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Ascorbic acid mitigates the myocardial injury after cardiac arrest and electrical shock

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Abstract

Purpose

To examine the effects of ascorbic acid (AA) administrated during cardiopulmonary resuscitation (CPR) on the myocardial injury in a rat model of ventricular fibrillation (VF) and electrical shock (ES).

Methods

VF was induced in male Wistar rats and left untreated for 5 min, followed by 1 min of CPR, and then one ES of 5 J. At the start of CPR, animals received either intravenous administration of AA (100 mg/kg) or Tempol (30 mg/kg), two antioxidants, or 0.9% saline (VF + ES group). After ES, animals were immediately killed. Myocardial lipoxidation was determined by malondialdehyde (MDA) assay. The histology and ultrastructural changes of myocardium were also evaluated. The mitochondrial permeability transition pore (mPTP) opening was measured based on the mitochondrial swelling rate. The complex activities and respiration of mitochondria were assessed, too.

Results

Increased myocardial injury and mitochondrial damage in the VF + ES group were noted. AA and Tempol alleviated such damages. Both AA and Tempol improved accelerated mitochondrial swelling; decreased complex activities and respiratory dysfunction occurred in the VF + ES group. The animals receiving AA and Tempol during CPR had better successful resuscitation rates and 72-h survival than the VF + ES group.

Conclusions

Intravenous administration of AA and Tempol at the start of CPR may reduce lipid peroxidation and myocardial necrosis, diminish mitochondrial damage, facilitate resuscitation, and improve outcomes after VF + ES.

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References

  1. Peatfield RC, Sillett RW, Taylor D, McNicol MW (1997) Survival after cardiac arrest in the hospital. Lancet 1:1223–1225

    Google Scholar 

  2. Schenenberger RA, von Planta M, von Planta I (1994) Survival after failed out of hospital resuscitation. Are further therapeutic efforts in the emergency department futile? Arch Intern Med 154:2433–2437

    Article  Google Scholar 

  3. Gazmuri RJ, Berkowitz M, Cajigas H (1999) Myocardial effects of ventricular fibrillation in the isolated rat heart. Crit Care Med 27:1542–1550

    Article  PubMed  CAS  Google Scholar 

  4. Xie J, Weil MH, Sun S, Tang W, Sato Y, Jin X, Bisera J (1997) High-energy defibrillation increases the severity of postresuscitation myocardial dysfunction. Circulation 96:683–688

    PubMed  CAS  Google Scholar 

  5. Krauthamer V, Jones JL (1997) Calcium dynamics in cultured heart cells exposed to defibrillator-type electrical shocks. Life Sci 60:1977–1985

    Article  PubMed  CAS  Google Scholar 

  6. Caterine MR, Spencer KT, Pagan-Carlo LA, Smith RS, Buettner GR, Kerber RE (1996) Direct current shocks to the heart generate free radicals: an electron paramagnetic resonance study. J Am Coll Cardiol 28:1598–1609

    Article  PubMed  CAS  Google Scholar 

  7. Weaver WD, Cobb LA, Copass MK, Hallstrom AP (1982) Ventricular defibrillation—a comparative trial using 175-J and 320-J shocks. N Engl J Med 307:1101–1106

    Article  PubMed  CAS  Google Scholar 

  8. Dorian P, Hohnloser SH, Thorpe KE, Roberts RS, Kuck KH, Gent M, Connolly SJ (2010) Mechanisms underlying the lack of effect of implantable cardioverter-defibrillator therapy on mortality in high-risk patients with recent myocardial infarction: insights from the defibrillation in acute myocardial infarction trial (DINAMIT). Circulation 122:2645–2652

    Article  PubMed  Google Scholar 

  9. Zhang Y, Boddicker KA, Rhee BJ, Davies LR, Kerber RE (2005) Effect of nitric oxide synthase modulation on resuscitation success in a swine ventricular fibrillation cardiac arrest model. Resuscitation 67:127–134

    Article  PubMed  CAS  Google Scholar 

  10. Tsai MS, Sun S, Tang W, Ristagno G, Chen WJ, Weil MH (2008) Free radicals mediate postshock contractile impairment in cardiomyocytes. Crit Care Med 36:3213–3219

