Abstract 221: The Beneficial Effects of Cytokine Combinations are Sustained During Long-term Follow-up
We have shown that administration of granulocyte colony-stimulating factor (G-CSF)+Flt-3 ligand (FL) or G-CSF+stem cell factor (SCF) halts left ventricular (LV) remodeling and improves LV function at 35 days after myocardial infarction (MI). However, it is unknown whether these beneficial effects are sustained in the long term - an issue of fundamental importance for clinical translation. Accordingly, mice underwent a 30-min coronary occlusion followed by reperfusion and received vehicle (group I), G-CSF+FL (group II), G-CSF+SCF (group III), or G-CSF alone (group IV) starting 4 h after reperfusion. Mice were euthanized after 48 weeks of follow-up. LV structure and function were assessed by serial echocardiography before and at 48 h, 4 wk, 8 wk, 16 wk, 32 wk, and 48 wk after MI. During follow-up, mice in group I exhibited worsening of LV function (Fig. 1A⇓) and progressive LV remodeling. Compared with group I, both groups II and III exhibited improved LV EF at 4 wk after MI (Fig. 1A⇓); however, this improvement was sustained at 48 wk only in group II (Fig. 1A⇓). Interestingly, the improvement in LV diameter (Fig. 1B⇓) and infarct wall thickness (Fig. 1B⇓) (by morphometry) was more pronounced in group III. We conclude that postinfarct administration of G-CSF+FL improves LV function that is sustained for at least 11 months. This finding has important translational implications. Although G-CSF+SCF does not afford sustained improvement in LV function, this regimen markedly improves LV anatomy, indicating differential effects of cytokine combinations on infarcted myocardium. G-CSF, given alone, is less effective in improving LV function and in limiting LV remodeling during long-term follow-up.