Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models.

Preclinical animal study using synchrotron radiation imaging techniques

“Herein, we describe our approach of utilizing synchrotron radiation microangiography to, first, ascertain whether the growth hormone secretagogue (GHS) hexarelin is a vasodilator in the coronary circulation of normal and anesthetized Sprague-Dawley rats, and next investigate if hexarelin is able to prevent the pathogenesis of right ventricle (RV) dysfunction in pulmonary hypertension in the sugen chronic hypoxia model rat.”

Male Sprague-Dawley rats

“Ten-week old male Sprague-Dawley rats (n = 10) were sourced from Japan SLC (Kyoto, Japan) for preliminary investigation of the coronary dilator mechanisms in response to acute administration of hexarelin in the healthy coronary circulation of rats during terminal experimentation under anesthesia as described below.”

60 total rats (10 in acute study, 50 in chronic studies)

“Seven-week old male Sprague-Dawley rats (n = 50) were sourced from Japan SLC (Kyoto, Japan).”

6 weeks for chronic studies (4 weeks pump administration, 3 weeks hypoxia, 3 weeks normoxia)

“Both hexarelin (100 μg·kg−1·day−1, equivalent to a ghrelin dose of 400 μg·kg−1·day−1) and vehicle (0.9% saline) were delivered with osmotic minipumps (model 2ML4, Alzet® Durect Corporation, Cupertino, CA, United States) for 4 weeks and by daily subcutaneous injections for the final 2 weeks (all the animals in a normoxic environment).”

Acute hexarelin administration evokes coronary microvascular dilation through GHS-receptor 1a and nitric oxide, and through endothelium-derived hyperpolarization.

“We show that acute hexarelin administration evokes coronary microvascular dilation through GHS-receptor 1a and nitric oxide, and through endothelium-derived hyperpolarization.”

Small-angle X-ray scattering revealed that super relaxed myosin filaments contributed to diastolic dysfunction, and that length-dependent activation might contribute to sustained contractility of the RV.

“Small-angle X-ray scattering revealed that super relaxed myosin filaments contributed to diastolic dysfunction, and that length-dependent activation might contribute to sustained contractility of the RV.”

Limited number of animals and ongoing nature of the study require further confirmation

“However, we must acknowledge that this is an ongoing study with a somewhat limited number of animals reported, and as such, further confirmation and more detailed studies are required focusing on both acute and chronic effects of hexarelin treatment in healthy and disease states other than myocardial infarction.”