ATS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
David J Chambers
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fujii, M.
Right arrow Articles by Chambers, D. J
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fujii, M.
Right arrow Articles by Chambers, D. J
Related Collections
Right arrow Myocardial protection

Ann Thorac Surg 2004;77:1398-1407
© 2004 The Society of Thoracic Surgeons

Original article: cardiovascular

Experimental studies on myocardial protection with intermittent cross-clamp fibrillation: additive effect of the sodium-hydrogen exchanger inhibitor, cariporide

Masahiro Fujii, MDa, Metin Avkiran, PhD,DScb, David J Chambers, PhD*a

a Cardiac Surgical Research and Cardiothoracic Surgery, The Rayne Institute, Guy's and St. Thomas' NHS Trust, St. Thomas' Hospital, London, United Kingdom
b Molecular Cardiology, The Rayne Institute, Guy's and St. Thomas' NHS Trust, St. Thomas' Hospital, London, United Kingdom

Accepted for publication September 15, 2003.

* Address reprint requests to Dr Chambers, Cardiac Surgical Research, Cardiothoracic Surgery, The Rayne Institute, Guy's and St Thomas' NHS Trust, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK
e-mail: david.chambers{at}kcl.ac.uk

BACKGROUND: We previously showed that intermittent cross clamping with fibrillation affords myocardial protection equivalent to cardioplegic arrest. In this study, we examined whether cariporide (Aventis Pharma, Frankfurt, Germany), a specific sodium-hydrogen exchanger inhibitor, enhanced the protective effect of intermittent cross-clamp fibrillation (ICCF).

METHODS: Isolated rat hearts were Langendorff-perfused (20 mins) with bicarbonate buffer and function (left ventricular developed pressure) measured. In each of three separate protocols that incorporated progressively longer ischemic durations, hearts were randomly allocated to one of three groups: group 1 was the control group with 40, 60, or 80 minutes of continuous global ischemia. Group 2 was the ICCF group with 4, 6, or 8 cycles of 10 minutes ICCF and 10 minutes of reperfusion in sinus rhythm. Group 3 was the ICCF plus cariporide group, which was the same as group 2, but also with 3 µmoles/L cariporide present in perfusate from 10 minutes before the ICCF cycles. Hearts were reperfused for 60 minutes with drug-free buffer and recovery (percentage of initial function) was measured. Hearts were maintained at 37°C throughout the protocols. In protocol 3 (80 minutes ischemia per 8 cycles of ICCF), creatine kinase leakage (myocardial injury) and triphenyl tetrazolium chloride staining (myocardial viability) were also measured. Protocols 1, 2, and 3 had n = 8 hearts, n = 6 hearts, and n = 6 hearts in each group, respectively.

RESULTS: In the three protocols, the recoveries of left ventricular developed pressure in the control group, the ICCF group, and the ICCF plus cariporide group, respectively, for protocol 1 were: 26% ± 3%, 70% ± 2% (p < 0.05 vs the control group) and 74% ± 2% (p < 0.05 vs the control group), respectively. For protocol 2 these were: 16% ± 2%, 55% ± 1% (p < 0.05 vs the control group), and 70% ± 3% (p < 0.05 vs the control and ICCF groups), respectively. For protocol 3 these were: 8% ± 2%, 41% ± 3% (p < 0.05 vs the control group), and 63% ± 2% (p < 0.05 vs the control and ICCF groups), respectively. Recovery of left ventricular end-diastolic pressure mirrored that of left ventricular developed pressure in all protocols. In protocol 3, total creatine kinase leakage (international units per gram wet weight) was 88 ± 12, 47 ± 4 (p < 0.05 vs the control group), and 17 ± 1 (p < 0.05 vs the control and ICCF groups), respectively, and triphenyl tetrazolium chloride staining (arbitrary units per gram wet weight) was 0.17 ± 0.04 in the control group, 0.39 ± 0.04 (p < 0.05 vs the control group) in the ICCF group, and 0.47 ± 0.08 (p < 0.05 vs the control group) in the ICCF plus cariporide group, respectively.

CONCLUSIONS: Sodium-hydrogen exchanger inhibition with cariporide enhances the myocardial protection afforded by ICCF, with the additive benefit becoming more apparent with increasing severity of the ischemic insult. Sodium-hydrogen exchanger inhibition may provide a significant protective reserve during ICCF, particularly when longer procedures are required.




This article has been cited by other articles:


Home page
 Eur. J. Cardiothorac. Surg.Home page
D. J. Chambers and M. Fujii
Reply to Mishra
Eur. J. Cardiothorac. Surg., May 1, 2006; 29(5): 861 - 861.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS
Copyright © 2004 by The Society of Thoracic Surgeons.