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Effects of exogenous oxytocin on uterine blood flow in puerperal dairy cows: The impact of days after parturition and retained fetal membranes
... A dosage of 50 international units (I.E.; 1 I.E. = 1.68 μg) oxytocin per 700 kg cow is known to have a profound effect on the uterus in vivo (Magata et al., 2013) and corresponds to an oxytocin concentration of approximately 1.2•10 -4 mg/kg tissue or 1.2•10 -10 mol/L, which was the lowest concentration of oxytocin used in the present study. An analogous calculation applies to PGF (clinically effective dose: 25 mg/cow [ (Richter and Ungemach, 2014)]) with tissue concentrations of 0.036 mg/kg or 1.007•10 -7 mol/L. ...
... ata using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25, 402-408.Lye, S.J., Nicholson, B.J., Mascarenhas, M., Mackenzie, L., Petrocelli, T., 1993. Increased expression of connexin-43 in the rat myometrium during labor is associated with an increase in the plasma estrogen:progesterone ratio. Endocrinology 132, 2380-2386.Magata, F., Hartmann, D., Ishii, M., Miura, R., Takahashi, H., Matsui, M., Kida, K., Miyamoto, A., Bollwein, H., 2013. Effects of exogenous oxytocin on uterine blood flow in puerperal dairy cows: the impact of days after parturition and retained fetal membranes.Vet. J. 196, 76-80. Marshall, J.M., 1984. Comparison of circular and longitudinal activity in the pregnant myometrium, in: Marshall, J.M. (Ed.), Uterine Contractility, Masson, New York, pp. 127- ...
... Animals with RFM did not react to the oxytocin challenge, indicating that their uteri are not able to respond to oxytocin at this time in these cows. [99]. ...
T HE Color Doppler ultrasonography is widely utilized in equines, dairy cattle, and small ruminants as a safe, non-invasive means of monitoring reproductive performance. Non-intrusive color Doppler ultrasonography was utilized to evaluate high-risk pregnancies and the health of the fetus. The alterations that take place in farm animals after giving birth are thought to be crucial in predicting future fertility. B mode ultrasonography has been applied in several studies on postpartum buffaloes. Color Doppler ultrasonography is a non-invasive technique that can be used before, during, and after delivery. Using the uterine and umbilical arteries, it is possible to evaluate the perfusion of the uteroplacental and fetoplacental blood flow in buffaloes. The motion of the transmitter and receiver affects the frequency of an ultrasonic pulse, which is a phenomenon called the Doppler Effect, and was initially described by Christian Doppler. Nowadays, the use of color Doppler ultrasonography has followed the same pattern as that of cows and other animals. Doppler ultrasound application's basis is likened to cows. The blood supply to the uterus is remarkably similar. Recent research have described the features of vaginal blood circulation in buffaloes throughout gestation and the early puerperium in addition to the uterine blood flow. The impact of vaginal blood circulation on buffalo fertility needs to be studied in the future. We highlight the different benefits of non-invasive color Doppler ultrasound applications in the buffalo's reproduction.
... Animals with RFM did not react to the oxytocin challenge, indicating that their uteri are not able to respond to oxytocin at this time in these cows. [99]. ...
The aim of the current study was to determine the changes in uterine blood flow as well as uterine biometry during the first 5 weeks after parturition in Egyptian buffaloes. The number of the experimental buffaloes used in the present thesis was 35.
In the first group (n=5) of the experiment, transrectal noninvasive color Doppler ultrasound was measured at different time points [-5, -4, -3, -2, -1, 0 (day of parturition), 1, 2, 3, 4, 5]. BFV, PSV, TAMV, PI, RI, S/D as well as diameter of uterine and vaginal arteries were the Doppler indices for the determination of uterine and vaginal blood flow changes. BFV of uterine artery was significantly higher in the days -5, -4, -3 and -2 (P<0.0001). The maximum increase was in the last day of pregnancy.
A steep decrease after parturition from day 1 to 5 (P<0.0001). RI and PI of the uterine artery of the gravid uterine horns increased steadily from day of parturition until day 5 postpartum in the Egyptian buffaloes (P<0.001).
