Differential Response of Right Ventricular Contractility to Lung Ischemia-Reperfusion Injury: Large Animal Model to Study Sequential Single Lung Transplantation

Abstract

<h3>Purpose</h3> Early outcome after lung transplantation (LTx) is often characterized by the presence of primary graft dysfunction (PGD). The exact role of the right ventricle (RV) in development of PGD and perioperative outcome is unknown. Firstly, increased afterload due to PGD might compromise RV function. Secondly, increased contractility and cardiac output (CO) of RV might contribute to pulmonary edema accumulation after reperfusion. We developed a unique large animal model to study RV behavior in a setting of pulmonary ischemia-reperfusion injury (IRI). <h3>Methods</h3> The left lung (LL) of a domestic pig in clamping group [CLA] was clamped (3h warm ischemia) and reperfused (3h) in situ (n=6). During the final hour of reperfusion, contralateral right lung (RL) was clamped to force RV CO to the injured LL. Control animals [CON] were fully instrumented (n=5) and followed for 6 hours. The RV function was monitored using a conductance catheter measuring pressure-volume (PV) loops. Lung injury was assessed by wet to dry (W/D) ratio and ex-vivo computed tomography (CT). Data was analyzed in time using 2-way ANOVA test or student T-test. <h3>Results</h3> Pulmonary vascular resistance (PVR) rose significantly at hour 6 in [CLA], reflecting an increase of afterload due to IRI and RL camping (<i>fig. A</i>). RV Contractility was stable in [CON]. In [CLA], it increased in 2 animals (<i>fig. D</i>) and 4 animals developed RV failure (<i>fig. B</i>). Lungs were injured as reflected by higher W/D ratio (<i>p=0.0019</i>) and parenchymal density on CT (<i>p=0.0089</i>) of [CLA] LL compared to [CON]. <h3>Conclusion</h3> RV response to increased afterload resulting from IRI occurs in a dichotomized way: with increased contractility or with failure. This occurs when the contralateral lung is clamped and mimics a specific intra-operative situation of sequential single LTx. Our model should be considered as an innovative platform to study the possible benefit of ECLS devices on RV function and PGD development after LTx.