適者生存課件

1、10/28/2021適者生存1適者生存：適者生存：心臟運(yùn)動(dòng)測(cè)試的新風(fēng)貌心臟運(yùn)動(dòng)測(cè)試的新風(fēng)貌Survival of the fittest: A new look at cardiac exercise test2007物理治療繼續(xù)再教育課程中華民國(guó)物理治療學(xué)會(huì)主辦慈濟(jì)技術(shù)學(xué)院物理治療系與研發(fā)中心承辦講員：黃千惠10/28/2021適者生存2主題大綱主題大綱n傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試（cardiac ex test，CET）介紹：歷史沿革與方法；強(qiáng)調(diào)運(yùn)動(dòng)中的變化n新近心臟運(yùn)動(dòng)測(cè)試發(fā)展：預(yù)測(cè)死亡率；強(qiáng)調(diào)運(yùn)動(dòng)開始運(yùn)動(dòng)恢復(fù)的變化，主要是心跳n文獻(xiàn)回顧：運(yùn)動(dòng)後心跳恢復(fù)率的預(yù)後意義n臺(tái)灣資料：血管正常者之心跳恢復(fù)

2、率10/28/2021適者生存3Cardiac exercise test: CETCardiac pulmonary exercise test: CPET10/28/2021適者生存4傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試n起源：the discovery that exercise in pt with coronary disease produced ST segment depressionnFeil &Siegel (1928) exercised pt with angina to bring about pain. uThey performed stress test b

3、y sit-ups.nMaster（1929） published paper using pulse and BP to evaluate the cardiac capacity. （His contribution : exercise protocol rather than use of ECG. ）10/28/2021適者生存5傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試重要沿革重要沿革1nGoldhammer & Scherf (1932): ST depression was present in 75% pt with angina and proposed the use of

4、 exercise to confirm the diagnosis of coronary ischemia.nKatz & Landt (1935): lead 5 is better in terms of discrimination than lead 4. Use of anoxia to bring changes in ST segment.10/28/2021適者生存6傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試重要沿革重要沿革2nMissal (1938): having pt run up 3-6 flights of stairs and he might be the f

5、irst to use a max stress test and to the point of pain and emphasized the necessity of taking the recording as quickly as possible thereafter. 10/28/2021適者生存7傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試重要沿革重要沿革3nRiseman et al (1940): the first to use continuous monitoring and discovered that ST depression appeared before the o

6、nset of pain and persisted for a time after the pain subsided. nThey concluded that exercise was of little value because of its poor discrimination between the normal and the abnormal subjects.10/28/2021適者生存8傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試重要沿革重要沿革4nJohnson et al (1942): developed Harvard Step Test. Use pulse count

7、s during recovery and provide an index of physical fitness.nHellerstein & katz (1949): ST depression is primarily a diastolic injury current manifested during the TQ interval.10/28/2021適者生存9傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試重要沿革重要沿革5nWood et al: Push the pt to the max level of their capacityuThe amount of work sh

8、ould not be fixed, but adjusted to the individualuThe more strenuous work would produce a higher percentage of positive testsnRecommend the use of the stress test to uncover latent myocardial ischemia.10/28/2021適者生存10傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試重要沿革重要沿革6nBruce (1956): work test performed on a treadmill and esta

9、blished guideline that would more or less group pt into the NYHDC I through IVnAstrand & Ryhming: max oxygen uptake could be predicted by the HR at submax exercise10/28/2021適者生存11傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試傳統(tǒng)心臟運(yùn)動(dòng)測(cè)試重要沿革重要沿革7nBlackburn (1969):90% of the ischemic changes could be demonstrated in the CM5 or V5 lead. S

10、o spread the use of test outside the research lab.nConventional exercise test, done with a treadmill, is being supplemented by many other techniques to improve the disgnostic certainty and help localize the disease vessels.10/28/2021適者生存12新近心臟運(yùn)動(dòng)測(cè)試發(fā)展新近心臟運(yùn)動(dòng)測(cè)試發(fā)展n功能量（functional capacity）預(yù)測(cè)死亡率；體適能越佳存活率越高

