Abstract 4841: The Impact of Chronic Uremia on Ichemic Preconditioning of the Myocardium
Background Ischemic Preconditioning (IPC) is a process by which brief non lethal periods of ischemia render the dependant tissue resistant to subsequent lethal injury. This process has been extensively studied in animal models and this has led to human clinical trials. There is evidence to suggest that additional co-morbidities may render hearts more resistant to the effects of IPC. There is no published data examining the effects of chronic uraemia on IPC. This is of clinical importance due to the burden of cardiovascular disease in CKD patients.
Can uremic hearts respond to an IPC stimulus
Can uremic hearts respond to an IPC stimulus as well as non uremic hearts
Methods The 5/6 nephrectomy model (SNx) in male Wistar rats was used as a model of chronic uraemia. We performed 2 experiments to test the hypothesises. Expt 1: SNx rats were divided into 2 groups. The control group (n=15) underwent myocardial ischemia using reversible LAD artery ligation. The LAD was occluded for 25 minutes and reperfused for 2 hours. The IPC group (n=4) had 3 cycles of 5 minutes LAD ligation and 5 minutes reperfusion followed by 25 min occlusion and 120min reperfusion. Expt 2: SNX animals (n=8) and Sham controls (n=6) underwent x1 cycle of IPC as above with 35minutes ischemia 2 hours reperfusion. At the end of the experiment the animals were sacrificed and the infarct size was measured and expressed as a percentage of the area at risk (AAR).
Results Expt 1: Median Infarct size was 61.2% and 7.5% in the control and IPC groups respectively (P=0.003) Expt 2: Median infarct size was 16.8% and 43.7% in the SNX and sham SNx groups respectively. (P=0.008) The AAR was not significantly different in any of the groups studied.
Discussion This is the first evidence that unlike ‘old’ hypertensive rats and diabetic rats, uremic rats can respond to a preconditioning stimulus. Furthermore it appears that the preconditioning may confer greater protection in uremic animals than controls. We hypothesize that the significantly lower haemoglobin in the uremic animals reduces microvascular occlusion which may occur during IPC. Work is underway to quantify this finding.
Conclusion This study suggests that clinical trials using IPC in uremic patients could improve outcomes following cardiac interventions.