Heart failure is associated with exaggerated endothelial ischaemia-reperfusion injury and attenuated effect of ischaemic preconditioning

Background Reperfusion is mandatory after ischaemia, but it also triggers ischaemia-reperfusion (IR)-injury. It is currently unknown whether heart failure alters the magnitude of IR-injury. Ischaemic preconditioning can limit IR-injury. Since ischaemic preconditioning is typically applied in subjects at risk for cardiovascular complications, it is of clinical importance to understand its efficacy in heart failure patients. Objective To examine the magnitude of endothelial IR-injury, and the ability of ischaemic preconditioning to protect against endothelial IR-injury in heart failure. Methods We included 15 subjects with heart failure (6710 years, New York Heart Association class II/III) and 15 healthy, age- and sex-matched controls (659 years). We examined brachial artery endothelial function using flow-mediated dilation before and after arm IR (induced by 5-min ischaemic handgrip exercise +15min reperfusion). IR was preceded by ischaemic preconditioning (consisting in three cycles of 5-min upper arm cuff inflation to 220mmHg) or no inflation. Results A significant interaction-effect was found for the change in flow-mediated dilation after IR between groups (two-way ANOVA interaction-effect: p=0.01). Whilst post-hoc analysis revealed a significantly decline in flow-mediated dilation in both groups (p<0.05), the decline in flow-mediated dilation in heart failure patients (6.2 +/- 3.6% to 3.3 +/- 1.8%) was significantly larger than that observed in controls (4.9 +/- 2.1 to 4.1 +/- 2.0). Neither in heart failure patients nor controls was the decrease in flow-mediated dilation after IR altered by ischaemic preconditioning (three-way ANOVA interaction: p=0.87). Conclusion We found that patients with heart failure are associated with exaggerated endothelial IR-injury compared with age- and sex-matched, healthy controls, which may contribute to the poor clinical prognosis in heart failure. Furthermore, we found no protective effect of ischaemic preconditioning (3x5-min forearm ischaemia) against endothelial IR-injury in heart failure patients.