BACKGROUND AND OBJECTIVE: 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. 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 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. 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+(i) 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-[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.
BACKGROUND AND OBJECTIVE: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. 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 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. 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+(i) 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-[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.
Authors: Mihai V Podgoreanu; Joseph P Mathew; Miklos D Kertai; Yen-Wei Li; Yi-Ju Li; Svati H Shah; William E Kraus; Manuel L Fontes; Mark Stafford-Smith; Mark F Newman Journal: Circ Cardiovasc Genet Date: 2014-07-21
Authors: Miklos D Kertai; Wenjing Qi; Yi-Ju Li; Frederick W Lombard; Yutao Liu; Michael P Smith; Mark Stafford-Smith; Mark F Newman; Carmelo A Milano; Joseph P Mathew; Mihai V Podgoreanu Journal: J Mol Cell Cardiol Date: 2016-02-06 Impact factor: 5.000