Spontaneous and Drug-induced Arteritis/Polyarteritis in the Göttingen Minipig—Review

Abstract

Arteritis/polyarteritis occurs spontaneously in many species used in preclinical toxicology studies. In Göttingen minipigs, arteritis/polyarteritis is an occasionally observed background change. In the minipig, this finding differs in frequency and nature from age-related polyarteritis nodosa in rats or monkeys, and Beagle pain syndrome in dogs. In minipigs, it can be present in a single small- or medium-sized artery of an organ or a few organs and is most commonly recorded in the cardiac and extracardiac blood vessels, vagina, oviduct, rectum, epididymis, spinal cord, pancreas, urinary bladder, kidneys, and stomach. The etiology is unknown although it has been considered in minipigs as well as in rats, dogs, and monkeys to be possibly immune mediated. This background change is important with respect to its nature and distribution in the minipig in order to distinguish it from drug-induced vascular changes, which might occur in similar locations and have similar morphologic features. This review summarizes the morphology, incidence, and predilection sites of arteritis as a spontaneously occurring background change and as a drug-induced vasculopathy in the minipig, and also describes the main aspects to consider when evaluating vascular changes in Göttingen minipig toxicity studies and their human relevance.

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of the Minipig

“…The prevalence of the finding ranges from 0.06% to 0.29%; it is most commonly recorded with descending frequency in the cardiac and extracardiac blood vessels, vagina, oviduct, rectum, epididymis, spinal cord, pancreas, urinary bladder, kidneys, and stomach. 9…”

“…In spontaneous cases, inflammatory cells infiltrate the media and/or all other layers of the artery, associated with necrosis and fibrin deposits of the vascular wall. 3,7,9,10…”

“…Treatment with the vasodilating antihypertensive drug, Minoxidil, caused endothelial injury, intramural accumulations of erythrocytes and platelets, periadventitial hemorrhage, fibrin deposits, and inflammatory cell reaction in epicardial small arteries. 9…”

“…Pigs treated with immunomodulating drugs, such as hydrocortisone or betamethasone, caused medial degeneration with fibrinoid necrosis in small/medium-sized arteries of intestines, peritoneum, spleen, pancreas, mesenteric plexus, liver, kidney, and adrenals. 9…”

Pathological Safety Assessment in Preclinical Neurothrombectomy Studies

“…A variety of vasculopathies such as arteritis and dissections have been recognized as spontaneous lesions in numerous preclinical safety studies performed in pigs (Dincer et al 2018; Rouselle et al 2016). In addition, vasospasm has been reported as a clinical concern associated with the use of thrombectomy devices (Kurre et al 2012), and it is also recognized as a frequent occurrence during preclinical endovascular intervention in the swine model (Gralla, Schroth, Remonda, Nedeltchev et al 2006).…”