| Abstract | BACKGROUND: Recent evidence indicates that reperfusion of the heart after a period of ischemia leads to the opening of the mitochondrial permeability transition pore (MPTP). The aim of this study was to investigate cardioprotective effects of cyclosporine A (CsA), an inhibitor of the MPTP, in an in vivo model of myocardial ischemia and reperfusion. METHODS: Male Sprague-Dawley rats were subjected to occlusion of the left anterior descending coronary artery for 30 min followed by 180 min of reperfusion. CsA (10 mg/kg) or vehicle was given 10 min prior to ischemia via the femoral vein. Sham myocardial ischemia-reperfusion rats (sham-operation group) were used as controls. Infarct size was measured using the staining agent TTC (2,3,5-triphenyl tetrazolium chloride) and myocardial apoptosis by caspase-3 activity was determined by fluorescent assay. The myocardium mitochondria ultrastructure was observed through a transmission electron microscope. RESULTS: CsA significantly reduced infarct size (48.8 +/- 5.8% of left ventricle in vehicle + I/R group and 30.3 +/- 2.7% of left ventricle in CsA + I/R, respectively) and decreased caspase-3 activity in the myocardium [(0.62 +/- 0.17)/microg of protein and (0.42 +/- 0.15)/microg of protein, respectively] and relieved the injury of mitochondria. CONCLUSION: CsA reduced the cardiac damage associated with ischemia-reperfusion injury of the heart. The cardioprotective effects of CsA might be associated with the protection of mitochondria and the inhibition of caspase-3 activity. It also suggests that the MPTP might play an important role in cardiomyocytes death after ischemia-reperfusion injury. |
| Authors | J-R Xie, L-N Yu
(Affiliation: Department of Anesthesiology, Sir Run Run Shaw Hospital, Hangzhou, China.)
|
| Journal | Acta anaesthesiologica Scandinavica
(Acta Anaesthesiol Scand)
Vol. 51
Issue 7
Pg. 909-13
(Aug 2007)
ISSN: 0001-5172 England |
| PMID | 17578461
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Cardiotonic Agents
- Immunosuppressive Agents
- Cyclosporine
- Caspase 3
|
| Topics |
- Animals
- Blood Pressure
(drug effects)
- Cardiotonic Agents
- Caspase 3
(metabolism)
- Cyclosporine
(pharmacology)
- Heart Rate
(drug effects)
- Immunosuppressive Agents
(pharmacology)
- Male
- Microscopy, Electron
- Mitochondria, Heart
(drug effects, ultrastructure)
- Myocardial Ischemia
(pathology, prevention & control)
- Myocardial Reperfusion Injury
(pathology, prevention & control)
- Rats
- Rats, Sprague-Dawley
|
