ID+DD P 0.05 II AMS ID+DD P 0.05 ; (7) Logistic SVR AMS F= 16.04,P=0.000 II AMS F=13.63, P= ACE I/D DD+ID II ACE I/D 2

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1 pulsemetric DynaPulse 200M ACE I/D ACE I/D AMS 1 24 BAC P 0.05 SVR 21% BAD 5.6% P 0.05 ; (2) SVR 9.2% P 0.05 BAC BAD P 0.05 ; (3) 30, SVR 10% P 0.05 BAC BAD P 0.05 ; (4) SVR SaO 2 SVR SaO 2 r=0.781 p<0.05 ; (5)ACE I/D SaO 2 SVR ID+DD p<0.05 ; (6) ACE I/D II SVR 1

2 ID+DD P 0.05 II AMS ID+DD P 0.05 ; (7) Logistic SVR AMS F= 16.04,P=0.000 II AMS F=13.63, P= ACE I/D DD+ID II ACE I/D 2

3 Investigation on clinical importance and measure of arterial compliance in healthy men under Hypoxia at High Altitude People s Hospital Peking University Department of cardiology MD student: Quanzhong Hu Supervisor: Professor Ningling Sun Abstract Objective Under study scopes of measure of arterial compliance, not only the relationship between hypoxia at high altitude and arterial compliance of healthy men, essential mechanism and clinical importance had not been studied at domestic investigation, but only a few had been studied at overseas investigation. however it has been playing an important role to comprehend high altitude adaptation, prevent and cure on high altitude disease and understand human body response mechanism to Hypoxia which was caused by other diseases. Methods 38 subjects who had lived in sea-level and 29 subjects who had lived in high altitude were included in our research. All subjects underwent non-invasive office BP measurement ( Dynapulse 200M;Pulse Metric,Inc.,USA) in sea-level or in high altitude (4000m)to obtain data of the arterial compliance of healthy men in high altitude. at the same time, ACE genotypes were determined by PCR and prevalence of AMS was determined in randomization 30 subjects of 38 cases who had lived in sea-level also. Finally, relationship among them was analyzed. Results (1) There is not difference in BAC between the sea-level natives and on acute exposure to high altitude in the sea-level natives at circumstance of hypoxia at high altitude P 0.05 ;but SVR was decreased by 21%,BAD was increased by 5.6%,there is remarkably difference at statistics. (2) Comparing with the sea-level natives, SVR was decreased by 9.2% at high altitude natives(p 0.05);but BAC and BAD did not differ between groups P (3) Comparing with the sea-level natives, SVR was still decreased by 10% at natives of 30 days acclimatized(p 0.05); but BAC and BAD did not differ between 3

4 groups P (4) Multiple regression analysis indicated that SVR was associated with significant alterations in SaO 2 0f arterial blood on acute exposure to high altitude in the sea-level natives. it means that SVR decrease with declining variety of SaO 2 (r=0.781 P 0.05). (5) According to ACE genotypes, layered study show that the variety of SVR and SaO 2 is affected chiefly by DD+ID type on acute exposure to high altitude in the sea-level natives (P 0.05). (6) Variety scopes of SVR of II type are markedly lower than that of DD+ID type on acute exposure to high altitude in the sea-level natives (P 0.05). prevalence of AMS of II type are markedly lower than that of DD+ID type on acute exposure to high altitude in the sea-level natives(p 0.05). (7) Logistic regression showed that significantly charged SVR was an importantly dangerous factor for AMS F= 16.04,P=0.000,and II genotype is a protecting factor for AMS on acute exposure to high altitude F=13.63, P= Conclusions (1) BA compliance(bac) did not affected by change between altitudes. it showed that circumstance of hypoxia at high altitude did not affect arterial compliance; (2)Circumstance of hypoxia at high altitude markedly affect SV Resistance (SVR). On acute exposure to high altitude in the sea-level natives, SVR and SaO 2 0f arterial blood decreased proportionably, there is positive correlation relation between both. SVR in high altitude natives and after 30 days acclimatized to high altitude in the sea-level natives still are lower than sea-level natives ; it showed that high altitude adaptation has particularity, variety in SVR is one of characteristics; (3) Degree of variety in SVR is related to prevalence of AMS.the more degree of variety in SVR, the more prevalence of AMS ; (4) There are some association among ACE genotypes, degree of variety in SVR and prevalence of AMS. Dominating variety in SVR and prevalence of AMS appear mostly at man of DD+ID type; but variety in SVR and prevalence of AMS is lower at man of II type. it showed that ACE genotypes at male has an important effect 4

