Pre-Clinical Research
Intracoronary Injection of In Situ Forming Alginate Hydrogel Reverses Left Ventricular Remodeling After Myocardial Infarction in Swine

https://doi.org/10.1016/j.jacc.2009.06.010Get rights and content
Under an Elsevier user license
open archive

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.

Key Words

biomaterials
heart failure
myocardial infarction
remodeling

Abbreviations and Acronyms

CT
computed tomography
ECG
electrocardiogram/electrocardiographic
ECM
extracellular matrix
LAD
left anterior descending
LV
left ventricle/ventricular
MI
myocardial infarction
MPG
myocardial perfusion grade
MR
mitral regurgitation
TFG
Thrombolysis In Myocardial Infarction flow grade
TIMI
Thrombolysis In Myocardial Infarction

Cited by (0)

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.