56The SGLT2 inhibitor empagliflozin reduces mortality in experimental pulmonary hypertension
| Autor: | Yi Pan, V. Luu, M G Kabir, A. Luu, Subodh Verma, C D Mazer, Adrian Quan, B Chowdhury, Hwee Teoh |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Lung business.industry Hemodynamics medicine.disease Pulmonary hypertension medicine.anatomical_structure Blood pressure Right ventricular hypertrophy Heart failure Internal medicine Empagliflozin Cardiology Medicine SGLT2 Inhibitor Cardiology and Cardiovascular Medicine business |
| Zdroj: | European Heart Journal. 40 |
| ISSN: | 1522-9645 0195-668X |
| Popis: | Introduction Empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, enhances urinary glucose excretion and profoundly reduces hospitalisation for heart failure and cardiovascular mortality in individuals with type 2 diabetes. While empagliflozin has been reported to reduce blood pressure, its effect on pulmonary arterial hypertension (PAH) is unknown. PAH is a serious and progressive disease that is characterised by pulmonary artery vasoconstriction, vascular remodelling, right ventricular hypertrophy, and ultimately heart failure. Purpose To investigate the impact of empagliflozin on PAH-associated mortality and the progression as well as reversal of PAH in monocrotaline (MCT)-treated Sprague-Dawley rats. Methods A total of 66 male rats (220–250 g) were randomly assigned to one of three studies. PAH was induced with a single intraperitoneal injection of MCT on day 0 and empagliflozin (10 mg/kg) was administered daily by oral gavage. Survival study: PAH was induced with 60 mg/kg MCT. Starting on day 1, rats were treated with empagliflozin (n=8) or vehicle (n=8) for 28 days and monitored for up to 45 days post-MCT injection. Prevention study: Rats were administered 60 mg/kg MCT and treated with empagliflozin (n=12) or vehicle (n=12) for 20 days from day 1 onwards. Reversal study: 21 days after being injected with 40 mg/kg MCT, rats were given empagliflozin (n=8) or vehicle (n=8) for 14 days. At the end of the treatment window, rats in the latter two studies underwent haemodynamic assessments before their tissues were harvested for histological review. Results Mortality rates between the two groups were significantly different (median survival 24 vs 33 days for vehicle vs empagliflozin; p Conclusion This is the first study demonstrating that SGLT2 inhibition with empagliflozin lowers mortality in experimental pulmonary hypertension in part via reduced pulmonary vascular remodelling. Acknowledgement/Funding This study was supported by grants from the Canadian Institutes of Health Research. |
| Databáze: | OpenAIRE |
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