Increased cardiac microvascular permeability and activation of cardiac endothelial nitric oxide synthase in high tidal volume ventilation-induced lung injury

Background: Positive pressure ventilation with large tidal volumes has been shown to cause lung injury via the serine/threonine kinase-protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS)-pathways. However, the effects of high tidal volume (V_T) ventilation on the heart are unclear. Objectives: Evaluate the effect of VT ventilation on the cardiac vascular permeability and intracellular Akt and eNOS signaling pathway. Methods: C57BL/6 and Akt knock-out (heterozygotes, +/−) mice were exposed to high V_T (30 mL/kg) mechanical ventilation with room air for one and/or five hours. Results: High V_T ventilation increased cardiac microvascular permeability and eNOS phosphorylation in a timedependent manner. Serum cardiac troponin I was increased after one hour of high V_T ventilation. Cardiac Akt phosphorylation was accentuated after one hour and attenuated after five hours of high V_T ventilation. Pharmacological inhibition of Akt with LY294002 and high V_T ventilation of Akt+/− mice attenuated cardiac Akt phosphorylation, but not eNOS phosphorylation. Conclusion: High V_T ventilation increased cardiac myocardial injury, microvascular permeability, and eNOS phosphorylation. Involvement of cardiac Akt in high V_T ventilation was transient.