Intramyocardial Hydrogel Delivery Decreases Left Ventricular Remodeling and Increases Angiogenesis Post Myocardial Infarction

Abstract

BACKGROUND: Intramyocardial injection of hydrogel into myocardial infarction (MI) areas can reduce left ventricular remodeling and potentially increase angiogenesis post-MI. The radiotracer 99m Tc-Maraciclatide binds to activated alpha-v-beta-3 (αvβ3)-integrin, a key factor in angiogenesis, and can be used to evaluate myocardial angiogenesis. This study used multimodality imaging to assess the effects of imageable intramyocardial hydrogel delivery on left ventricular remodeling and angiogenesis after MI. METHODS: Fourteen pigs (N=14) underwent 90 minutes of balloon occlusion and reperfusion. Five days post-MI, they were randomized to receive either intramyocardial hydrogel (n=8) or control saline injections (n=6). Contrast cine–computed tomography was used to assess biomechanical changes before and after treatment (day 1, day 5, and day 12). 99m Tc-Maraciclatide uptake was measured with gamma well counting. Scar burden and angiogenesis were evaluated through histology. RESULTS: Both groups initially showed a decrease in ejection fraction and an increase in end-diastolic volume post-MI. Hydrogel delivery on day 5 led to a reduction in end-diastolic volume and improvement in left ventricular ejection fraction by day 12. The hydrogel group also exhibited decreased compensatory radial strain in remote myocardial segments, but decreased strain in the hydrogel myocardial segments. There was increased uptake of 99m Tc-maraciclatide in the infarct segments after hydrogel delivery, associated with increased αvβ3-integrin and factor VIII expression in the hydrogel treatment group on histology. However, there was no difference in regional inflammation or scar size between the groups. CONCLUSIONS: Intramyocardial delivery of hydrogel early post-MI resulted in decreased left ventricular remodeling and increased αvβ3-integrin activation associated with an increase in angiogenesis.