Cellular mechanisms and pathways in myocardial reperfusion injury.

Despite the progress of cardiovascular medicine, ischemia-reperfusion injury can contribute to increased mortality and prolonged hospitalization after myocardial infarction. Ischemia-reperfusion injury pathophysiology encompasses many cells including cardiomyocytes, fibroblasts, mesenchymal stromal cells, vascular endothelial and smooth muscle cells, platelets, polymorphonuclear cells, macrophages, and T lymphocytes. However, specific mechanisms for all contributing cells and molecular pathways are still under investigation. What is definitely known is that endothelial dysfunction, immunity activation and inflammatory response are crucial events during ischemia-reperfusion injury while toll-like receptors, inflammasomes, reactive oxygen species, intracellular calcium overload and mitochondrial permeability transition pore opening consist of key molecular mediators. Indicatively, cardiac fibroblasts through inflammasome activation mediate the initial inflammatory response. Cardiac mesenchymal stromal cells can respond to myocardial injury by pro-inflammatory activation. Endothelial cell activation contributes to the impaired vasomotion, inflammation and thrombotic events and together with platelet activation leads to microcirculation dysfunction and polymorphonuclear cells recruitment promoting inflammation. Polymorphonuclear cells and monocytes/macrophages subsets are critically involved in the inflammation process by producing toxic proteolytic enzymes and reactive oxygen species. T cells subsets are also involved in several stages of ischemia-reperfusion injury. In this review, we summarize the specific contribution of each of the above cells and the related molecular pathways in the pathophysiology of ischemia-reperfusion injury.

Use of Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Relation to Cardiovascular Events. A Systematic Pharmacoepidemiological Review.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used, having numerous indications. However, despite their therapeutic role, they are associated with serious cardiovascular (CV) adverse events. Objectives-Methods: This review comprising recent observational studies and metaanalyses over the past few years aims at updating the assessment of CV adverse events, namely stroke, myocardial infarction (MI), CV death, atrial fibrillation (AF), serious bleeding and heart failure related to the use of 4 of the most widely prescribed NSAIDs: ibuprofen, naproxen, diclofenac and mefenamic acid. RESULTS: The best safety profile related to MI was found for naproxen, while the worst safety profile, with excessively increased risk for stroke, MI and major bleeding, was for diclofenac. Naproxen showed higher risk for major bleeding than ibuprofen and the risk for stroke was slightly higher than ibuprofen. Regarding heart failure, ibuprofen presented the highest risk while the highest risk for AF was attributed to the current use of diclofenac. There are few data related to mefenamic acid, which showed a strong association with increased risk for stroke and a moderately increased risk for MI. CONCLUSION: Further research is needed in order to devise new guidelines for safer use of NSAIDs.