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. 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, 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. CONCLUSION: Conditioning strategies may present the best opportunity to improve outcomes for patients with chronic kidney disease after an acute coronary syndrome.
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. 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, 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. CONCLUSION: Conditioning strategies may present the best opportunity to improve outcomes for patients with chronic kidney disease after an acute coronary syndrome.
Authors: Kieran McCafferty; Conor J Byrne; Julius Kieswich; Martin Raftery; Christoph Thiemermann; Muhammad M Yaqoob Journal: Heart Asia Date: 2014-05-24
Authors: David S Gardner; Simon J M Welham; Louise J Dunford; Thomas A McCulloch; Zsolt Hodi; Philippa Sleeman; Saoirse O'Sullivan; Mark A J Devonald Journal: Am J Physiol Renal Physiol Date: 2014-02-12
Authors: Petros Andrikopoulos; Julius Kieswich; Steven M Harwood; Akemichi Baba; Toshio Matsuda; Olivier Barbeau; Keith Jones; Suzanne A Eccles; Muhammad M Yaqoob Journal: J Biol Chem Date: 2015-05-15 Impact factor: 5.157
Authors: Jonas Agerlund Povlsen; Bo Løfgren; Christian Dalgas; Rune Isak Dupont Birkler; Mogens Johannsen; Nicolaj Brejnholt Støttrup; Hans Erik Bøtker Journal: PLoS One Date: 2013-05-21 Impact factor: 3.240