| Objective: Obstructive sleep apnea—hyponea syndrome(OSAHS)is a commonly-seen chronic sleep disorder. The main pathogenesis ofOSAHS is characterized by repeated episodes of apnea and hyponeaduring sleep. OSAHS is regarded as a dangerous disease on account ofits high morbility and great impairment to multisystems and multiorgans.Complications caused by repetitive noct-apnea of OSAHS happens after along time, so it is difficult to conduct prospective study about OSAHS onhuman. Moreover, many intervening factors exist in clinical research, soexperiments carried out on human beings are limited. Therefore,researches on OSAHS animal model would be useful to clarify theinfluence of OSAHS and its mechanism. Besides clinical researchsimultaneously, we look forward to establishing a suitable chronic-intermittent hypoxia model in rat, so that we can do some furtherresearches on a relationship between obstructive sleep apnea—hyponeasyndrome and cardiovascular and cerebrovascular diseases and the possible pathogenesis. It will supply with essential laboratory evidencesfor the clinical therapy and prevention of OSAHS.Methods: 1. Establishment of chronic-intermittent hypoxia model inrat: Sixteen three-month old male Sprague-Dawley rats were chosen,Preliminary experiment was carded out on six objects of the total.Arterial blood oxygen saturation of six rats exposed to intermittenthypoxia was monitored by automatic blood gas analyzer. The remainedsixteen rats were randomly assigned to two experimental groups (n=8/group): chronic intermittent hypoxia group(CIH),unhandled controlgroup (UC).Animals from UC group were raised under physiologicalconditions, animals in CIH group were kept in the plexiglass chamberbetween 9Am-5Pm and underwent intermittent hypoxic challenge(oxygen concentration ranged from lowest 8.5%—21%, 8 minutes of eachcycle) for 8h/day for 4weeks. Room temperature was 25±1℃, Thefeedstuff and water were same for all rats. Pressure, temperature andhumidity inside the plexiglass chamber were standardized. The durationof experiment was 4 weeks.2.The functional test:①The measurements of arteria caudilis blood pressure of rats (TailCannulation): All measurements were done in the morning. The baselineblood pressure was measured on the day before experiment. Bloodpressure was measured once a week during the experiment. All objects were still exposed to intermittent hypoxia(7h everyday) after bloodpressure measurement. The measurements of arteria caudilis bloodpressure of rats was conducted according to the instruction of themeasurement meter of arteria caudilis blood pressure of rats.②The determination of the ability of learning and memory: Theability of learning was evaluated according to mean escape latency. Theability of memory was evaluated according tour the number of times ofcrossing the platform and the percentage of time spending on the targetquadrant to the total swimming time.3. The determination of morphology and serology: The rats wereroutinely sacrificed at the end of experiment, the changes of the followingindexes were observed: the general pathological changes(HE staining)and the ultrastructure of myocardium, brain, lung and kidney and vessels;the capillary density of myocardium(histochemistry staining); theexpression of IGF-1 protein in CA1 region of hippocampus(immunohistochemistry staining, SP stain);the expression of VEGF inmyocardium, lung, kidney and vessels (immunohistochemistry staining,SP stain);the level of VEGF in plasma(ELISA).Results:1.The blood gas analysis:At the point of lowest O2concentration, arterial blood oxygen pressure was between 20.9—29.7mmHg,while blood oxygen concentration was between 31.2%—58.3%.When the O2 concentration inside the chamber raised to 21%, arterial blood oxygen pressure was between 71.6—106.4mmHg,the blood oxygenconcentration was between 92.2%—97.4%.The change is concordant withthe blood oxygen saturation criteria for the diagnosis of severe OSAHS.2. Functional test results:①. The arteria caudilis blood pressure of rats: IH rats showedsignificant increase in arteria caudilis systolic pressure from the secondweek, blood pressure increased by 13.75mmHg, 22.25mmHg and29.87mmHg,at the 2nd,3rd,4th week respectively(all P＜0.01). arteriacaudilis systolic pressure did not change from that before experiment inUC.②.Morris water maze testLearning scores(position navigation):After 5 days training, theescape latency in CIH rats was significantly longer compared withthat in UC rats (p＜0.05);2. Morris water maze test memory scores: Thenumber of times of crossing the platform in CIH group [(1.38±0.92)] wassignificantly reduced compared with that in UC group [(3.75±1.04), p＜0.01];The percentage of time spent on crossing the target quadrant to thetotal swimming time in CIH group (20.52±3.41) was also significantlydecreased compared with that in UC group [(39.89±5.63),P＜0.01];3. morphological results:①.The tissue of myocardium, brain, lung and kidney and vesselsin CIH all showed obvious hypoxic change;②The expression of insulin-like growth factor-1 in CA1 region of hippocampus in CIH wasobviously decreased compared with that in UC group (p＜0.05, Therewas negative correlation between cognition impairment in rats and theexpression of IGF-1 in CA 1 region of hippocampus(r=0.867, p＜0.01).;③The expression of VEGF in heart, brain, lung, kidney andvessel tissues in CIH was obviously increased compared with that inUC group (p＜0.05;④The levels of plasm VEGF concentration in CIHrats was increased compared with that in UC rats (P＜0.05)Conclusion: 1,The chronic-intermittent hypoxia model in rat inour experiment is a mature animal model for OSAHS. It can satisfy theneed of fundamental study on OSAHS.2,Chronic intermittent hypoxia can lead to myocardial cell damage;CIH causes the upregulated expression of VEGF, which can promotecompensation changes after myocardial anoxia as well as enhanceatherosclerotic plague progression.3,Chronic intermittent hypoxia can lead to persistent increase ofblood pressure and the thickening of kidney arteriola wall. The degree ofthickening was associated with the up-regulation expression of VEGF.4,Chronic intermittent hypoxia can lead to cognitive impairment ofthe rats; the extent of cognitive impairment was associated with theneuron injury in CA1; IGF-1 may play a protective role for CA1 neuron. Background and the aim of stuty: Obstructive Sleep apnoea/hypopnoea syndrome (OSAHS), with a prevalence 2～4% of the generalpopulation, constitutes a major public health problem. It has beenassociated with a lack of normal nocturnal decrease in blood pressure andthe presence of diurnal systemic arterial hypertension. Cross-sectionalstudies have related OSAHS to coronary heart disease and stroke. Theaim of the study was to determine mortality in elderly coronary heartdisease patients with obstructive sleep apnoea/hypopnoea syndrome(OSAHS) according to the treatments employedDesign: A prospective study.Patients: 196 old patients with coronary heart disease weredivided into two groups by polysomnography. There were 128 patients inthe middle and severe OSAHS group (apnea and hypopnea index≥15/hour). The others were in the control group. 33 patients in the severeOSAHS group were selected to nasal continuous positive airway pressuretreatment group by their willing.Measurements and results: By the end of 3 years follow-up, 21patients had died of cardiovascular causes, stroke and coronary artery reconstr-uction. According to Cox regression analysis, mortality intreated patients was lower than in those not treated, and was no significantdifference with control. Mortality in nontreated patients compared withthat of the general population, adjusted for age and weight, showedexcessive mortality, which decreased in treated patients: These findingswere maintained when mortality from cardiovascular causes and strokewere compared.Conclusion: In conclusion, a rise in mortality was found innontreated sleep apnoea/hypopnoea syndrome patients compared with thegeneral elderly coronary heart disease population, whereas mortality inthose treated for sleep apnoea/hypopnoea syndrome did not differsignificantly from that of the general elderly coronary heart diseasepopulation.
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