Why the study?
CKD-induced HFpEF and cardiorenal syndromes have a high prevalence, lack effective therapies, and have few large-animal models available for investigation.
Does daily subcutaneous injection of a growth hormone-releasing hormone agonist improve cardiac diastolic hemodynamics in a swine model of CKD-induced HFpEF?
Does daily subcutaneous injection of a growth hormone-releasing hormone agonist improve cardiac diastolic hemodynamics in a swine model of CKD-induced HFpEF?
In a large-animal swine model of CKD-induced HFpEF, daily administration of a GHRH agonist significantly improved diastolic hemodynamics, titin phosphorylation, and cardiomyocyte calcium handling.
Supports GHRH agonist evaluation in HFpEF; leaves open translation from swine models to patients.
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.
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Rieger et al. (2021) studied this question.
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