Protecting against ischemia-reperfusion injury: antiplatelet drugs, statins, and their potential interactions.
Statins and antiplatelet agents are currently used as therapeutic agents for patients with acute myocardial infarction. Statins limit myocardial infarct size by activating phosphatidylinositol-3-kinase (PI3K), ecto-5'-nucleotidase, Akt/endothelial nitric oxide synthase (eNOS), and the downstream effectors inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Inhibition of PI3K, adenosine receptors, eNOS, iNOS, or COX-2 abrogates the protective effects of statins. At >5 mg/kg, aspirin attenuates the myocardial infarct-size-limiting effect of statins. In contrast, the combination of low-dose atoravastatin with either the phosphodiesterase-III inhibitor cilostazol or the adenosine reuptake inhibitor dipyridamole synergistically limits infarct size. Low-dose aspirin with dipyridamole started during ischemia augmented the infarct-size-limiting effects of simvastatin. In contrast, high-dose aspirin blocked the protective effect of simvastatin. The combination of dipyridamole with low-dose aspirin and simvastatin resulted in the smallest infarct size. According to the most current data available, we believe that antiplatelet regimens may require modification for patients who are receiving statins.
Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, Texas, USA.
Yumei
Y
Ye
Jose R
JR
Perez-Polo
Yochai
Y
Birnbaum
D001241:Aspirin / Q000008:administration & dosage; D000077407:Cilostazol; D004176:Dipyridamole / Q000008:administration & dosage; D004347:Drug Interactions; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D019821:Simvastatin / Q000008:administration & dosage; D013777:Tetrazoles / Q000008:administration & dosage
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D004176:Dipyridamole; D019821:Simvastatin; D000077407:Cilostazol; D001241:Aspirin