oxytocin and aglepristone

The aim of this in vitro study was to compare the uterokinetic activity of oxytocin and dinoprost, the natural PGF2α, with or without aglepristone, in canine myometrial fibers. Thirty-three bitches were allocated into one of four groups, depending on their estrous stage and whether or not they had received a treatment with aglepristone (metestrus aglepristone, n = 5; metestrus without treatment, n = 9; anestrus aglepristone, n = 9; anestrus without treatment, n = 10). After hysterectomy, longitudinal and circular uterine strips were mounted in organ baths. Oxytocin or PGF2α (10 nmol/l to 10 micromol/l) were applied non-cumulatively. A linear mixed effects models theory was used to compare the fiber effect, the aglepristone effect, and the treatment effect, from the area under the curves calculated from the contractile effect/concentration curves for each drug. Oxytocin and PGF2α induced concentration-dependent myometrial contractions in longitudinal (LF) and circular myometrial fibers (CF), indicating the presence of functional contractile oxytocin- and PGF2α-receptors in metestrus and anestrus. The contractile response to oxytocin was greater in LF than in CF in all of the groups; the response to PGF2α was greater in LF than in CF in non-treated bitches in anestrus and in treated bitches in metestrus. These results suggest that there is a difference in sensitivity or a heterogeneous distribution of oxytocin and PGF2α-receptors in the myometrial layers, which is independent of hormonal impregnation. The contractile response to oxytocin and PGF2α was significantly increased after aglepristone treatment in LF during metestrus, suggesting that the progesterone withdrawal induced by aglepristone has a role to play. The longitudinal myometrial layer also appeared to be the target for the two drugs at this stage. This study provides new information about canine uterine contractile activity, notably the differing behavior of myometrial CF and LF; in vivo studies are required to test the use of a combination of aglepristone and oxytocin in the treatment of canine pyometra.

Topics: Animals; Dinoprost; Dogs; Estrenes; Estrus; Female; In Vitro Techniques; Myometrium; Oxytocics; Oxytocin; Progesterone; Uterine Contraction

To evaluate the efficacy and safety of aglepristone 15 mg kg(-1) for induction of parturition in bitches, 22 pregnant beagle bitches were injected subcutaneously on day 60 post-estimated LH surge, and again 24 h later with aglepristone and subsequently were given 0.15 IU kg(-1) oxytocin at hourly intervals until delivery of the last puppy. Six pregnant beagle bitches were used as a non-treated control group. In the control group, parturition occurred at 63.2 +/- 0.5 days, 29 pups were born and the average expulsion time per puppy was 1.0 +/- 0.6 h. In the treated group, parturition was obtained on average 29.7 +/- 5.6 h after aglepristone administration, 121 pups were born and average expulsion time per pup was 1.1 +/- 0.4 h. The percentage of live puppies, 7 weeks after birth, was 86.1% (25/29) and 86.8% (105/121) for the control and treated groups, respectively. No significant difference was observed between the control and treated groups for the average expulsion time per live puppy and for the percentage of live puppies at birth, 48 h, 7 days or 7 weeks after birth (p > 0.05). This study confirms previous results and demonstrates that the combination of aglépristone and oxytocin can be safely and reliably used to induce parturition in beagle bitches, at 60 days post-estimated LH surge.

Topics: Animals; Dogs; Estrenes; Female; Labor, Induced; Oxytocics; Oxytocin; Pregnancy

Induction of parturition in guinea pigs appears to be essential because these animals have a higher rate of reproductive problems than rabbits and small rodents.. Since aglepristone (AGL) is a competitive progesterone antagonist acting through binding to progesterone receptors while oxytocin (OT) is a powerful constituent of uterine smooth muscle, the aim of this study was to evaluate the clinical and ultrasonographic impacts of AGL and OT on guinea pig parturition induction.. In this study, guinea pigs were allocated into five groups; each included five animals on the 61st day of pregnancy. In the aglepristone group (Agle), AGL was administrated subcutaneously (SC) once daily on 2 consecutive days (Days 61 and 62 post mating). Oxytocin (OT) was administered subcutaneously once and twice at 4-h intervals on Day 62 post mating in oxytocin 1 (Oxy1) and oxytocin 2 (Oxy2) groups, respectively. The animals in the aglepristone-oxytocin group (Agle-Oxy) received AGL subcutaneously once daily on 2 consecutive days (Days 61 and 62 post mating) and OT on Day 62 post mating. The remaining sows received saline solution (0.9% NaCl) in the control group.. According to the results, fetal heart rate, temperature, neonatal and maternal survival rates were not significantly different between the treatment and control groups (p > 0.05). Biparietal diameter of head and body weight of neonates in the Agle, Oxy2 and Agle-Oxy groups showed a significant decline, compared to the control group (p < 0.05). The time interval between injection and delivery and the duration of pregnancy was significantly reduced in Agle, Oxy2, Agl-Oxy groups, compared to the control and Oxy1 groups.. In conclusion, it seems that treatment Oxy2 can induce parturition in guinea pigs without side effects and lower pain during induction of parturition.

