{"id":38068,"date":"2024-07-31T09:50:00","date_gmt":"2024-07-31T07:50:00","guid":{"rendered":"https:\/\/www.etap-lab.com\/?post_type=ressource&p=38068"},"modified":"2026-05-13T09:52:12","modified_gmt":"2026-05-13T07:52:12","slug":"poster-heart-rv-dysfunction-pah-induced","status":"publish","type":"ressource","link":"https:\/\/www.etap-lab.com\/en\/ressource\/poster-heart-rv-dysfunction-pah-induced\/","title":{"rendered":"POSTER: “Effect of SGLT2i on RV failure: comparison between Empagliflozin and current therapies in a preclinical model of RV dysfunction PAH-induced\u201d"},"content":{"rendered":"\n

Presented by Christophe Muller at the Heart Failure Drug Discovery & Development Summit (in July-August 2024, in Boston, USA, MA). <\/p>\n\n\n\n

EASY POSTER REQUEST<\/a><\/p>\n\n\n\n

<\/p>\n\n\n\n

Authors<\/strong>: Guillaume Bourdier1<\/sup>, Jessica Morand1<\/sup>, Audrey Bourdet1<\/sup>, Sandra Robelet1<\/sup>, Nicolas Violle2<\/sup><\/p>\n\n\n\n

Affiliations<\/strong>:<\/p>\n\n\n\n

1<\/sup> SYNCROSOME, 13288, Marseille, France<\/p>\n\n\n\n

2<\/sup> ETAP-Lab, 54500, Vand\u0153uvre-l\u00e8s-Nancy, France<\/p>\n\n\n\n

\u00a0Keywords<\/strong>: RV failure, pulmonary hypertension, echocardiography, empagliflozin<\/p>\n\n\n\n

Background<\/strong>: Pulmonary arterial hypertension (PAH) is a rare disease characterized by a progressive right ventricular (RV) failure because of pulmonary vasculopathy1<\/sup>. Current therapeutic targets of PAH are focused on improving vasodilation in pulmonary arterioles with drugs as Selexipag or Sildenafil. Unfortunately, no currently available therapy directly targets the RV, which still represents the strongest predictor of mortality in PAH2<\/sup>. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor reduces cardiovascular events and mortality in HFpEF patients3<\/sup>. However, its effect on RV failure PAH-induced are poorly described.<\/p>\n\n\n\n

Objectives<\/strong>: This study compares the cardiovascular effects of Empagliflozin with benchmark molecules Selexipag and Sildenafil in PAH treatments in a preclinical rat model. Our translational evaluation assessed the potential of Empagliflozin in targeting RV failure in PAH.<\/p>\n\n\n\n

Methods<\/strong>: Six-week-old Sprague-Dawley male rats were used. Following a single dose of the vascular endothelial growth factor receptor blocker, Sugen (20 mg\/kg, SC), rats were exposed to hypoxia (10% O2<\/sub>) for 3 weeks. Then, rats were treated for 3 other weeks, with either Vehicle control or Empagliflozin, Sildenafil or Selexipag at dose of 30 mg\/kg once or twice daily, respectively. At the end of the treatment, echocardiography and terminal catheterization were performed to assess RV dysfunction and hypertension. Finally, cardiac and arteriolar remodeling were assessed by gravimetric analysis and histology.<\/p>\n\n\n\n

Results<\/strong>: It was found that, the Sugen\/hypoxia followed by normoxia protocol (SuHxNx), induced a large RV dysfunction, including a significant decrease of stroke volume (SV) and cardiac output (CO), a significant decrease of pulmonary artery hemodynamic (PAAT\/ET) and clear rise in RV systolic pressure (RVSP). Moreover, the SuHxNx model was associated with an important RV remodeling (RV hypertrophy and fibrosis), as well as a robust arteriolar PAH phenotype evaluated by histopathological scoring (global arterial score or GAS): with marked vascular lumen occlusion, intimal proliferation and fibrosis compared to the situation in tissues from control animals. Current drugs used to treat PAH, Selexipag and Sildenafil, were able to prevent the evolution of the deleterious phenotype to RV failure. In addition to a strong effect on RV function: including significant improvement of SV, CO, PAAT\/ET and RVSP, they induced a decrease of cardiac hypertrophy and an amelioration of the vascular remodeling induced by the SuHxNx protocol: including reduced arteriolar vessel occlusion, intimal proliferation (including a reduction of plexiform lesions) and fibrosis. Empagliflozin, despite a slight effect on SV and CO, was not able to significantly prevent the SuHxNx effects on PAAT\/ET, RVSP and RV remodeling. Finally, Empagliflozin was not able to reverse the vascular remodeling and arteriolar occlusion PAH-induced.<\/p>\n\n\n\n

Conclusion<\/strong>: <\/em>In conclusion, Empagliflozin failed to prevent the RV failure, contrary to Sildenafil and Selexipag, that showed major effects in the SuHxNx preclinical model of PAH. They prevented the vascular remodeling leading to RV failure and confirmed the strong predictivity of the Sugen\/hypoxia model.<\/p>\n","protected":false},"excerpt":{"rendered":"

Discover POSTER: “Pro-healing effects of Plasana One\u00ae, an argon-generated cold plasma on ischemic skin wounds\u201d: Discover the excellent on ischemic skin wounds in our Poster:\u2026<\/p>\n","protected":false},"featured_media":37803,"template":"","meta":{"_acf_changed":false},"categorie-de-ressource":[236],"marque-de-ressource":[243],"class_list":["post-38068","ressource","type-ressource","status-publish","has-post-thumbnail","hentry","categorie-de-ressource-posters","marque-de-ressource-syncrosome"],"acf":[],"yoast_head":"\nPOSTER: "Effect of SGLT2i on RV failure: comparison between Empagliflozin and current therapies in a preclinical model of RV dysfunction PAH-induced\u201d - ETAP-LAB<\/title>\n<meta name=\"description\" content=\"POSTER: "Effect of SGLT2i on RV failure: comparison between Empagliflozin and current therapies in a preclinical model of RV dysfunction PAH-induced\u201d\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.etap-lab.com\/en\/ressource\/poster-heart-rv-dysfunction-pah-induced\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"POSTER: "Effect of SGLT2i on RV failure: comparison between Empagliflozin and current therapies in a preclinical model of RV dysfunction PAH-induced\u201d - 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