TY - JOUR
T1 - Intracoronary Injection of In Situ Forming Alginate Hydrogel Reverses Left Ventricular Remodeling After Myocardial Infarction in Swine
AU - Leor, Jonathan
AU - Tuvia, Shmuel
AU - Guetta, Victor
AU - Manczur, Ferenc
AU - Castel, David
AU - Willenz, Udi
AU - Petneházy, Örs
AU - Landa, Natali
AU - Feinberg, Micha S.
AU - Konen, Eli
AU - Goitein, Orly
AU - Tsur-Gang, Orna
AU - Shaul, Mazal
AU - Klapper, Lea
AU - Cohen, Smadar
N1 - Funding Information:
Supported by a research grant from BiolineRx, Jerusalem, Israel, and Ben-Gurion University of the Negev, Beer-Sheva, Israel. Drs. Leor and Cohen applied for a patent on injectable alginate for myocardial repair via Ben-Gurion University of the Negev, Beer-Sheva, Israel, and are advisers of BiolineRx, Jerusalem, Israel. Drs. Tuvia, Shaul, and Klapper are employees of BiolineRx, Jerusalem, Israel. Dr. Cohen holds the Claire and Harold Oshry Professor Chair in Biotechnology. Drs. Leor and Tuvia contributed equally to this work.
PY - 2009/9/8
Y1 - 2009/9/8
N2 - Objectives: This study sought to determine whether alginate biomaterial can be delivered effectively into the infarcted myocardium by intracoronary injection to prevent left ventricular (LV) remodeling early after myocardial infarction (MI). Background: Although injectable biomaterials can improve infarct healing and repair, the feasibility and effectiveness of intracoronary injection have not been studied. Methods: We prepared a calcium cross-linked alginate solution that undergoes liquid to gel phase transition after deposition in infarcted myocardium. Anterior MI was induced in swine by transient balloon occlusion of left anterior descending coronary artery. At 4 days after MI, either alginate solution (2 or 4 ml) or saline was injected selectively into the infarct-related coronary artery. An additional group (n = 19) was treated with incremental volumes of biomaterial (1, 2, and 4 ml) or 2 ml saline and underwent serial echocardiography studies. Results: Examination of hearts harvested after injection showed that the alginate crossed the infarcted leaky vessels and was deposited as hydrogel in the infarcted tissue. At 60 days, control swine experienced an increase in left ventricular (LV) diastolic area by 44%, LV systolic area by 45%, and LV mass by 35%. In contrast, intracoronary injection of alginate (2 and 4 ml) prevented and even reversed LV enlargement (p < 0.01). Post-mortem analysis showed that the biomaterial (2 ml) increased scar thickness by 53% compared with control (2.9 ± 0.1 mm vs. 1.9 ± 0.3 mm; p < 0.01) and was replaced by myofibroblasts and collagen. Conclusions: Intracoronary injection of alginate biomaterial is feasible, safe, and effective. Our findings suggest a new percutaneous intervention to improve infarct repair and prevent adverse remodeling after reperfused MI.
AB - Objectives: This study sought to determine whether alginate biomaterial can be delivered effectively into the infarcted myocardium by intracoronary injection to prevent left ventricular (LV) remodeling early after myocardial infarction (MI). Background: Although injectable biomaterials can improve infarct healing and repair, the feasibility and effectiveness of intracoronary injection have not been studied. Methods: We prepared a calcium cross-linked alginate solution that undergoes liquid to gel phase transition after deposition in infarcted myocardium. Anterior MI was induced in swine by transient balloon occlusion of left anterior descending coronary artery. At 4 days after MI, either alginate solution (2 or 4 ml) or saline was injected selectively into the infarct-related coronary artery. An additional group (n = 19) was treated with incremental volumes of biomaterial (1, 2, and 4 ml) or 2 ml saline and underwent serial echocardiography studies. Results: Examination of hearts harvested after injection showed that the alginate crossed the infarcted leaky vessels and was deposited as hydrogel in the infarcted tissue. At 60 days, control swine experienced an increase in left ventricular (LV) diastolic area by 44%, LV systolic area by 45%, and LV mass by 35%. In contrast, intracoronary injection of alginate (2 and 4 ml) prevented and even reversed LV enlargement (p < 0.01). Post-mortem analysis showed that the biomaterial (2 ml) increased scar thickness by 53% compared with control (2.9 ± 0.1 mm vs. 1.9 ± 0.3 mm; p < 0.01) and was replaced by myofibroblasts and collagen. Conclusions: Intracoronary injection of alginate biomaterial is feasible, safe, and effective. Our findings suggest a new percutaneous intervention to improve infarct repair and prevent adverse remodeling after reperfused MI.
KW - biomaterials
KW - heart failure
KW - myocardial infarction
KW - remodeling
UR - http://www.scopus.com/inward/record.url?scp=69249163009&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2009.06.010
DO - 10.1016/j.jacc.2009.06.010
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AN - SCOPUS:69249163009
SN - 0735-1097
VL - 54
SP - 1014
EP - 1023
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 11
ER -