Elsevier

Theriogenology

Volume 65, Issue 2, 20 January 2006, Pages 400-414
Theriogenology

The effect of a single oxytocin or carbetocin treatment on uterine contractility in early postpartum dairy cows

https://doi.org/10.1016/j.theriogenology.2005.05.040Get rights and content

Abstract

The uterotonic characteristics and effectiveness of a single treatment with either oxytocin or carbetocin were quantified in early postpartum dairy cows after normal, uncomplicated calvings. Both the short-term (within 4 h), and the long-term effects (between 12 and 36 h) of the two treatments were compared.

Between 14 and 16 h after parturition, 27 multiparous Holstein-Friesian dairy cows, without fetal membrane retention, were selected and divided into three groups. The first group (n = 9) was administered 50 IU oxytocin intramuscularly, the second group (n = 10) received 0.35 mg carbetocin, while animals of the third group (n = 8), serving as a control, were administered 5 mL saline solution. A transcervically introduced open tip catheter system was used for the non-invasive acquisition of the intrauterine pressure (IUP) recording. After digitalization, the signals were analyzed, using a specially adapted graphical software program.

A significant short-term effect was found both in the oxytocin and carbetocin treated groups from the analysis of the contraction frequencies (FREQ) and of the total area under the curve (TAUC). After significant peaking during the first post-treatment hour, the values of the parameters for these two groups remained higher during the second hour, returning to the initial levels again during the third hour and reaching the level of the control group by the 12th hour. Mean amplitude (AMP), duration (DUR) and area under the curve (AUC) of pressure cycles were not significantly affected by any of the treatments. Although mean FREQ and TAUC significantly declined from the initial values to 12, 24 and 36 h in all groups, mean AMP and AUC in the oxytocin and carbetocin treated groups, and mean DUR only in the carbetocin treated group to 12 and 36 h, the long-term analysis revealed no significant treatment differences for any IUP parameters.

Because treatment with either oxytocin, or carbetocin elicited similar uterotonic effects in healthy, early postpartum cows, it cannot be expected, that using carbetocin in preference to oxytocin, will result in a more beneficial clinical effect on uterine involution during this period.

Introduction

During the bovine puerperal stage, involution of the uterus has an important role in a cow to becoming pregnant again. During involution, beside the morphological changes of the endometrium, the size of the uterus also markedly decreases. The greatest size reduction in normal cows occurs during the first few days after parturition [1]. Regression processes accelerate between days 10 and 14, resulting in that by day 25, uterine diameter almost reaches its final size [2]. This can be judged from the size measured after involution is completed. However, the time of complete involution can vary within wide ranges; 25–50 days after parturition in cows [1], [2], [3].

Uterine muscle activity is important in the process of involution. A contractile uterus is advantageous in removing excessive fluid and debris from the uterine lumen early postpartum. Our previous observations on cows without fetal membrane retention showed us, that while there was a high variability among individual animals, uterine contractions generally diminished rapidly, with a major decline between 12 and 24 h after calving, and with very little spontaneous contractility left at 48 h [4].

Treatment protocols, in which uterotonic drugs are administered during the puerperal phase in cows to evacuate the uterus by increasing its contractility, aim to accelerate the process of involution. Natural prostaglandin F, or its synthetic analogues [5], [6], [7], [8], [9] and oxytocin (OT) [5], [10], [11], [12], are frequently used for this purpose. However, the efficiency of prostaglandin treatments in evacuating the puerperal uterus, by promoting its contractility, is questionable. Because both an induced [13] and a failing uterotonic effect [5], [9], [14], [15] have been reported for such treatments, and because OT did not show such contradictory results, the use of OT-like drugs seems to be preferred during the puerperal phase. However, only a few studies [5], [10], [11], [12] have quantified the uterotonic effects of OT if administered shortly (within 12 h) after calving [10], [11]. It can therefore be anticipated that this effect would be short lasting, as the half-life of OT has been reported to be short in cows (mean rapid T1/2 = 3.87 ± 0.1 min; and mean slow T1/2 = 25.53 ± 1 min) [16].