Topics: Animals; Estrenes; Female; Guinea Pigs; Oxytocin; Parturition; Pregnancy; Rabbits; Swine; Uterus

In order to evaluate the efficacy, the safety and the variation in plasma concentrations of estrogens, progesterone, PGFM, oxytocin, cortisol and prolactin after mid-pregnancy termination induced by aglepristone, 61 pregnant queens (33.3 + 4.2 days), were injected subcutaneously with 15 [corrected] mg/kg aglepristone, (Alizine) [corrected] repeated once 24 h later. Five queens served as control and received a placebo. The efficacy of aglepristone was 88.5% and termination of pregnancy was achieved in 50% of the queens within 3 days. Brief periods of depression and anorexia were noted in 9.3% of the queens before fetal expulsion (these symptoms were attributed to the phenomenon of fetal expulsions). Not one of the queens that aborted developed uterine disease. There were no changes in plasma concentrations of estrogen, prostaglandin, prolactin or oxytocin following aglepristone administration. However, there were significant increases in plasma concentrations of progesterone and cortisol 60 and 30 h, respectively, after aglepristone administration. Termination of pregnancy occurred with high plasma progesterone concentrations. Fetal expulsion was characterised by an increase in estrogen, PGFM and oxytocin concentrations, whereas prolactin and cortisol levels remained at a basal level.

Topics: Abortifacient Agents, Steroidal; Abortion, Induced; Abortion, Veterinary; Animals; Cats; Dinoprost; Estrenes; Estrogens; Female; Male; Oxytocin; Pregnancy; Progesterone

Parturition was induced in ten Beagle bitches by injecting them subcutaneously with 15 mg aglepristone kg-1 (Alizine) at day 58 of gestation and 24 h later and subsequently at 2 h intervals with either 0.08 mg alfaprostol kg-1 (Alfabedyl) (group 1; five bitches) or 0.15 iu oxytocin kg-1 (Ocytocine S) (group 2; five bitches). Blood samples were collected every 4 h until the end of parturition to assay plasma concentrations of progesterone, dihydro-keto prostaglandin F2 alpha (PGFM), oxytocin, prolactin and cortisol. Parturition occurred in all bitches. The mean time of onset of parturition for both groups was not significantly different (32.6 +/- 3.7 h for group 1 versus 31.6 +/- 3.6 h for group 2), although the mean expulsion time for bitches from group 2 (4.5 +/- 1.8 h) was significantly shorter than that of bitches in group 1 (9.1 +/- 2.0 h). At birth, 93% of the pups were alive in group 2 compared with 86% in group 1. Peripheral plasma concentrations of progesterone increased significantly after the administration of aglepristone, but direct or indirect luteolysis was not induced, and plasma concentrations of oxytocin or cortisol did not change during the first 24 h after administration of aglepristone. PGFM concentrations increased significantly after 4 h of aglepristone administration. During the first 20 h after aglepristone administration, prolactin concentrations increased significantly. At parturition, bitches in group 2, which had the shorter expulsion time of pups, were characterized by significantly higher concentrations of oxytocin and PGFM than bitches in group 1.

Topics: Animals; Dinoprost; Dogs; Drug Administration Schedule; Estrenes; Female; Hormone Antagonists; Hydrocortisone; Labor, Induced; Oxytocin; Pregnancy; Progesterone; Prolactin; Prostaglandins F; Random Allocation

Seven bitches in early pregnancy (12.8 +/- 3.8 days after ovulation; group 1) and seven bitches in mid-pregnancy (32.0 +/- 1.53 days after ovulation; group 2) were used in this study. For each group, five bitches were treated with 0.10 mg aglepristone (Alizine) kg-1 and this dose was repeated 24 h later. Two control bitches received a placebo. Blood samples were collected at 6 h intervals to determine plasma concentrations of progesterone, dihydro-keto prostaglandin F2 alpha (PGFM), oxytocin, prolactin and cortisol. Parturition occurred in the four control bitches. All bitches treated with aglepristone aborted. In group 1, embryonic death occurred; in group 2, fetal expulsion occurred 60-132 h after administration of aglepristone. After pregnancy termination, the interoestrous interval of aglepristone-treated bitches was significantly shorter than that before treatment. Treatment with aglepristone did not modify plasma concentrations of progesterone, prostaglandin, oxytocin or cortisol within 24 h after its administration, but it induced, in mid-pregnancy (group 2) a discharge of prolactin within 12 h after its administration. As an abortifacient, aglepristone acted on the uterus and, therefore, did not have direct or immediate luteolytic properties. Termination of pregnancy occurred with high plasma progesterone concentrations. Fetal expulsion was characterized by an increase in the concentration of PGFM, but oxytocin and cortisol remained at basal concentrations.

Topics: Abortifacient Agents; Abortion, Induced; Abortion, Veterinary; Animals; Dinoprost; Dogs; Estrenes; Female; Gestational Age; Hormones; Hydrocortisone; Oxytocin; Pregnancy; Progesterone; Prolactin; Random Allocation