11、n不正常的運(yùn)動(dòng)後心跳恢復(fù)率與死亡危險(xiǎn)性有關(guān)n心跳加速不能（chronotropic imcompetence）與心跳保留量（heart rate reserve）在測(cè)試上的應(yīng)用10/28/2021適者生存13新近心臟運(yùn)動(dòng)測(cè)試發(fā)展新近心臟運(yùn)動(dòng)測(cè)試發(fā)展1nGreater fitness results in longer survival (Myers et al, NEJM 2002):u3679 men with CVD V.S. 2534 men without CVD on treadmill max ETuAfter adjusting for age, peak exercise ca

12、pacity measured in METs is the strongest predictor of the risk of death in both groups. uAbsolute peak ex ca is a stronger predictor than age-predicted value achieved.uRisk of death doubled among those MET less then 5 when compared to whose MET more than 810/28/2021適者生存14nExercise capacity is a more

13、 powerful predictor of mortality among men than other established risk factors for CV disease10/28/2021適者生存1510/28/2021適者生存16新近心臟運(yùn)動(dòng)測(cè)試發(fā)展新近心臟運(yùn)動(dòng)測(cè)試發(fā)展2nAbnormal heart rate recovery and risk of deathuHRR after ex as a predictor of mortality（Cole et al, NEJM 1999）uSlow HRR after ex is associated with carot

14、id atherosclerosis (Jae et al, Atherosclerosis)uPrognostic value of HRR in pt with HF (Arena, Am H J )uHRR after ex is a predictor of mortality, independent of the angiographic severity of CD (Vivekananthan et al, J Am Col Cardio)uHRR improved as a result of ex training during CR (MacMillan et al, H

15、eart Lung)10/28/2021適者生存17運(yùn)動(dòng)後心跳恢復(fù)率的預(yù)後運(yùn)動(dòng)後心跳恢復(fù)率的預(yù)後意義意義12 bpm, 26% abnormal HRR, No further improvement for value above 20Cole et al, NEJM 199910/28/2021適者生存18A strong association between ex ca and ab HRR10/28/2021適者生存19新近心臟運(yùn)動(dòng)測(cè)試發(fā)展新近心臟運(yùn)動(dòng)測(cè)試發(fā)展3nChronotropic incompetence（心跳加速不能）：最快的心跳數(shù)不易達(dá)到預(yù)期之目標(biāo)心跳數(shù)uPeak HR

16、is related to age: referred as CI when 85 of the age-predicted HR is achieved.nHR reserve（心跳保留量, HRR）：安靜與最大心跳數(shù)之差異uAzarbal et al found that failure to reach 85 of the age-predicted maximum HR was predictive of death but that failure to use 80of HRR was a stronger predictor of risk.10/28/2021適者生存20女性功

17、能量常模的預(yù)後價(jià)值女性功能量常模的預(yù)後價(jià)值nThe prognostic value of a normogram for ex ca in women (Gulati et al, NEJM 2005):uEx ca: an independent predictor of mortalityu5721 asymptomatic women underwent a symptom-limited max ex test.uA nomogram established on the basis of age and ex ca uUse the nomogram to determine th

18、e % of original women and another 4471 women with CVD10/28/2021適者生存21 : 14.7-(0.13*age) : 14.7-(0.11*age)10/28/2021適者生存22Active :17.9-(0.16*age)Sedentary : 14.7-(0.12*age)10/28/2021適者生存2310/28/2021適者生存24新近心臟運(yùn)動(dòng)測(cè)試發(fā)展新近心臟運(yùn)動(dòng)測(cè)試發(fā)展3nHR reserve approach should be used when assessing HR to exnThe ex test prov

19、ides critical prognostic information beyond that provided by nuclear imagingnAzarbal et al also found that chronotropic response predicts outcome over and above functional capacity, one of the most powerful predictors of all-cause and cardiac death. 10/28/2021適者生存25傳統(tǒng)傳統(tǒng)CET V.S. 現(xiàn)代現(xiàn)代CET傳統(tǒng)CET現(xiàn)代CET診斷診斷

20、 +預(yù)後運(yùn)動(dòng)中運(yùn)動(dòng)中+恢復(fù)期ST-segment depression: CADLacking Q wave: ischemiaChronotropic incompetenceST depression: CADVentricular arrhythmias : predict mortality better10/28/2021適者生存26傳統(tǒng)傳統(tǒng)CET V.S. 現(xiàn)代現(xiàn)代CETDuring exerciseDuring recoveryMaximal exercise capacityST-segment depressionHR responseST-segment depressio

