Longitudinal histomechanical heterogeneity of the internal thoracic artery

Abstract

The internal thoracic artery (ITA) is the principal choice for coronary artery bypass grafting (CABG) due to its mechanical compatibility, histological composition, anti-thrombogenic lumen, and single anastomotic junction. Originating at the subclavian artery, traversing the thoracic cavity, and terminating at the superior epigastric and musculophrenic bifurcation, bilateral ITAs follow a protracted circuitous pathway. The physiological hemodynamics, anatomical configuration, and perivascular changes that occur throughout this length influence the tissue's microstructure and gross mechanical properties. Since histomechanics play a major role in premature graft failure we used inflation-extension testing to quantify the regional material and biaxial mechanical properties at four distinct locations along the left (L) and right (R) ITA and fit the results to a structurally-motivated constitutive model. Our comparative analysis of 44 vessel segments revealed a significant increase in the amount of collagen but not smooth muscle and a significant decrease in elastin and elastic lamellae present with distance from the heart. A subsequent decrease in the total deformation energy and isotropic contribution to the strain energy was present in the LITA but not RITA. Circumferential stress and compliance generally decreased along the length of the LITA while axial stress increased in the RITA. When comparing RITAs to LITAs, some morphological and histological differences were found in proximal sections while distal sections revealed differences predominantly in compliance and axial stress. Overall, this information can be used to better guide graft selection, graft preparation, and xenograft-based tissue-engineering strategies for CABG.

Keywords: Bypass grafting; Internal mammary; Porcine xenograft; Vascular mechanics.

Fig. 1 -

Full length porcine left (LITA) and right (RITA) internal thoracic arteries with sections labeled that approximate the (1) Proximal, (2) Submuscularis, (3) Middle, (4) Distal. All segments were taken from the same relative distance from the subclavian artery and distal bifurcation.

Fig. 2 -

Movat’s Pentachrome stain of LITA [A–D] and RITA [E–H] comparing the vascular wall composition across the proximal [A & E], submuscular [B & F], middle [C & G], and distal [D & H] segments.

Fig. 3 -

Constituent area fraction of collagen, elastin, smooth muscle cells (SMCs), and glycosaminoglycans (GAGs) determined by thresholding Movat’s Pentachrome stained cross-sections for the four anatomical locations along the LITA and RITA. Statistical significance is denoted as (*) when p<0.05, (**) at p<0.01, and (***) at p<0.001. Mean ± SD, n=5 for each group.

Fig. 4 -

Morphometric analysis of ITA wall composition. Intima, media, and adventitia thicknesses measured from Movat’s Pentachrome stained cross-sections and normalized to relative ITA complete wall thickness. Statistical significance is denoted as (*) when p<0.05, (**) at p<0.01, and (***) at p<0.001. Mean ± SD, n=6 for each group.

Fig. 5 -

Propidium Iodide nucleic acid stain and elastin autofluorescence LITA [A–D] and RITA [E–H] comparing the medial smooth muscle cell count and elastic lamellar count of the proximal [A & E], submuscular [B & F], middle [C & G], and distal [D & H] segments.

Fig. 6 -

[A] Medial smooth muscle cell density and [B] elastic lamellae count measured from the propidium iodide and elastin autofluorescence cross-sections along the LITA and RITA. Statistical significance is denoted as (*) when p<0.05, (**) at p<0.01, and (***) at p<0.001. Mean ± SD, n=3 for each group.

Fig. 7 -

Biaxial mechanical data for LITA [A, C, E, G] and RITA [B, D, F, H]. Pressure-outer diameter [A & B], axial force-pressure [C & D], circumferential stress-stretch [E & F] were all plotted at λ_z = 1.55. All vessels were tested at axial stretch ratios above and below the one shown but these data were omitted for clarity.

Fig. 8 -

Biaxial mechanical data of LITA [A, C, E, G] and RITA [B, D, F, H] plotted at common loading conditions of 100 mmHg and λ_z = 1.55. Inner radius [A & B], circumferential stress [C & D], axial stress [E & F], and area compliance [G & H] were plotted at the four anatomical segments for each vessel. Statistical significance is denoted as (*) when p<0.05, (**) at p<0.01, and (***) at p<0.001. Statistical significance between the LITA and RITA segments is denoted as (#) at p<0.05. Mean ± SD, n=6 for each group.

Fig. 9 -

Results of the best fit parameters using the 4-fiber family HGO model (solid lines) to average (n=5–6) experimental pressure-force data (symbols) for the LITA [top] and RITA [bottom] at the three axial stretch ratios. The proximal, submuscularis, middle, and distal segments are shown [left-to-right].

Fig. 10 -

Average strain energy contours (kPa) for the LITA [top] and RITA [bottom] proximal, submuscularis, middle, and distal segments [left-to-right]. Open circles represent approximate in vivo values of strain energy at 100 mmHg. Statistical significance is indicated by (*) when found between a given segment and its proximal section, (‡) when found between sequential segments, and (#) when found between the corresponding Left and Right segments.