Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
5-Year IF – 2.0, IF – 1.9, JCI (2024) – 0.43
Scopus CiteScore – 4.3
Q1 in SJR 2024, SJR score – 0.598, H-index: 49 (SJR)
ICV – 161.00; MNiSW – 70 pts
Initial editorial assessment and first decision within 24 h

ISSN 1899–5276 (print), ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2012, vol. 21, nr 6, November-December, p. 713–726

Publication type: original article

Language: English

Sodium Nitrite and Cardioprotective Effect in Pig Regional Myocardial Ischemia–Reperfusion Injury Model

Azotyn sodu i jego działanie kardioprotekcyjne na miejscowe niedokrwienie–reperfuzję mięśnia sercowego na modelu świńskim

Suat Doganci1,A,C,D,F, Vedat Yildirim2,B,C,D, Cengiz Bolcal1,B,C, Petek Korkusuz3,B, Ahmet Aydin4,C,E, Bulent Gumusel5,C,F, Ufuk Demirkilic1,A,E,F

1 Gulhane Military Academy of Medicine, Department of Cardiovascular Surgery, Ankara, Turkey

2 Gulhane Military Academy of Medicine, Department of Anesthesiology, Ankara, Turkey

3 Hacettepe University, Faculty of Medicine, Department of Histology, Ankara, Turkey

4 Gulhane Military Academy of Medicine, Department of Toxicology, Ankara, Turkey

5 Hacettepe University, Faculty of Pharmacy, Department of Pharmacology, Ankara, Turkey

Abstract

Objectives. The present study was designed to investigate the cardioprotective effect of sodium nitrite (NaNO2) and sodium nitrate (NaNO3) against myocardial ischemia–reperfusion (I/R) injury in a pig regional ischemia model.
Material and Methods. Eighteen pigs were randomly divided into three groups as control (Group 1), sodium nitrite (Group 2) and sodium nitrate (Group 3) groups. Before the exploration of the heart, blood samplings were taken for alanine aminotranspherase (ALT), aspartate aminotranspherase (AST), lactate dehydrogenase (LDH), creatinine kinase–muscle band (CK-MB), troponin-t, glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nitrite/nitrate (NO2 –/NO3 –) in all groups (T0). Following sternotomy and stabilization, blood and tissue samples were repeated (T1). Then, intracoronary sodium nitrite and sodium nitrate were given (0.5 μg/kg) in Groups 2 and 3. Five minutes later, the left anterior descending (LAD) artery was ligated for I/R experiments. Blood and tissue samplings were repeated after 60 minutes of ischemia (T2) and 180 minutes of reperfusion period (T3). Light and electron microscopic investigations were performed.
Results. There were statistically significant results in favor of Group 2 in all studied parameters. Hemodynamic parameters showed a decrease in mean arterial pressure (MAP), cardiac output (CO), cardiac index (CI) and an increase in heart rate, mean pulmonary artery pressure (MPAP), left ventricle end-diastolic pressure (LVEDP), pulmonary capillary wedge pressure (PCWP) during ischemia. Following the ischemia these parameters returned to their near normal levels. This was prominent in group 2. Oxidative parameters showed protective increases in GPx, SOD, CAT and NO2 –/NO3 – levels and a decrease at MDA both in tissue and blood samples in group 2. There were statistical differences only in T3 for AST, troponin-t and CK-MB levels in favor of Group 2. Histological and electron microscopy examinations were also in favor of NO2 – group.
Conclusion. The results of the present study indicate that NaNO2 provides protection against myocardial I/R injury when compared to control and NaNO3 groups.