21、n/ elevationDelay slowing of HRAngina pectoris Ventricular arrhythmiaVentricular arrhythmiaInadequate BP/HR response10/28/2021適者生存27運(yùn)動(dòng)後心跳恢復(fù)率的臨床意運(yùn)動(dòng)後心跳恢復(fù)率的臨床意義義:n傳統(tǒng)上重視運(yùn)動(dòng)中的心跳變化，現(xiàn)發(fā)現(xiàn)運(yùn)動(dòng)停止後的心跳恢復(fù)變化具顯著的臨床意義n運(yùn)動(dòng)中的心跳的上升變化是副交感退縮與交感興奮的合併結(jié)果；運(yùn)動(dòng)後的心跳降低則是副交感神經(jīng)系統(tǒng)再活化的結(jié)果n因迷走活化的提高經(jīng)常與死亡率降低相伴發(fā)生，研究開始朝向運(yùn)動(dòng)後的心跳率與預(yù)後因子的關(guān)係10/28/20

22、21適者生存28運(yùn)動(dòng)後心跳恢復(fù)率的臨床運(yùn)動(dòng)後心跳恢復(fù)率的臨床意義意義1:nCole et al 1999：2428 subjects without HD history undergoing symptom-limited ex test. Heart rate recovery (HRR) was defined as the reduction in the HR from the peak ex to one min after the cessation of exnAn abnormal HRR was found using log-rank chi-square test st

23、atistic. HRR12 beats per min is considered abnormal 10/28/2021適者生存29n傳統(tǒng)上認(rèn)為運(yùn)動(dòng)後快速的心跳回復(fù)是體適能好的表徵，現(xiàn)在則加上了預(yù)後的價(jià)值nRapid HRR is due to high vagal tone associated with fitness and good healthnHRR is prognostic usually at 1 or 2 min after ex in populations related to ex testnVivekananthan et al: HRR predicts mo

24、rtality, independent of the angiographic severity of CD運(yùn)動(dòng)後心跳恢復(fù)率的臨床運(yùn)動(dòng)後心跳恢復(fù)率的臨床意義意義2:10/28/2021適者生存30運(yùn)動(dòng)後心跳恢復(fù)率的臨床運(yùn)動(dòng)後心跳恢復(fù)率的臨床意義意義3:Cheng 2003, DiabetesHRR5, Quartile 155HRR independently predictive of CV and all cause deathSpies 2005,Metabolic SdMET5,HRR116Metabolic Sd is associated with low ex ca and H

25、RRWatanabe 2001, LVSDHRR118HRR remained predicitve of death after accounting for LVSDPanzer 2002, healthy SubHRR2 42Impaired plasma glucose indep. Predictor of ab HRR10/28/2021適者生存31運(yùn)動(dòng)後心跳恢復(fù)率的臨床運(yùn)動(dòng)後心跳恢復(fù)率的臨床意義意義4:n在心肌梗塞上發(fā)現(xiàn)自主神經(jīng)異常與死亡的密切關(guān)係n自主神經(jīng)不平衡（autonomic imbalance）：指迷走神經(jīng)活動(dòng)相對(duì)或絕對(duì)的降低或交感神經(jīng)活動(dòng)的升高n最普遍的現(xiàn)象是，一旦迷

26、走降低，死亡危險(xiǎn)性即升高n可證諸baroreflex sensitivity, heart rate variability, and heart rate recovery10/28/2021適者生存32血管正常者之心跳恢復(fù)率：前言血管正常者之心跳恢復(fù)率：前言n根據(jù)先前國(guó)外研究結(jié)果，推論體適能水準(zhǔn)與心跳恢復(fù)應(yīng)有某程度相關(guān)（體適能及心跳恢復(fù)皆成功預(yù)測(cè)死亡率）n肥胖程度與自主神經(jīng)系統(tǒng)有關(guān)（Mona Lisa Hypothesis: most obesities known are low in sympathetic activity）n副交感神經(jīng)與脂肪儲(chǔ)存、胰島素釋放有關(guān)n基於以上結(jié)果，推論體

27、適能與肥胖程度應(yīng)會(huì)影響心跳恢復(fù)10/28/2021適者生存33血管正常者之心跳恢復(fù)率：方法血管正常者之心跳恢復(fù)率：方法n本篇研究乃是以接受導(dǎo)管檢查者證實(shí)冠狀動(dòng)脈正常未阻塞者為對(duì)象n受測(cè)者接受 symptom-limited maximal treadmill exercise（Bruce protocol），達(dá)90 age-predicted maximal heart rate reserve者進(jìn)入接下來(lái)之分析n將合格之受測(cè)者依體適能水準(zhǔn)與肥胖程度各分為3組。10/28/2021適者生存34血管正常者之心跳恢復(fù)率：方法血管正常者之心跳恢復(fù)率：方法n以雙因子變異數(shù)分析（two way ANOV

