Abstract 949: Local Controlled Intramyocardial Delivery of PDGF Improves Post-Infarction Ventricular Function without Pulmonary Toxicity
Background: Local delivery methods can target therapies to specific tissues and potentially avoid toxicity to other organs. Platelet-derived growth factor can protect the myocardium, but it also plays an important role in promoting pulmonary hypertension. It is unknown if local myocardial delivery of platelet-derived growth factor during myocardial infarction (MI) can lead to sustained cardiac benefit without causing pulmonary hypertension.
Methods and Results: We performed a randomized and blinded experiment of 127 rats that survived experimental MI or sham surgery. We delivered platelet-derived growth factor-BB (PDGF) with self-assembling peptide nanofibers (NF) to provide controlled release within the myocardium. There were six groups with n≥20 in each group: sham, sham+NF, sham+NF/PDGF, MI, MI+NF, and MI+NF/PDGF. Serial echocardiography from 1 day to 3 months showed significant improvement of ventricular fractional shortening, end-systolic dimension, and end-diastolic dimension (P<0.05 for MI+NF/PDGF vs. MI or MI+NF). Catheterization at 4 months revealed improved ventricular function in the controlled delivery group (LVEDP, cardiac index, +dP/dt, −dP/dt and τ all P<0.05 MI+NF/P vs. MI or MI+NF). Infarcted myocardial volume was reduced by NF/PDGF therapy (34.0±13.3% in MI, 28.9±12.9% in MI+NF, and 12.0±5.8% in MI+NF/ PDGF, P<0.001). There was no evidence for pulmonary toxicity from the therapy, with no differences in RV end-systolic pressure, RV dP/dt, BrdU staining or pulmonary artery medial wall thickness.
Conclusion: Intramyocardial delivery of PDGF by self-assembling peptide nanofibers leads to long-term improvement in cardiac performance after experimental infarction without apparent pulmonary toxicity. Local myocardial protection may allow prevention of heart failure without systemic toxicity.