Abstract
Background: We investigated the safety and efficacy of GCSF therapy in a porcine model of ischemia–reperfusion with left ventricle ejection fraction of <45% using a clinically relevant dosing and timing regimen. Methods: MI was induced in pigs by a 90 min balloon occlusion of the left anterior descending coronary artery. Sixteen animals were randomized to either GCSF (IV bolus of 10 μg/kg at time of reperfusion, followed by SC injections of 5 μg/kg days 5–9 post-MI) or saline (control group). Inflammatory markers, bone marrow cell mobilization and LV function (echocardiography and pressure–volume measurements) were assessed at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI. Results: GCSF therapy was associated with a significant increase in white blood cell counts. At week 6, GCSF therapy resulted in less deterioration of LVEF compared to control (38 ± 2% vs. 33 ± 2%, p < 0.02) and improved wall motion score index ( p < 0.05). Histopathology revealed increased vascular density ( p < 0.05) and a trend toward increased areas of viable myocardium compared to control ( p = 0.058). Conclusion: GCSF therapy prevents further deterioration of LV function in a porcine model of MI with lower EF (<45%). These results support future clinical trials with GCSF in selected patients with larger MI.
Published Version
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