Therapeutic hypothermia attenuates physiologic, histologic, and metabolomic markers of injury in a porcine model of acute respiratory distress syndrome

Abstract

Acute respiratory distress syndrome (ARDS) is a lung injury characterized by noncardiogenic pulmonary edema and hypoxic respiratory failure. The purpose of this study was to investigate the effects of therapeutic hypothermia on short‐term experimental ARDS. Twenty adult female Yorkshire pigs were divided into four groups (n = 5 each): normothermic control (C), normothermic injured (I), hypothermic control (HC), and hypothermic injured (HI). Acute respiratory distress syndrome was induced experimentally via intrapulmonary injection of oleic acid. Target core temperature was achieved in the HI group within 1 h of injury induction. Cardiorespiratory, histologic, cytokine, and metabolomic data were collected on all animals prior to and following injury/sham. All data were collected for approximately 12 h from the beginning of the study until euthanasia. Therapeutic hypothermia reduced injury in the HI compared to the I group (histological injury score = 0.51 ± 0.18 vs. 0.76 ± 0.06; p = 0.02) with no change in gas exchange. All groups expressed distinct phenotypes, with a reduction in pro‐inflammatory metabolites, an increase in anti‐inflammatory metabolites, and a reduction in inflammatory cytokines observed in the HI group compared to the I group. Changes to respiratory system mechanics in the injured groups were due to increases in lung elastance (E) and resistance (R) (ΔE from pre‐injury = 46 ± 14 cmH2O L−1, p < 0.0001; ΔR from pre‐injury: 3 ± 2 cmH2O L−1 s−, p = 0.30) rather than changes to the chest wall (ΔE from pre‐injury: 0.7 ± 1.6 cmH2O L−1, p = 0.99; ΔR from pre‐injury: 0.6 ± 0.1 cmH2O L−1 s−, p = 0.01). Both control groups had no change in respiratory mechanics. In conclusion, therapeutic hypothermia can reduce markers of injury and inflammation associated with experimentally induced short‐term ARDS.

Advanced Diagnostic Tools in Hypothermia-Related Fatalities—A Pathological Perspective

“…The literature contains relatively scarce data regarding the ensemble of autopsy morphological changes in the interalveolar septum that appear in fatal hypothermia, with these being mainly focused on the therapeutic applicability of exposure to low temperatures (therapeutic hypothermia) in the context of different injuries by reducing alveolar septum leukocyte infiltration and increasing the proportion of dipalmitoylphosphatidylcholine upon compression [30,31].…”