Ischemic Conditioning Protects the Uremic Heart in a Rodent Model of Myocardial Infarction
Background—Outcomes following acute myocardial infarction in patients with chronic kidney disease are extremely poor. Ischemic conditioning techniques are amongst the most powerful cytoprotective strategies discovered to date. However, experimental data suggests that comorbidity may attenuate the protective effects of ischemic conditioning.
Methods and Results—We conducted investigations into the effects of chronic uremia on myocardial infarct size and the protective effects of ischemic preconditioning (IPC), remote ischemic preconditioning (RIPC) and ischemic post-conditioning (iPost) in two rodent models of chronic uremia. In addition, a limited investigation into the signaling mechanisms involved in cardioprotection following IPC was performed in both uremic and non-uremic animals. Myocardial infarct size was increased in uremic animals but all three conditioning strategies (IPC, RIPC, iPost) proved highly efficacious in reducing myocardial infarct size (relative reduction [RR] 86% p<0.005, RR 39% p<0.05, RR 65% p<0.05, respectively). Moreover some protocols (IPC and iPost) appeared to be more effective in uremic than in sham (non-uremic) animals. Analysis of the signaling mechanisms revealed that components of both the RISK and SAFE pathways were similarly upregulated in both uremic and non-uremic animals following an IPC stimulus.
Conclusions—We conclude that conditioning strategies may present the best opportunity to improve outcomes for patients with chronic kidney disease following an acute coronary syndrome.
- Received July 24, 2011.
- Accepted January 12, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited