Granulocyte colony-stimulating factor stabilizes cardiac electrophysiology and decreases infarct size during cardiac ischaemic/reperfusion in swine

Aim: Effects of granulocyte colony‐stimulating factor (G‐CSF) on cardiac electrophysiology during ischaemic/reperfusion (I/R) period are unclear. We hypothesized that G‐CSF stabilizes cardiac electrophysiology during I/R injury by prolonging the effective refractory period (ERP), increasing the ventricular fibrillation threshold (VFT) and decreasing the defibrillation threshold (DFT), and that the cardioprotection of G‐CSF is via preventing cardiac mitochondrial dysfunction. Methods: In intact‐heart protocol, pigs were infused with either G‐CSF or vehicle (n = 7 each group) without I/R induction. In I/R protocol, pigs were infused with G‐CSF (0.33 μg kg^?1 min^?1) or vehicle (n = 8 each group) for 30 min prior to a 45‐min left anterior descending artery occlusion and at reperfusion. Diastolic pacing threshold (DPT), ERP, VFT and DFT were determined in all pigs before and during I/R period. Rat’s isolated cardiac mitochondria were used to test the protective effect of G‐CSF (100 nm ) in H₂O₂‐induced mitochondrial oxidative damage. Results: Neither G‐CSF nor vehicle altered any parameter in intact‐heart pigs. During ischaemic period, G‐CSF significantly increased the DPT, ERP and VFT without altering the DFT. During reperfusion, G‐CSF continued to increase the DPT without altering other parameters. The infarct size was significantly decreased in the G‐CSF group, compared to the vehicle. G‐CSF could also prevent cardiac mitochondrial swelling, decrease ROS production, and prevent mitochondrial membrane depolarization. Conclusion: G‐CSF increases the DPT, ERP and VFT and reduces the infarct size, thus stabilizing the myocardial electrophysiology, and preventing fatal arrhythmia during I/R. The protective mechanism could be via its effect in preventing cardiac mitochondrial dysfunction.