NHE-1 inhibition with BIIB 513 was more efficacious than ischemic preconditioning at reducing infarct size after a 90-minute ischemic insult (P<0.05).
Does NHE-1 inhibition reduce infarct size more effectively than ischemic preconditioning in a canine model of myocardial ischemia?
NHE-1 inhibition provides greater cardioprotection than ischemic preconditioning against prolonged (90-minute) myocardial ischemia in a canine model, and their combination yields greater-than-additive benefits.
valor p: p=<0.05
BACKGROUND: This study compared the efficacy of ischemic preconditioning (IPC) and sodium-hydrogen exchanger (NHE)-1 inhibition to reduce infarct size (IS) induced by a 90-minute ischemic insult and examined the interaction between NHE-1 inhibition and IPC. METHODS AND RESULTS: In a canine infarct model, either IPC, produced by 1 or four 5-minute coronary artery occlusions, or the specific NHE-1 inhibitor BIIB 513, 0.75 or 3.0 mg/kg, was administered 15 minutes before either a 60- or 90-minute coronary artery occlusion followed by 3 hours of reperfusion. IS was determined by TTC staining and expressed as a percentage of the area at risk (IS/AAR). Although both IPC and BIIB 513 at 0.75 mg/kg produced comparable and significant reductions in IS/AAR in the 60-minute occlusion model, insignificant reductions in IS/AAR were observed in the 90-minute occlusion model. However, BIIB 513 at 3.0 mg/kg markedly reduced IS in both models (P<0.05). Next, to examine the interaction between NHE-1 blockade and IPC, BIIB 0.75 mg/kg was administered either before IPC or during the washout phase of IPC before 90 minutes of coronary artery occlusion. Both combinations resulted in a greater-than-additive reduction in IS/AAR (P<0.05). CONCLUSIONS: These data demonstrate that although IPC and NHE-1 inhibition provide comparable protection against 60 minutes of myocardial ischemia, NHE-1 inhibition is more efficacious than IPC at protecting against a 90-minute ischemic insult. Furthermore, the combination of NHE-1 inhibition and IPC produces a greater-than-additive reduction in IS/AAR, suggesting either that NHE activity limits the efficacy of IPC or that different mechanisms are involved in the cardioprotective effect of IPC and NHE-1 inhibition.
Gumina et al. (Tue,) conducted a other in Myocardial ischemia. NHE-1 inhibitor BIIB 513 vs. Ischemic preconditioning (IPC) was evaluated on Infarct size as a percentage of the area at risk (IS/AAR) (p=<0.05). NHE-1 inhibition with BIIB 513 was more efficacious than ischemic preconditioning at reducing infarct size after a 90-minute ischemic insult (P<0.05).