Abstract | 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.
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Authors | Masahiro Fujii, David J Chambers |
Journal | European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
(Eur J Cardiothorac Surg)
Vol. 28
Issue 6
Pg. 821-31
(Dec 2005)
ISSN: 1010-7940 [Print] Germany |
PMID | 16242951
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Potassium Channel Blockers
- Potassium Channels
- mitochondrial K(ATP) channel
- Protein Kinase C
- Creatine Kinase
- Glyburide
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Topics |
- Animals
- Constriction
- Coronary Artery Bypass
- Creatine Kinase
(metabolism)
- Glyburide
(pharmacology)
- Ischemic Preconditioning, Myocardial
(methods)
- Male
- Myocardial Reperfusion Injury
(prevention & control)
- Myocardium
(metabolism)
- Organ Culture Techniques
- Potassium Channel Blockers
(pharmacology)
- Potassium Channels
(physiology)
- Protein Kinase C
(antagonists & inhibitors, physiology)
- Rats
- Rats, Wistar
- Recovery of Function
- Ventricular Fibrillation
- Ventricular Function, Left
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