Na+/H+Exchanger Activity Does Not Contribute to Protection by Ischemic Preconditioning in the Isolated Rat Heart

• DOI: 10.1161/01.cir.96.10.3617
• Publication Date: 2012-06-12T00:41:02Z
• Authors: Alex R. Shipolini; Hiroyuki Yokoyama; Manuel Galiñanes; Stephen J. Edmondson; David J. Hearse; Metin Avkiran
• Keywords: Sodium–hydrogen antiporter; Ischemic Preconditioning; Washout

Background Despite evidence that pharmacological inhibition of the Na + /H exchanger (NHE) is cardioprotective, activation NHE has been proposed as a protective mechanism ischemic preconditioning (PC). Methods and Results In isolated rat ventricular myocytes (n=8 to 11 per group) loaded with fluorescent pH indicator C-SNARF-1, we showed HOE-642 (HOE) was potent inhibitor sarcolemmal (80% at 1 μmol/L); such readily reversible by washout drug. We confirmed μmol/L HOE produces significant activity in hearts well (n=4), this model, tested whether presence drug during (1) prolonged period ischemia (40 or 60 minutes) (2) preceding brief periods PC (3 minutes plus 5 modulates efficacy PC. protocol 1, infused for immediately before period. With 40 ischemia, postischemic recovery left developed pressure (LVDP) 15±2% controls improved 45±7% ( P <.05), 55±5% 68±2% PC+HOE <.05 versus all groups). When extended minutes, an additive effect apparent LVDP (66±2%) almost double observed (37±4%) (34±5%) alone <.05). 2, 3 each episode subsequently washed out 40-minute (HOE+PC). 34±4% 57±2% <.05) 55±3% HOE+PC Improved matched reduced creatine kinase leakage cases. Conclusions Because coadministration (at concentration sufficient inhibit activity) did not reduce either protocol, conclude does contribute cardioprotective actions On contrary, may enhance protection afforded