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

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

Complex electrophysiological remodeling in postinfarction ischemic heart failure

“…Four-to 6-mo-old adult Yucatan minipigs were subjected to microbead embolization of the first diagonal branch of the LAD, which caused transmural MI and progressive reduction in EF over 5 mo (Table S1), at which time left ventricular (LV) myocytes were isolated. The porcine model of chronic MI used is this study was developed to provide a clinically relevant large-animal ischemic cardiomyopathy model, as previously described (6). Cardiomyocytes from the remote or border zone of the infarct were obtained by enzymatic digestion using cannulation and perfusion of the left coronary vasculature.…”

Role of Epinephrine and Extracorporeal Membrane Oxygenation in the Management of Ischemic Refractory Ventricular Fibrillation

“…The model of coronary ischemia imperfectly represents real-life conditions, with simulated revascularization consisting only of balloon deflation. To our knowledge, no model incorporating atherosclerosis, calcification, or thrombus associated with coronary occlusion is currently available in pigs 25 , 26 . In addition, no defibrillations were provided during the ACLS phase, resulting in prolonged resuscitation for all animals.…”

Dietary normalization from a fat, fructose and cholesterol-rich diet to chow limits the amount of myocardial collagen in a Göttingen Minipig model of obesity

“…Before the assay, the LV samples were freeze-dried at − 55 °C (Heto FD3, Heto-Holten A/S, Allerød, Denmark) for 24 h, dry weight was determined and the freeze-dried samples were crushed using mortar and pestle. An acid hydrolysis was then performed using 200 μl 5 N hydrochloric acid per 10 mg wet weight cardiac tissue, and samples were incubated at 99 °C for 36 h according to Hanes and coworkers [ 34 ]. After incubation, samples were cooled to room temperature and centrifuged for 3 min at 9000×g.…”