Received 2008-06-03Comparison of the effects of chronic intermittent hypobaric hypoxia and continuous hypobaric hypoxia on hemodynamics in rats

( views:84, downloads:0 )
YUAN Fang(Department of Physiology,Hebei Medical University,Shijiazhuang 050017,China)
GUO Zan(Department of Physiology,Hebei Medical University,Shijiazhuang 050017,China)
XU Ying(Department of Physiology,Hebei Medical University,Shijiazhuang 050017,China)
WANG Xin(Department of Physiology,Hebei Medical University,Shijiazhuang 050017,China)
BU Hui-Min(Department of Physiology,Hebei Medical University,Shijiazhuang 050017,China)
ZHONG Ning(Gladstone Institutes of Cardiovascular and Neurological Diseases University of California,San Francisco,CA94158,USA)
ZHANG Yi(Department of Physiology,Hebei Medical University,Shijiazhuang 050017,China)
ZHOU Zhao-Nian(Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China)
Journal Title:
Volume 60, Issue 06, 2008
Key Word:
chronic intermittent hypobaric hypoxia;chronic continued hypobaric hypoxia;cardioprotection;hemodynamics;antioxygenation;rat

Abstract: The aim of this study is to investigate the effects of chronic intermittent hypobaric hypoxia(IHH) and chronic continuous hypobaric hypoxia(CHH)on hemodynamics under basic normoxia and acute hypoxia conditions and to find the difference of two types of chronic hypoxia.Forty adult male Sprague-Dawley(SD)rats were randomly divided into 5 groups:Control group(CON),28 days IHH group(IHH28),42 days IHH group(IHH42),28 days CHH group(CHH28)and 42 days CHH group(CHH42).The rats in IHH groups were treated with intermittent hypoxia(11.1% O2)mimicking 5 000 m altitude in a hypobaric chamber for 28 or 42 d,6 h a day,respectively.The rats in CHH groups lived in the hypobaric chamber with the same degree of hypoxia like IHH rats except half an hour in normoxia each day for feeding and cleaning.The body weight of rats was measured once a week.The parameters in hemodynamics,such as mean artery blood pressure(MAP),heart rate(HR),left ventricular systolic pressure(LVSP),maximum change rate of left ventricular pressure(±LVdp/dtmax)were recorded under basic normoxia and acute hypoxia conditions through catheterization technique.The superoxide dismutase(SOD)activity and malondialdehyde(MDA)content in myocardium of rats wen measured by biochemical method.The weights of whole heart,left and fight ventricles were measured separately.The results showed:(1)The basic HR and MAP in CHH42 rats were lower than those in CON,IHH and CHH28 rats(P<0.05).(2)IHH showed a cardioprotection against acute hypoxia and reoxygenation injury,manifested as the result that the changes of HR,MAP, LVSP, and ±LVdp/dtmax were smaller than those in CON rats during acute hypoxia and reoxygenation.CHH showed a rather strong cardioprotection during acute hypoxia,manifested as the result that the decreases of HR,MAP,LVSE and±LVdp/dtmax were much smaller,but it did damage during reoxygenation,manifested as the result that the recovery of hemodynamics was the worst among three groups(P<0.05).(3)The antioxygenation of heart was increased in both IHH and CHH rats compared with that in CON rats manifested by the increased SOD activity and decreased MDA content(P<0.05,P<0.01).(4)IHH had no effect on heart weight,but CHH rats showed an obvious right ventricular hypertrophy compared with CON and IHH animals(P<0.01).The result indicates that IHH can induce a more effective cardioprotection with no much side effect,which might have a potential value for practical use.

  • [1]Hurtado A.Some clinical aspects of life at high altitudes.Ann Intern Med 1960; 53:247-258.
  • [2]Poupa O,Krofta K,Prochazka J,Turek Z.Acclimatization to simulated high altitude and acute cardiac necrosis.Fed Proc 1966;25:1243-1246.
  • [3]Pei SX,Cben XJ,Si Ren BZ,Liu YH,Cheng XS,Harris EM,Anand IS,Harris PC.Chronic mountain sickness in Tibet.Q J Meal 1989; 266:555-574.
