Are ovine and porcine carotid arteries equivalent animal models for experimental cardiac surgery: A quantitative histological comparison
Abstract
Background: Coronary artery bypass grafting (CABG) is a common cardiac surgery. Manufacturing small-diameter (2-5mm) vascular grafts for CABG is important for patients who lack first-choice autologous arterial, or venous conduits.
Ovine and porcine common carotid arteries (CCAs) are used as large animal models for in vivo testing of newly developed tissue-engineered arterial grafts. It is unknown to what extent these models are interchangeable and whether the left and right arteries of the same subjects can be used as experimental controls.
Therefore, we compared the microscopic structure of paired left and right ovine and porcine CCAs in the proximodistal direction and compared these animal model samples to samples of human coronary arteries (CAs) and human internal thoracic arteries (ITAs). Methods: We compared the histological composition of whole CCAs of sheep (n=22 animals) with whole porcine CCAs (n=21), segments of human CAs (n=21), and human ITAs (n=21).
Using unbiased sampling and stereological methods, we quantified the fractions of elastin, total collagen, type I collagen, type III collagen, smooth muscle actin (SMA) and chondroitin sulfate (CS) A, B, and C. We also quantified the densities and distributions of nuclear profiles, nervi vasorum and vasa vasorum as well as the thickness of the intima-media and total wall thickness.
Results: The differences between the paired samples of left and right CCAs in sheep were substantially greater than the differences in laterality in porcine CCAs. The right ovine CCAs had a smaller fraction of elastin (p<0.001), greater fraction of SMA (p<0.01), and greater intima-media thickness (p<0.001) than the paired left side CCAs.
In pigs, the right CCAs had a greater fraction of elastin (p<0.05) and a greater density of vasa vasorum in the media (p<0.001) than the left-side CCAs. The fractions of elastin and CS decreased and the fraction of SMA increased in the proximodistal direction in both the ovine (p<0.001) and porcine (p<0.001) CCAs.
Ovine CCAs had a muscular phenotype along their entire length, but porcine CCAs were elastic-type arteries in the proximal segments but muscular type arteries in middle and distal segments. The CCAs of both animals differed from the human CAs and ITAs in most parameters, but the ovine CCAs had a comparable fraction of elastin and CS to human ITAs.
Conclusions: From a histological point of view, ovine and porcine CCAs were not equivalent in most quantitative parameters to human CAs and ITAs. Left and right ovine CCAs did not have the same histological composition, which is limiting for their mutual equivalence as sham-operated controls in experiments.
These differences should be taken into account when designing and interpreting experiments using these models in cardiac surgery. The complete morphometric data obtained by quantitative evaluation of arterial segments were provided to facilitate the power analysis necessary for justification of the minimum number of samples when planning further experiments.
The middle or distal segments of ovine and porcine CCAs remain the most realistic and the best characterized large animal models for testing artificial arterial CABG conduits.