The Effect of PEEP on RV Function in ECPR: A Pre-Clinical VA-ECMO-Supported Swine Model
Principal Investigator: Manuel Martin-Flores
Co-PI: Joaquin Araos
DESCRIPTION (provided by applicant):
Right ventricle dysfunction (RVDYS) predicts poor outcomes in venoarterial extracorporeal membrane oxygenation (VA ECMO) independent of left ventricle (LV) function. Specifically, failure to improve PA pulse pressure (as a proxy for RVDYS) after ECMO initiation associates with worsened mortality in large registry data. Unfortunately, there is not a well-proven therapy to improve RV function. Ventilator pressures 1) directly affect the RV and 2) associate with survival in ECMO for cardiac arrest (i.e., extracorporeal cardiopulmonary resuscitation [ECPR]); however, it is unknown if and how ventilator settings affect RV function in ECPR.
We propose leveraging an existing VF swine model to examine if and how the ventilator affects RV function in ECPR. Specific ventilator settings like positive end-expiratory pressure (PEEP), the pressure remaining in the airways at end of passive exhalation, are known to affect RV afterload with a U-shaped relationship in non-ECMO populations. Extreme low and high PEEP both increase RV afterload albeit via different mechanisms. To address if PEEP affects RV function in ECMO, we will compare three PEEP levels on the primary outcome of RV ejection fraction in an ECPR model. Our RV ejection fraction (EF) primary outcome will be quantified via single-beat, pressure-based methods as previously described and validated by members of my mentor team. Secondary endpoints will be clinically useful pressure and echo metrics of RV function. Swine will be supported with ECMO during CA and assigned to one of three mechanical ventilation strategies: fixed low PEEP, fixed moderate PEEP, or fixed high PEEP. Our ultimate objective is to characterize the physiologic mechanisms of heart-lung interactions to improve patient outcomes and optimize the use of resuscitative ECMO.