  • [4]Zhuang J,Zhou Z.Protective effects of intermittent hypoxic adaptation on myocardium and its mechanisms.Biol Signals Recept 1999; 8:316-322.
  • [5]Zhang Y (张翼),Yang HT,Zhou ZN.The cardioprotection of intermittent hypoxic adaptation.Acta Physiol Sin (生理学报)2007; 59(5):601-613 (Chinese,English abstract).
  • [6]Zhang Y (张翼),Zhong N,Zhou ZN.Antiarrhythmia and antioxidation effects of intermittent hypoxiaon rat myocardium.Acta Physiol Sin (生理学报) 2000; 52(2):89-92 (Chinese,English abstract).
  • [7]Zhang Y,Zhong N,Gia J,Zhou Z.Effects of chronic intermit-tent hypoxia on the hemodynamics of systemic circulation in rats.Jpn J Physiol 2004; 54(2):171-174.
  • [8]Zhong N,Zhang Y,Fang QZ,Zhou ZN.Intermittent hypoxia exposure-induced heat-shock protein 70 expression increases resistance of rat heart to ischemic injury.Acta Pharmacol Sin 2000; 21(5):467-472.
  • [9]Dong JW,Zhu HF,Zhu WZ,Ding HL,Ma TM,Zhou ZN.Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bci-2/Bax expression.Cell Res 2003; 13(5):385-391.
  • [10]Ostadal B,Kolar F.Cardiac adaptation to chronic high-altitude hypoxia:Beneficial and adverse effects.Respir Physiol Neurobiol 2007; 158 (2-3):224-236.
  • [11]Marklund S,Marklund G..Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase.Eur J Biochem 1974; 47:469-474.
  • [12]Ohkawa H,Ohishi N,Yagi K.Assay for lipid peroxides in animal tissues by thiobarturic acid reaction.Anal Biochem 1979; 95:351-358.
  • [13]Rodway GW,Sethi JM,Hoffman LA,Conley YP,Choi AM,Sereika SM,Zullo TG,Ryter SW,Sanders MH.Hemodynamic and molecular response to intermittent hypoxia (IH) versus con-tinuous hypoxia (CH) in normal humans.Transl Res 2007; 149(2):76-84.
  • [14]Marcus JN,Philippi N,Bird CE,Olson EB,Morgan BJ.Differ-ential effects of chronic intermittent versus continuous hypoxia on cardiovascular function and skeletal muscle resistance arteries.FASEB J 2007; 21:733.12.
  • [15]Honda HM,Korge P,Weiss JN.Mitochondria and ischemia/reperfusion injury.Ann NY Acad Sci 2005; 1047:248-258.
  • [16]Brookes PS,Yoon Y,Robotham JL,Sheu SS.Calcium,ATP,and ROS:a mitochondrial love-hate triangle.Am J Physiol Cell Physiol 2004; 287:C817-C833.
  • [17]Petrosillo G,Di Venosa N,Pistolese M,Casanova G,Tiravanfi E,Colantuono G,Federici A,Paradies G,Ruggiero FM.Protective effect of melatonin against mitochondrial dysfunction associated with cardiac ischemia-reperfusion:role of cardiolipin.FASEB J 2006; 20:269-276.
  • [18]Zhu WZ,Xie Y,Chen L,Yang HT,Zhou ZN.Intermittent high altitude hypoxia inhibits opening of mitochondrial permeability transition pores against reperfusion injury.J Mol Cell Cardiol 2006; 40:96-106.
  • [19]Chamberlain BK,Volpe P,Fleischer S.Calcium-induced calcium release from purified cardiac sarcoplasmic reticulum vesicles.General characteristics.J Biol Chem 1984; 259:7540-7546.
  • [20]Birkeland JA,Sejersted OM,Taraldsen T,Sjaastad I.EC-coupling in normal and failing hearts.Scand Cardiovasc J 2005; 39:13-23.