5 on susceptibility to AMS. Key word Arterial elasticity Polymorphism of ACE gene High altitude Acute mountain sickness (AMS) 5

6 ACE AI AMS ANP AOCS AT BAC BAD BAR C1 C2 CC DC EPO GT HAPE HIF-1 HO PAC PCA PI PRA PWA PWV RAAS ROS SVC Angiotensin-converting enzyme Argumentation index Acute mountain sickness Atrial natriuretic peptide Analysis of the oscillometric cuff signal Angiotensin Brachial Arterial Compliance Brachial Arterial Distensbility Brachial Arterial resistance Large artery elasticity index Small artery elasticity index Compliance coefficient Distensibility coefficient Erythropoietin Glucose transporter-1 High altitude pulmonary edema Hypoxia-inducible factor-1 Heme oxygenase-1 Plasma aldosterone and cortisol Pulse contour analysis Pulse Index Plasma renin activity Pulse wave analysis pulse wave velocity Renin angiotensin aldosterone system Reactive oxygen Systemic Vascular Compliance -1 6

7 SVR VEGF VP Systemic Vascular Resistance Vascular endothelial growth factor Vasopressin 7

8 elasticity compliance stiffness distensibility [3] [4] [2] [5] [6] [7][8] [9] [3][10][11] 5- A P I 2 F 2 E 1 [3] [3][12][13] [1] MBP MBP MBP 8

9 Compliance P V V/ P ml/mmhg Distensibility dv/dp V %/mmhg [1][2]][3] Windkessel 40% 60% 50% SBP DBP DBP 30% 70% MBP DBP PWV argumentation index AI NO NO NO 9

10 1 Stephrn Hales air chamber air Windkessel Windkessel Windkessel Elastic Chamber [2] C=SV/PP SV PP 2 [14] [2] 10

11 [15] (1) pulse wave analysis PWA pulse contour analysis PCA (1.1)C 1 C 2 Goldwyn Watt 1967 Windkessel [17] C 1 C 2 cm 3 /mmhg C 2 HDI-DO2020 [18] (1.2) (Augment Index, AI) 0.5mm 1.0mm [19] AI AI (2) analysis of the oscillometric cuff signal AOCS pulsemetric DynaPulse 200M Brinton [20] 2 PWV pulse wave velocity, PWV 11

12 [16] Moens Korteweg Bramwell Hill C= r 2 / PWV 2 PWV=L/t r L t [3] PWV PWV PWV 3 C= Ds-Dd / SBP-DBP Dd Ds Dd [3] distensibility coefficient DC compliance coefficient CC Pulse Index PI 1 hypoxia hypoxia 1 hypoxic hypoxia 2 hypemic hypoxia 12

13 3 stagnant hypoxia 4 Histotoxic hypoxia Ward [21] Acclimatization Adaption [22] Kelloge [23] 13

14 PCO 2 [24] ph Ward 1995 [25] PCO 2 PO 2 PO 2 PO 2 PCO 2 PCO 2 PCO 2 PCO 2 PCO 2 CO 2 H + HCO PCO 2 CO 2 H + H + Lloyd [26] CO 2 PCO 2 Imray 2003 [27] O 2 CO 2 Hickling 1995 [28] PO 2 [29] Kazmaier 1998 [30] Kontos [31] 15 Kontos 14

15 1985 Forster [32] 40 2 SBP DBP MAP 3 Forster 1999 Kanstrup [33] 5 Kontos 5 SBP DBP MAP DBP MAP [34] RAAS plasma renin activity PRA angiotensin AT --- plasma aldosterone and cortisol PAC Atrial natriuretic peptide ANP SBP DBP PP 4 [35][36][37] 15

16 [38][39] 2001 Schneider [40] Cannon [41] [42][43] 1954 Nahas [44] [45][46][47] 1967 Richardson [48] 1969 Angell [49] 1998 Rostrup [50] noradrenaline 4 adrenaline Rostrup MSNA

1 ABSTRACT 3 5 13 14 14 15 15 16 17 18 18 18 18-21 28 33 34 46 47 53 54 2

: - S99017212 O O 1 1 ABSTRACT 3 5 13 14 14 15 15 16 17 18 18 18 18-21 28 33 34 46 47 53 54 2 - A L Aeq CNE 463 3-5 L Aeq L Aeq CNE WHO/ISH 1999 [49] 18.6kPa / 12.0kPa EpiInfo6.04 SPSS10.0 Logistic 10