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(Circulation. 2008;117:1388-1396.)
© 2008 American Heart Association, Inc.

Heart Failure

Effect of Injectable Alginate Implant on Cardiac Remodeling and Function After Recent and Old Infarcts in Rat

Natali Landa, BSc^*; Liron Miller, MSc^*; Micha S. Feinberg, MD; Radka Holbova, BSc; Michal Shachar, PhD; Inbar Freeman, MSc; Smadar Cohen, PhD; Jonathan Leor, MD

From the Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Aviv University, Tel-Hashomer (N.L., L.M., M.S.F., R.H., J.L.) and Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva (M.S., I.F., S.C.), Israel.

Correspondence to Jonathan Leor, MD, Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer 52621, Israel (e-mail leorj{at}post.tau.ac.il); or Smadar Cohen, PhD, Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer-Sheva, Israel (e-mail scohen@bgu.ac.il).

Received July 13, 2007; accepted January 18, 2008.

Background— Adverse cardiac remodeling and progression of heart failure after myocardial infarction are associated with excessive and continuous damage to the extracellular matrix. We hypothesized that injection of in situ–forming alginate hydrogel into recent and old infarcts would provide a temporary scaffold and attenuate adverse cardiac remodeling and dysfunction.

Methods and Results— We developed a novel absorbable biomaterial composed of calcium-crosslinked alginate solution, which displays low viscosity and, after injection into the infarct, undergoes phase transition into hydrogel. To determine the outcome of the biomaterial after injection, calcium-crosslinked biotin-labeled alginate was injected into the infarct 7 days after anterior myocardial infarction in rat. Serial histology studies showed in situ formation of alginate hydrogel implant, which occupied up to 50% of the scar area. The biomaterial was replaced by connective tissue within 6 weeks. Serial echocardiography studies before and 60 days after injection showed that injection of alginate biomaterial into recent (7 days) infarct increased scar thickness and attenuated left ventricular systolic and diastolic dilatation and dysfunction. These beneficial effects were comparable and sometimes superior to those achieved by neonatal cardiomyocyte transplantation. Moreover, injection of alginate biomaterial into old myocardial infarction (60 days) increased scar thickness and improved systolic and diastolic dysfunction.

Conclusions— We show for the first time that injection of in situ–forming, bioabsorbable alginate hydrogel is an effective acellular strategy that prevents adverse cardiac remodeling and dysfunction in recent and old myocardial infarctions in rat.

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CLINICAL PERSPECTIVE

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Clinical Summaries
Circulation 2008 117: 1353. [Full Text]

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