28、A）探討體適能與 肥胖（ BMI ：body mass index）對(duì)心跳恢復(fù)的影響n體適能：分為below average（BA）, average (A), above average (AA) 三組 n肥胖：分為NOR（BMI25）, OW（25 BMI 30 ）, OB（BMI30）三組 n心跳恢復(fù)：運(yùn)動(dòng)停止後的第一分鐘、第三分鐘及第五分鐘之心跳率與運(yùn)動(dòng)中最大心跳率之差異，稱為HRR1, HRR3, HRR510/28/2021適者生存35Estimated Functional Capacity (METs)Age (yr)BAAverage (A)A AWomen291010-13

29、1330-3999-111140-4988-101050-5977-996066-88Men291111-141430-391010-12.512.540-498.58.5-11.511.550-5988-11116077-9.59.510/28/2021適者生存36Total subjectsMale subjectsFemale subjectsP valueN553025Age (yrs) 59.710.1( 41-79)61.610.8(41-79)58.19.1(42-75)Height (cm)161.0 8.4(146-179)166.8 6.3(156-179)154.6 4.

30、9(146-166)Weight (kg)69.2 12.9(46.4-100)73.28 6.3(46.4-100)64.4 10.5(47-86.4)BMI26.64.2(18.3-39.6)26.44.1(18.3-35.0)27.04.3(20.3-39.6)Number (%) of people having dyslipidemia14(25.4%)9(30.0%)5(20.0%)Number (%) of people having hypertension21(38.2%)16(53.3%)5(20.0%)Number (%) of people having diabete

31、s9(16.4%)5(16.7%)4(16.0%)Number (%) of people smoke5(9.1%)5(16.7%)0(0%)Number (%) of people drink8(14.5%)7(23.3%)1(4.0%)Number (%) of people chew bittle nuts6(10.9%)5(16.7%)2(8.0%)Number (%) of people over 6516(38.5%)7(36.7%)5(20.0%)10/28/2021適者生存37Group BAGroup AGroup AAP valueN91927Female: Male3:6

32、7:1215:12Age63.012.5958.311.2259.68.4Height163.011.0162.28.71.597.4Weight70.910.372.314.266.512.6BMI27.33.927.33.926.04.5Age over 65: Age under 656:37:128:19Resting HR89.9 17.580.7 15.875.2 9.3Resting SBP139.921.9143.425.7143.029.9Maximal HR 157.111.2161.612.5162.09.7Maximal SBP172.827.3176.927.0187

33、.223.8% predicted HR100.12.2100.03.6101.14.510/28/2021適者生存38Group BAGroup AGroup AAP valueMETs6.1 1.18.8 1.510.7 1.3Slope MHR-HR1-17.3 7.2-29.6 10.5-33.3 13.2Slope MHR-HR3-16.3 3.5-20.5 4.8-21.2 4.2Slope MHR-HR5-11.62.4-12.82.3-13.62.4Number of people taking NTG054Number of people having abnormal EC

34、G28910/28/2021適者生存39Group BMI25Group 25BMI30Group BMI30P valueN20268Female: Male10:1015:114:4Age62.57.856.811.159.98.7Height159.07.7163.18.5159.39.2Weight57.2 7.173.8 8.486.4 10.4#BMI22.6 1.827.7 1.433.5 3.1#Age over 65: Age under 658:128:184:4Resting HR82.712.977.213.777.317.7Resting SBP139.030.914

35、3.520.0145.032.4Maximal HR 159.87.9162.811.8161.313.4Maximal SBP183.626.5177.827.2185.521.710/28/2021適者生存40Group 1BMI25Group 225BMI30Group 3BMI30P value% predicted HR101.54.199.83.5100.64.5METs9.52.29.71.98.01.9Slope MHR-HR1-26.87.3-33.11514.9-26.512.4Slope MHR-HR3-19.03.5-21.14.7-20.66.1Slope MHR-H

