Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery that occurs in up to 60% of patients. POAF is associated with increased risk of cardiovascular mortality, stroke and other arrhythmias that can impact on early and long term clinical outcomes and health economics. Many factors such as disease-induced cardiac remodelling, operative trauma, changes in atrial pressure and chemical stimulation and reflex sympathetic/parasympathetic activation have been implicated in the development of POAF. There is mounting evidence to support a major role for inflammation and oxidative stress in the pathogenesis of POAF. Both are consequences of using cardiopulmonary bypass and reperfusion following ischaemic cardioplegic arrest. Subsequently, several anti-inflammatory and antioxidant drugs have been tested in an attempt to reduce the incidence of POAF. However, prevention remains suboptimal and thus far none of the tested drugs has provided sufficient efficacy to be widely introduced in clinical practice. A better understanding of the cellular and molecular mechanisms responsible for the onset and persistence of POAF is needed to develop more effective prediction and interventions.

Studies with different ATP‐sensitive potassium (K_ATP) channel openers and blockers have implicated opening of mitochondrial K_ATP (mitoK_ATP) channels in ischaemic preconditioning (IPC). It would be predicted that this should increase mitochondrial matrix volume and hence respiratory chain activity. Here we confirm this directly using mitochondria rapidly isolated from Langendorff‐perfused hearts. Pre‐ischaemic matrix volumes for control and IPC hearts (expressed in μl per mg protein ±s.e.m., n= 6), determined with ³H₂O and [¹⁴C]sucrose, were 0.67 ± 0.02 and 0.83 ± 0.04 (P < 0.01), respectively, increasing to 1.01 ± 0.05 and 1.18 ± 0.02 following 30 min ischaemia (P < 0.01) and to 1.21 ± 0.13 and 1.26 ± 0.25 after 30 min reperfusion. Rates of ADP‐stimulated (State 3) and uncoupled 2‐oxoglutarate and succinate oxidation increased in parallel with matrix volume until maximum rates were reached at volumes of 1.1 μl ml⁻¹ or greater. The mitoK_ATP channel opener, diazoxide (50 μm), caused a similar increase in matrix volume, but with inhibition rather than activation of succinate and 2‐oxoglutarate oxidation. Direct addition of diazoxide (50 μm) to isolated mitochondria also inhibited State 3 succinate and 2‐oxoglutarate oxidation by 30 %, but not that of palmitoyl carnitine. Unexpectedly, treatment of hearts with the mitoK_ATP channel blocker 5‐hydroxydecanoate (5HD) at 100 or 300 μm, also increased mitochondrial volume and inhibited respiration. In isolated mitochondria, 5HD was rapidly converted to 5HD‐CoA by mitochondrial fatty acyl CoA synthetase and acted as a weak substrate or inhibitor of respiration depending on the conditions employed. These data highlight the dangers of using 5HD and diazoxide as specific modulators of mitoK_ATP channels in the heart.

The development of the cardiopulmonary bypass (CPB) revolutionized cardiac surgery and contributed immensely to improved patients outcomes. CPB is associated with the activation of different coagulation, proinflammatory, survival cascades and altered redox state. Haemolysis, ischaemia, and perfusion injury and neutrophils activation during CPB play a pivotal role in oxidative stress and the associated activation of proinflammatory and proapoptotic signalling pathways which can affect the function and recovery of multiple organs such as the myocardium, lungs, and kidneys and influence clinical outcomes. The administration of agents with antioxidant properties during surgery either intravenously or in the cardioplegia solution may reduce ROS burst and oxidative stress during CPB. Alternatively, the use of modified circuits such as minibypass can modify both proinflammatory responses and oxidative stress.

Myocardial infarction (MI) is the leading cause of death worldwide. MicroRNAs regulate the expression of their target genes, thus mediating a plethora of pathophysiological functions. Recently, miRNA-24 emerged as an important but controversial miRNA involved in post-MI responses. Here, we aimed at clarifying the effect of adenovirus-mediate intra-myocardial delivery of a decoy for miRNA-24 in a mouse MI model and to investigate the impact of miRNA-24 inhibition on angiogenesis and cardiovascular apoptosis. After MI induction, miRNA-24 expression was lower in the peri-infarct tissue and its resident cardiomyocytes and fibroblasts; while it increased in endothelial cells (ECs). Local adenovirus-mediated miRNA-24 decoy delivery increased angiogenesis and blood perfusion in the peri-infarct myocardium, reduced infarct size, induced fibroblast apopotosis and overall improved cardiac function. Notwithstanding these beneficial effects, miRNA-24 decoy increased cardiomyocytes apoptosis. In vitro, miRNA-24 inhibition enhanced ECs survival, proliferation and networking in capillary-like tubes and induced cardiomyocyte and fibroblast apoptosis. Finally, we identified eNOS as a novel direct target of miR-24 in human cultured ECs and in vivo. Our findings suggest that miRNA-24 inhibition exerts distinct biological effects on ECs, cardiomyocytes and fibroblasts. The overall result of post-infarction local miRNA-24 inhibition appears to be therapeutic.