Antibiotic-Associated Eosinophilic and Occlusive Arteritis in Calves Complicating Preclinical Studies of Left Ventricular Assist Devices

Abstract

Repeated bolus intravenous (IV) administration of large doses of beta-lactams and aminoglycosides has previously been associated with the development of eosinophilic and occlusive arterial lesions limited to the lungs in calves. Reviewing 13 years worth of records from left ventricular assist device implantation studies, morphologically identical segmental arterial lesions were present in 32 of the 56 calves receiving IV antibiotics, affecting lungs (6/50), kidneys (12/56), or lungs and kidneys (14/50). In 16 of these calves, renal arterial lesions spatially colocalized with renal cortical infarctions. Lesions were noted in additional abdominal organs in 4 of the 50 calves and were exclusively present in the liver in a single calf. Similar arterial lesions were also noted in the lungs (3/4), kidneys (1/4), liver (1/4), and spleen (1/4) of unimplanted calves receiving similar IV antibiotic regimens for bacterial infections. Lesions were observed with therapeutic IV doses of cephalosporins with or without aminoglycosides over shorter intervals than previously implicated. Lesions were significantly associated with increased peripheral eosinophil counts and mildly elevated, not reduced, arterial pulse pressures. This report documents the features of an idiosyncratic drug reaction with features strongly suggestive of an acute type-I hypersensitivity in this species.Keywords: antibiotics; arteritis; eosinophilic; occlusive; calves; LVAD.Because of their size, physiology, anatomy, cost, and tractable nature, calves are used for in vivo testing of cardiovascular support devices. In the development and preclinical in vivo testing of left ventricular assist devices (LVADs), the inflow cannula of the implanted pump is placed in the ventricular apex, and the outflow cannula is anastomosed to the descending thoracic aorta. As part of device development, the kidneys, because of their downstream location, high blood flow, and end-arterial circulation, are carefully evaluated for the presence of infarctions that could be caused by thromboembolic events related to the device. To prevent infection in chronically implanted animals, prophylactic antibiotics are administered starting prior to the first skin incision and extending for several days postoperatively. Often these animals are anticoagulated to limit device-related thrombosis, and therefore antibiotics are given intravenously (rather than intramuscularly) to avoid both intramuscular hemorrhage and artifactual elevations in serum enzymes due to skeletal muscle injury from injection.In 1979, Majeski and Fitts described the development of eosinophilic and occlusive pulmonary arterial lesions (EOA) in female Hereford calves receiving repeated bolus intravenous (IV) administration of supratherapeutic doses of antibiotics (Majeski and Fitts 1979). Antibiotics given were penicillin (one or two million units) and streptomycin (1 or 2 g) or sodium cephalothin (12 g), and these dosages were administered over a course of 20 to 76 days. More recently, Morton et al. described a...

Letter to the Editor regarding the article “Left ventricular assist devices: a kidney’s perspective”

“…We have recently published a large retrospective study describing lesions of the renal arcuate and radial arteries and pulmonary arteries in 56 calves, including those implanted with either pulsatile or non-pulsatile LVADs as well as unimplanted calves [6]. Lesions included both smooth muscle cell hyperplasia and inflammation.…”