Growth hormone-releasing hormone agonists ameliorate chronic kidney disease-induced heart failure with preserved ejection fraction
Angela C. Rieger, Luiza Bagno, Alessandro G. Salerno, Victoria Florea, Jose Rodriguez, Marcos Rosado, Darren Turner, Raúl A Dulce, Lauro M Takeuchi, Rosemeire M. Kanashiro‐Takeuchi, Péter Buchwald, Amarylis Wanschel, Wayne Balkan, Ivonne Hernandez Schulman, Andrew V. Schally, Joshua M. Hare
Abstract
Significance This randomized, blinded study used rigorous hemodynamic tools to test the efficacy of a synthetic growth hormone-releasing hormone agonist (GHRH‐A) on the restoration of diastolic function in a large animal model of chronic kidney disease (CKD)-induced heart failure with preserved ejection fraction (HFpEF). CKD was produced in Yorkshire swine by performing a 5/6 nephrectomy via catheter-based renal artery embolization. HFpEF was evident at 12 wk postembolization. Daily injection of GHRH-A improved cardiac diastolic hemodynamics, including end-diastolic pressure, end-diastolic pressure–volume ratio, and stroke work, compared to placebo. Development of this swine model and therapeutic approach has important implications because of the high prevalence of CKD-induced HFpEF and cardiorenal syndromes, lack of effective therapies, and few large-animal models available for investigation.