Intracoronary injection of in situ forming alginate hydrogel reverses left ventricular remodeling after myocardial infarction in Swine.
OBJECTIVE
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.
Leor
Jonathan
J
Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Aviv University, Tel-Hashomer 52621, Israel. leorj@post.tau.ac.il
Tuvia
Shmuel
S
Guetta
Victor
V
Manczur
Ferenc
F
Castel
David
D
Willenz
Udi
U
Petneházy
Ors
O
Landa
Natali
N
Feinberg
Micha S
MS
Konen
Eli
E
Goitein
Orly
O
Tsur-Gang
Orna
O
Shaul
Mazal
M
Klapper
Lea
L
Cohen
Smadar
S
D000464:Alginates / Q000008:administration & dosage*; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D020723:Glucuronic Acid / Q000008:administration & dosage; D006339:Heart Rate; D006603:Hexuronic Acids / Q000008:administration & dosage; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000008:administration & dosage*; D015552:Injections, Intralesional; D009203:Myocardial Infarction / Q000150:complications* / Q000473:pathology* / Q000503:physiopathology; D013318:Stroke Volume; D013552:Swine; D020257:Ventricular Remodeling / Q000187:drug effects*
D000464:Alginates; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid