Abstract 18705: Simian Immunodeficiency Virus Induces Pulmonary Arterial Hypertension in Rhesus Macaques: A Hemodynamic Study

Abstract

Background: Our prior studies have shown that the Cyno Macaques and Resus Macaques infected with simian immunodeficiency virus (SIV) develop pulmonary arterial hyperplasia by histopathology. The hemodynamic changes with infection, however, remain unknown. The purpose of this study was to determine the relationship of the SIV infection and cardiac hemodynamic changes as assessed by invasive right heart catheterization. Methods: Five Rhesus macaques underwent pulmonary artery catheterization at baseline and 6 months after infection with SIV. Right atrial pressure (RAP), right ventricular end systolic pressure (RVESP), end diastolic pressure (RVEDP), and mean pulmonary artery pressure (mPAP) were measured directly using a pediatric pulmonary artery catheter. RV dp/dt min, dp/dt max, Tau and contractility index were calculated by Matlab software. In addition, mPAP was calculated in a larger cohort (n=24) by the regression formula: mPAP=RVSP*0.65+0.55 in order to validate this calculation in non-human primates. Results: After 6 months of SIV infection, RAP, RVSP, and mPAP increased significantly compared to baseline values. RVEDP trended toward being higher but was not statistically significant from baseline. The RV dp/dt min, dp/dt max and Tau didn’t show significant changes. The contractility index had a markedly decrease with SIV infection compared with baseline. Moreover, direct measure mPAP correlated well with the calculation of mPAP (R 2 =0.954; P<0.0001). Conclusion: Based on the presented data we conclude that SIV induces pulmonary arterial hypertension in Rhesus monkeys concordant with the histopathological observation in our prior studies. SIV infection also decreases the RV contractility as well. These data suggest that this may be a viable large animal, preclinical model of PAH with hemodynamics and histology consistent with the human condition.