Embolization of the first diagonal branch of the left anterior descending coronary artery as a porcine model of chronic trans-mural myocardial infarctionReport as inadecuate




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Journal of Translational Medicine

, 13:187

Cardiovascular, Metabolic and Lipoprotein Translation

Abstract

BackgroundAlthough the incidence of acute death related to coronary artery disease has decreased with the advent of new interventional therapies, myocardial infarction remains one of the leading causes of death in the US. Current animal models developed to replicate this phenomenon have been associated with unacceptably high morbidity and mortality. A new model utilizing the first diagonal branch of the left anterior descending artery D1-LAD was developed to provide a clinically relevant lesion, while attempting to minimize the incidence of adverse complications associated with infarct creation.

MethodsEight Yucatan miniature pigs underwent percutaneous embolization of the D1-LAD via injection of 90 µm polystyrene micro-spheres. Cardiac structure and function were monitored at baseline, immediately post-operatively, and at 8-weeks post-infarct using transthoracic echocardiography. Post-mortem histopathology and biochemical analyses were performed to evaluate for changes in myocardial structure and extracellular matrix ECM composition respectively. Echocardiographic data were evaluated using a repeated measures analysis of variance followed by Tukey’s HSD post hoc test. Biochemical analyses of infarcted to non-infarcted myocardium were compared using analysis of variance.

ResultsAll eight pigs successfully underwent echocardiography prior to catheterization. Overall procedural survival rate was 83% 5-6 with one pig excluded due to failure of infarction and another due to deviation from protocol. Ejection fraction significantly decreased from 69.7 ± 7.8% prior to infarction to 50.6 ± 14.7% immediately post-infarction, and progressed to 48.7 ± 8.9% after 8-weeks p = 0.011. Left ventricular diameter in systole significantly increased from 22.6 ± 3.8 mm pre-operatively to 30.9 ± 5.0 mm at 8 weeks p = 0.016. Histopathology showed the presence of disorganized fibrosis on hematoxylin and eosin and Picro Sirius red stains. Collagen I and sulfated glycosaminoglycan content were significantly greater in the infarcted region than in normal myocardium p = 0.007 and p = 0.018, respectively; however, pyridinoline crosslink content per collagen I content in the infarcted region was significantly less than normal myocardium p = 0.048.

ConclusionSystolic dysfunction and changes in ECM composition induced via embolization of the D1-LAD closely mimic those found in individuals with chronic myocardial infarction MI, and represents a location visible without the need for anesthesia. As a result, this method represents a useful model for studying chronic MI.

KeywordsMyocardial infarction Model Porcine D1-LAD Chronic AbbreviationsD1-LADfirst diagonal branch of the left anterior descending coronary artery

MImyocardial infarction

ECMextracellular matrix

LADleft anterior descending coronary artery

MRImagnetic resonance imaging

Tc-SPECTtechnetium single photon emission tomography

LVEFleft ventricular ejection fraction

IVintravenous

CO2carbon dioxide

SpO2pulse oximetry

ACTactivated clotting time

HandEhematoxylin and eosin

VVGVerhoeff Van Gieson

GAGglycosaminoglycan

ANOVAanalysis of variance

LVIDsleft ventricular internal diameter in systole

LVIDdleft ventricular internal diameter in diastole

DWdry weight

WWwet weight

LCxleft circumflex coronary artery

Derek W Hanes and Maelene L Wong contributed equally to this work

Electronic supplementary materialThe online version of this article doi:10.1186-s12967-015-0547-4 contains supplementary material, which is available to authorized users.

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Author: Derek W Hanes - Maelene L Wong - C W Jenny Chang - Sterling Humphrey - J Kevin Grayson - Walter D Boyd - Leigh G Grif

Source: https://link.springer.com/







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