RI and PI of vaginal artery values decrease during the last 5 days of gestation and then increase after the day of parturition. The lowest values were on the 3rd day after parturition (P<0.05). Also we used the changes of the plasma steroids in uterine and vaginal blood flow dynamics as reference values for normal puerperium in the Egyptian buffaloes.
In the second group (n=30) of the experiment, transrectal color Doppler indices was measured at different time points [-7, 0 (day of parturition), 7, 14, 21, 28, 35] after postpartum periods. BFV, PSV, TAMV, PI, RI, S/D as well as the diameter of uterine arteries were the Doppler indices for determination of uterine artery blood flow changes during different time points after parturition. BFV of uterine arteries decreased linearly during the postpartum period in Egyptian buffaloes. The BFV decreased from 3029.21 ml/min (-7 day) to 343.84 ml/min
(35 day pp) and moderately (P < 0.01) to 731 ml/min on (day 28).
The TAMV and PSV showed fluctuation in changes during different time points postpartum (P < 0.05). But PI, RI, and S/D showed significant increases during the different time points postpartum (P < 0.01). The mean diameter of the uterine horn decreased significantly from day 0 to day 35 after parturition (P < 0.0001). The uterine involution was completed on day 28, as demonstrated by transrectal palpation and B-mode sonography. The mean diameter of the dominant follicle at day 7 postpartum in Egyptian buffaloes was 5.4 ± 0.4 mm and by days 28 and 35 we investigated a significant change in the dominant follicle diameter, which was 12.9 ± 0.6 and 14.06 ± 0.56 mm respectively. Altogether, the results show that transrectal color Doppler ultrasound is a successful tool for examining uterine changes during the first 5 weeks after parturition in Egyptian buffaloes. The robust changes in uterine blood flow were demonstrated during the first week of the puerperium, The PI, RI, and S/D were also suitable to investigate alterations in uterine perfusion during the next 5 weeks after parturition.
... The blood flow volume was decreased by about 84 % during the first week of parturition. A linear decrease in uterine blood flow was reported in previous studies ( Magata et al., 2013;Abdelnaby, 2020). ...
... It is also reported that OXT in 10 − 11 -10 − 7 M levels causes relatively weaker contraction of the basilar artery compared to vasopressin and has no effects on mesenteric arteries in rats [149]. Intramuscular injection of OXT decreases uterine blood flow during uterine contractions in puerperal dairy cows [150], which occurs at postpartum day 2 but not day 5. Lastly, patterns of OXT actions are also important for its effect. For example, pulsatile but not tonic secretion of OXT plays the role of anti-precancerous lesions of the mammary glands in rat dams [151]; social desirability and milk transferred from the mother to the baby are largely dependent on OXT pulsatility [152]. ...
SARS-CoV-2 infection or COVID-19 has become a worldwide pandemic; however, effective treatment for COVID-19 remains to be established. Along with acute respiratory distress syndrome (ARDS), new and old cardiovascular injuries are important causes of significant morbidity and mortality in COVID-19. Exploring new approaches managing cardiovascular complications is essential in controlling the disease progression and preventing long-term complications. Oxytocin (OXT), an immune-regulating neuropeptide, has recently emerged as a strong candidate for treatment and prevention of COVID-19 pandemic. OXT carries special functions in immunologic defense, homeostasis and surveillance. It suppresses neutrophil infiltration and inflammatory cytokine release, activates T-lymphocytes, and antagonizes negative effects of angiotensin II and other key pathological events of COVID-19. Additionally, OXT can promote γ-interferon expression, which inhibits cathepsin L and raises superoxide dismutase expression, to reduce heparin and heparan sulphate fragmentation. Through these mechanisms, OXT can block viral invasion, suppress cytokine storm, reverse lymphocytopenia, and prevent progression to ARDS and multiple organ failures. Importantly, besides prevention of metabolic disorders associated with atherosclerosis and diabetes mellitus, OXT can protect the heart and vasculature through suppressing hypertension, brain-heart syndrome, and social stress, and promoting regeneration of injured cardiomyocytes. Unlike other therapeutic agents, exogenous OXT can be used safely without the side-effects seen in remdesivir and corticosteroid. Importantly, OXT can be mobilized endogenously to prevent pathogenesis of COVID-19. This article summarizes our current understandings of cardiovascular pathogenesis caused by COVID-19, explores the protective potentials of OXT against COVID-19-associated cardiovascular diseases, and discusses challenges in applying OXT in treatment and prevention of COVID-19.