    Article  PubMed  Google Scholar 

  11. Woodward B, Zakaria MN (1985) Effect of some free radical scavengers on reperfusion induced arrhythmias in the isolated rat heart. J Mol Cell Cardiol 17:485–493

    Article  PubMed  CAS  Google Scholar 

  12. Tan DX, Manchester LC, Reiter RJ, Qi W, Kim SJ, El-Sokkary GH (1998) Ischemia/reperfusion-induced arrhythmias in the isolated rat heart: prevention by melatonin. J Pineal Res 25:184–191

    Article  PubMed  CAS  Google Scholar 

  13. Karahaliou A, Katsouras C, Koulouras V, Nikas D, Niokou D, Papadopoulos G, Nakos G, Sideris D, Michalis L (2008) Ventricular arrhythmias and antioxidative medication: experimental study. Hellenic J Cardiol 49:320–328

    PubMed  Google Scholar 

  14. Senthil S, Veerappan RM, Ramakrishna Rao M, Pugalendi KV (2004) Oxidative stress and antioxidants in patients with cardiogenic shock complicating acute myocardial infarction. Clin Chim Acta 348:131–137

    Article  PubMed  CAS  Google Scholar 

  15. Gao F, Yao CL, Gao E, Mo QZ, Yan WL, McLaughlin R, Lopez BL, Christopher TA, Ma XL (2002) Enhancement of glutathione cardioprotection by ascorbic acid in myocardial reperfusion injury. J Pharmacol Exp Ther 301:543–550

    Article  PubMed  CAS  Google Scholar 

  16. Johnston CS, Cox SK (2001) Plasma-saturating intakes of vitamin C confer maximal antioxidant protection to plasma. J Am Coll Nutr 20:623–627

    PubMed  CAS  Google Scholar 

  17. Huang CH, Hsu CY, Tsai MS, Wang TD, Chang WT, Chen WJ (2008) Cardioprotective effects of erythropoietin on postresuscitation myocardial dysfunction in appropriate therapeutic windows. Crit Care Med 36:S467–S473

    Article  PubMed  Google Scholar 

  18. Sodha NR, Boodhwani M, Ramlawi B, Clements RT, Mieno S, Feng J, Xu SH, Bianchi C, Sellke FW (2008) Atorvastatin increases myocardial indices of oxidative stress in a porcine model of hypercholesterolemia and chronic ischemia. J Card Surg 23:312–320

    Article  PubMed  Google Scholar 

  19. Shiva S, Brookes PS, Patel RP, Anderson PG, Darley-Usmar VM (2001) Nitric oxide partitioning into mitochondrial membranes and the control of respiration at cytochrome c oxidase. Proc Natl Acad Sci USA 98:7212–7217

    Article  PubMed  CAS  Google Scholar 

  20. Argaud L, Gateau-Roesch O, Raisky O, Loufouat J, Robert D, Ovize M (2005) Postconditioning inhibits mitochondrial permeability transition. Circulation 111:194–197

    Article  PubMed  CAS  Google Scholar 

  21. Chowdhury SK, Drahota Z, Floryk D, Calda P, Houstek J (2000) Activities of mitochondrial oxidative phosphorylation enzymes in cultured amniocytes. Clin Chim Acta 298:157–173

    Article  PubMed  CAS  Google Scholar 

  22. Di Maria CA, Bogoyevitch MA, McKitrick DJ, Arnolda LF, Hool LC, Arthur PG (2009) Changes in oxygen tension affect cardiac mitochondrial respiration rate via changes in the rate of mitochondrial hydrogen peroxide production. J Mol Cell Cardiol 47:49–56

    Article  PubMed  CAS  Google Scholar 

  23. Murphy MP (2001) How understanding the control of energy metabolism can help investigation of mitochondrial dysfunction, regulation and pharmacology. Biochim Biophys Acta 1504:1–11

    Article  PubMed  CAS  Google Scholar 

  24. Trouton TG, Allen JD, Yong LK, Rooney JJ, Adgey AA (1989) Metabolic changes and mitochondrial dysfunction early following transthoracic countershock in dogs. Pacing Clin Electrophysiol 12:1827–1834

