Background: Acute respiratory distress syndrom/acute lung injury (ARDS/ALI) can lead to excessive pulmonary hypertension (PH) which imposes strain on the right ventricle (RV). Low tidal volume ventilation (LTVV) might be detrimental to RV-function for its potential hypercapnia.
Objective: In a pig model of acute PH secondary to ALI we evaluated the cardiopulmonary effects of LTVV with and without pulmonary vasodilation by tezosentan (TEZO), a dual ET-1 receptor blocker. We hypothesized that ET-1 blockade would attenuate PH in this setting.
Method: Eighteen 4-week–old white farm piglets were randomly assigned to low tidal volume ventilation (LTVV) (6ml/kg) (n=6), LTVV plus continous iv TEZO (5mg/kg/h) (n=6), or to normal ventilation (controls, n=6). ALI was induced by bronchoalveolar lavage with normal saline and 2ml/kg 0.1 molar hydrochloric acid.
Results: After 4 hours of ALI mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance index (PVRi) as well as ratios of pulmonary to systemic artery pressure (PAP/SAP), and resistance (PVR/SVR) were lower in the LTVV+TEZO group than in controls (p<0.0001 for all parameters), not different from baseline values (before induction of ALI). Central venous saturation was higher in the treatment groups (71% ± 6 vs. 55% ± 13, p<0.002), while partial arterial pressure of oxygen (PaO2)did not differ.
Conclusion: In experimental ALI low tidal volume ventilation in combination with dual ET-1 receptor blockade by tezosentan completely blocks pulmonary vasoconstriction, thereby deminishing right ventricular strain. Combining lung and heart protective strategies without afflicting pulmonary gas exchange might be beneficial in the treatment of ALI/ARDS.