Is the Dog a Useful Model for Accelerated Calcification Study of Cardiovascular Bioprostheses?

Abstract

Chitosan posttreatment has been shown to be effective in prevention of calcification of the glutaraldehyde treated bovine pericardium when implanted subdermally in rats for 12 weeks. The efficacy of chitosan posttreatment in complete calcium mitigation of the glutaraldehyde treated porcine aortic valves implanted in the right side of the heart in dogs was well-documented in our previous study. In this study, an attempt has been made to evaluate the merit of the chitosan posttreatment in prevention of calcification of the glutaraldehyde (GA) treated porcine aortic valved conduits in the systemic circulation in dogs for a period of 5 months. Eleven mongrel dogs underwent left thoracotomy. Porcine aortic valved conduits treated with 0.625% GA (n = 5) and GA-chitosan (n = 6) were implanted in the descending thoracic aortas of the dogs for 5 months. Gross histological observations showed no calcification in either the 0.625% GA treated or in the GA-chitosan treated valved conduits at 5 months. This was confirmed by results of quantitative analyses for calcium in each explant. There was no significant difference in calcium content between the GA only (Ca, 0.43 * 0.26 mg/g) and GA-chitosan treated (Ca, 0.51 f 0.19 mg/g; p = 0.5959) valved conduits. This study suggests that the dog is not a suitable model for evaluating the efficacy of a calcium mitigating agent in bioprostheses implanted in systemic circulation. Key Words: Aortic surgery-Bioprosthetic valved conduit-Glutaraldehyde-ChitosanApicoaortic shunt.The quality of life after mechanical heart valve replacement is not ideal, mainly because of the necessity of lifelong anticoagulation and the ever present risk of thromboembolism (1). Valve repair instead of valve replacement is thus increasingly attempted, but the procedure is not always feasible (2,3), and the hemodynamic results can be unsatisfactory (4). The alternative to mechanical valve replacement is the use of biological prostheses: there is no need for lifelong anticoagulation even in the presence of chronic atrial fibrillation, and the risk of systemic thromboembolism is very low. Furthermore, the quality of life can be considered very close to normal, allowing heavy work, sports, normal pregnancy and delivery, and life in remote areas (5,6). The primary concern with bioprostheses, welldocumented over the previous years, is skepticism regarding the durability and the potential morbidity

Concomitant Dual Intravascular and Subcutaneous Microsurgical Implantation of Xenograft Tissue in a Rodent Model for Evaluation of Structural Degeneration

“…Large-animal models, including sheep, pig, dogs, baboons, and calves, have previously been used for studying structural degeneration of xenograft tissue. [22][23][24][25][26][27][28][29] We created a single animal model that incorporated the subcutaneous and intravascular implantation methods concomitantly, to allow comparison of lipid deposition, calcification, and immunologic rejection of biological xenograft tissue between these two implantation methods.…”

“…,37 Chanda and coauthors24 suggested that dogs are not a suitable model for evaluating the efficacy of xenograft tissue implanted in systemic circulation. Ozaki et al 33 suggested differing results in the rat subcutaneous model and sheep blood contact model.…”

“…Implantation of the bioprosthetic leaflet tissue as a valve substitute in large animals (sheep, pigs, or dogs) with cardiopulmonary bypass is expensive and requires specially trained personnel and a well-equipped laboratory [22][23][24][25][26][27][28][29] but may offer the optimal in vivo physiological conditions for the study of structural degenerative changes. On the other hand, small animals afford the ability to study pathophysiological processes in a cost-effective manner have been used widely in research.…”