Abstract P162: Granulocyte Colony-Stimulating Factor Administration Reduced the Inducibility of Ventricular Tachyarrhythmias in Cardiac Hypertrophied Rats Through Phosphorylated Connexin-43
Introduction: Cardiac hypertrophy is an independent risk factor for sudden cardiac death from ventricular tachyarrhythmias (VT). Granulocyte colony-stimulating factor (G-CSF) has recently been reported to suppress VT after myocardial infarction by modulating the function of gap junctions between cardiomyocytes via maintaining Connexin-43 (Cx43). We hypothesized that the G-CSF could also regress an enhanced vulnerability to VT in the cardiac hypertrophy without ischemic fibrosis through regulating Cx43.
Methods: Dahl salt-sensitive rats were maintained for a 6 week-period on a high-salt diet as left ventricular hypertrophy models (LVHs) and a low-salt diet as controls (CONs). After 3-time subcutaneous injection (50 μ g/kg) of G-CSF and vehicle, the inducibility of VT was evaluated by rapid ventricular burst pacing. The electrical pulses for the induction of VT were square waves with 6 ms width at 6 V and delivered at 25 Hz for 30 sec. White blood cell was counted to confirm a response to the G-CSF treatment. Expression levels of phosphorylated and total Cx43 in the rat ventricles were analyzed by immunoblotting.
Results: The LVHs showed apparent cardiac hypertrophy without pathological fibrotic changes. The G-CSF reduced the inducibility of VT compared to the vehicle in the LVHs (11 % vs. 63 %, p=0.04). Furthermore, the G-CSF eliminated the inducibility of VT in the CONs, although a difference in the inducibility of VT between with and without the G-CSF treatment did not reach statistical significance in the CONs (0 % vs. 33 %, p=0.60). White blood cell count in one microliter of blood was elevated by the G-CSF treatment in both LVHs (15083±4397 vs. 6976±1308, p<0.01) and CONs (19370±1174 vs. 7700±2335, p<0.01). The G-CSF increased phosphorylated Cx43 levels compared to the vehicle in both LVHs (1.4-fold vs. 1.2-fold, p<0.01) and CONs (1.4-fold vs. 1.0-fold, p=0.04), whereas the G-CSF did not affect total Cx43 levels in all groups.
Conclusion: We demonstrated that the G-CSF administration ameliorated the electrophysiological stability in the rat model of cardiac hypertrophy by modulating the function of gap junctions through accelerating phosphorylation of Cx43.
- © 2011 by American Heart Association, Inc.