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

Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea（OSA）.We used a well-described OSA rat model induced with simultaneous intermittent hypoxia.Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and 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 of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot.Chronic intermittent 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 fraction and fractional shortening.Chronic intermittent hypoxia increased TUNNEL-positive myocytes,disrupted normal arrangement of cardiac fibers,and increased Sirius stained collagen fibers.The expression levels of hypoxia induced factor（HIF）-l α,NF-κB,IL-6,and matrix metallopeptidase 2（MMP-2） were significantly increased in the heart of rats exposed to chronic intermittent hypoxia.In conclusion,the left ventricular function was adversely affected by chronic intermittent hypoxia,which is associated with increased expression of HIF-lα and NF-κB signaling molecules and development of cardiac inflammation,apoptosis and fibrosis.

Uric acid is associated with cardiac death in patients with hypertrophic obstructive cardiomyopathy

BACKGROUND The role of uric acid(UA) in survival of patients with hypertrophic obstructive cardiomyopathy(HOCM) has not been fully evaluated. This study aimed to determine whether UA could be an independent risk factor of cardiac death in patients with HOCM.METHODS A total of 317 patients with HOCM, who were receiving conservative treatment in Fuwai Hospital from October2009 to December 2014, all of them completed UA evaluations, were analyzed. Patients were divided into three groups according to the UA levels: Tertile 1(≤ 318 μmol/L, n = 106), Tertile 2(319 to 397 μmol/L, n = 105), and Tertile 3(≥ 398 μmol/L, n = 106).RESULTS During a median follow-up of 45 months, 29 cardiac deaths(9.1%) occurred, including 6 sudden cardiac deaths and23 heart failure-related deaths. Cardiac death in Tertile 3(n = 16, 55.2%) was significantly higher than in Tertile 1(n = 6, 20.7%)and Tertile 2(n = 7, 24.1%). In univariate model, UA level(continuous value) showed predictive value of cardiac death [hazard ratio(HR) = 1.006, 95% CI: 1.003-1.009, P = 0.009]. Univariate Cox survival analysis had shown a significant higher property of cardiac death in patients of Tertile 3 when compared with those of Tertile 1, but cardiac death in patients of Tertile 2 did not show significant prognositic value compared with those of Tertile 1(HR = 3.927, 95% CI: 0.666-23.162, P = 0.131). UA was found to be an independent risk factor(HR = 1.005, 95% CI: 1.001-1.009, P = 0.009) of cardiac death in the multivariate regression analysis after the adjustment for age, body mass index, atrial fibrillation, hemoglobin, creatinine, high-sensitivity C-reactive protein, interventricular septum/left ventricular posterior wall ratio, left ventricular outflow tract and left ventricular ejection fraction.CONCLUSIONS UA concentration was found to be independently associated with cardiac death in HOCM patients receiving conservative treatment. Randomized trials of UA-lowering agents for HOCM patients are warranted.