Background: Coronary artery occlusion and reperfusion may trigger reversible and irreversible ischemic and reperfusion injury. The primary aim of this study was to evaluate protein release into the myocardium in a porcine model during ischemia and reperfusion to search for clarifying models for reperfusion injury and secondarily to investigate release and production of the immunophilins FKBP12/12.6 in this model and in cell cultures. Methods: In a porcine model local myocardial ischemia was induced during 45 min followed by 120 min of reperfusion. Microdialysis samples from ischemic and non-ischemic areas were analyzed with surface-enhanced laser desorption ionization (SELDI) mass spectrometry (MS) and Western blotting (WB). Myocardial biopsies from areas at risk and control areas were analyzed with reverse transcription polymerase chain reaction (RT-PCR). Myocardial cell cultures from mice (HL-1 cells) were exposed to hypoxia and then analyzed with WB and RT-PCR. Results: FK binding protein12 (FKBP12), ubiquitin and myoglobin were identified as being released during ischemia and reperfusion in microdialysates. RT-PCR analysis on the biopsies after ischemia revealed a non-significant increase in mRNA expression of FKBP12 and a significant increase in mRNA expression of FKBP12.6. Lysates from HL-1 cells exposed to hypoxia demonstrated increase of FKBP12 and a significant increase in mRNA expression of FKBP12.6. Conclusion: In a myocardial ischemic-reperfusion porcine model as well as in hypoxic HL-1 cells, release of FKBP12 and increased production of FKBP12.6 was demonstrated. The findings indicate important mechanisms related to these immunophilins in the reaction to ischemia/hypoxia and reperfusion in the heart. (C) 2009 Elsevier Inc. All rights reserved.