36、R5-12.71.7-13.1692.6-13.6752.6Number of people taking NTG252Number of people having abnormal ECG79310/28/2021適者生存41血管正常者之心跳恢復(fù)率：結(jié)果血管正常者之心跳恢復(fù)率：結(jié)果n交互作用未達(dá)顯著n體適能因子呈顯著(F (2,45) =3.66, p.05) ，LSD事後比較顯示AA組與A組之HRR1與 HRR3顯著高於BA組n肥胖水準(zhǔn)因子未達(dá)顯著10/28/2021適者生存42Recovery periodHRR1HRR3HRR5Heart rate recovery (bpm)020

37、406080BAAAA*10/28/2021適者生存43Recovery periodHRR1HRR3HRR5Heart Rate Recovery (bpm)020406080NOROWOB10/28/2021適者生存44血管正常者之心跳恢復(fù)率：討論血管正常者之心跳恢復(fù)率：討論n本研究發(fā)現(xiàn)冠狀動(dòng)脈血管正常者,體適能水準(zhǔn)顯著影響運(yùn)動(dòng)後的心跳恢復(fù)率; 體適能高於,等於平均者有較高的心跳恢復(fù)率u與已知趨勢(shì)符合, 體適能高心跳反應(yīng)及時(shí)u雖本研究未探討死亡率, 但過(guò)去研究結(jié)果顯示,體適能高死亡率低, 心跳恢復(fù)率高死亡率低, 兩者方向一致10/28/2021適者生存45血管正常者之心跳恢復(fù)率：討論血管正

38、常者之心跳恢復(fù)率：討論n而肥胖的程度對(duì)心跳恢復(fù)率的影響在本研究中並無(wú)發(fā)現(xiàn)u肥胖對(duì)自主神經(jīng)的影響不一,有的認(rèn)為腹部脂肪影響較大u本研究所使用的肥胖指數(shù)為BMI, 無(wú)法從BMI得知肌肉骨骼脂肪之相對(duì)比例u另一思考方向, 所有危險(xiǎn)因子的加總結(jié)果為血管正常, 亦即肥胖之效果為其他因子所抵銷u統(tǒng)計(jì)上因素, 肥胖組有較少的人10/28/2021適者生存46血管正常者之心跳恢復(fù)率：結(jié)果血管正常者之心跳恢復(fù)率：結(jié)果n在導(dǎo)管證實(shí)冠狀動(dòng)脈正常者之受試者身上, 接受最大運(yùn)動(dòng)測(cè)試, 達(dá)90% 年齡預(yù)測(cè)心跳保留量者發(fā)現(xiàn), 體適能較佳者有較高之運(yùn)動(dòng)後心跳恢復(fù)率n但在以BMI分類的肥胖指數(shù)上, 不同的肥胖指數(shù)對(duì)運(yùn)動(dòng)後心跳恢

39、復(fù)率並未造成影響n為臺(tái)灣首度以冠動(dòng)正常者為對(duì)象所完成的運(yùn)動(dòng)後心跳恢復(fù)率研究, 更多這方面的研究可以幫助我們更進(jìn)一步了解機(jī)轉(zhuǎn)10/28/2021適者生存47要運(yùn)動(dòng)多少才夠？要運(yùn)動(dòng)多少才夠？nThe amount, intensity, and duration of physical activity required to reduce the risk of coronary heart disease is debated. nHarvard Alumni Study: no further reduction in events associated with CAD in men wi

40、th an energy expenditure of more than 2000 Kcal per week.nEither a threshold effect or a progressive decline with progressive activity, possibly because of differences in the range of activity in the populations.10/28/2021適者生存48要運(yùn)動(dòng)多少才夠？要運(yùn)動(dòng)多少才夠？n大多數(shù)文獻(xiàn)將運(yùn)動(dòng)強(qiáng)度大於6MET定義為強(qiáng)烈，中度強(qiáng)烈則是產(chǎn)生輕微的喘及達(dá)到50的最大運(yùn)動(dòng)強(qiáng)度。n一天一個(gè)小時(shí)中

41、度以上運(yùn)動(dòng)即接近最佳狀況，而漸進(jìn)增加運(yùn)動(dòng)量則導(dǎo)致漸進(jìn)降低心臟危險(xiǎn)性。nACSM的運(yùn)動(dòng)建議是謹(jǐn)慎的，當(dāng)作一個(gè)最低的建議量。More vigorous exercise is probably more beneficial, but also carries a cardiovascular risk, especially for those who are usually inactive. 10/28/2021適者生存49Survival of the fittest適者生存適者生存nCardiorespiratory fitness enables a person to perform

