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

Abstract

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 (67 ± 10 years, New York Heart Association class II/III) and 15 healthy, age- and sex-matched controls (65 ± 9 years). We examined brachial artery endothelial function using flow-mediated dilation before and after arm IR (induced by 5-min ischaemic handgrip exercise +15 min reperfusion). IR was preceded by ischaemic preconditioning (consisting in three cycles of 5-min upper arm cuff inflation to 220 mmHg) 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 (3 × 5-min forearm ischaemia) against endothelial IR-injury in heart failure patients.

Keywords: Cardiovascular disease; cardiovascular risk; endothelial function; flow-mediated dilation; ischaemia.