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

Hanes DW, Wong ML, Jenny Chang CW, Humphrey S, Grayson JK, Boyd WD, Griffiths LG - J Transl Med (2015)

Bottom Line: 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).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).As a result, this method represents a useful model for studying chronic MI.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Medicine and Epidemiology, University of California, Davis, One Shields Ave., Davis, CA, 95616, USA. dwhanes@ucdavis.edu.

ABSTRACT

Background: Although 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.

Methods: Eight 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.

Results: All 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).

Conclusion: Systolic 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.

No MeSH data available.


Related in: MedlinePlus

Biochemical composition of normal and infarcted myocardium. Collagen I content was significantly greater in infarcted myocardium than normal septum (A). Although pyridinoline crosslink content trended lower in the septum than the MI, the difference was not statistically significant (B). Pyridinoline crosslink content per collagen I content was significantly lower in infarcted myocardium than normal septum (C). Sulfated GAG content was significantly greater in infarcted myocardium than normal septum (D). Water content in MI was not significantly different than that in normal septum (E). Results plotted as mean ± standard deviation. Groups not connected by same letter are significantly different, p < 0.05 (n = 5 per group).
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Fig6: Biochemical composition of normal and infarcted myocardium. Collagen I content was significantly greater in infarcted myocardium than normal septum (A). Although pyridinoline crosslink content trended lower in the septum than the MI, the difference was not statistically significant (B). Pyridinoline crosslink content per collagen I content was significantly lower in infarcted myocardium than normal septum (C). Sulfated GAG content was significantly greater in infarcted myocardium than normal septum (D). Water content in MI was not significantly different than that in normal septum (E). Results plotted as mean ± standard deviation. Groups not connected by same letter are significantly different, p < 0.05 (n = 5 per group).

Mentions: The water content of infarcted myocardium (76.30 ± 2.84%) was not significantly different from that of normal myocardium (74.74 ± 1.82%) (p = 0.332) (Figure 6E). The collagen I content of infarcted myocardium (223.51 ± 111.13 µg/mg DW) was significantly greater than that of normal myocardium (42.72 ± 14.64 µg/mg DW) (p = 0.007) (Figure 6A). The pyridinoline content of infarcted myocardium (1.56 × 10−10 ± 6.93 × 10−11 mol/mg DW) was not significantly different than that of normal myocardium (7.75 × 10−11 ± 3.79 × 10−11 mol/mg DW) (p = 0.058) (Figure 6B). Pyridinoline content per collagen I content was significantly lower in infarcted myocardium (7.38 × 10−13 ± 2.18 × 10−13 mol/µg) than normal myocardium (1.97 × 10−12 ± 1.16 × 10−12 mol/µg) (p = 0.048) (Figure 6C). The GAG content of infarcted myocardium (7.84 ± 2.16 µg/mg DW) was significantly greater than that of normal myocardium (4.92 ± 0.43 µg/mg DW) (p = 0.018) (Figure 6D).Figure 6


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

Hanes DW, Wong ML, Jenny Chang CW, Humphrey S, Grayson JK, Boyd WD, Griffiths LG - J Transl Med (2015)

Biochemical composition of normal and infarcted myocardium. Collagen I content was significantly greater in infarcted myocardium than normal septum (A). Although pyridinoline crosslink content trended lower in the septum than the MI, the difference was not statistically significant (B). Pyridinoline crosslink content per collagen I content was significantly lower in infarcted myocardium than normal septum (C). Sulfated GAG content was significantly greater in infarcted myocardium than normal septum (D). Water content in MI was not significantly different than that in normal septum (E). Results plotted as mean ± standard deviation. Groups not connected by same letter are significantly different, p < 0.05 (n = 5 per group).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4634919&req=5

Fig6: Biochemical composition of normal and infarcted myocardium. Collagen I content was significantly greater in infarcted myocardium than normal septum (A). Although pyridinoline crosslink content trended lower in the septum than the MI, the difference was not statistically significant (B). Pyridinoline crosslink content per collagen I content was significantly lower in infarcted myocardium than normal septum (C). Sulfated GAG content was significantly greater in infarcted myocardium than normal septum (D). Water content in MI was not significantly different than that in normal septum (E). Results plotted as mean ± standard deviation. Groups not connected by same letter are significantly different, p < 0.05 (n = 5 per group).
Mentions: The water content of infarcted myocardium (76.30 ± 2.84%) was not significantly different from that of normal myocardium (74.74 ± 1.82%) (p = 0.332) (Figure 6E). The collagen I content of infarcted myocardium (223.51 ± 111.13 µg/mg DW) was significantly greater than that of normal myocardium (42.72 ± 14.64 µg/mg DW) (p = 0.007) (Figure 6A). The pyridinoline content of infarcted myocardium (1.56 × 10−10 ± 6.93 × 10−11 mol/mg DW) was not significantly different than that of normal myocardium (7.75 × 10−11 ± 3.79 × 10−11 mol/mg DW) (p = 0.058) (Figure 6B). Pyridinoline content per collagen I content was significantly lower in infarcted myocardium (7.38 × 10−13 ± 2.18 × 10−13 mol/µg) than normal myocardium (1.97 × 10−12 ± 1.16 × 10−12 mol/µg) (p = 0.048) (Figure 6C). The GAG content of infarcted myocardium (7.84 ± 2.16 µg/mg DW) was significantly greater than that of normal myocardium (4.92 ± 0.43 µg/mg DW) (p = 0.018) (Figure 6D).Figure 6

Bottom Line: 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).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).As a result, this method represents a useful model for studying chronic MI.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Medicine and Epidemiology, University of California, Davis, One Shields Ave., Davis, CA, 95616, USA. dwhanes@ucdavis.edu.

ABSTRACT

Background: Although 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.

Methods: Eight 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.

Results: All 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).

Conclusion: Systolic 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.

No MeSH data available.


Related in: MedlinePlus