Abstract 13051: Impact of a Novel Hybrid Device by Combination of Cardiac Support Net and Prostacyclin Agonist in a Canine Ischemic Cardiomyopathy Model: A Preclinical Trial of SaveHeart
Background: The cardiac support net, which was designed to “mechanically” prevent dilatation of the left ventricle (LV), has been shown to halt LV remodeling in ischemic cardiomyopathy, though the therapeutic efficacy is reportedly limited possibly due to a lack of “biological” effects. In contrast, ONO-1301, synthetic prostacyclin agonist, has been reported to act as a myocardial regenerative “biological” drug to enhance reverse LV remodeling. We hypothesized that the cardiac support net immersed with the slow-release ONO-1301 might enhance the therapeutic effects in ischemic cardiomyopathy compared to the single treatment.
Methods: An anterior infarct was created by ligation of the left anterior descending coronary artery in 20 canines. At 1-week post-infarct, the canines were randomly assigned into 4 treatment groups as follows; SaveHeart (S group), cardiac support net only (C group), ONO-1301 only (O group), or sham operation (N group).
Results: At 8-week post-infarct, multi-detector computed tomography showed a significantly greater LV ejection fraction in the S group (54±2%) than that in the C (51±0.7%), the O (50±0.3%) or the N (43±2%) groups. In addition, LV τ, assessed by catheter study, was significantly lower in the S group (30±0.9 msec) than the O (38±2 msec) or the N (41±1 msec) groups. Moreover, end-systolic wall stress of the LV was significantly smaller in the S group (67 ± 7 kdyne/cm2) than the O (92±4 kdyne/cm2), or the N (131±14 kdyne/cm2) groups. Plasma N-terminal pro-B-type natriuretic peptide was the lowest in the S group (560 ± 91 pmol/L) compared to the other groups (895 ± 79 pmol/L group in the C, 1013 ± 144 pmol/L in the O and 1678 ± 209 pmol/L in the N groups; P < 0.05). The S group had significantly higher vascular density, evaluated by immunohistolabeling, than the C or the N groups, while the amount of interstitial fibrosis, assessed by Masson’s trichrome staining, was the smallest in the S group among the groups (P < 0.05).
Conclusions: SaveHeart, prostacyclin agonist-immersed cardiac support net, elicited a greater recovery in both systolic and diastolic function of canine ischemic cardiomyopathy model, compared to the single treatment, suggesting a novel device for ischemia-induced failing heart.
- © 2012 by American Heart Association, Inc.