Differential Cardiovascular Physiology and Pathology in Selected Lineages of Miniature Swine and Comparison to Human

Authors

Stricker-Krongrad, A., Madsen, T.J., Hanks, B.C., Brocksmith, D., Liu, J., Brown, L.D., Bouchard, G.F., 

Abstract

The miniature swine has been increasingly recognized as a valid alternative to canine and non-human primates in regulatory toxicity. This poster presents the results of cardiovascular assessments in the Yucatan, Hanford, and Sinclair miniature swine conducted during clinical investigations and control toxicity testing. Anatomic parameters were obtained at necropsy. Blood vessels diameter, velocity, and flow were obtained by Doppler ultrasonography. Cardiac electrophysiology was obtained using clinical ECG and surgical monitor units. Macroscopic lesions and histopathology assessments were conducted on heart and kidneys. Data were compared to published measurements of adult human illustrating similarities or differences (for practicality, male data are reported here). Across the three lineages, heart-to-body weights ratio ranged from 0.41 to 0.50 and were higher than human (0.42). The geometric corrections for heart rate adjustment to body size ranged from 219 to 349 and were comparable to human (241), indicating that heart volume and function were well adjusted to the reduction in body size. The miniswinehearts showed a coronary artery distribution comparable to human. The right coronary internal diameters ranged from 1.44 to 1.79 mm and were comparable to human (3.9 mm) when adjusted to body surface area (weight range: 51-85 kg). External femoral blood flows at rest averaged 93 mL/min and were slightly lower than human (260 mL/min) when adjusted to body size. Electrophysiological heart segments duration (e.g. RR ranged from 360 to 662 msec) and their ratio (QT/RR) were proportional to human and well-adjusted to body size. Macroscopic lesions were nonexistent. Histopathology findings were rare and limited to sub-level myocardial inflammation with low incidence in the Hanford lineage. In conclusion, the similarities between the cardiovascular systems make these three lineages of miniature swine suitable animals to model the human counterpart. In addition, the differences will aid investigators select a relevant lineage of miniature swine if specific cardiovascular parameters are required.

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