Experiments were carried out to investigate rat aortic allograft calcification using valved abdominal aortic allografts. Results indicated that this was a potentially useful model for investigating fresh allograft calcification, as well as mineralization of glutaraldehyde-crosslinked valved allografts. Valve cusp results, however, were not comparable to those noted in large animal or human studies, while aortic wall calcification was more comparable. Calcification inhibitor investigations demonstrated that nearly complete inhibition of the calcification of the aortic wall of glutaraldehyde-crosslinked allografts was achieved using a number of individual inhibitors, including controlled release diphosphonates, and pretreatment with either ferric chloride or aluminum chloride. However, aminopropanehydroxydiphosphonate pretreatment was not efficacious, and sodium dodecyl sulfate pretreatment was only partially effective for inhibiting the aortic wall calcification in the glutaraldehyde-crosslinked allografts. It is concluded that valved aortic allografts in rats provide a useful model for investigating aortic wall (but not valve cusp) calcification and its inhibition.

Abstract. Objective: Bites from the brown recluse spider and other arachnids from the genus Loxosceles frequently induce necrotic skin lesions that can be recalcitrant to treatment and disfiguring. The authors used a rabbit model of dermonecrotic arachnidism to address the therapeutic efficacy of intradermal (id) polyclonal anti-Loxosceles Fab fragments (␣Loxd Fab) raised against Loxosceles deserta spider venom. Methods: Fab fragments were prepared by papain digestion and affinity chromatography from the IgG fraction of L. deserta antivenom raised in rabbits. Eighteen inbred New Zealand white rabbits were assigned to six groups of three. The rabbits received L. deserta venom (3 g, id) injections into each flank. Cohorts of rabbits received single id injections (at one venom site/rabbit) of 30 g ␣Loxd Fab at different times (T = 0, 1, 2, 4, 8, and 12 hours) after venom injection. In each rabbit the opposite flank was left untreated. As an additional control, one group of rabbits (T = 0) received nonspecific Fab (30 g, id) in the opposite flank. Dermal lesions were quantified as a function of time through the use of a series of digital photographs and imaging software. In addition, myeloperoxidase (MPO) activity, a measure of neutrophil accumulation, was determined in lesion biopsies. Lesion areas and MPO activities were analyzed by repeated-measures analysis of variance (ANOVA). Results: Lesion areas and MPO activity were markedly reduced when ␣Loxd Fab was administered very early after venom injections. As the interval between venom inoculation and antivenom treatment increased, the therapeutic benefit of ␣Loxd Fab decreased. The final time tested that demonstrated therapeutic efficacy of ␣Loxd Fab was T = 4 hours. Lesion attenuation was no longer apparent when ␣Loxd Fab was given 8 hours post inoculation. Conclusions: Intradermal administration of ␣Loxd Fab attenuates Loxosceles-induced dermonecrotic lesion formation when given up to 4 hours after venom inoculation in this rabbit model.

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