Received November 11, 2006
Revised December 6, 2006
Accepted after revision December 20, 2006

¹ Center of General Education, Central Taiwan University of Science & Technology
² Department of Biological Science and Technology, China Medical University, Taichung , Taiwan
³ School of Dentistry, Chung-Shan Medical University, Taichung, Taiwan
⁴ Department of Physiology, National Yang-Ming University, Taipei, Taiwan
⁵ Department of Pathology, Changhua Christian Hospital, Changua, Taiwan
⁶ Department of Pediatrics, Medical Research and Medical Genetics, China Medical College Hospital, Tai
⁷ School of Psychology, Chung Shan Medical University Taichung, Taiwan
⁸ Division of Cardiology, Armed Forces Taichung General Hospital, Taichung, Taiwan
⁹ Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan
¹⁰ China Medical University

^* To whom correspondence should be addressed. E-mail: shinda{at}mail.cmu.edu.tw.

	Abstract

Background. It is unclear whether the cardiac hypertrophy and hypertrophic pathways will be induced by long-term intermittent hypoxia. Methods. Thirty-six Sprague-Dawley rats were randomized assigned into three groups: normoxia, long-term intermittent hypoxia (12%O₂, 8 hours per day) for 4 weeks (4WLTIH) and for 8 weeks (8WLTIH). Myocardial morphology, trophic factors, and signaling pathways in the three groups were determined by heart weight index, histological analysis, Western blotting, RT-PCR from the excised left ventricle. Results. The ratio of whole heart weight to body weight, the ratio of left ventricular weight to body weight, the vertical cross section of gross heart, and myocardial morphological changes were increased in the 4WLTIH group, and were further augmented by 8WLTIH. In the 4WLTIH group, TNF, IGF-II, phosphorylated p38, STAT-1, and STAT-3 showed significantly increased in the cardiac tissues. However, in the 8WLTIH group, except above factors, IL-6, MEK5, and ERK5 were significantly increased, compared with the normoxia group. Conclusions. The cardiac hypertrophy associated with TNF and IGF-II was induced by intermittent hypoxia. The longer duration of intermittent hypoxia further activated the eccentric hypertrophy related pathway, IL-6 related MEK5-ERK5 and STAT3 pathways, which might lead to the cardiac dilated and pathological development.

Key Words: Heart, Hypoxia, Rat

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