期刊
JOURNAL OF THE AMERICAN HEART ASSOCIATION
卷 8, 期 5, 页码 -出版社
WILEY
DOI: 10.1161/JAHA.118.011227
关键词
Fischer rats; mitochondria; pulmonary heart disease; pulmonary hypertension; rats; right heart failure; transmission electron microscopy
资金
- National Institutes of Health (NIH) [R01HL72844]
Background-Pulmonary arterial hypertension (PAH) is a serious disease without cure. Elevated pulmonary vascular resistance puts strain on the right ventricle (RV) and patients die of RV failure. Subjecting Sprague-Dawley rats to SU5416 injection and hypoxia promotes severe PAH with pulmonary vascular lesions similar to human disease and has been well utilized to investigate pulmonary vascular pathology. However, despite exhibiting severe RV fibrosis, these rats do not die. Recently, subjecting Fischer (CDF) rats to the same treatment to promote PAH was found to result in mortality. Thus, the present study performed detailed morphological characterizations of Fischer rats with PAH. Methods and Results-Rats were subjected to SU5416 injection and hypoxia for 3 weeks, followed by maintenance in normoxia. More than 90% of animals died within 6 weeks of the SU5416 injection. Necropsy revealed the accumulation of fluid in the chest cavity, right ventricular hypertrophy and dilatation, hepatomegaly, and other indications of congestive heart failure. Time course studies demonstrated the progressive thickening of pulmonary arteries with the formation of concentric lamellae and plexiform lesions as well as RV fibrosis in PAH rats. Transmission electron microscopy demonstrated the destruction of the myofilaments, T-tubules, and sarcoplasmic reticulum. RV mitochondrial damage and fission were found in Fischer rats, but not in Sprague-Dawley rats, with PAH. Conclusions-These results suggest that the destruction of RV mitochondria plays a role in the mechanism of PAH-induced death. The SU5416/hypoxia model in Fischer rats should be useful for further investigating the mechanism of RV failure and finding effective therapeutic agents to increase the survival of PAH patients.
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