期刊
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
卷 108, 期 8, 页码 1736-1746出版社
WILEY
DOI: 10.1002/jbm.a.36941
关键词
hydrogel; matrix metalloproteinases-2; myocardial contraction; myocardial infarction; reactive oxygen species
资金
- National Heart, Lung and Blood Institute [R01-HL-084431]
- Department of Veterans Affairs Merit Review Award [I01BX000740]
- American Heart Association [14GRNT20380813, 15GRNT25550041]
The decrease in contractility in myocardium adjacent (border zone; BZ) to a myocardial infarction (MI) is correlated with an increase in reactive oxygen species (ROS). We hypothesized that injection of a thermoresponsive hydrogel, with ROS scavenging properties, into the MI would decrease ROS and improve BZ function. Fourteen sheep underwent antero-apical MI. Seven sheep had a comb-like copolymer synthesized from N-isopropyl acrylamide (NIPAAm) and 1500 MW methoxy poly(ethylene glycol) methacrylate, (NIPAAm-PEG1500), injected (20 x 0.5 mL) into the MI zone 40 min after MI (MI + NIPAAm-PEG1500) and seven sheep were MI controls. Cardiac MRI was performed 2 weeks before and 6 weeks after MI + NIPAAm-PEG1500. BZ wall thickness at end systole was significantly higher for MI + NIPAAm-PEG1500 (12.32 +/- 0.51 mm/m(2) MI + NIPAAm-PEG1500 vs. 9.88 +/- 0.30 MI; p = .023). Demembranated muscle force development for BZ myocardium 6 weeks after MI was significantly higher for MI + NIPAAm-PEG1500 (67.67 +/- 2.61 mN/m(2) MI + NIPAAm-PEG1500 vs. 40.53 +/- 1.04 MI; p < .0001) but not significantly different from remote myocardium or BZ or non-operated controls. Levels of ROS in BZ tissue were significantly lower in the MI + NIPAAm-PEG1500 treatment group (hydroxyl p = .0031; superoxide p = .0182). We conclude that infarct injection of the NIPAAm-PEG1500 hydrogel with ROS scavenging properties decreased ROS and improved contractile protein function in the border zone 6 weeks after MI.
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