Ischemic conditioning protects the uremic heart in a rodent model of myocardial infarction.
BACKGROUND
Outcomes after acute myocardial infarction in patients with chronic kidney disease are extremely poor. Ischemic conditioning techniques are among the most powerful cytoprotective strategies discovered to date. However, experimental data suggest that comorbidity may attenuate the protective effects of ischemic conditioning.


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, and ischemic postconditioning in 2 rodent models of chronic uremia. In addition, a limited investigation into the signaling mechanisms involved in cardioprotection after IPC was performed in both uremic and nonuremic animals. Myocardial infarct size was increased in uremic animals, but all 3 conditioning strategies (IPC, remote IPC, ischemic postconditioning) proved highly efficacious in reducing myocardial infarct size (relative reduction, 86%, 39%, and 65% [P<0.005, P<0.05, and P<0.05], respectively). Moreover, some protocols (IPC and ischemic postconditioning) appeared to be more effective in uremic than in sham (nonuremic) animals. Analysis of the signaling mechanisms revealed that components of both the reperfusion injury salvage kinase and survivor activating factor enhancement pathways were similarly upregulated in both uremic and nonuremic animals after an IPC stimulus.


CONCLUSIONS
Conditioning strategies may present the best opportunity to improve outcomes for patients with chronic kidney disease after an acute coronary syndrome.
Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, UK. c.byrne@qmul.ac.uk
Conor J
CJ
Byrne
Kieran
K
McCafferty
Julius
J
Kieswich
Steven
S
Harwood
Petros
P
Andrikopoulos
Martin
M
Raftery
Christoph
C
Thiemermann
Muhammad M
MM
Yaqoob
D054058:Acute Coronary Syndrome / Q000473:pathology / Q000628:therapy; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D017202:Myocardial Ischemia / Q000209:etiology / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000150:complications; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D014511:Uremia / Q000150:complications*