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H 2 S Therapy Improves Diastolic Dysfunction and Exercise Capacity in Two‐Hit Murine Model of Heart Failure with Preserved Ejection Fraction
Author(s) -
Doiron Jake E.,
Lapenna Kyle,
Li Zhen,
Xia Huijing,
Goodchild Traci,
Xian Ming,
Kang Jianming,
Lefer David
Publication year - 2022
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2022.36.s1.r4073
Subject(s) - medicine , heart failure with preserved ejection fraction , heart failure , cardiology , ejection fraction , preload , diastole , exercise intolerance , cardiac function curve , hemodynamics , blood pressure
Background HFpEF is a complex multi‐organ disease expected to represent >60% of all clinical heart failure cases by 2030. To date, the majority of therapeutic approaches to treat HFpEF have largely failed in either preclinical or clinical trials. Given the recent reports of diminished H 2 S bioavailability in HFpEF combined with the robust cardioprotective actions of H 2 S in cardiovascular disease, we sought out to test the effects of H 2 S therapy in a well‐established pre‐clinical HFpEF murine model. Methods HFpEF was induced in nine‐week‐old C57/BL6N mice (n=10 per group) by high fat diet and L‐NAME (0.5g/L/day) via drinking water for 5 weeks. Mice were treated with either vehicle or the H 2 S donor, JK‐1 (100 mg/kg/day B.I.D., I.P.) for a period of 5 weeks. Echocardiography and exercise capacity were performed at study weeks 0, 5, and 10 for monitoring of cardiac function and progression of exercise intolerance. At week 10, endothelium‐dependent and independent aortic vascular reactivity and left ventricular invasive hemodynamic studies were performed. Results Treatment with JK‐1 significantly improved cardiac function as measured by decreases in both left ventricular end diastolic pressure (LVEDP) and E/e’ after 5 weeks of treatment. Similarly, endothelium‐dependent vascular relaxation with acetylcholine exhibited significant improvement. Treadmill exercise performance expressed as total work showed improvement for the JK‐1 group, demonstrating changes in exercise capacity are irrespective of body weight. Conclusion These results suggest that the H 2 S donation therapy exerts beneficial effects in the setting of severe HFpEF. Studies are currently ongoing to determine the mechanisms by which H 2 S therapy improves both cardiac and vascular function in this devastating cardiovascular disease.