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PRECLINICAL STUDIES

Thickening of the Infarcted Wall by Collagen Injection Improves Left Ventricular Function in Rats

A Novel Approach to Preserve Cardiac Function After Myocardial Infarction

The Heart Institute, Good Samaritan Hospital, Division of Cardiovascular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California

Manuscript received March 18, 2005; accepted April 20, 2005.

^_* Reprint requests and correspondence: Dr. Robert A. Kloner, The Heart Institute, Good Samaritan Hospital, University of Southern California, 1225 Wilshire Boulevard, Los Angeles, California 90017 (Email: Rkloner{at}goodsam.org).

OBJECTIVES: We determined whether collagen implantation could thicken the infarcted left ventricular (LV) wall and improve LV function.

BACKGROUND: We hypothesized that thickening the infarcted wall by using collagen might result in some benefits that are similar to what previously had been reported when the infarcted wall was thickened with cells.

METHODS: Fischer rats with one-week-old myocardial infarcts were injected with collagen or saline (100 µl) into the scar (n = 12 each group). Six weeks later, LV angiograms, hemodynamics, and regional myocardial blood flow were assessed. The hearts were processed for measurements of postmortem LV volume and histology.

RESULTS: Collagen injection significantly increased scar thickness (719 ± 26 µm) compared with the saline-treated group (440 ± 34 µm, p = 2.6 x 10^–6). By LV angiography, stroke volume was significantly larger in the collagen-treated group (163 ± 8 µl) than in the saline-treated group (129 ± 6 µl, p = 0.005), and LV ejection fraction was also greater in the collagen-treated group (48.4 ± 1.8%) than in the saline-treated group (40.7 ± 1.0%, p = 0.002). Analysis of regional wall motion demonstrated paradoxical systolic bulging in 5 of 10 saline-treated rats that averaged 20.3 ± 2.6% of the LV diastolic circumference, but in none of the 11 collagen-treated rats (p = 0.012). The LV end-diastolic and end-systolic volumes were 319 ± 12 µl and 190 ± 7 µl in the saline-treated group, respectively. There was a trend for larger LV end-diastolic volumes (343 ± 23 µl), but smaller end-systolic volumes (180 ± 16 µl) in the collagen-treated group.

CONCLUSIONS: This study shows that collagen injection thickens an infarct scar and improves LV stroke volume and ejection fraction, and prevents paradoxical systolic bulging after myocardial infarction.

Abbreviations and Acronyms   dp/dt = change in pressure over time   EF = ejection fraction   LV = left ventricle/ventricular   MI = myocardial infarction   RMBF = regional myocardial blood flow

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