Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5972708 | International Journal of Cardiology | 2014 | 6 Pages |
BackgroundReperfusion injury and its modulation are incompletely characterized. The purpose of the present study was to characterize the dynamics of reperfusion injury by portraying the temporal release of lactate dehydrogenase (LDH) during ischemia-reperfusion injury in an isolated heart model.MethodsWe studied infarct size and LDH release in the following groups: I) Effect of reperfusion length was evaluated in 79 rats subjected to 40Â minute ischemia and 60, 90, 120 or 180Â minute reperfusion and a) ischemic preconditioning (IPC) or b) No IPC (control). II) LDH release kinetics was studied in 6 rats subjected to calcium-paradox to verify the applicability of LDH as a dynamic marker of cellular injury. III) Ischemia-reperfusion injury modification was studied in 36 rats subjected to: a) ischemic postconditioning, b) prolonged ischemia, c) Reperfusion Injury Salvage Kinase (RISK) pathway inhibition with wortmannin in IPC hearts, d) RISK activation with insulin or e) mitochondrial permeability transition pore (mPTP) inhibition with cyclosporine A.ResultsInfarct size increased from 60 to 180Â minute reperfusion in control hearts. LDH was released in two separate peaks from 2 to 20 and 30 to 120Â min of reperfusion. IPC attenuated both peaks. Postconditioning and agents known to modify reperfusion injury attenuated the second peak.ConclusionsFrequent measurement of myocardial ischemia markers for 120Â min of reperfusion allows identification of two phases of reperfusion injury that are affected by cardioprotective stimuli. The second phase contributes significantly to final infarct size, which is modifiable and a potential target for cardioprotective interventions.