Late anti-apoptotic effect of K(ATP) channel opening in skeletal muscle.

Necrosis and apoptosis caused by ischaemia-reperfusion (IR) result in myocyte death and atrophy. ATP-sensitive K(+) (K(ATP) ) channels activation increases tissue tolerance of IR-injury. Thus, in the present study, we evaluated the effects of K(ATP) channel activation on skeletal muscle apoptosis after IR. Male Wistar rats were treated with 40 mg/kg, i.p., diazoxide (a K(ATP) channel opener) or 5 mg/kg, i.p., glibenclamide (a K(ATP) channel inhibitor) 30 min before the induction of 3 h ischaemia, followed by 6, 24 or 48 h reperfusion. At the end of the reperfusion period, the gastrocnemius muscle was removed for the analysis of tissue malondialdehyde content, superoxide dismutase (SOD) and catalase (CAT) activity, Bax and Bcl-2 protein expression, histological damage and the number of apoptotic nuclei. Ischaemia-reperfusion increased malondialdehyde content (P < 0.01) and Bax expression (P < 0.01) and induced severe histological damage, in addition to decreasing CAT and SOD activity (P < 0.01 and P < 0.05, respectively) and Bcl-2 expression (P < 0.01). Diazoxide reversed the effects of IR on tissue damage, MDA content, SOD and CAT activity (after 6 and 24 h reperfusion; P < 0.05) and Bax and Bcl-2 expression (after 24 and 48 h reperfusion; P < 0.01). In contrast, glibenclamide pretreatment had no effect. The number of apoptotic nuclei in the IR and glibenclamide-pretreated groups increased significantly (P < 0.001 vs Sham). In contrast, diazoxide pretreatment decreased the number of apoptotic nuclei compared with the IR group (P < 0.01). The results of the present study suggest that the K(ATP) channel activator diazoxide attenuates lipid peroxidation during the first hour of reperfusion and modulates apoptotic pathways at later time points.

Protective effect of epicardial adiponectin on atrial fibrillation following cardiac surgery.

OBJECTIVE: Inflammation has been implicated in the pathogenesis of postoperative atrial fibrillation (AF). Adipose tissue secretes both pro-inflammatory cytokines such as interleukin-6 (IL-6) and anti-inflammatory mediators such as adiponectin. We set out to examine the association of adiponectin and IL-6, both circulating and locally produced by the epicardial adipose tissue, with AF development after cardiac surgery. METHODS: A total of 90 consecutive patients undergoing cardiac surgery were evaluated. Blood samples were collected before induction of anaesthesia. Epicardial fat was obtained upon commencement of cardiopulmonary bypass. IL-6 and adiponectin levels were determined in serum and supernatant of epicardial adipose tissue organ cultures with two-site enzyme-linked immunosorbent assay (ELISA). Heart rhythm was assessed with continuous tele-monitoring for 72 h postoperatively, and with 6-hourly clinical examinations and daily electrocardiograms (ECGs) thereafter. RESULTS: A total of 36 patients developed postoperative AF (40%). Baseline-serum IL-6 and adiponectin were not associated with AF (p = 0.86 and 0.95, respectively). Epicardial adipose tissue IL-6 levels did not correlate with the development of the arrhythmia either (p = 0.37). However, epicardial adiponectin release was lower in patients who developed AF than in those who remained in sinus rhythm (76 (interquartile range (IQR) 35-98) vs 53 ((IQR) 35-69) ng h(-1)g(-1) of tissue cultured, p = 0.066). Following linear regression, the association of epicardial adiponectin with AF almost reached statistical significance (p = 0.066). Multivariate logistic regression analysis of identified risk factors for AF, with the inclusion of epicardial adiponectin as an independent variable, revealed increased age (odds ratio (OR) 1.09, 95% confidence interval (CI) 1.02-1.17, p = 0.013) and epicardial adiponectin levels (OR 0.98, 95% CI 0.97-1.00, p = 0.054) as independent predictors of postoperative AF. CONCLUSIONS: Increased epicardial adiponectin is associated with maintenance of sinus rhythm following cardiac surgery. This reinforces the inflammatory hypothesis in the pathogenesis of postoperative AF and may represent a novel therapeutic target for its effective prevention.