Abstract

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is generated after one or repited pulmonary embolism (PE).

Objectives: To study the relationship between the levels of microvesicles (MVs) and hemodynamic changes on mean pulmonary arterial pressures (mPAP) from PE to CTEPH.

Methods: Experimental procedures were performed in large white pigs. Acute PE was generated by pulmonary embolization with polydextrane-microspheres with a diameter of 300 ?m, pre-capillary PH was obtained by repeated microsphere embolizations. Next, we carried out a case-control study with 9 patients with CTEPH and 18 with PE without CTEPH. We measured total MVs, endothelial (EMVs), leukocytes (LMVs) and mesenchymal origin by flow cytometry. U-Mann Whitney, Friedman and Spearman's coefficient were applied according to analysis.

Results: The animal model achieved to increase mPAP after an acute embolism (p=0.02) and after repeat embolisms (p=0.034) reproducing the hemodynamic features seen in the patients.
Negative correlations were found between EMVs and mPAP after repeated embolisms (Rho: -0.886, p=0.019) and between LMVs and mPAP in an acute embolism (Rho: -0.986, p<0.001). 
Positive correlation was shown between mPAP after an acute embolism and CD90+CD105+Mvs measured after repeated embolisms (Rho: 832, p=0.040).
In patients, MVs in CTEPH group are higher than in PE (p=0.046). EMVs decreased in the most severe patients while LMVs increased in these patients.

Conclusions: Inverse relationship between EMVs levels and mPAP suggests a lack of endothelial reserve in the experimental model and in the most severe patients.