Comparing the efficacy of serotonin and ethylene glycol tetraacetate on postpartum hypocalcemia

ABSTRACT: Inducing a transient state of hypocalcemia prepartum mobilizes stored Ca before the abrupt demand for Ca at parturition thus more tightly regulating postpartum hypocalcemia. Prepartum transient hypocalcemia can be achieved through intravenous infusions of either the precursor to serotonin, 5-hydroxy-tryptophan (5HTP) or a Ca chelating agent, ethylene glycol tetraacetic acid (EGTA). This study aimed to compare the ability of 5HTP and EGTA treatments to prevent postpartum hypocalcemia. We hypothesized that the 2 methods would be similarly effective compared with the control. Cows received either 5HTP, EGTA, 5HTP+EGTA, or control saline (n = 6/treatment) beginning 7 d before expected calving date through parturition (range 4–13 d). The 5HTP treatment was administered daily as a single 1-L dose at 1 mg/kg of BW. Saline and EGTA were infused for 6 h/d. Infusion rates of EGTA were adjusted to maintain blood ionized Ca (iCa) between 0.7 and 0.8 mM, inducing subclinical hypocalcemia, which occurs when iCa is 0.61–0.9 mM. Mammary biopsies were collected from rear quarters at 6, 30, 54, and 78 h postpartum. Cows in the 5HTP+EGTA group required less EGTA to maintain low iCa during infusions and had the lowest total Ca concentrations during infusions. Therefore, 5HTP and EGTA likely use different mechanisms to reduce blood Ca, which can occur simultaneously, resulting in an additive effect in blood Ca reduction. Control cows were subclinically hypocalcemic through 48 h postpartum, and 2 became clinically hypocalcemic. All other treatments were normocalcemic through 96 h postpartum and had significantly greater iCa than the control from 12 to 24 h postpartum. Administering 5HTP increased blood serotonin concentrations from the start of infusions through 72 h postpartum. Cows receiving EGTA or 5HTP+EGTA had decreased mammary Ca compared with the control at 54 and 78 h after calving. Mammary tissue quantitative PCR and Western blot analysis revealed increased gene and protein expression of Ca release-activated Ca modulator 1 on the day of parturition compared with 30 and 78 h postpartum. Mammary gland gene expression of the calcium-sensing receptor was decreased 78 h postpartum compared with 6 and 30 h postpartum. Although 5HTP and EGTA both prevented postpartum hypocalcemia, EGTA significantly increased iCa through 48 h post-calving rather than the 24 h in the 5HTP group. The 5HTP+EGTA and EGTA treatments were equally effective at regulating periparturient calcemic status, indicating that the additive effect of 5HTP and EGTA did not persist beyond parturition.