Ischemic preconditioning improved recovery of left ventricular developed pressure compared to control (72% vs 36%; P<0.001), an effect blocked by PI3-kinase inhibitors.
Ischemic preconditioning protects the heart via a signaling pathway where PI3-kinase acts upstream of protein kinase C and nitric oxide production.
Absolute Event Rate: 72% vs 36%
p-value: p=<0.001
The present study is designed to test whether phosphatidylinositol 3-kinase (PI3-kinase) has a role in the signaling pathway in ischemic preconditioning (PC) and whether it is proximal or distal to protein kinase C (PKC). Before 20 minutes of global ischemia, Langendorff-perfused rat hearts were perfused for 20 minutes (control); preconditioned with 4 cycles of 5-minute ischemia and 5-minute reflow (PC); treated with either wortmannin (WM) or LY 294002 (LY), each of which is a PI3-kinase inhibitor, for 5 minutes before and throughout PC; treated with 1,2-dioctanoyl-sn-glycerol (DOG), an activator of PKC for 10 minutes (DOG); treated identically to the DOG group except with WM added 10 minutes before and during perfusion with DOG; or treated with either WM or LY for 25 minutes. Recovery of left ventricular developed pressure (LVDP; percentage of initial preischemic LVDP), measured after 30 minutes of reflow, was improved by PC (72+/-2% versus 36+/-4% in control; P0.05 compared with DOG; P<0.05 compared with control). PC induced phosphorylation of protein kinase B and translocation of PKC epsilon, and it increased NO production, and these effects were blocked by WM, which suggests a role for PI3-kinase in PC upstream of PKC and NO.
Tong et al. (2000) studied Ischemia. Ischemic preconditioning (PC) vs. Control (perfused for 20 minutes before ischemia) was evaluated on Recovery of left ventricular developed pressure (LVDP; percentage of initial preischemic LVDP) (p=<0.001). Ischemic preconditioning improved recovery of left ventricular developed pressure compared to control (72% vs 36%; P<0.001), an effect blocked by PI3-kinase inhibitors.