  • [21]Chen L,Lu XY,Li J,Fu JD,Zhou ZN,Yang HT.Intermittent hypoxia protects cardiomyocytes against ischemia-reperfusion injury-induced alterations in Ca2+ homeostasis and contraction via the sarcoplasmic reticulum and Na+/Ca2+ exchange mechanisms.Am J Physiol Cell Physiol 2006; 290:C1221-C1229.
  • [22]Yeung HM,Kravtsov GM,Ng KM,Wong TM,Fung ML.Chronic intermittent hypoxia alters Ca2+ handling in rat cardiomyocytes by augmented Na+/Ca2+ exchange and ryanodine receptor activities in ischemia-reperfusion.Am J Physiol Cell Physiol 2007; 292:C2046-C2056.
  • [23]Pei JM,Yu XC,Fung ML,Zhou JJ,Cheung CS,Wong NS,Leung MP,Wong TM.Impaired Gs and adenylyl cyclase cause adrenoceptor desensitization in chronically hypoxic rat hearts.Am J Physiol Cell Physiol 2000; 279:C1455-C1463.
  • [24]Pei JM,Kravtsov GM,Wu S,Das R,Fung ML,Wong TM.Calcium homeostasis in rat cardiomyocytes during chronic hypoxia:a time course study.Am J Physiol Cell Physiol 2003;285:C1420-C1428.
  • [25]Starnes JW,Bumes BD,Olsen ME.Exercise training decreases rat heart-mitochondria free radical generation but does not pre-vent Ca2+ induced dysfunction.J Appl Pliysio12007; 102:1793-1798.
  • [26]Lu YD(吕永达).High Altitude Medicine and Physiology(高原医学与生理学).Tianjin:Tianjin Science and Technology Trans-lation and Publishing Corp.(天津科技翻译出版社)1995,23-51(Chinese).
  • [27]Yu Y(于伊),Liu Y,Li SL,Mao HQ,Li L,Fan SM,Mei F,Liu LJ,Yan PZ,Ren M,Ma YM.Changes of heart rate variability in native tibetan healthy adults at high altitude.J High Altitude Medicine(高原医学杂志)2005;15(2):26.28(Chinese,En-glish abstract).
  • [28]Bernardi L.Heart rate and cardiovascular variability at high altitude.Proceedings of 29th Annual Intemafional Conference of the IEEE:2007 Aug 22-26,Lyon.USA:Engineering in Medicine and Biology Society,2007.
  • [29]Cornolo J,Mollard P,Bmgniaux JV,Robach P,Richalet JP.Autonomic control of the cardiovascular system during acelima-tization to high altitude:effects of sildenafil.J Appl Physiol 2004;97(3):935-940.
  • [30]Otsuka K,Norboo T,Otsuka Y,Highchi H,Hayajiri M,Narushima C,Sato Y,Tsugoshi T,Murakami S,Wada T,Ishine M,Okumiya K,Matsubayashi K,Yano S,Choygal T,Angchuk D,Ichihara K,Corntlissen G,Halberg F.Effect of aging on blood pressure in Leh,tadakh,ahigh-altitude(3524m)community,by comparison with a Japanese town.Biomed Pharmacother 2005;59(Suppl 11:S54-S57.
  • [31]Sizlan A,Ogur R,Ozer M,Irmak MK.Blood pressure changes in young male subjects exposed to amedian altitude.Clin Auton Res 2008;18(2):84-89.
  • [32]Clifiord PS,Helsten Y.Vasodilatory methanisms in contracting skeletal muscle.J Appl Physiol 2004;97(1):393-403.
  • [33]Murry CE,Jennings RB,Reimer KA.Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium.Circulation 1986;74(5):1124-1136.
  • [34]Murphy E.Primary and secondary signaling pathways in early preconditioning that converge on the mitochondria to produce cardioprotection.Circ Res 2004;94:7-16.
  • [35]Serebrovskaya TV.Intermittent hypoxia:cause of or therapy for systemic hypertension?Exp Biol Med(Maywood)2008;233(6):627-650.
  • [36]Beidleman BA,Muza SR,Fulco CS,Cymerman A,Sawka MN,Lewis SF,Skrinar GS.Seven intermittent exposures to altitude improves exercise performanceat 4300m.Med Sci Sports Exerc 2008:40(1):141-148.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615