Intramyocardial injection of tannic acid attenuates postinfarction remodeling: a novel approach to stabilize the breaking extracellular matrix.
OBJECTIVE
Myocardial infarction is associated with early matrix metalloproteinase activation and extracellular matrix degradation. We tested the hypothesis that stabilizing the original extracellular matrix of the infarcted left ventricle with local injection of tannic acid would preserve cardiac structure and function.


METHODS
In vitro cytotoxicity of tannic acid was performed first; myocardial infarction model was induced by ligation of the left anterior descending branch in rats. Tannic acid was intramyocardially injected into infarcted site 24 hours after myocardial infarction (n = 30), and saline solution was injected in the same way as in the control (n = 30). The matrix metalloproteinase activity from tannic acid/saline solution-treated tissues was assayed by gelatin zymography 24 hours and 1 week after the treatment. The collagen content in the infarcted area was evaluated by hydroxyproline colorimetry assay 1 and 4 weeks after the treatment. Left ventricular structure and function were also evaluated with echocardiography, hemodynamics, and histologic examination.


RESULTS
Tannic acid at a concentration of 0.05% had minimal cytotoxic effects on cultured cardiomyocytes and thus was subsequently chosen as the optimal concentration for injection. Compared with the saline solution injection group, tannic acid treatment inhibited the matrix metalloproteinase-2/-9 activity and increased the collagen content at the early post-myocardial infarction stage (48.6 +/- 7.2 vs 37.3 +/- 6 microg/mg dry weight). Tannic acid treatment also significantly reduced infarct expansion (infarct expansion index: 1.04 +/- 0.15 vs 1.42 +/- 0.21) and left ventricular dilatation at 4 weeks after infarction. Although tannic acid treatment improved fractional shortening (26% +/- 2.4% vs 23.3% +/- 3.2%), it failed to alter blood pressure (systolic blood pressure: 93.8 +/- 8.2 vs 90.6 +/- 8.5 mm Hg) and rate of pressure rise.


CONCLUSIONS
Local delivery of tannic acid prevents collagen matrix degradation via cross-linking fibrous collagen and inhibiting matrix metalloproteinase activity but does not improve the intrinsic contractile function of myocardium. This treatment may be helpful to attenuate the adverse topographic remodeling after acute myocardial infarction.
Zhang
Hao
H
Research Center for Cardiac Regenerative Medicine, the Ministry of Health, Cardiovascular Institute, Fu Wai Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, China.
Zhu
Shen-jun
SJ
Wang
De
D
Wei
Ying-jie
YJ
Hu
Sheng-Shou
SS
D000818:Animals; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism*; D007267:Injections; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism*; D009206:Myocardium; D051381:Rats; D013634:Tannins / Q000008:administration & dosage* / Q000627:therapeutic use; D020257:Ventricular Remodeling / Q000187:drug effects*
D013634:Tannins