42、 physical activity and is influenced by several other factors, including age, sex, heredity, and medical status.n A nearly linear reduction in mortality was observed as fitness levels increased, and each increase of 1MET in exercise capacity conferred a 12% improvement in survival. 10/28/2021適者生存50結(jié)

43、論結(jié)論nThe lowest threshold for a dose and an intensity that would confer specific survival and cardiovascular benefits is not known.nTo compel the clinician to go beyond the identification of risk to the initiation of interventions, such as the prescription of increased physical activity and exercise

44、to modify risk, particularly in patients with low levels of fitness.10/28/2021適者生存51結(jié)論結(jié)論n建議盡量每日運(yùn)動(dòng)，因?yàn)檫\(yùn)動(dòng)對(duì)於部分危險(xiǎn)因子的效果；如三高的血糖、血壓，血脂的三酸甘油脂、與HDL皆具有程度上的運(yùn)動(dòng)急性效果。10/28/2021適者生存528G5D2A-x*u$qZnVkShPdMaJ7F4C0z)w&s!pYmUjRfOcL9H6E3B+y(u%r#oWlTiQeNbJ8G5D1A-x*t$qYnVkSgPdMaI7F4C0z)v&s!pXmUjRfOcK9H6E2B+y(u%rZo

45、WlThQeNbJ8G4D1A-w*t$qYnVjSgPdLaI7F3C0y)v&s#pXmUiRfNcK9H5E2B+x(u%rZoWkThQeMbJ8G4D1z-w*t!qYnVjSgOdLaI6F3C0y)v%s#pXlUiRfNcK8H5E2A+x(u$rZnWkThPeMbJ7G4C1z-w&t!qYmVjRgOdL9I6F3B0y)v%s#oXlUiQfNcK8H5D2A+x*u$rZnWkShPeMaJ7G4C1z)w&t!pYmVjRgOcL9I6E3B0y(v%r#oXlTiQfNbK8G5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&am

46、p;s!pYmUjRgOcL9H6E3B+y(v%r#oWlTiQeNbK8G5D1A-x*t$qZnVkSgPdMaI7F4C0z)v&s!pXmUjRfOcK9H6E2B+y(u%r#oWlThQeNbJ8G5D1A-w*t$qYnVkSgPdLaI7F3C0z)v&s#pXmUiRfOcK9H5E2B+x(u%rZoWkThQeMbJ8G4D1z-w*t!qYnVjSgPdLaI6F3C0y)v&s#pXlUiRfNcK9H5E2A+x(u$rZoWkThPeMbJ7G4D1z-w&t!qYmVjSgOdL9I6F3B0y)v%s#oXlUiQfNcK8H

47、5E2A+x*u$rZnWkThPeMaJ7G4C1z-w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlTiQfNbK8H5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!pYmUjRgOcL9I6E3B+y(v%r#oXlTiQeNbK8G5D2A-x*t$qZnVkShPdMaI7F4C0z)w&s!pXmUjRfOcL9H6E2B+y(u%r#oWlThQeNbJ8G5D1A-x*t$qYnVkSgPdMaI7F3C0z)v&s!pXmUiRfOcK9H6E2B+x(u%rZoWlThQeMbJ8G4D1A-w*t!qYnVjSg

48、PdLaI6F3C0y)v&s#pXmUiRfNcK9H5E2Bt$qYnVkSgPdMaI7F3C0z)v&s!pXmUiRfOcK9H6E2B+x(u%rZoWlThQeMbJ8G4D1A-w*t!qYnVjSgPdLaI7F3C0y)v&s#pXmUiRfNcK9H5E2B+x(u$rZoWkThQeMbJ7G4D1z-w*t!qYmVjSgOdLaI6F3B0y)v%s#pXlUiQfNcK8H5E2A+x(u$rZnWkThPeMbJ7G4C1z-w&t!qYmVjRgOdL9I6F3B0y(v%s#oXlUiQfNbK8H5D2A+x*u$qZnWk

49、ShPeMaJ7F4C1z)w&t!pYmUjRgOcL9I6E3B0y(v%r#oXlTiQfNbK8G5D2A-x*u$qZnVkShPdMaJ7F4C0z)w&s!pYmUjRfOcL9H6E3B+y(u%r#oWlTiQeNbJ8G5D1A-x*t$qZnVkSgPdMaI7F4C0z)v&s!pXmUjRfOcK9H6E2B+y(u%rZoWlThQeNbJ8G4D1A-w*t$qYnVjSgPdLaI7F3C0y)v&s#pXmUiRfNcK9H5E2B+x(u%rZoWkThQeMbJ8G4D1z-w*t!qYnVjSgOdLaI6F3C0y)v%

