Pregnancy impairs ketone body disposal in late gestating ewes: implications for onset of pregnancy toxaemia.

The impact of pregnancy on ketone body disposal during a hyperketonaemic clamp was examined by tracer isotope dilution techniques in seven 12 h fasted sheep in three reproductive states, in the dry non-gestating period, late in gestation and during early lactation. After a sampling period of 60 min under basal conditions a DL-BHB racemate solution was continuously infused intravenously for 3 h at rates of 14.3-24.3 micromol/(kg min) to elevate the D-BHB concentration in blood plasma to values between 5 and 7 mmol/l. Two separate experiments were carried out with the same sheep in each of the three reproductive states. During pregnancy three ewes were pregnant with a single lamb and four ewes carried twins. Maximal D-BHB turnover rates fell significantly in late gestation by 26% relative to early lactation and by 22% when compared with the dry non-pregnant state. Reduction of maximal D-BHB disposal rate during late gestation was accompanied by a significant 297% (p<0.005) and a non-significant 49% increase in the basal BHB concentration in blood, a non-significant 10% and 4% decrease in the rate constant of D-BHB turnover and a non-significant 24% and 13% rise in the incremented increase of D-BHB concentration per unit D-BHB infusion, relative to the dry and the lactating period, respectively. Induction of hyperketonaemia significantly lowered NEFA and glycerol concentrations in blood by 67% and 57%, respectively, compared to the pre-infusional concentrations. The magnitude of this effect was the same in all reproductive states and was explained as a direct antilipolytic action of D-BHB on adipose tissue. It is concluded that the reduced ability of the late gestating ewe to utilize D-BHB promotes hyperketonaemia. Since hyperketonaemia exerts several adverse effects, e.g. on energy balance and glucose metabolism it appears that the impairment of ketone bodies disposal in late pregnancy facilitates development of pregnancy toxaemia, especially in ewes carrying twins.