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Updated: Oct 4, 2025
High-Resolution Cardiac Positron Emission Tomography/Computed Tomography for Small Animals
Published on: December 16, 2022
Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal
Mark T Waddingham1, Hirotsugu Tsuchimochi2, Takashi Sonobe2
1Department of Advanced Medical Research for Pulmonary Hypertension, National Cerebral and Cardiovascular Center, Suita, Japan.
Insights
Hexarelin dilates coronary microvasculature via GHS-receptor 1a and nitric oxide. However, chronic hexarelin did not prevent right ventricle dysfunction in a pulmonary hypertension rat model, revealing insights into diastolic dysfunction.
Area of Science:
- Cardiovascular Research
- Physiology
- Medical Imaging
Background:
- Assessing cardiomyocyte and microvascular function in preclinical models is challenging.
- Distinguishing origins of cardiac dysfunction (microvascular vs. cardiomyocyte) in diseases like heart failure and pulmonary hypertension remains difficult.
Purpose of the Study:
- To investigate the vasodilatory effects of hexarelin in coronary circulation.
- To determine if hexarelin prevents right ventricle dysfunction in a rat model of pulmonary hypertension.
Main Methods:
- Synchrotron radiation microangiography to assess coronary microvascular function.
- SugEN chronic hypoxia model in Sprague-Dawley rats to induce pulmonary hypertension.
- Small-angle X-ray scattering to analyze myosin filament structure.
Main Results:
- Acute hexarelin administration caused coronary microvascular dilation via GHS-receptor 1a, nitric oxide, and endothelium-derived hyperpolarization.
- Chronic hexarelin treatment did not prevent right ventricle hypertrophy or impaired cardiomyocyte relaxation in pulmonary hypertension.
- Small-angle X-ray scattering indicated super-relaxed myosin filaments contribute to diastolic dysfunction.
Conclusions:
- Synchrotron-based imaging provides novel insights into cardiac and coronary function.
- Hexarelin's acute vasodilatory effects do not translate to preventing chronic pulmonary hypertension-induced right ventricle dysfunction.
- Myosin filament dynamics play a role in diastolic dysfunction in this model.
Abstract:
The majority of the conventional techniques that are utilized for investigating the pathogenesis of cardiovascular disease in preclinical animal models do not permit microlevel assessment of in situ cardiomyocyte and microvascular functions. Therefore, it has been difficult to establish whether cardiac dysfunction in complex multiorgan disease states, such as heart failure with preserved ejection fraction and pulmonary hypertension, have their origins in microvascular dysfunction or rather in the cardiomyocyte. 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. We show that acute hexarelin administration evokes coronary microvascular dilation through GHS-receptor 1a and nitric oxide, and through endothelium-derived hyperpolarization. Previous work indicated that chronic exogenous administration of ghrelin largely prevented the pathogenesis of pulmonary hypertension in chronic hypoxia and in monocrotaline models. Unexpectedly, chronic hexarelin administration prior to sugen chronic hypoxia did not prevent RV hypertrophy or RV cardiomyocyte relaxation impairment. 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. Thus, synchrotron-based imaging approaches can reveal novel insights into cardiac and coronary functions in vivo.
