Reduction in animal numbers by long-term implantation of intravenous and intra-arterial catheters in thyroparathyroidectomized rats.
The thyroparathyroidectomized (TPTx) rat has been extensively used to study parathyroid hormone (PTH)-mediated bone resorption by measuring systemic Ca2+ concentrations. Animals have been traditionally used acutely; that is, they are often infused immediately after surgery and are sacrificed after a single use. To perform multiple experiments using a single group of animals we developed a system of long-term implanted intravenous/arterial catheters. Using calcitonin (CT) as a positive control, we successfully completed 12 separate controlled subexperiments documenting significant reductions in PTH-induced hypercalcemia in rats of the CT group. We then successfully completed two separate TPTx subexperiments, using a 3 x 3 Latin square experimental design. In both subexperiments, CT significantly inhibited the increase of blood Ca2+ concentration resulting from continuous PTH infusion. Our results indicate that, by combining the long-term use of catheters with the Latin square design, we can successfully reduce the number of animals used, increase the number of compounds screened, and improve the quality of the data. Although results of this study confirmed the acceptability of multiple infusions in anti-resorptive studies, investigations into the applicability of this set up to other areas of study requiring infusions and frequent blood sample collections seem appropriate.
Lechowska
B A
BA
Department of Musculoskeletal Diseases, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA.
Bhattacharyya
A
A
Vasko-Moser
J
J
Stroup
G B
GB
D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D002116:Calcitonin / Q000008:administration & dosage; D002118:Calcium / Q000097:blood; D002404:Catheterization / Q000379:methods / Q000662:veterinary*; D002408:Catheters, Indwelling / Q000662:veterinary*; D003627:Data Interpretation, Statistical; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D007262:Infusions, Intravenous; D008297:Male; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000502:physiology*; D016105:Parathyroidectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018401:Sample Size; D013965:Thyroidectomy
D010281:Parathyroid Hormone; D002116:Calcitonin; D002118:Calcium