HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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

Eur J Cardiothorac Surg 2005;28:821-831
© 2005 Elsevier Science NL

Myocardial protection with intermittent cross-clamp fibrillation: does preconditioning play a role?

Cardiac Surgical Research/Cardiothoracic Surgery, The Rayne Institute, Guy's and St Thomas’ NHS Foundation Trust, St Thomas’ Hospital, London SE1 7EH, UK

Received 4 April 2005; received in revised form 14 June 2005; accepted 27 June 2005.

^_* Corresponding author. Tel.: +44 20 7261 0157; fax: +44 20 7928 0658. (Email: david.chambers{at}kcl.ac.uk).

Objective: Previously, we showed intermittent cross-clamp fibrillation afforded equivalent protection to cardioplegia. This study examined whether protection induced by intermittent cross-clamp fibrillation involves an ischemic preconditioning mechanism. Methods: Isolated Langendorff-perfused rat hearts were subjected to three different studies to determine: Study 1, whether a single intermittent cross-clamp fibrillation episode (10 min) and reperfusion (10 min) before prolonged ischemia acts as a preconditioning trigger for protection; Study 2, whether cardioprotection induced by intermittent cross-clamp fibrillation alone (no prolonged ischemia) involves a preconditioning mechanism; Study 3, whether intermittent cross-clamp fibrillation cardioprotection can be prevented by targeting putative components of the preconditioning mechanism (protein kinase C or the mitochondrial ATP-sensitive potassium (K_ATP) channel). Hearts were reperfused (60 min) and recovery of function (left ventricular developed pressure measured using an intraventricular balloon) and myocardial injury (creatine kinase leakage) were measured. Results: In Study 1, recovery of function in the single intermittent cross-clamp fibrillation hearts was 61 ± 3% (mean ± SEM) (p < 0.05) compared to 41 ± 2% in control group; glibenclamide (a non-specific ATP-sensitive potassium (K_ATP)-channel blocker) prevented this preconditioning protection (37 ± 4%). In Study 2, recovery of function in intermittent cross-clamp fibrillation hearts (62 ± 3%) was significantly (p < 0.05) higher than intermittent cross-clamp fibrillation hearts treated with glibenclamide (33 ± 2%) and ischemia hearts (30 ± 5%). In Study 3, protection by intermittent cross-clamp fibrillation (60 ± 3%; p < 0.05) was attenuated by protein kinase C inhibition (chelerythrine, 34 ± 3%) and mitochondrial K_ATP-channel blockade (5-hydroxydecanoate, 27 ± 4%) to levels not significantly different from that of ischemia hearts (25 ± 4%). Conclusions: The cardioprotective efficacy of intermittent cross-clamp fibrillation was attenuated by protein kinase C inhibition or K_ATP-channel blockade. Involvement of these putative preconditioning cascade components in association with cardioprotection induced by intermittent cross-clamp fibrillation, suggests a role for the ischemic preconditioning mechanism.

Key Words: Research • Ischemia • Preconditioning • Left ventricular function • Heart preservation

This article has been cited by other articles:

				P. K. Mishra Fibrillatory arrest technique: is it worth tasting the old wine in new bottle? Eur. J. Cardiothorac. Surg., May 1, 2006; 29(5): 860 - 860. [Full Text] [PDF]

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

				J. Vaage Editorial comment: Old skills in a new context--But do we want to use it? Eur. J. Cardiothorac. Surg., December 1, 2005; 28(6): 831 - 832. [Full Text] [PDF]