Abstract
Pulmonary arterial hypertension (PAH) has a complex pathogenesis involving both heart and lungs. Animal models can reflect aspects of the human pathology and provide insights into the development and underlying mechanisms of disease. Because of the variability of most animal models of PAH, serial in vivo measurements of cardiopulmonary function, morphology, and markers of pathology can enhance the value of such studies. Therefore, quantitative in vivo SPECT/CT imaging was performed to assess cardiac function, morphology and cardiac perfusion utilizing 201Thallium (201Tl) in control and monocrotaline-treated rats. In addition, lung and heart apoptosis was examined with 99mTc-Annexin V (99mTc-Annexin) in these cohorts. Following baseline imaging, rats were injected with saline or monocrotaline (50 mg/kg, i.p.) and imaged weekly for 6 weeks. To assess a therapeutic response in an established pulmonary hypertensive state, a cohort of rats received resveratrol in drinking water (3 mg/kg/day) on days 28–42 post-monocrotaline injection to monitor regression of cardiopulmonary apoptosis. PAH in monocrotaline-treated rats was verified by conventional hemodynamic techniques on day 42 (right ventricular systolic pressure (RSVP) = 66.2 mmHg in monocrotaline vs 28.8 mmHg in controls) and in terms of right ventricular hypertrophy (RV/LVS = 0.70 in monocrotaline vs 0.32 in controls). Resveratrol partially reversed both RVSP (41.4 mmHg) and RV/LVS (0.46), as well as lung edema and RV contractility +dP/dtmax. Serial 99mTc-Annexin V imaging showed clear increases in pulmonary and cardiac apoptosis when compared to baseline, which regressed following resveratrol treatment. Monocrotaline induced modest changes in whole-heart perfusion as assessed by 201TI imaging and cardiac morphological changes consistent with septal deviation and enlarged RV. This study demonstrates the utility of functional in vivo SPECT/CT imaging in rodent models of PAH and further confirms the efficacy of resveratrol in reversing established monocrotaline-induced PAH presumably by attenuation of cardiopulmonary apoptosis.
Highlights
Idiopathic pulmonary artery hypertension (PAH) is a devastating lung vascular disease mainly afflicting women in their fourth decade of life [1]
Because the disease is difficult to diagnose until later stages, much of what is known about PAH comes from animal models
The present study explores a SPECT/CT characterization of the major pathophysiological changes in response to monocrotaline, a toxin selectively injurious to the pulmonary vascular endothelium that leads to pulmonary artery and right ventricular remodeling
Summary
Idiopathic pulmonary artery hypertension (PAH) is a devastating lung vascular disease mainly afflicting women in their fourth decade of life [1]. Right ventricular failure is the major cause of mortality in patients diagnosed with idiopathic or severe secondary varieties of PAH [3]. Because the disease is difficult to diagnose until later stages, much of what is known about PAH comes from animal models. With varying coherence to the human disease. Such models provide an opportunity to observe factors that may contribute to the early stages of pulmonary arterial remodeling, lesion formation, and right ventricular hypertrophy, as in humans we are mostly knowledgeable regarding outcomes of fulminant disease. Recent findings by Marsboom et al [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
