Characterization of medial calcification of the large pulmonary arteries in racehorses

Racehorses die or are euthanized due to fatal injuries every year worldwide. In many cases, the cause of death cannot be determined by gross postmortem and/or histological examination. Racehorse mortalities in Ontario showed a similar high prevalence of undetermined cause of death in many horses. As such, the main objective of this study was to perform an in-depth investigation of racehorse mortalities, and particularly those cases classified grossly as undetermined deaths.;These studies support the hypothesis that medial calcification of large arteries is a degenerative and progressive condition highly prevalent in racing horses of all ages. The occurrence of arterial medial calcification in young racing horses indicates the need to investigate its pathogenesis and determine potential hemodynamic changes or adaptations that may occur as result of this lesion and whether such changes are clinically relevant.;While examining racehorses submitted for postmortem examination to the Animal Health Laboratory, it was noted that patchy, hard and irregularly shaped lesions were frequently identified on the endothelial surface of the pulmonary arteries. Prospective investigation of these lesions revealed calcification of the arterial wall, predominantly involving the tunica media of the main pulmonary artery branches, was present in 82% of young adult racehorses. The lesions appeared as white-to-yellow, hard, and gritty plaques of variable sizes protruding into the endothelial surface. Microscopically, elastic fibers in the tunica media were thinned, fragmented and calcified, and surrounded by dense collagen matrix and chondroid metaplasia, with a mineralized matrix containing calcium and phosphorus that was consistent with an apatite mineral. This lesion resembles the medial calcification that occurs as an age-associated degenerative condition in major vessels of humans. Since the mechanisms of medial calcification in humans are poorly understood, the pathogenesis of the condition in young horses was further characterized. By immunohistochemistry, metaplastic cells in the lesions were smooth muscle alpha-actin and SM22alpha-actin negative, in contrast to this predominant phenotype of smooth muscle cells of the tunica media of normal arteries. Attempts to further characterize the underlying pathogenesis by proteomic and gene expression studies of dissected artery wall fragments did not reveal consistent changes in the macromolecular composition of the lesions. Arterial calcification can occur as a result of wall stress, which may explain the presence of lesions in a highly stressed vessel such as the pulmonary artery of a racehorse. Thus, the effect of geometry and pressure on arterial wall stress of the pulmonary artery was investigated ex-vivo. Biomechanical analysis showed that high wall stress levels coincided with the sites where calcified lesions typically form in the pulmonary artery bifurcation.