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DOI: 10.1055/s-0030-1269013
The role of metalloproteinases and tissue inhibitors of metalloproteinases in extracorporeal circulation mediated cardiac dysfunction in rats
Objectives: Metalloproteinases (MMPs) and their inhibitors (TIMPs) regulate matrix remodeling in the heart. Changes in synthesis and release of MMPs and TIMPs are observed after extracorporeal circulation (ECC). Thus, MMPs and TIMPs are supposed to be involved in ECC-mediated cardiac dysfunction. The aim was to examine the role of MMPs and TIMPs in ECC-mediated cardiac dysfunction.
Methods: ECC was instituted in rats for 60min at a flow rate of 120ml*kg-1*min-1. 3 groups (n=10) were studied: Group CAO: 60min ECC without aortic cross-clamp, Group CAC: 60min ECC including 30min aortic cross-clamp (crystalloid Inzolen® cardioplegia), and Group CAB: 60min ECC including 30min aortic cross-clamp (blood cardioplegia). Left ventricular (LV) function was measured with conductance catheter. MMP-activity was determined by zymography and TIMP-activity was determined by reverse zymography. Gene expression of MMPs and TIMPs was determined by real-time PCR.
Results: 60min after weaning from bypass there was a preserved LV function in the CAO and CAB group and an impaired LV function in the CAC group. We observed an increased myocardial activity and an increased myocardial mRNA expression of MMP-2, MMP-9, TIMP-1, and TIMP-4 in all ECC groups, when compared to sham animals. With regard to enzyme activity, there was an imbalance of MMP-2/TIMP-ratio leading to an increased activity of MMP-2 in the CAC group. In terms of gene expression, there was an imbalance of MMP-2/TIMP-4-ratio leading to an increased expression of MMP-2 in the CAC group.
Conclusions: MMP-2 contributes to myocardial reperfusion injury in this in-vivo model of ECC with cardioplegic arrest.