Nuclear factor-[kappa]B inhibition provides additional protection against ischaemia/reperfusion injury in delayed...

Sevoflurane anaesthetic preconditioning (SPC) has been shown to limit nuclear factor-[kappa]B (NF-[kappa]B) activation and the production of inflammatory cytokines during myocardial ischaemia/reperfusion (I/R). Similarly, pharmacological inhibition of NF-[kappa]B 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-[kappa]B inhibition during I/R.

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 I[kappa]B 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+(i) were measured after I/R.

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+(i) seen with I/R was significantly blunted (P = 0.005).

SPC followed by parthenolide provides a significant protection from I/R injury in this model. As each intervention alone limits NF-[kappa]B activation with I/R, these data are consistent with additive effects of these dual modalities in limiting I/R injury due to NF-[kappa]B activation.