The Study Of The Impact And Mechanisms Of Chronic Intermittent Hypoxia On Cardiac Function In Rats

Objective:The aim of this study was to investigate the impact of chronic intermittent hypoxia(CIH) on cardiac function,and explore the role of NF-κB in the mechanisms of cardiac dysfunction due to CIH.Methods:Twenty four adult male Sprague-Dawley rats(body weight about 200g) were randomly divided into three groups.The CIH group exposed to CIH(nadir O₂ 6～7%),the PDTC group exposed to CIH and intraperitoneal injected proline dithiocarbamate(PDTC,special inhibitor of NF-κB)(10mg/kg·d),and the NC group was handled normoxic controls.Exposure last 8h/d for 5 weeks.At the end of the exposure,blood pressure was measured by tail cuff plethysmograph;left global function was accessed by echocardiographic and invasive cardiac catheterization. Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL). Expressions of apoptosis related proteins caspase 3,Fas,caspase 8,Bax,Bcl-2,and nucleoprotein NF-κB were detected by Western blot.Results:1.The impact of CIH on cardiac function in rats.At the end of the 5-weeks exposure,there were no significant differences among the groups in the weight gain.Compared with NC,CIH and PDTC animals demonstrated elevations in arterial pressure(122.3±4.1 mmHg vs.136.3±6.8mmHg, P＜0.001;122.3±4.1mmHg vs.134.3±6.7 mmHg,P＜0.001).Left ventriaclar ejection fraction measured by echocardiogram was lower in CIH than in NC(73.0±5.6%vs. 86.0±4.3%,P＜0.001),and was not significantly different between NC and PDTC (84.0±4.1%vs.86.0±4.3%,P=0.117).Compared with NC,left ventricular end-diastolic pressure was higher(6.2±3.0mmHg vs 13.6±1.0mmHg,P＜0.001),and maximal rates of left ventricular pressure in systole and diastole were lower in CIH (3764.3±784.8 vs 4894.9±651.7,P＜0.001).However,there were no significant differences between NC and PDTC.There were no significant differences in heart rate among the groups. 2.Apoptosis assays.The incidences of TUNEL-positive cells from the CIH group was approximately seven folds greater compared with the NC group(17.5%vs.1.9%,P＜0.001). Expression of caspase 3 increased in CIH than in NC(3.5%vs.0.1%,P＜0.001), which showed myocyte apoptosis increases too.Pearson anylasis showed that LVEF was negatively related with apoptosis index(r=-0.792,P＜0.001) and with caspase 3 activity(r=-0.784,P＜0.001).Left ventricular end-diastolic pressure was positively related with apoptosis index(r=0.807,P＜0.001) and with caspase 3 activity(r= 0.847,P＜0.001).3.Expression of apoptosis related proteins and the role of NF-κB.Compared with NC,the expression of Fas,caspase 8 increased,Bcl-2 decreased in CIH(P＜0.001),but the expression of Bax was not different(P=0.213).Compared with PDTC,the findings in CIH are similar.However,there were no significant differences in Fas,caspase 8,Bcl-2 and Bax between the PDTC group and the NC group.Conclusion:CIH may activate NF-κB,which upregulates Fas and downregulates Bcl-2.CIH may lead to increased apoptosis through activated NF-κB.NF-κB is the important factor in the impact of CIH on cardiac dysfunction. Objective:The aim of this study was to assess the impact of untreated sleep apnea (SA) on mortality,heart transplantation,and hospitalization in patients with congestive heart failure(CHF) in China.Methods:This was a prospective case controlled study.Patients who met criterias followed:age less than 18 years,left ventricular ejection fraction(LVEF) less than 35.4%and NYHA classⅡ～Ⅳ,were enrolled.The patients were performed ploysomonlography and were divided into three groups.They were followed up regularly.At the end of follow-up,we compared mortality and combined events (including death,transplantation,and hospitalization due to heart failure) among the three groups.Results:128 CHF patients were enrolled in this study.Eighteen percent had no SA (CHF-N),43%had obstructive sleep apnea(CHF-OSA),and 39%had central sleep apnea(CHF-CSA).Mortality was significantly greater in the CHF-CSA group than in the CHF-N group(18.2 vs 6.7 per 100 person-years,P=0.017),and the survivors had more prevalence of SA(78.9%) than the non-survivors(89.5%).However, multivariate analysis identified age and NYHA class function but not CSA,OSA,or the severity of SA as predictors for survival in heart failure.In addition,the percentages of combined events were not significantly different among three groups. When we defined presence of SA as apnea-hyponea index above 10/h and 15/h respectively,mortality and combined etents rate were not significantly different among the groups.Conclusion:Untreated SA(OSA or CSA) has no significant impact on the prognosis of patients with congestive heart failure in China.