Abstract 16907: A Light-powered Symbiosis With a Primordial Chloroplast Attenuates Myocardial Injury in the Absence of Blood Perfusion
Objective: The treatment for acute myocardial infarction (MI) is prompt revascularization. Our goal is to develop a novel therapy that mimics perfusion, but is not reliant on restitution of blood flow. We hypothesized that targeted delivery of a photosynthetic agent to the ischemic heart would restore myocardial energetics, attenuate damage, and improve long-term performance.
Methods: Ten-week old male Wistar rats were used for the ischemia-reperfusion model. The left anterior descending artery (LAD) was temporarily ligated 2mm below the left atrial appendage via a left thoracotomy. Following ligation, animals were randomized to receive direct intramyocardial injection of 200μL PBS (n=7), 10x106 photosynthetic Synechecoccus elongatus (SE) of equivalent volume (n=10), or sham surgery (n=7). A light source illuminated the ischemic region for 1 hr after injection. The LAD tourniquet was subsequently removed and the heart reperfused. Ventricular function, geometry, and hemodynamics were assessed 4 weeks after surgery with MRI and LV catheterization.
Results: Myocardial injury was attenuated by the photosynthetic agent: troponin-I concentration in peripheral blood was significantly lower in SE treated animals compared with controls 24 hrs post MI (6.5±4.8 vs. 16.5±10.5 ng/mL, P=0.05). Four weeks after MI, the mean LV ejection fraction was significantly greater in SE treated rats compared with controls (36.9±4.7 vs. 48.3±10.5%, P=0.02). Similarly, SE treated animals demonstrated a decreased end-systolic volume (327±133 vs. 487±140 μL, P=0.03) and a steeper slope of the end-systolic pressure-volume relationship (0.35±0.12 vs. 0.19±0.08, P=0.01). Histologic analyses revealed no evidence of intramyocardial abscess formation or persistent SE. Furthermore, the photosynthetic agent prevented upregulation of genes associated with hypoxia (downregulated Hsp-1b 11 fold).
Conclusions: Delivery of a photosynthetic agent to ischemic myocardium creates a localized symbiotic relationship that safely attenuates myocardial injury and improves long-term ventricular function in a rat model of ischemia-reperfusion. Energizing myocardium with light in the absence of perfusion is a completely novel strategy for treating cardiac ischemia.
Author Disclosures: A.B. Goldstone: None. J.E. Cohen: None. Y. Shudo: None. A.N. Steele: None. M.S. Hopkins: None. J.B. Patel: None. B.B. Edwards: None. W.L. Patrick: None. C.E. Burnett: None. M.J. Paulsen: None. Y. Woo: None.
- © 2015 by American Heart Association, Inc.