Table 1.
Various mechanism underlying the pathophysiology of myocardial ischemia/reperfusion injury (modified according to reference [60]) JNK = c-Jun N-terminal kinase, AMPK = AMP-activated protein kinase, HIF-1α = Hypoxia-inducible factor 1-alpha.
| Alteration Caused by I/R Injury | Mechanism |
|---|---|
| Changes in ion flux | Accumulation of intracellular calcium Ca2+-induced “stone-heart” |
| Increased sodium influx | |
| Abnormal potassium flux | |
| Drop in pH followed by normalization upon reperfusion | |
| Loss of mitochondrial membrane potential | Opening of mitochondrial permeability transition pore (mPTP) |
| Cytochrome c release | |
| Reduction of ATP synthesis | |
| Reactive oxygen species (ROS) | Substrate-level induction of xanthine oxidase resulting in more ROS |
| Impaired mitochondrial function | |
| Neutrophil infiltration | |
| ROS-induced ROS | |
| Dysregulated nitric oxide (NO) metabolism | Loss of NO-vasodilation |
| Production of peroxynitrite | |
| Abnormal S-nitrosation | |
| Apoptosis | JNK pathway |
| Ceramide generation | |
| Cytoplasm acidification | |
| Caspase activation | |
| Autophagic cell death | Excessive AMPK activation |
| Excessive induction of HIF-1α | |
| Endothelial dysfunction | Cytokine, myokine, chemokine signaling |
| Expression of cellular adhesion markers | |
| Impaired vasodilation | |
| Platelet aggregation | |
| Immune activation | Innate immunity (e.g., complement activation, induction of Toll-like receptors) |
| Neutrophil accumulation |