Chronic intermittent hypoxia induces cardiac inflammation anddysfunction in a rat obstructive sleep apnea model

Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during thedevelopment of obstructive sleep apnea (OSA). We used a well-described OSA rat model induced with simultaneousintermittent hypoxia. Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressureand components were electronically controlled. The rats were exposed to intermittent hypoxia 8 hours daily for 5weeks. The changes of cardiac structure and function were examined by ultrasound. The cardiac pathology, apoptosis,and fibrosis were analyzed by H&E staining, TUNNEL assay, and picosirius staining, respectively. The expression ofinflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot. Chronicintermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters (LVIDs), endsystolic volume (ESV), end-diastolic volume (EDV), and blood lactate level and marked reduction in ejection fractionand fractional shortening. Chronic intermittent hypoxia increased TUNNEL-positive myocytes, disrupted normalarrangement of cardiac fibers, and increased Sirius stained collagen fibers. The expression levels of hypoxia inducedfactor (HIF)-1α, NF-kB, IL-6, and matrix metallopeptidase 2 (MMP-2) were significantly increased in the heart of ratsexposed to chronic intermittent hypoxia. In conclusion, the left ventricular function was adversely affected by chronicintermittent hypoxia, which is associated with increased expression of HIF-1α and NF-kB signaling molecules anddevelopment of cardiac inflammation, apoptosis and fibrosis.