Document Detail

Protective effects of calpain inhibitor for prolonged hypothermic cardiac preservation.
MedLine Citation:
PMID:  10358944     Owner:  NLM     Status:  MEDLINE    
PURPOSE: For successful organ transplantation, it is important to properly preserve the donor organ. This study was carried out to investigate tissue damage generated by the activation of calpain during prolonged hypothermic cardiac preservation using specific antibodies for mu- and m-calpain proenzymes, and to ensure the protective effect of calpain inhibitor 1 (N-acetyl-leucyl-leucyl-norleucinal). METHODS: Excised rat hearts were divided into two groups: in Group I, the heart was arrested and immersed in University of Wisconsin solution with 20 microM of calpain inhibitor 1 (n = 28) and in Group N, the heart was arrested and immersed in University of Wisconsin solution without calpain inhibitor (n = 27). After a 12-hour preservation period at 4 degrees C, the hearts were reperfused on an isolated perfusion apparatus. Separation of the myocardial calpain isozymes was carried out by DEAE cellulose chromatography and both calpain proenzymes were detected by immunoblotting. RESULTS: The cardiac function was more satisfactorily maintained in Group I in comparison with Group N. Remarkable leakage of creatine kinase, glutamic-oxaloacetic transaminase and lactate dehydrogenase was detected in Group N, while it was efficiently suppressed in Group I. During ischemia, mu-calpain proenzyme decreased in Group N (p < 0.01), but there was no significant change in m-calpain. However, during reperfusion, both mu- and m-calpains decreased more in Group N (p < 0.01). CONCLUSION: Activation of calpain proenzymes and a decrease in cardiac function during preservation and reperfusion were demonstrated. The use of calpain inhibitor to protect against tissue damage was suggested as being useful for the prolonged preservation of the heart.
T Saito; A Mishima; M Asano; T Ukai; S Yamamoto; M Kunimatsu; M Sasaki; T Manabe
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Japanese journal of thoracic and cardiovascular surgery : official publication of the Japanese Association for Thoracic Surgery = Nihon Kyōbu Geka Gakkai zasshi     Volume:  47     ISSN:  1344-4964     ISO Abbreviation:  Jpn. J. Thorac. Cardiovasc. Surg.     Publication Date:  1999 Apr 
Date Detail:
Created Date:  1999-07-06     Completed Date:  1999-07-06     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  100884261     Medline TA:  Jpn J Thorac Cardiovasc Surg     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  145-52     Citation Subset:  IM    
Division of Cardiovascular Surgery, Nagoya City University Medical School, Japan.
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MeSH Terms
Calpain / analysis,  antagonists & inhibitors*,  immunology
Enzyme Precursors / analysis,  immunology
Heart / physiology*
Heart Transplantation
Hypothermia, Induced
Leupeptins / pharmacology*
Organ Preservation / methods*
Organ Preservation Solutions
Rats, Wistar
Time Factors
Reg. No./Substance:
0/Antibodies; 0/Enzyme Precursors; 0/Leupeptins; 0/Organ Preservation Solutions; 0/University of Wisconsin-lactobionate solution; 110044-82-1/acetylleucyl-leucyl-norleucinal; 11061-68-0/Insulin; 315-30-0/Allopurinol; 512-69-6/Raffinose; 58-61-7/Adenosine; 70-18-8/Glutathione; EC 3.4.22.-/Calpain

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