The Effect of Short-Term Intermittent Hypoxia Exposure on Mouse Myocardial Oxidative Stress and Cardiac Function

OU Wei, LIANG Yu, QING Yu, DENG Yan, WU Wei, LI Tao

Abstract

To investigate the effect of short-term intermittent hypoxia (IH) on the structure and function of mouse myocardium.  Methods  Thirty male C57BL6/J mice were randomly assigned to two groups, a control (Con) group and an IH group exposed to hypoxic treatment at atmospheric pressure. The IH group received 10% oxygen pretreatment for 8 hours per day on 14 consecutive days, while the Con group was exposed to normoxia environment and all the other treatment the group received were identical to those given to the IH group, The body mass of the mice was monitored daily during the treatment. The exercise tolerance and the cardiac function of isolated heart were assessed at the end of IH exposure. Additionally, analysis was conducted regarding myocardial enzymology, histology, and other indicators relevant to oxidative stress, including protein carbonylation and lipid peroxidation.   Results  There was no significant difference in the exercise tolerance between the two groups. Nevertheless, IH mice showed enhanced cardiac function during isolated heart perfusion (P<0.05). As compared to the control group, prominent alterations of myocardial structure were detected by transmission electron microscopy of the IH heart, accompanied by elevated creatine kinase-MB levels (P<0.05). The levels of myocardial reactive oxygen species, protein carbonylation and lipid peroxidation were all significantly upregulated in the IH group as compared to the control group (P<0.05).   Conclusion  IH exposure induced myocardial oxidative stress damage and myofibrillar structural alteration in mice, but did not impair the exercise tolerance of the mice or the contractile function of the isolated heart.

 

Keywords: Intermittent hypoxia, Myocardium, Cardiac function, Oxidative stress

 

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VISCOR G, TORRELLA J R, CORRAL L, et al. Physiological and biological responses to short-term intermittent hypobaric hypoxia exposure: From sports and mountain medicine to new biomedical applications. Front Physiol, 2018, 9: 814[2021-08-20]. https://pubmed. ncbi.nlm.nih.gov/30038574/. doi: 10.3389/fphys.2018.00814.

SAVLA J J, LEVINE B D, SADEK H A. The effect of hypoxia on cardiovascular disease: Friend or foe? High Alt Med Biol,2018,19(2): 124–130.

NAVARRETE-OPAZO A, MITCHELL G S. Therapeutic potential of intermittent hypoxia: A matter of dose. Am J Physiol Regul Integr Comp Physiol,2014,307(10): R1181–R1197.

MALLET R T, MANUKHINA E B, RUELAS S S, et al. Cardioprotection by intermittent hypoxia conditioning: evidence, mechanisms, and therapeutic potential. Am J Physiol Heart Circ Physiol,2018,315(2): H216–H232.

OU W, LIANG Y, QING Y, et al. Hypoxic acclimation improves cardiac redox homeostasis and protects heart against ischemia-reperfusion injury through upregulation of O-GlcNAcylation. Redox Biol, 2021, 43: 101994[2021-08-20]. https://www.sciencedirect.com/science/article/pii/S221323172100152X. doi: 10.1016/j.redox.2021.101994.

GUO H C, ZHANG Z, ZHANG L N, et al. Chronic intermittent hypobaric hypoxia protects the heart against ischemia/reperfusion injury through upregulation of antioxidant enzymes in adult guinea pigs. Acta Pharmacol Sin,2009,30(7): 947–955.

CHEN L, LU X Y, LI J, et al. 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(4): C1221–C1229.

ZHU W Z, XIE Y, CHEN L, et al. Intermittent high altitude hypoxia inhibits opening of mitochondrial permeability transition pores against reperfusion injury. J Mol Cell Cardiol,2006,40(1): 96–106.

DENG Y, XIE M, LI Q, et al. Targeting mitochondria-inflammation circuit by β-hydroxybutyrate mitigates HFpEF. Circ Res,2021,128(2): 232–245.

OYEWOLE A O, BIRCH-MACHIN M A. Mitochondria-targeted antioxidants. FASEB J,2015,29(12): 4766–4771.

BOU-TEEN D, KALUDERCIC N, WEISSMAN D, et al. Mitochondrial ROS and mitochondria-targeted antioxidants in the aged heart. Free Radic Biol Med,2021,167: 109–124.

MURPHY M P. How mitochondria produce reactive oxygen species. Biochem J,2008,417(1): 1–13.

YIN X, ZHENG Y, LIU Q, et al. Cardiac response to chronic intermittent hypoxia with a transition from adaptation to maladaptation: The role of hydrogen peroxide. Oxid Med Cell Longev, 2012, 2012: 569520[2021-08-20]. https://pubmed.ncbi.nlm.nih.gov/22685619/. doi: 10.1155/2012/569520.

SABBAH H N. Targeting the mitochondria in heart failure: A translational perspective. JACC Basic Transl Sci,2020,5(1): 88–106. TAKIMOTO E, KASS D A. Role of oxidative stress in cardiac hypertrophy and remodeling. Hypertension,2007,49(2): 241–248. STEINBERG S F. Oxidative stress and sarcomeric proteins. Circ Res, 2013,112(2): 393–405.

FARRÉ N, OTERO J, FALCONES B, et al. Intermittent hypoxia mimicking sleep apnea increases passive stiffness of myocardial extracellular matrix. A multiscale study. Front Physiol, 2018, 9: 1143[2021-08-20]. https://pubmed.ncbi.nlm.nih.gov/30158879/. doi: 10.3389/FPHYS.2018.01143.

CASTRO A, ALVAREZ-BUVÉ R, TORRES M, et al. Intermittent hypoxia-induced cardiovascular remodeling is reversed by normoxia in a mouse model of sleep apnea. Chest,2016,149(6): 1400–1408.

ESTRADA J A, WILLIAMS A G J, SUN J, et al. δ-Opioid receptor (DOR) signaling and reactive oxygen species (ROS) mediate intermittent hypoxia induced protection of canine myocardium. Basic Res Cardiol, 2016, 111(2): 17[2021-08-20]. https://pubmed.ncbi.nlm.nih.gov/268 79900/. doi: 10.1007/s00395-016-0538-5.

YOULE R J, VAN DER BLIEK A M. Mitochondrial fission, fusion, and stress. Science,2012,337(6098): 1062–1065.

JEŽEK J, COOPER K F, STRICH R. Reactive oxygen species and mitochondrial dynamics: The Yin and Yang of mitochondrial dysfunction and cancer progression. Antioxidants (Basel), 2018, 7(1): 13[2021-08-20]. https://pubmed.ncbi.nlm.nih.gov/29337889/. doi: 10.3390/antiox7010013.

TAKAHASHI K, UEDA S, KOBAYASHI T, et al. Chronic intermittent hypoxia-mediated renal sympathetic nerve activation in hypertension and cardiovascular disease. Sci Rep, 2018, 8(1): 17926[2021-08-20]. https://pubmed.ncbi.nlm.nih.gov/30560943. doi: 10.1038/s41598-018-36159-9.

RIO R D, ANDRADE D C, LUCERO C, et al. Carotid body ablation abrogates hypertension and autonomic alterations induced by intermittent hypoxia in rats. Hypertension,2016,68(2): 436–445.


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