50、s#pXlUiRfNcK8H5E2A+x(u$rZnWkThPeMbJ7G4C1z-w&t!qYmVjSgOdL9I6F3B0y)v%s#oXlUiQfNcK8H5D2A+x*u$rZnWkShPeMaJ7G4C1z)w&t!pYmVjRgOcL9I6E3B0y(v%r#oXlTiQfNbK8H5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!pYmUjRgOcL9H6E3B+y(v%r#oWlTiQeNbK8G5D1A-x*t$qZnVkSgPdMaI7F4C0z)v&s!pXmUjRfOcL9H6E2B+y(u%r#oWlThQeNbJ8G5D

51、1A-w*t$qYnVkSgPdLaI7F3C0z)v&s#pXmUiRfOcK9H5E2B+x(u%rZoWkThQeMbJ8G4D1A-w*t!qYnVjSgPdLaI6F3C0y%r#oWlThQeNbJ8G5D1A-w*t$qYnVkSgPdLaI7F3C0z)v&s#pXmUiRfOcK9H5E2B+x(u%rZoWlThQeMbJ8G4D1A-w*t!qYnVjSgPdLaI6F3C0y)v&s#pXlUiRfNcK9H5E2A+x(u$rZoWkThPeMbJ7G4D1z-w&t!qYmVjSgOdLaI6F3B0y)v%s#pXlUiQfNcK8

52、H5E2A+x*u$rZnWkThPeMaJ7G4C1z-w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlTiQfNbK8H5D2A+x*u$qZnWkShPeMaJ7F4C1z)w&t!pYmUjRgOcL9I6E3B+y(v%r#oXlTiQeNbK8G5D2A-x*t$qZnVkShPdMaI7F4C0z)w&s!pXmUjRfOcL9H6E3B+y(u%r#oWlTiQeNbJ8G5D1A-x*t$qYnVkSgPdMaI7F3C0z)v&s!pXmUiRfOcK9H6E2B+x(u%rZoWlThQeMbJ8G4D1A-w*t$qYnVjS

53、gPdLaI7F3C0y)v&s#pXmUiRfNcK9H5E2B+x(u$rZoWkThQeMbJ7G4D1z-w*t!qYmVjSgOdLaI6F3B0y)v%s#pXlUiRfNcK8H5E2A+x(u$rZnWkThPeMbJ7G4C1z-w&t!qYmVjRgOdL9I6F3B0y(v%s#oXlUiQfNbK8H5D2A+x*u$qZnWkShPeMaJ7F4C1z)w&t!pYmRfNcK8H5E2A+x(u$rZnWkThPeMbJ7G4C1z-w&t!qYmVjRgOdL9I6F3B0y(v%s#oXlUiQfNbK8H5D2A+x*u$rZn

54、WkShPeMaJ7G4C1z)w&t!pYmVjRgOcL9I6E3B0y(v%r#oXlTiQfNbK8G5D2A-x*u$qZnVkShPdMaJ7F4C0z)w&s!pYmUjRfOcL9H6E3B+y(v%r#oWlTiQeNbK8G5D1A-x*t$qZnVkSgPdMaI7F4C0z)v&s!pXmUjRfOcK9H6E2B+y(u%rZoWlThQeNbJ8G4D1A-w*t$qYnVkSgPdLaI7F3C0z)v&s#pXmUiRfOcK9H5E2B+x(u%rZoWkThQeMbJ8G4D1z-w*t!qYnVjSgOdLaI6F3C0y)

55、v%s#pXlUiRfNcK8H5E2A+x(u$rZoWkThPeMbJ7G4D1z-w&t!qYmVjSgOdL9I6F3B0y)v%s#oXlUiQfNcK8H5D2A+x*u$rZnWkShPeMaJ7G4C1z)w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlTiQfNbK8H5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!UiQfNcK8H5D2A+x*u$rZnWkThPeMaJ7G4C1z-w&t!pYmVjRgOdL9I6E3B0y(v%s#oXlTiQfNbK8H5D2A-x*u$qZnWkShPdMaJ7F4C1z)w&s!pYm