    Article  PubMed  CAS  Google Scholar 

  25. Rigoulet M, Yoboue ED, Devin A (2011) Mitochondrial ROS generation and its regulation mechanisms involved in H2O2 signaling. Antioxid Redox Signal 14:459–468

    Article  PubMed  CAS  Google Scholar 

  26. Jackson CV, Mickelson JK, Stringer K, Rao PS, Lucchesi BR (1986) Electrolysis-induced myocardial dysfunction. A novel method for the study of free radical mediated tissue injury. J Pharmacol Methods 15:305–320

    Article  PubMed  CAS  Google Scholar 

  27. Schrier GM, Hess ML (1988) Quantitative identification of superoxide anion as a negative inotropic species. Am J Physiol 255:H138–H143

    PubMed  CAS  Google Scholar 

  28. Xu KY, Zweier JL, Becker LC (1997) Hydroxyl radical inhibits sarcoplasmic reticulum Ca2+-ATPase function by direct attack on the ATP binding site. Circ Res 80:76–81

    PubMed  CAS  Google Scholar 

  29. Crompton M (1999) The mitochondrial permeability transition pore and its role in cell death. Biochem J 341:233–249

    Article  PubMed  CAS  Google Scholar 

  30. Crompton M, Virji S, Doyle V, Johnson N, Ward JM (1999) The mitochondrial permeability transition pore. Biochem Soc Symp 66:167–179

    PubMed  CAS  Google Scholar 

  31. Halestrap AP, Clarke SJ, Javadov SA (2004) Mitochondrial permeability transition pore opening during myocardial reperfusion–a target for cardioprotection. Cardiovasc Res 61:372–385

    Article  PubMed  CAS  Google Scholar 

  32. Hausenloy DJ, Maddock HL, Baxter GF, Yellon DM (2002) Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning? Cardiovasc Res 55:534–543

    Article  PubMed  CAS  Google Scholar 

  33. O’Rourke B (2004) Evidence for mitochondrial K+ channels and their role in cardioprotection. Circ Res 94:420–432

    Article  PubMed  Google Scholar 

  34. Suleiman MS, Halestrap AP, Griffiths EJ (2001) Mitochondria: a target for myocardial protection. Pharmacol Ther 89:29–46

    Article  PubMed  CAS  Google Scholar 

  35. Sönmez MF, Narin F, Akkuş D, Ozdamar S (2009) Effect of melatonin and vitamin C on expression of endothelial NOS in heart of chronic alcoholic rats. Toxicol Ind Health 25:385–393

    Article  PubMed  Google Scholar 

  36. Korantzopoulos P, Kolettis TM, Kountouris E, Dimitroula V, Karanikis P, Pappa E, Siogas K, Goudevenos JA (2005) Oral vitamin C administration reduces early recurrence rates after electrical cardioversion of persistent atrial fibrillation and attenuates associated inflammation. Int J Cardiol 102:321–326

    Article  PubMed  Google Scholar 

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Acknowledgments

We are grateful to Prof. Kuo-Shyan Lu, Dr. Pei-Hsin Huang, Yu-Jen Su, and Shu-mei Lai for their assistance. The study was supported by a research grant from the Taiwan National Science Council.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Emergency Medicine, National Taiwan University Hospital, No. 7, Chung-Shan S. Road, Taipei, 100, Taiwan

    Min-Shan Tsai, Chien-Hua Huang, Chia-Ying Tsai, Hsaio-Ju Cheng, Chiung-Yuan Hsu, Wei-Tien Chang & Wen-Jone Chen

  2. Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan

    Huei-Wen Chen

  3. Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan

    Hsin-Chen Lee

  4. Division of Cardiology, Department of Internal Medicine, National Taiwan University Medical College and Hospital, Taipei, Taiwan

    Tzung-Dau Wang

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  1. Min-Shan Tsai
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Correspondence to Wen-Jone Chen.

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Tsai, MS., Huang, CH., Tsai, CY. et al. Ascorbic acid mitigates the myocardial injury after cardiac arrest and electrical shock. Intensive Care Med 37, 2033–2040 (2011). https://doi.org/10.1007/s00134-011-2362-6

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  • DOI: https://doi.org/10.1007/s00134-011-2362-6

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