Inhibition of NF-κB Activation by β-Glucan Is Not Associated with Protection from Global Ischemia-Reperfusion Injury in Pigs

Abstract

Pretreatment with β-glucan has been shown to protect against regional ischemia-reperfusion injury, through inhibition of myocardial NF-κB activation. The aim was to examine whether β-glucan pretreatment could protect against the global ischemia-reperfusion injury, which is encountered in the clinical setting during open heart surgery. Twenty-one pigs were randomized to pretreatment with oral β-glucan (SBGo, n = 7), pretreatment with i.p. β-glucan (SBGip, n = 7), and untreated controls (n = 7). The pigs were subjected to cardiopulmonary bypass (CPB) with 1 h of global cardioplegic ischemia followed by wean from CPB and reperfusion for 4 h. Cardiac function was determined by a conductance catheter, and troponin T was sampled from the coronary sinus. Atrial biopsies obtained at baseline, following 30 min, and 3 h of reperfusion were analyzed for phosphorylated NF-κB by Western blot. Following reperfusion, phosphorylated NF-κB increased by 210% in the control group, 197% in the SBGo group, but was reduced by 5% in the SBGip group (P < 0.01 versus control). After 4 h of reperfusion, preload recruitable stroke work dropped by 19% in the control group and 25% in the SBGo group compared with 60% in the SBGip group (P < 0.01 versus control). The area under the curve for troponin T was larger in the SBGip group compared with the control group (P< 0.05) and the SBGo group (P < 0.01). Inhibition of NF-κB activation by i.p. β-glucan does not protect against ischemia-reperfusion injury in pigs subjected to global ischemia and reperfusion, and may be associated with aggravation of ischemia-reperfusion injury.