Preservation from left ventricular remodeling by front-integrated Revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte-colony-stimulating factor (FIRSTLINE-AMI)

Background - Considering experimental evidence that stem cells enhance myocardial regeneration and granulocyte colony - stimulating factor ( G-CSF) mediates mobilization of CD34 + mononuclear blood stem cells ( MNCCD34+), we tested the impact of G-CSF integrated into primary percutaneous coronary intervention ( PCI) management of acute myocardial infarction in man. Methods and Results - Fifty consecutive patients with ST-segment elevation myocardial infarction were subjected to primary PCI stenting with abciximab and followed up for 6 months; 89 +/- 35 minutes after successful PCI, 25 patients were randomly assigned in this pilot study ( PROBE design) to receive subcutaneous G-CSF at 10 mu g/kg body weight for 6 days in addition to standard care, including aspirin, clopidogrel, an ACE inhibitor, beta-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNCCD34+ to between 3.17 +/- 2.93 MNCCD34+/mu L at baseline and 64.55 +/- 37.11 MNCCD34+/mu L on day 6 ( P < 0.001 versus control); there was no indication of leukocytoclastic effects, significant pain, impaired rheology, inflammatory reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and MNCCD34+ liberation led to enhanced resting wall thickening in the infarct zone of between 0.29 +/- 0.22 and 0.99 +/- 0.32 mm versus 0.49 +/- 0.29 mm in control subjects ( P < 0.001); under inotropic challenge with dobutamine ( 10 mu g (.) kg(-1) (.) min(-1)), wall motion score index showed improvement from 1.66 +/- 0.23 to 1.41 +/- 0.21 ( P < 0.004 versus control) and to 1.35 +/- 0.24 after 4 months ( P < 0.001 versus control), respectively, coupled with sustained recovery of wall thickening to 1.24 +/- 0.31 mm ( P < 0.001 versus control) at 4 months. Accordingly, resting wall motion score index improved with G-CSF to 1.41 +/- 0.25 ( P < 0.001 versus control), left ventricular end-diastolic diameter to 55 +/- 5 mm ( P < 0.002 versus control), and ejection fraction to 54 +/- 8% ( P < 0.001 versus control) after 4 months. Morphological and functional improvement with G-CSF was corroborated by enhanced metabolic activity and F-18-deoxyglucose uptake in the infarct zone ( P < 0.001 versus control). Conclusions - G-CSF and mobilization of MNCCD34+ after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis.