TY - JOUR
T1 - Nuclear factor-κB inhibition provides additional protection against ischaemia/reperfusion injury in delayed sevoflurane preconditioning
AU - Konia, Mojca Remskar
AU - Schaefer, Saul
AU - Liu, Hong
PY - 2009/6
Y1 - 2009/6
N2 - 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.
AB - 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.
KW - Delayed preconditioning
KW - Myocardium
KW - Nuclear factor-κB
KW - Rat
KW - Sevoflurane
UR - http://www.scopus.com/inward/record.url?scp=68849121799&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=68849121799&partnerID=8YFLogxK
U2 - 10.1097/EJA.0b013e328324ed2e
DO - 10.1097/EJA.0b013e328324ed2e
M3 - Article
C2 - 19445059
AN - SCOPUS:68849121799
SN - 0265-0215
VL - 26
SP - 496
EP - 503
JO - European Journal of Anaesthesiology
JF - European Journal of Anaesthesiology
IS - 6
ER -