Abstract 17030: Therapeutic Time Window for Acute Myocardial Infarction in Pigs Using Peptide Nanofibers Combined with Autologous Bone Marrow Cells
Background-We have previously shown that a combined autologous bone marrow mononuclear cells (MNC) with self-assembling peptide nanofibers (NF) injection immediately following coronary artery ligation improves post-infarction cardiac performance in pigs (Lin YD et al. Circulation, 2010). However, the therapeutic time window of this approach to the treatment of acute myocardial infarction (MI) remains uncharacterized. We thus tested if delayed NF/MNC therapy may improve cardiac functions after MI in pigs.
Methods and Results-A total of 36 adult Lanyu minipigs were used in the study with 6 animals in each of the 6 groups-- sham, MI + NS (normal saline), MI + NF and MI + NF/MNC-1D (day), -4D and -7D. MI was induced by a permanent ligation of mid-left anterior descending coronary artery. After 1D, 4D and 7D, pigs received injection of a total of 2 ml NS or 1% NF, with or without 1×108 freshly isolated autologous MNC, divided among ∼40 injections into the infarcted area. Cardiac functions were assessed by echocardiography before, immediately after, and 1 or 2 months after MI, and together with hemodynamic measurements via catheterization 2 months post-MI. Pigs were then sacrificed for histology. We found that pigs in the MI + NF/MNC-1D group had the highest left ventricle ejection fraction (55.07 ± 1.6%; P < 0.01 vs. MI + NS) compared with those in MI + NF/MNC-4D (48.88 ± 0.8%; P < 0.05 vs. MI + NS) and those in MI + NF/MNC-7D (43.47 ± 2.3%; n.p. vs. MI + NS) after 8 weeks. The +dP/dt and -dP/dt, indicators of cardiac systolic and diastolic functions, respectively, were also higher in the MI + NF/MNC-1D and -4D but not -7D group. Furthermore, the infarct size was significantly reduced only in the MI + NF/MNC-1D and -4D groups. Consistent with these findings, the MI + NF/MNC-1D and -4D groups showed reduced left ventricular dilatation and less collagen content at the remote area, suggesting prevention of pathological remodeling after MI.
Conclusions-We demonstrated that intramyocardial injection of NF/MNC at 1 and 4 days but not at 7 days post-MI improves cardiac performance and prevents ventricular remodeling in pigs. These results suggest 4-day post-MI as the therapeutic time window for NF/MNC therapy, confirming the importance of early intervention for the current therapy for MI.
- © 2012 by American Heart Association, Inc.