Skip to main content

Advertisement

Log in

Periods of systemic partial hypoxia induces apoptosis and inflammation in rat skeletal muscle

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Critical illness myopathy (CIM) causes significant morbidity. In this study, we investigated the effect of repeated mild hypoxia on the skeletal muscle inflammation. Sprague–Dawley rats anesthetized with 2% inhaled isoflurane were divided into two groups (n = 6 each), normoxia and hypoxia (12.5% for 12 min followed by 35% for 12 min, at which point the cycle was repeated for three times). We measured the tissue oxygen tension and perfusion (simultaneously) in hind limb skeletal muscle. Inflammation in skeletal muscle was assessed by light microcopy (Hematoxylin-Eosin staining) and apoptosis (Fluorescein-FragEL DNA fragmentation detection) and expressed as percent normoxia. Compared to the control group, hypoxia significantly (P < 0.001) altered histomorphometrics. Similarly, DNA fragmentation analysis revealed that hypoxia significantly (P < 0.001) induced apoptosis. We conclude that after a mild but repeated hypoxic insult there is marked histological alterations and induced apoptosis in skeletal muscle. We postulate that variable periods of hypoxia in the critically ill may be playing a role in the etiology of CIM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Douglass JA, Tuxen DV, Horne M, Scheinkestel CD, Weinmann M, Czarny D, Bowes G (1992) Myopathy in severe asthma. Am Rev Respir Dis 146:517–519

    PubMed  CAS  Google Scholar 

  2. Lacomis D, Petrella JT, Giuliani MJ (1998) Causes of neuromuscular weakness in the intensive care unit: a study of ninety-two patients. Muscle Nerve 21:610–617

    Article  PubMed  CAS  Google Scholar 

  3. Op de Coul AA, Lambregts PC, Koeman J, van Puyenbroek MJ, Ter Laak HJ, Gabreels-Festen AA (1985) Neuromuscular complications in patients given Pavulon (pancuronium bromide)during artificial ventilation. Clin Neurol Neurosurg 87:17–22

    Article  Google Scholar 

  4. Op de Coul AA, Verheul GA, Leyten AC, Schellens RL, Teepen JL (1991) Critical illness polyneuromyopathy after artificial respiration. Clin Neurol Neurosurg 93:27–33

    Article  Google Scholar 

  5. Showalter CJ, Engel AG (1997) Acute quadriplegic myopathy: analysis of myosin isoforms andevidence for calpain-mediated proteolysis. Muscle Nerve 20:316–322

    Article  PubMed  CAS  Google Scholar 

  6. Di Giovanni S, Mirabella M, D’Amico A, Tonali P, Servidei S (2000) Apoptotic features accompanyacute quadriplegic myopathy. Neurology 55:854–858

    PubMed  CAS  Google Scholar 

  7. de Moissac D, Gurevich RM, Zheng H, Singal PK, Kirshenbaum LA (2000) Caspase activationand mitochondrial cytochrome C release during hypoxia-mediated apoptosis of adult ventricular myocytes. J Mol Cell Cardiol 32: 53–63

    Article  PubMed  CAS  Google Scholar 

  8. Aravindan N, Williams MT, Riedel BJ, Shaw AD (2005) Transcriptional responses of rat skeletal muscle following hypoxia-reoxygenation and near ischaemia-reperfusion. Acta Physiol Scand 183:367–377

    Article  PubMed  CAS  Google Scholar 

  9. National-Research-Council: Guide for the Care and Use of Laboratory Animals. Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council. Washington, D.C. National Academy Press, pp 1–118, 1996

  10. Aravindan N, Cata JP, Dougherty PM, Shaw AD (2006) Effect of fenoldopam on ischemia/reperfusion-induced apoptosis. Ren Fail 28:337–344

    Article  PubMed  CAS  Google Scholar 

  11. Aravindan N, Natarajan M, Shaw AD (2006) Fenoldopam inhibits nuclear translocation of nuclear factor kappa B in a rat model of surgical ischemic acute renal failure. J Cardiothorac Vasc Anesth 20:179–186

    Article  PubMed  CAS  Google Scholar 

  12. Aravindan N, Samuels J, Riedel B, Shaw A (2006) Fenoldopam Improves Corticomedullary Oxygen Delivery and Attenuates Angiogenesis Gene Expression in Acute Ischemic Renal Injury. Kidney Blood Press Res 29:165–174

    Article  PubMed  CAS  Google Scholar 

  13. Aravindan N, Shaw A (2006) Effect of furosemide infusion on renal hemodynamics and angiogenesis gene expression in acute renal ischemia/reperfusion. Ren Fail 28:25–35

    Article  PubMed  CAS  Google Scholar 

  14. Maas W, de Graaf I, Schoen E, Koster H, Van de Sandt J, Groten J (2000) Assessment of some critical factors in the freezing technique for the cryopreservation of precision-cut rat liver slices. Cryobiology 40:250–263