Streszczenie

Cel pracy. Zbadanie działania kardioprotekcyjnego azotynu sodu (NaNO2) i azotanu sodu (NaNO3) na niedokrwienie–reperfuzję mięśnia sercowego na modelu świńskim.
Materiał i metody. 18 świń losowo podzielono na 3 grupy: kontrolną (grupa 1), azotyn sodu (grupa 2) i azotan sodu (grupa 3). Przed otwarciem serca pobrano próbki krwi do oznaczenia aminotransferazy alaninowej (ALT), aminotransferazy asparaginianowej (AST), dehydrogenazy mleczanowej (LDH), izoenzymu MB kinazy kreatyniny (CK-MB), troponiny-T, peroksydazy glutationowej (GPx), dysmutazy ponadtlenkowej (SOD), katalazy (CAT), aldehydu malonowego (MDA) i azotynów/azotanów (NO2 –/NO3 –) we wszystkich grupach (T0). Po sternotomii i stabilizacji ponownie pobrano próbki krwi i tkanek (T1). Następnie podano azotyn sodu i azotan sodu śródwieńcowo (0,5 μg/kg) w grupach 2 i 3. Pięć minut później sklejono tętnicę zstępującą przednią (LAD), aby przeprowadzić eksperyment I/R. Pobieranie próbek krwi i tkanek powtórzono po 60 min. w fazie niedokrwienia (T2) i po 180 min w fazie reperfuzji (T3). Wykonano badanie z użyciem mikroskopii optycznej i elektronowej.
Wyniki. Nie było istotnych statystycznie różnic na korzyść grupy 2 wszystkich badanych parametrów. Parametry hemodynamiczne wykazały zmniejszenie średniego ciśnienia tętniczego (MAP), rzutu serca (CO), wskaźnika sercowego (CI) i zwiększenie częstości akcji serca, średniego ciśnienia w tętnicy płucnej (MPAP), lewokomorowego ciśnienia końcowo-rozkurczowego (LVEDP), ciśnienia zaklinowania (PCWP) podczas niedokrwienia. Po niedokrwieniu te wskaźniki wróciły prawie do normy. Było to widoczne w grupie 2. Wskaźniki oksydacyjne wykazały ochronne zwiększenie stężenia GPx, SOD, CAT i NO2–/NO3– i zmniejszenie MDA zarówno w tkance, jak i krwi w grupie 2. Nie było różnic statystycznych tylko w T3 dla stężenia AST, troponiny-T i CK-MB na korzyść grupy 2. Badania histologiczne i mikroskopia elektronowa były również korzystne dla grupy NO2 –.
Wnioski. Wyniki badania wskazują, że NaNO2 chroni przed uszkodzeniem I/R mięśnia sercowego w porównaniu z grupą kontrolną i grupą NaNO3.

Key words

sodium nitrite, myocardium, ischemia-reperfusion injury

Słowa kluczowe

azotyn sodu, mięsień serca, niedokrwienie–reperfuzja

References (11)

  1. Bolli R: Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of a decade of research. J Mol Cell Cardiol 2001, 33, 1897–1918.
  2. Gladwin MT, Raat NJ, Shiva S, Dezfulian C, Hogg N, Kim-Shapiro DB, Patel RP: Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection and vasodilatation. Am J Physiol 2006, 291, H2026–H2035.
  3. Dezfulian C, Shiva S, Alekseyenko A, Pendyal A, Beiser DG, Munasinghe JP, Anderson SA, Chesley CF, Vanden Hoek TL, Gladwin MT: Nitrite therapy after cardiac arrest reduces reactive oxygen species generation, improves cardiac and neurological function, and enhances survival via reversible inhibition of mitochondrial complex I. Circulation 2009 Sep 8, 120, 897–905.
  4. Bolcal C, Yildirim V, Doganci S, Sargin M, Aydin A, Kuralay E, Ozal E, Demirkilic U, Oz BS, Sayal A, Tatar H: Do N-acetylcystein, beta-glucan, and coenzyme Q10 mollify myocardial ischemia-reperfusion injury? Heart Surg Forum 2007, 10, E222–227.
  5. Aebi H: Catalase in vitro. Methods Enzymol 1984, 105, 121–126.
  6. Millar TM, Stevens CR, Benjamin N, Eisenthal R, Harrison R, Blake DR: Xanthine oxidoreductase catalyses the reduction of nitrates and nitrite to nitric oxide under hypoxic conditions. FEBS Lett 1998, 427, 225–228.
  7. Zweier JL, Wang P, Samouilov A, Kuppusamy P: Enzyme-independent formation of nitric oxide in biological tissues. Nat Med 1995, 1, 804–809.
  8. Huang Z, Shiva S, Kim-Shapiro DB, Patel RP, Ringwood LA, Irby CE, Huang KT, Ho C, Hogg N, Schechter AN, Gladwin MT: Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control. J Clin Invest 2005, 115, 2099–2107.
  9. Gonzalez FM, Shiva S, Vincent PS, Ringwood LA, Hsu LY, Hon YY, Aletras AH, Cannon RO 3rd, Gladwin MT, Arai AE: Nitrite anion provides potent cytoprotective and antiapoptotic effects as djunctive therapy to reperfusion for acute myocardial infarction. Circulation 2008 Jun 10, 117, 2986–2994.
  10. Rassaf T, Poll LW, Brouzos P, Lauer T, Totzeck M, Kleinbongard P, Gharini P, Andersen K, Schulz R, Heusch G, Mödder U, Kelm M: Positive effects of nitric oxide on left ventricular function in humans. Heart J 2006 Jul, 27(14), 1699–1705.
  11. Dhalla NS, Elmoselhi AB, Hata T, Makino N: Status of myocardial antioxidants in ischemia-reperfusion injury. Cardiovasc Res 2000 Aug 18, 47, 446–456.
© Wroclaw Medical University