Abstract 10072: Ischemic Preconditioning Attenuates No-Reflow by Enhancing the Phosphorylation of eNOS at Ser 1179 and Ser 635 via PKA Pathway
Aims: To investigate whether ischemic preconditioning (IPC) protects hearts from myocardial ischemia-reperfusion injury and no-reflow by enhancing the activity of endothelial nitric oxide synthase (eNOS) via protein kinase A (PKA) pathway.
Methods and Results: In 90-minute ischemia and 3-hour reperfusion model, Minipigs were randomly assigned to 5 groups: (1) Sham; (2) Control; (3) IPC; (4) IPC+H-89 (1.0μg<52>kg−1<52>min−1, an inhibitor of PKA); (5) H−89. Compared with control group, IPC significantly decreased the activity of creatine kinase (CK) and myeloperoxidase (MPO) (P<0.05), but H-89 suppressed this effect. The infarct size reduced from 78.5% to 31.3% and 50.4% in IPC and IPC+H-89 group respectively (P<0.05), and the size of no-reflow decreased from 48.6% to 9.7%, 27.3% and 29.5% in IPC, IPC+H-89 and H-89 group respectively (P<0.05). IPC increased the activity of PKA and NOS, and the expression of PKA, Thr 198 p-PKA, Ser1179 p-eNOS and Ser 635 p-eNOS in no-reflow myocardium; while H-89 completely inhibited the inductive effect of IPC on the activity of PKA and NOS, repressed the phosphorylation of eNOS at Ser1179 and Ser 635, and partially diminished the expression of PKA and Thr 198 p-PKA. Although H-89 alone had little influence on the size of necrosis, CK activity, and MPO activity in no-reflow area, it increased NOS activity in reflow area and attenuated the size of no-reflow and MPO activity in reflow area.
Conclusions: IPC reduces myocardial ischemia-reperfusion injury and no-reflow by enhancing the phosphorylation of eNOS at Ser1179 and Ser 635 in no-reflow area in a partially PKA-dependant mechanism.
- © 2010 by American Heart Association, Inc.