therapeutic option for regulating cytokine production and respiratory parameters in ALI/ARDS.

Keywords:

• Acute lung injury (ALI)
• acute respiratory distress syndrome (ARDS)
• mild therapeutic hypothermia (TH)
• external cooling
• inflammatory factors
• lung damage

Compliance with ethical standards

The investigation complies with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health and was approved by the Animal Ethics Committee of Bağcılar Training and Research Hospital, Istanbul, Turkey (approval protocol number: 2017/60, 25th April 2017). This article does not contain any studies with human participants.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability

Data can be provided if requested.

Additional information

Funding

This work was supported by the T.C. Health Ministry, Health Sciences University, Bağcılar Training and Research Hospital, Turkey (Grant number: 2016/6.27.06.2016).