ABSTRACT
BACKGROUND: Sudden cardiac death is a leading cause of death in patients with chronic kidney disease and end stage renal disease. Ischaemic conditioning strategies confer profound myocardial protection and, in the absence of uraemia, have been reported to reduce myocardial dysrhythmias. Recent data confirms that ischaemic conditioning can protect the uraemic heart. However, the effect of uraemia on myocardial arrhythmogenesis in the context of ischaemia-reperfusion injury and whether ischaemic conditioning can modulate this is unknown. OBJECTIVE: We investigated the effect of underling chronic uraemia on the duration of arrhythmias in the context of cardioprotective ischaemic conditioning strategies. METHODS: We examined the effect of chronic uraemia on arrhythmias occurring in the context of myocardial ischaemia-reperfusion injury and the ability of ischaemic preconditioning (IPC), remote ischaemic preconditioning (RIPC) and ischaemic postconditioning (iPOST) to suppress arrhythmogenesis in uraemic and non-uraemic animals. RESULTS: IPC led to a reduction in the frequency and duration of arrhythmias occurring during ischaemia and reperfusion. Neither RIPC nor iPOST affected the duration or frequency of ischaemic or reperfusion arrhythmias. Underlying uraemia did not alter the frequency or duration of ischaemic arrhythmias in any of the experiments however it was associated with a reduction in reperfusion arrhythmia duration in the IPC and iPOST experiments. CONCLUSIONS: These studies demonstrate that underlying chronic uraemia does not reduce the threshold for arrhythmia timing or duration resulting from myocardial ischaemia-reperfusion and underlying uraemia did not alter the effects of these cardioprotective ischaemic conditioning strategies in the context of arrhythmia duration. SUMMARY: This novel work in a rodent model of chronic uraemia establishes that underlying uraemia does not increase the susceptibility to myocardial ischaemia-reperfusion induced arrhythmias. When compared with the non-uraemic heart, the uraemic heart has a similar response to the effects of ischaemic conditioning strategies in terms of their effect on arrhythmia timing and duration.
ABSTRACT
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.
