Adenosine injection prior to cardioplegia enhances preservation of senescent hearts in rat heterotopic heart transplantation

Sang Hyun Lim, Sungsoo Lee, Kentaro Noda, Tomohiro Kawamura, Yugo Tanaka, Norihisa Shigemura, Atsunori Nakao, Yoshiya Toyoda

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objectives: Advanced donor age is one of the risk factors for graft failure and is the leading cause of early death after heart transplantation. Better myocardial preservation methods should reduce graft failure. The purpose of this study was to determine if adenosine, which is known to enhance cardioplegic protection, enhances myocardial preservation during heart transplantation using older donors. Methods: We used a rat heterotopic heart transplantation model with Lewis rats that were at least 60 weeks old as donors. We injected saline (control) or adenosine (0.1 or 0.2 mg/kg) before cardioplegia, perfused with cold Celsior and stored the hearts in Celsior for 6 h at 4°C. The grafts were transplanted into syngenic, 12-16-week old recipients, and blood and tissue were collected 3 h after reperfusion. Results: Bolus injection of adenosine led to faster mechanical arrest after perfusion with Celsior and faster reanimation after reperfusion compared with controls. Adenosine treatment significantly reduced myocardial injury, as indicated by serum troponin I and creatine phosphokinase levels. The mRNAs for inflammatory cytokines were markedly increased in the control grafts, but were less upregulated in the grafts treated with adenosine. The grafts treated with adenosine also exhibited less mitochondrial damage, fewer infiltrating cells and a higher adenosine triphosphate content. Conclusions: Adenosine injection prior to perfusion of cardioplegia significantly reduced cold ischaemia/reperfusion injury in cardiac grafts from older donors and improved the stores of cellular energy after reperfusion. This procurement protocol may be clinically feasible and should be considered in the clinical setting, particularly for older donors.

Original languageEnglish
Article numberezs509
Pages (from-to)1202-1208
Number of pages7
JournalEuropean Journal of Cardio-thoracic Surgery
Volume43
Issue number6
DOIs
Publication statusPublished - Jun 2013
Externally publishedYes

Fingerprint

Heterotopic Transplantation
Induced Heart Arrest
Heart Transplantation
Adenosine
Transplants
Injections
Reperfusion
Perfusion
Cold Ischemia
Troponin I
Creatine Kinase
Reperfusion Injury
Cause of Death
Adenosine Triphosphate
Cytokines
Messenger RNA
Wounds and Injuries
Serum

Keywords

  • Adenosine
  • Cold preservation
  • Heart transplantation
  • Ischaemia reperfusion

ASJC Scopus subject areas

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

Cite this

Adenosine injection prior to cardioplegia enhances preservation of senescent hearts in rat heterotopic heart transplantation. / Lim, Sang Hyun; Lee, Sungsoo; Noda, Kentaro; Kawamura, Tomohiro; Tanaka, Yugo; Shigemura, Norihisa; Nakao, Atsunori; Toyoda, Yoshiya.

In: European Journal of Cardio-thoracic Surgery, Vol. 43, No. 6, ezs509, 06.2013, p. 1202-1208.

Research output: Contribution to journalArticle

Lim, Sang Hyun ; Lee, Sungsoo ; Noda, Kentaro ; Kawamura, Tomohiro ; Tanaka, Yugo ; Shigemura, Norihisa ; Nakao, Atsunori ; Toyoda, Yoshiya. / Adenosine injection prior to cardioplegia enhances preservation of senescent hearts in rat heterotopic heart transplantation. In: European Journal of Cardio-thoracic Surgery. 2013 ; Vol. 43, No. 6. pp. 1202-1208.
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AU - Lee, Sungsoo

AU - Noda, Kentaro

AU - Kawamura, Tomohiro

AU - Tanaka, Yugo

AU - Shigemura, Norihisa

AU - Nakao, Atsunori

AU - Toyoda, Yoshiya

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N2 - Objectives: Advanced donor age is one of the risk factors for graft failure and is the leading cause of early death after heart transplantation. Better myocardial preservation methods should reduce graft failure. The purpose of this study was to determine if adenosine, which is known to enhance cardioplegic protection, enhances myocardial preservation during heart transplantation using older donors. Methods: We used a rat heterotopic heart transplantation model with Lewis rats that were at least 60 weeks old as donors. We injected saline (control) or adenosine (0.1 or 0.2 mg/kg) before cardioplegia, perfused with cold Celsior and stored the hearts in Celsior for 6 h at 4°C. The grafts were transplanted into syngenic, 12-16-week old recipients, and blood and tissue were collected 3 h after reperfusion. Results: Bolus injection of adenosine led to faster mechanical arrest after perfusion with Celsior and faster reanimation after reperfusion compared with controls. Adenosine treatment significantly reduced myocardial injury, as indicated by serum troponin I and creatine phosphokinase levels. The mRNAs for inflammatory cytokines were markedly increased in the control grafts, but were less upregulated in the grafts treated with adenosine. The grafts treated with adenosine also exhibited less mitochondrial damage, fewer infiltrating cells and a higher adenosine triphosphate content. Conclusions: Adenosine injection prior to perfusion of cardioplegia significantly reduced cold ischaemia/reperfusion injury in cardiac grafts from older donors and improved the stores of cellular energy after reperfusion. This procurement protocol may be clinically feasible and should be considered in the clinical setting, particularly for older donors.

AB - Objectives: Advanced donor age is one of the risk factors for graft failure and is the leading cause of early death after heart transplantation. Better myocardial preservation methods should reduce graft failure. The purpose of this study was to determine if adenosine, which is known to enhance cardioplegic protection, enhances myocardial preservation during heart transplantation using older donors. Methods: We used a rat heterotopic heart transplantation model with Lewis rats that were at least 60 weeks old as donors. We injected saline (control) or adenosine (0.1 or 0.2 mg/kg) before cardioplegia, perfused with cold Celsior and stored the hearts in Celsior for 6 h at 4°C. The grafts were transplanted into syngenic, 12-16-week old recipients, and blood and tissue were collected 3 h after reperfusion. Results: Bolus injection of adenosine led to faster mechanical arrest after perfusion with Celsior and faster reanimation after reperfusion compared with controls. Adenosine treatment significantly reduced myocardial injury, as indicated by serum troponin I and creatine phosphokinase levels. The mRNAs for inflammatory cytokines were markedly increased in the control grafts, but were less upregulated in the grafts treated with adenosine. The grafts treated with adenosine also exhibited less mitochondrial damage, fewer infiltrating cells and a higher adenosine triphosphate content. Conclusions: Adenosine injection prior to perfusion of cardioplegia significantly reduced cold ischaemia/reperfusion injury in cardiac grafts from older donors and improved the stores of cellular energy after reperfusion. This procurement protocol may be clinically feasible and should be considered in the clinical setting, particularly for older donors.

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