COMMENTARY Pulmonary and renal protection: targeting PARP to ventilator-induced lung and kidney injury?

Abstract

Both acute lung injury and acute kidney injury (AKI) are frequent and serious problems in intensive care medicine. Therefore, the avoiding of any iatrogenic insult to these organs is of great importance. While an increasing body of evidence suggests that mechanical ventilation is capable of inducing lung and distant organ injury, the complex underlying molecular mechanisms remain insufficiently understood. In the previous issue of Critical Care, Vaschetto and colleagues reported the results of an experimental study designed to further explore pathways linking injurious ventilation with AKI. The authors demonstrated that scavenging of peroxynitrite or inhibiting poly(ADP-ribose) polymerase (PARP) afforded protection against AKI induced by double-hit lung injury. Although PARP inhibition or peroxynitrite detoxification or both may become viable candidates for a protective strategy in this setting, the implementation of a lung-protective ventilatory strategy remains the only clinical tool to mitigate the lung biotrauma and its systemic consequences. In the previous issue of Critical Care, Vaschetto and colleagues [1] sought to determine whether and by which mechanism(s) the activation of poly(ADP-ribose) polymerase (PARP) contributes to the acute kidney injury (AKI) induced by injurious mechanical ventilation (MV). The authors used a double-hit rat model of acute lung injury comprising lipopolysaccharide-induced lung inflammation and MV with either very high tidal volume (19 mL/ kg, zero positive end-expiratory pressure [PEEP]) or low tidal volume (6 mL/kg, PEEP 5 cm H 2 O). To address th