Comparative Cardiovascular Physiology & Pathology in Selected Lineages of Minipigs: Relation to Drug Safety Evaluation

Introduction

The minipig has been increasingly recognized as a valid alternative to canines and nonhuman primates in regulatory toxicity. This article presents the results of cardiovascular assessments in the Yucatan, Hanford, Sinclair, and Göttingen minipigs conducted during nonclinical investigations and control toxicity testing. Cardiac electrophysiology was obtained using clinical electrocardiogram and surgical monitor units. Peripheral vessel diameter, velocity, and flow were obtained by Doppler ultrasonography, and cardiac vessel diameter was obtained postmortem. Anatomic parameters were obtained at necropsy. Histopathology assessments were conducted on heart, blood vessels, and kidneys. Collected data were compared to published cardiovascular measurements of adult humans to illustrate similarities and differences. Each lineage of minipigs was found to have specific anatomic and physiologic characteristics that may accurately reflect response of human cardiovascular systems in clinical investigations and toxicity testing. In conclusion, the interspecies similarities between the cardiovascular systems make these lineages of minipigs suitable as models for the human counterpart. In addition, these reported differences between lineages will aid investigators in selecting a relevant lineage of minipigs if specific cardiovascular parameters are required during drug safety evaluation.

Authors

Alain Stricker-Krongrad, Catherine Shoemake, Derek Brocksmith, Jason Liu, Robert Hamlin, and Guy Bouchard

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