    Article  PubMed  CAS  Google Scholar 

  15. Liss P, Nygren A, Erikson U, Ulfendahl HR (1998) Injection of low and iso-osmolar contrast medium decreases oxygen tension in the renal medulla. Kidney Int 53:698–702

    Article  PubMed  CAS  Google Scholar 

  16. Daemen MA, van’t Veer C, Denecker G, Heemskerk VH, Wolfs TG, Clauss M, Vandenabeele P, Buurman WA (1999) Inhibition of apoptosis induced by ischemia-reperfusion prevents inflammation. J Clin Invest 104:541–549

    PubMed  CAS  Google Scholar 

  17. Sternberg S (ed) (1997) Histology for pathologists, 2nd edn. Philadelphia, Lippincott-Raven; ISBN 0–397-51718, pp 1–1216

  18. Kerr JF (1991) Shrinkage necrosis: a distinct mode of cellular death. J Pathol 105:13–20

    Article  Google Scholar 

  19. Anversa P, Fitzpatrick D, Argani S, Capasso JM (1991) Myocyte mitotic division in the aging mammalian rat heart. Circ Res 69:1159–1164

    PubMed  CAS  Google Scholar 

  20. Liu Y, Cigola E, Cheng W, Kajstura J, Olivetti G, Hintze TH, Anversa P (1995) Myocyte nuclear mitotic division and programmed myocyte cell death characterize the cardiac myopathy induced by rapid ventricular pacing in dogs. Lab Invest 73:771–787

    PubMed  CAS  Google Scholar 

  21. Orrenius S, McConkey DJ, Bellomo G, Nicotera P (1989) Role of Ca2+ in toxic cell killing. Trends Pharmacol Sci 10:281–285

    Article  PubMed  CAS  Google Scholar 

  22. Gottlieb RA, Burleson KO, Kloner RA, Babior BM, Engler RL (1994) Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest 94:1621–1628

    Article  PubMed  CAS  Google Scholar 

  23. Tanaka M, Ito H, Adachi S, Akimoto H, Nishikawa T, Kasajima T, Marumo F, Hiroe M (1994) Hypoxia induces apoptosis with enhanced expression of Fas antigen messenger RNA in cultured neonatal rat cardiomyocytes. Circ Res 75:426–433

    PubMed  CAS  Google Scholar 

  24. Goussev A, Sharov VG, Shimoyama H, Tanimura M, Lesch M, Goldstein S, Sabbah HN (1998) Effects of ACE inhibition on cardiomyocyte apoptosis in dogs with heart failure. Am J Physiol 275:H626-631

    PubMed  CAS  Google Scholar 

  25. Kajstura J, Cigola E, Malhotra A, Li P, Cheng W, Meggs LG, Anversa P (1997) Angiotensin II induces apoptosis of adult ventricular myocytes in vitro. J Mol Cell Cardiol 29:859–870

    Article  PubMed  CAS  Google Scholar 

  26. Communal C, Singh K, Pimentel DR, Colucci WS (1998) Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the beta-adrenergic pathway. Circulation 98:1329–1334

    PubMed  CAS  Google Scholar 

  27. Tidball JG, Albrecht DE, Lokensgard BE, Spencer MJ (1995) Apoptosis precedes necrosis of dystrophin-deficient muscle. J Cell Sci 108(Pt 6):2197–2204

    PubMed  CAS  Google Scholar 

  28. Olive M, Blanco R, Rivera R, Cinos C, Ferrer I (1995) Cell death induced by gamma irradiation of developing skeletal muscle. J Anat 187(Pt 1):127–132

    PubMed  Google Scholar 

  29. Webster KA, Discher DJ, Bishopric NH (1993) Induction and nuclear accumulation of fos and jun proto-oncogenes in hypoxic cardiac myocytes. J Biol Chem 268:16852–16858

    PubMed  CAS  Google Scholar 

  30. Buttke TM, Sandstrom PA (1994) Oxidative stress as a mediator of apoptosis. Immunol Today 15:7–10

    Article  PubMed  CAS  Google Scholar 

  31. Ray PS, Estrada-Hernandez T, Sasaki H, Zhu L, Maulik N (1994) Early effects of hypoxia/reoxygenation on VEGF, ang−1, ang−2 and their receptors in the rat myocardium: implications for myocardial angiogenesis. Mol Cell Biochem 213:145–153

    Article  Google Scholar 

  32. Yellon DM, Marber MS (1994) Hsp70 in myocardial ischaemia. Experientia 50:1075–1084

    Article  PubMed  CAS  Google Scholar 

  33. Jennings RB, Reimer KA (1983) Factors involved in salvaging ischemic myocardium: effect of reperfusion of arterial blood. Circulation 68:I25–36

    PubMed  CAS  Google Scholar 

  34. Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Natarajan Aravindan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aravindan, N., Aravindan, S., Shanmugasundaram, K. et al. Periods of systemic partial hypoxia induces apoptosis and inflammation in rat skeletal muscle. Mol Cell Biochem 302, 51–58 (2007). https://doi.org/10.1007/s11010-007-9424-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-007-9424-7

Keywords

Navigation