The biological effect of OT and its analogues depends on two factors: on how quickly it is removed from the circulation by excretion and through metabolism, and on whether there are enough specific receptors available, which are capable of binding the drug. Numerous attempts have been made to achieve a longer uterotonic effect by using oxytocin. A continuous, slow-rate intravenous drip infusion, as is often used in humans, is difficult to perform with cows under farm conditions. The increased plasma oestrogen levels in the cow around calving could enhance the effect of oxytocin in a very early postpartum uterus, possibly by stimulating the synthesis of endometrial OT-receptors, but not affecting or even prohibiting that of myometrial OT-receptors, as it was shown in mid-pregnant, parturient and non-pregnant cows [17], [18]. Because the effects of oestrogens with respect to expression of oestrogen receptors in the uterine wall are still unclear, and because of their human food safety implications, the possibility as to enhance uterotonic activity by external oestrogen treatment, should be rejected.

An alternative way to produce a prolonged uterotonic effect is to use OT-analogues with a longer biological activity, such as carbetocin (CB) [6], [8], which appeared to have a prolonged uterotonic activity in swine [19] and cows [20]. The short plasma half-life of the native OT molecule can be partly explained by its chemical structure. The circulating hormone is sensitive to the effects of aminopeptidase and disulfidase enzymes; the aminopeptidase can cleave the Csingle bondN bond at position 1–2 of the molecule, while the disulfidase affects the S–S bridge at position 1–6 [21]. It has been shown that desamination of the N-terminus and replacement of the sulphur bridge with a CH2S group [21], protects the structure of the molecule and results in a prolonged oxytocin effect in rats [22], [23], [24]. The OT-analogue carbetocin (CB; 1-deamino-1-monocarba-[2-O-methyltyrosine]-OT) also produced uterotonic activity in rats [25], in sows during oestrus [19], [26] and in parturient cows [27], although its uterotonic activity, measured in vivo or in vitro, was 10 [27], more than 25 [25] or even 30 [28] times weaker than that of OT. The prolonged uterotonic effect of CB is associated with a biphasic half-life [26]. Side-effects, such as uterine tetany or tachyprophylaxis, did not occur in vivo or in vitro after CB treatment in swine [19], but did more often occur with the use of higher dose rates of OT in cows [27].

The aim of the present study was to evaluate to what extent a single treatment with either OT or CB, 14–16 h after normal parturition, influences uterine contractility on days 1 and 2 postpartum in dairy cows. Therefore, this field study addressed the following questions:

  • 1.

    What is the short-term intrauterine pressure response to a single treatment with OT or CB, when injected intramuscularly between 14 and 16 h postpartum?

  • 2.

    Do the long-term (12–36 h post-treatment) characteristics of uterine contractility, induced by OT or CB given between 14 and 16 h postpartum, differ from that recorded in untreated control animals?

  • 3.

    Are there any differences between the OT and CB induced contractility characteristics in terms of their short-term and long-term effects?

Section snippets

Cows and treatment

Twenty seven Holstein–Friesian dairy cows, kept at a large-scale dairy cattle farm in Hungary, were used in this study during the autumn of 2001. All the cows had shed their fetal membranes within 12 h of normal calving. If necessary, light assistance only, the aid of one or two persons, was provided during calving. Cows with lacerations or ruptures of the soft birth canal were excluded from the study. For 2–3 weeks preceding the expected calving, the cows were housed in a calving barn with two

Results

Fig. 2a and b present typical examples of 90-min recordings around the single intramuscular treatment at 14–16 h postpartum, with either 50 IU OT or 0.35 mg CB, showing their effect on IUP changes.

Table 1 summarizes the mean values (±S.E.M.) of the IUP parameters for each 1-h IUP recording, in each experimental group—for the statistical analysis of both the short- and the long-term effects.

Fig. 3a–d illustrate the changes in the FREQ, AMP, AUC and TAUC values for the two treated groups and the

Discussion

The uterotonic effects caused by the administration of a single intramuscular treatment of either oxytocin (50 IU), or its long-acting analogue, carbetocin (0.35 mg), were compared in this field study on early postpartum dairy cows, after normal parturition. It turned out that both drugs significantly increased the FREQ and TAUC values of the pressure cycles, mainly during the first post-treatment hour. The uterotonic effects of the two drugs were almost equal, and a prolonged uterotonic effect

Acknowledgements

This study was carried out within the framework of the International PhD Programme of Utrecht University, The Netherlands, and was partly supported by the Hungarian Scientific Research Fund, Grant No. OTKA T 043505, the Hungarian State Eötvös Scholarship and the Bolyai János Research Scholarship of the Hungarian Academy of Science.

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