J. Vet. Med. A 46, 389–407 (1999) © 1999 Blackwell Wissenschafts-Verlag, Berlin ISSN 0931–184X Clinical Department, Royal Veterinary and Agricultural University, Copenhagen, Denmark Induced Hypocalcaemia by Na 2 EDTA Infusion. A Review R. J. JO šRGENSEN 1,3 , N. R. NYENGAARD 1 , R. C. W. DANIEL 2 , L. S. B. MELLAU 1 and J. M. D. ENEMARK 1 Addresses of authors: 1 Cattle Production Medicine Research Group, Clinical Department, Royal Veterinary and Agricultural University, DK 1870 Frederiksberg C, Denmark; 2 Division of Farm Animal Studies, School of Veterinary Science, University of Queensland, St Lucia, Queensland, Australia; 3 Corresponding author With 7 figures and 3 tables (Received for publication December 21, 1998) Summary Disodium ethylenediaminetetraacetate (Na 2 EDTA) has been used in infusion studies in cows and other species for more than 35 years, primarily for the induction of hypocalcemia as a model for milk fever. This paper reviews such studies and discusses blood calcium kinetics, toxicology, changes in various blood parameters and the effect on blood circulation, cardiac function and smooth muscle motility in the gastro-intestinal tract and in the pregnant uterus. It is concluded that Na 2 EDTA infusion may serve as a valid model for spontaneous hypocalcemia. However, experimental results may vary with factors such as the choice of method for blood total calcium analysis, and the rate of EDTA infusion. Standardization of these and certain other experimental conditions may greatly improve the comparability of results obtained in EDTA infusion studies. For cows, an infusion rate of 1.2 ml/kg/h of a 5 % (w/v) solution, corresponding to 0.25 mmol/kg/min, has been suggested as a standard infusion. Introduction Most dairy cows undergo transient hypocalcaemia around calving. Hypocalcaemia occurs as a result of an imbalance between, on the one hand, the sudden draw upon calcium from the vascular pool to the colostrum and, on the other hand, the inflow of calcium mobilized from the skeleton and calcium absorbed across the gut wall. To produce 10 l of colostrum requires 23 g of calcium, which is about 10-fold the amount circulating in the plasma (Radostitis et al., 1994). However, during mid-lactation, calcium requirements are even greater. Thus, the duration and severity of periparturient hypocalcaemia are not caused by the fast calcium turnover itself, but rather depend on the ability of the cow to accelerate its calcium mobilization rate around calving. With decreasing plasma calcium, the cow will finally enter the clinical stage, milk fever. This occurs at a frequency of 4–10 %, and in some herds even up to 50 %, of the calving cows (Oetzel, 1988). In order to create an experimental model which mimics milk fever, intravenous infusion with Na 2 EDTA has been used since 1963 (Smith and Brown, 1963). Such infusions result in the complex binding or chelation of ionized calcium, resulting in a stage of hypo- calcaemia. Although other calcium chelators such as EGTA [ethyleneglycol-bis (beta-aminoethyl ether)-N,N,N?,N?-tetraacetic acid] (Kigoshi et al., 1997) and calcium binders such as sodium citrate (Deetz et al., 1981, 1982; Naylor and Forsyth, 1986) and oxalate (Hallgren et al., 1959) have been used, none of these has been applied to the same extent as has Na 2 EDTA to bind plasma calcium in infusion experiments. This review discusses the results obtained by such U.S. Copyright Clearance Center Code Statement: 0931-184X/99/4607-0389 $14.00/0