Amelioration of rat cardiac cold ischemia/reperfusion injury with inhaled hydrogen or carbon monoxide, or both

Atsunori Nakao, David J. Kaczorowski, Yinna Wang, Jon S. Cardinal, Bettina M. Buchholz, Ryujiro Sugimoto, Kimimasa Tobita, Sungsoo Lee, Yoshiya Toyoda, Timothy R. Billiar, Kenneth R. McCurry

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Background: Recent advances in novel medical gases, including hydrogen and carbon monoxide (CO), have demonstrated significant opportunities for therapeutic use. This study was designed to evaluate the effects of inhaled hydrogen or CO, or both, on cold ischemia/reperfusion (I/R) injury of the myocardium. Methods: Syngeneic heterotopic heart transplantation was performed in rats after 6 or 18 hours of cold ischemia in Celsior solution. Survival, morphology, apoptosis and marker gene expression were assessed in the grafts after in vivo inhalation of hydrogen (1% to 3%), CO (50 to 250 ppm), both or neither. Both donors and recipients were treated for 1 hour before and 1 hour after reperfusion. Results: After 6-hour cold ischemia, inhalation of hydrogen (>2%) or CO (250 ppm) alone attenuated myocardial injury. Prolonged cold ischemia for 18 hours resulted in severe myocardial injury, and treatment with hydrogen or CO alone failed to demonstrate significant protection. Dual treatment with hydrogen and CO significantly attenuated I/R graft injury, reducing the infarcted area and decreasing in serum troponin I and creatine phosphokinase (CPK). Hydrogen treatment alone significantly reduced malondialdehyde levels and serum high-mobility group box 1 protein levels as compared with air-treated controls. In contrast, CO only marginally prevented lipid peroxidation, but it suppressed I/R-induced mRNA upregulation for several pro-inflammatory mediators and reduced graft apoptosis. Conclusions: Combined therapy with hydrogen and CO demonstrated enhanced therapeutic efficacy via both anti-oxidant and anti-inflammatory mechanisms, and may be a clinically feasible approach for preventing cold I/R injury of the myocardium.

Original languageEnglish
Pages (from-to)544-553
Number of pages10
JournalJournal of Heart and Lung Transplantation
Volume29
Issue number5
DOIs
Publication statusPublished - May 2010
Externally publishedYes

Fingerprint

Cold Ischemia
Carbon Monoxide
Reperfusion Injury
Hydrogen
Transplants
Inhalation
Reperfusion
Myocardium
Isogeneic Transplantation
Heterotopic Transplantation
Apoptosis
HMGB1 Protein
Therapeutics
Troponin I
Wounds and Injuries
Therapeutic Uses
Heart Transplantation
Creatine Kinase
Malondialdehyde
Serum

Keywords

  • carbon monoxide
  • heart transplantation
  • hydrogen
  • ischemia/reperfusion
  • preservation
  • rat

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

Cite this

Amelioration of rat cardiac cold ischemia/reperfusion injury with inhaled hydrogen or carbon monoxide, or both. / Nakao, Atsunori; Kaczorowski, David J.; Wang, Yinna; Cardinal, Jon S.; Buchholz, Bettina M.; Sugimoto, Ryujiro; Tobita, Kimimasa; Lee, Sungsoo; Toyoda, Yoshiya; Billiar, Timothy R.; McCurry, Kenneth R.

In: Journal of Heart and Lung Transplantation, Vol. 29, No. 5, 05.2010, p. 544-553.

Research output: Contribution to journalArticle

Nakao, A, Kaczorowski, DJ, Wang, Y, Cardinal, JS, Buchholz, BM, Sugimoto, R, Tobita, K, Lee, S, Toyoda, Y, Billiar, TR & McCurry, KR 2010, 'Amelioration of rat cardiac cold ischemia/reperfusion injury with inhaled hydrogen or carbon monoxide, or both', Journal of Heart and Lung Transplantation, vol. 29, no. 5, pp. 544-553. https://doi.org/10.1016/j.healun.2009.10.011
Nakao, Atsunori ; Kaczorowski, David J. ; Wang, Yinna ; Cardinal, Jon S. ; Buchholz, Bettina M. ; Sugimoto, Ryujiro ; Tobita, Kimimasa ; Lee, Sungsoo ; Toyoda, Yoshiya ; Billiar, Timothy R. ; McCurry, Kenneth R. / Amelioration of rat cardiac cold ischemia/reperfusion injury with inhaled hydrogen or carbon monoxide, or both. In: Journal of Heart and Lung Transplantation. 2010 ; Vol. 29, No. 5. pp. 544-553.
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abstract = "Background: Recent advances in novel medical gases, including hydrogen and carbon monoxide (CO), have demonstrated significant opportunities for therapeutic use. This study was designed to evaluate the effects of inhaled hydrogen or CO, or both, on cold ischemia/reperfusion (I/R) injury of the myocardium. Methods: Syngeneic heterotopic heart transplantation was performed in rats after 6 or 18 hours of cold ischemia in Celsior solution. Survival, morphology, apoptosis and marker gene expression were assessed in the grafts after in vivo inhalation of hydrogen (1{\%} to 3{\%}), CO (50 to 250 ppm), both or neither. Both donors and recipients were treated for 1 hour before and 1 hour after reperfusion. Results: After 6-hour cold ischemia, inhalation of hydrogen (>2{\%}) or CO (250 ppm) alone attenuated myocardial injury. Prolonged cold ischemia for 18 hours resulted in severe myocardial injury, and treatment with hydrogen or CO alone failed to demonstrate significant protection. Dual treatment with hydrogen and CO significantly attenuated I/R graft injury, reducing the infarcted area and decreasing in serum troponin I and creatine phosphokinase (CPK). Hydrogen treatment alone significantly reduced malondialdehyde levels and serum high-mobility group box 1 protein levels as compared with air-treated controls. In contrast, CO only marginally prevented lipid peroxidation, but it suppressed I/R-induced mRNA upregulation for several pro-inflammatory mediators and reduced graft apoptosis. Conclusions: Combined therapy with hydrogen and CO demonstrated enhanced therapeutic efficacy via both anti-oxidant and anti-inflammatory mechanisms, and may be a clinically feasible approach for preventing cold I/R injury of the myocardium.",
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AU - Cardinal, Jon S.

AU - Buchholz, Bettina M.

AU - Sugimoto, Ryujiro

AU - Tobita, Kimimasa

AU - Lee, Sungsoo

AU - Toyoda, Yoshiya

AU - Billiar, Timothy R.

AU - McCurry, Kenneth R.

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