Body temperature effects on lung injury in ventilated preterm lambs.

Abstract

Mechanical ventilation causes lung injury in premature infants. Hypothermia may protect against and hyperthermia may augment lung injury. We tested the effects of hypo- and hyperthermia on ventilation induced acute lung injury in preterm lambs. Twin sheep fetuses at 128 d GA (term 150 d) were surgically delivered and randomized to unventilated control (UVC), normothermia (38-39 degrees C) without lung injury (NTNI), or to 1 of 3 injurious ventilation groups: hypothermic (33-34 degrees C, LT), normothermic (38-39 degrees C, NT) or hyperthermic (40-41 degrees C, HT). NT, LT and HT groups had 15 min of injurious ventilation (PEEP 0 cmH(2)O, V(T) escalation to 15 mL/kg) following delivery and prior to surfactant. The animals were then gently ventilated (PEEP 5cmH(2)O, V(T) 7.5 mL/kg) for 2h 45 min. NTNI lambs received surfactant at birth prior to gentle ventilation. The lambs were then euthanized, and bronchoalveolar lavage (BAL) fluid and lung tissue were used to evaluate lung injury, inflammatory cell counts, inflammatory markers and cytokine mRNA. Target temperatures were achieved by 15 min of age and maintained for 3h. All ventilated groups had increased BAL protein, lung inflammation and increased cytokine mRNA. HT animals developed acidosis, premature death, pneumothoraces, impaired lung function and increased inflammatory mRNA expression. LT animals remained clinically stable without pneumothoraces or death, had improved ventilatory efficiency and trended toward lower inflammatory mRNA expression than NT animals. Hyperthermia exacerbated ventilator induced lung injury, while hypothermia may protect against lung injury in the preterm lamb.