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

N Kanlop, S Thommasorn, S Palee, P Weerateerangkul, S Suwansirikul, S Chattipakorn, N Chattipakorn

Cardiac Electrophysiology Unit, Department of Physiology, Chiang Mai University, Thailand.

Acta physiologica (Oxford, England) 2011 May

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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. 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 H(2) O(2) -induced mitochondrial oxidative damage. 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. 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. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

Citation

N Kanlop, S Thommasorn, S Palee, P Weerateerangkul, S Suwansirikul, S Chattipakorn, N Chattipakorn. Granulocyte colony-stimulating factor stabilizes cardiac electrophysiology and decreases infarct size during cardiac ischaemic/reperfusion in swine. Acta physiologica (Oxford, England). 2011 May;202(1):11-20