Nuclear factor-κB inhibition provides additional protection against ischaemia/reperfusion injury in delayed sevoflurane preconditioning

Background and objective Sevoflurane anaesthetic preconditioning (SPC) has been shown to limit nuclear factor-κB (NF-κB) activation and the production of inflammatory cytokines during myocardial ischaemia/ reperfusion (I/R). Similarly, pharmacological inhibition of NF-κB using parthenolide is effective in limiting I/R injury. We, therefore, postulated that the protective effect of delayed SPC would be enhanced by pharmacological NF- κB inhibition during I/R. Methods Hearts from 2-month-old male Fisher 344 rats were exposed to 25 min global ischaemia followed by 60 min reperfusion. Rats were divided into four groups prior to I/R: control group; parthenolide group, treated with the IκB kinase inhibitor parthenolide intraperitoneally 10 min prior to heart isolation; SPC group, treated for 60 min with sevoflurane 48 h prior to heart isolation; and SPC + parthenolide group, treated with SPC for 1 h followed by parthenolide 48 h later. Infarct area, left ventricular function and Ca²⁺,- were measured after I/R. Results Delayed SPC + parthenolide resulted in greater protection than either intervention alone, resulting in a significant reduction in infarct area and left ventricular developed pressure (mmHg; 84 ± 19 compared with 15 ± 14 in control hearts; P = 0.007). Left ventricular end- diastolic pressure also remained close to baseline values (9 ± 2 mmHg, P = 0.02) during I/R, and the increase in Ca²⁺,- seen with I/R was significantly blunted (P = 0.005). Conclusion SPC followed by parthenolide provides a significant protection from I/R injury in this model. As each intervention alone limits NF-κB activation with I/R, these data are consistent with additive effects of these dual modalities in limiting I/R injury due to NF-κB activation.