Relationship between post-cardiac arrest myocardial oxidative stress and myocardial dysfunction in the rat

Fernanda Schäfer Hackenhaar, Francesca Fumagalli, Giovanni Li Volti, Valeria Sorrenti, Ilaria Russo, Lidia Staszewsky, Serge Masson, Roberto Latini, Giuseppe Ristagno

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Reperfusion after resuscitation from cardiac arrest (CA) is an event that increases reactive oxygen species production leading to oxidative stress. More specifically, myocardial oxidative stress may play a role in the severity of post-CA myocardial dysfunction. This study investigated the relationship between myocardial oxidative stress and post-CA myocardial injury and dysfunction in a rat model of CA and cardiopulmonary resuscitation (CPR). Ventricular fibrillation was induced in 26 rats and was untreated for 6 min. CPR, including mechanical chest compression, ventilation, and epinephrine, was then initiated and continued for additional 6 min prior to defibrillations. Resuscitated animals were sacrificed at two h (n = 9), 4 h (n = 6) and 72 h (n = 8) following resuscitation, and plasma collected for assessment of: high sensitivity cardiac troponin T (hs-cTnT), as marker of myocardial injury; isoprostanes (IsoP), as marker of lipid peroxidation; and 8-hydroxyguanosine (8-OHG), as marker of DNA oxidative damage. Hearts were also harvested for measurement of tissue IsoP and 8-OHG. Myocardial function was assessed by echocardiography at the corresponding time points. Additional 8 rats were not subjected to CA and served as baseline controls.

Results: Compared to baseline, left ventricular ejection fraction (LVEF) was reduced at 2 and 4 h following resuscitation (p <0.01), while it was similar at 72 h. Inversely, plasma hs-cTnT increased, compared to baseline, at 2 and 4 h post-CA (p <0.01), and then recovered at 72 h. Similarly, plasma and myocardial tissue IsoP and 8-OHG levels increased at 2 and 4 h post-resuscitation (p <0.01 vs. baseline), while returned to baseline 72 h later. Myocardial IsoP were directly related to hs-cTnT levels (r = 0.760, p <0.01) and inversely related to LVEF (r = -0.770, p <0.01). Myocardial 8-OHG were also directly related to hs-cTnT levels (r = 0.409, p <0.05) and inversely related to LVEF (r = -0.548, p <0.01).

Conclusions: The present study provides evidence that lipid peroxidation and DNA oxidative damage in myocardial tissue are closely related to myocardial injury and LV dysfunction during the initial hours following CA.

Original languageEnglish
Article number70
JournalJournal of Biomedical Science
Volume21
Issue number1
DOIs
Publication statusPublished - Aug 19 2014

Keywords

  • 8-hydroxyguanosine
  • Cardiopulmonary resuscitation
  • Isoprostanes
  • Myocardial injury
  • Oxidative damage

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)
  • Medicine(all)

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