Susceptibility to ventilator induced lung injury is increased in senescent rats

Introduction: The principal mechanisms of ventilator induced lung injury (VILI) have been investigated in numerous animal studies. However, prospective data on the effect of old age on VILI are limited. Under the hypothesis that susceptibility to VILI is increased in old age, we investigated the pulmonary and extrapulmonary effects of mechanical ventilation with high tidal volume (VT) in old compared to young adult animals. Interventions: Old (19.1 +/- 3.0 months) and young adult (4.4 +/- 1.3 months) male Wistar rats were anesthetized and mechanically ventilated (positive end-expiratory pressure 5 cmH2O, fraction of inspired oxygen 0.4, respiratory rate 40/minute) with a tidal volume (VT) of either 8, 16 or 24 ml/kg for four hours. Respiratory and hemodynamic variables, including cardiac output, and markers of systemic inflammation were recorded throughout the ventilation period. Lung histology and wet-to-dry weight ratio, injury markers in lung lavage and respiratory system pressure-volume curves were assessed post mortem. Basic pulmonary characteristics were assessed in non-ventilated animals. Results: Compared to young adult animals, high VT (24 ml/kg body weight) caused more lung injury in old animals as indicated by decreased oxygenation (arterial oxygen tension (PaO2): 208 +/- 3 vs. 131 +/- 20 mmHg; P <0.05), increased lung wet-to-dry-weight ratio (5.61 +/- 0.29 vs. 7.52 +/- 0.27; P <0.05), lung lavage protein (206 +/- 52 mg/l vs. 1,432 +/- 101; P < 0.05) and cytokine (IL-6: 856 +/- 448 vs. 3,283 +/- 943 pg/ml; P < 0.05) concentration. In addition, old animals ventilated with high VT had more systemic inflammation than young animals (IL-1 beta: 149 +/- 44 vs. 272 +/- 36 pg/ml; P < 0.05 young vs. old, respectively). Conclusions: Ventilation with unphysiologically large tidal volumes is associated with more lung injury in old compared to young rats. Aggravated pulmonary and systemic inflammation is a key finding in old animals developing VILI.