Chemical compounds
Angiotensin-converting enzyme 2 (ACE2); atrial natriuretic peptide (ANP); cathepsin L; heparan sulphate proteoglycans (HSPGs); interferons; interleukin; oxytocin; superoxide dismutase; transmembrane serine protease Isoform 2 (TMPRSS2).
... Its is also important to highlight that puerperium is considered a very susceptible phase to uterine diseases, in which pathological conditions may development (Feldman & Nelson, 1986) and for this reason, follow-up of uterine involution is essential to ensure future reproductive capacity, since failure to complete reproductive organs regression can lead to endometritis, metritis and placental retention (Hirt et al., 2000;Magata et al., 2013). In this sense ultrasound is an important tool to evaluate canine reproductive system, being accurate, innocuous and providing real-time information of ovarian and uterine conditions, pregnancy, embryonic loss and puerperium (England & Russo, 2006;Davidson & Baker, 2009;Yilmaz & Uçar, 2012). ...
Elastography is an actual imaging method used to qualitatively and quantitatively evaluate the elastic properties of tissues. The aim of this study was to evaluate and compare uterine tissue biometry and stiffness during postpartum period in brachycephalic bitches (n = 12) after c‐section (GCS; n = 8) or normal delivery (GNB; n = 4). These animals were evaluated daily by abdominal ultrasound from the day of delivery until the 10th day postpartum; measuring uterine diameter, myometrial and endometrial thickness (mm) and Shear Wave Velocity (SWV; m/s), by B‐mode and ARFI (Acoustic Radiation Force Impulse) elastography, respectively. Uterine diameter was higher (p = .012) in animals submitted to c‐section (15.26 ± 4.73 mm) than in normal birth (12.53 ± 2.64 mm) during the first seven days postpartum. Uterine thickness gradually involuted in both groups (p < .0001), the myometrium during the first nine days (p = .005) and the endometrium during the first six days (p = .003). The myometrial and endometrial SWVs were similar between types of delivery (p = .7846 and 0.8273) and presented a gradual increase (p = .411; 0.0043, respectively), during the first 10 day postpartum. It was concluded that bitches with normal delivery had smaller uterine thickness and faster puerperal involution than submitted to c‐section, while uterine tissue stiffness were similar between delivery types and increased gradually during postpartum.
... Verondersteld wordt dat de toegenomen oxytocineafgifte als gevolg van zogen, het uitdrijven van de nageboorte bespoedigt. Het effect van verhoogde oxytocinespiegels op de samentrekking van de baarmoeder werd op dag 2, maar niet op dag 5 aangetoond maar trad op dag 2 niet op bij koeien die aan de nageboorte stonden (Magata et al. 2013). ...
... Pulsed-wave (PW) Doppler is a non-invasive technique for the evaluation of blood perfusion of an organ. Doppler ultrasonography has been used in cattle to study uterine blood flow [21][22][23], fatty liver syndrome [24], the musculophrenic vein [25] and as a tool for echocardiography [26]. A literature search (pubmed, October 2016, keywords: PW Doppler limb cattle) failed to identify publications describing the use of PW Doppler ultrasonography in the bovine foot. ...
Background
Local circulatory disturbances have been implicated in the development of foot disorders in cattle. The goals of this study were to evaluate the suitability of the interdigital artery in the pastern region in both hind limbs using pulsed-wave (PW) Doppler ultrasonography and to investigate quantitative arterial blood flow variables at that site in dairy cows. An Esaote MyLabOne ultrasound machine with a 10-MHz linear transducer was used to assess blood flow in the interdigital artery in the pastern region in both hind limbs of 22 healthy German Holstein cows. The cows originated from three commercial farms and were restrained in a standing hoof trimming chute without sedation.
Results
A PW Doppler signal suitable for analysis was obtained in 17 of 22 cows. The blood flow profiles were categorised into four curve types, and the following quantitative variables were measured in three uniform cardiac cycles: vessel diameter, pulse rate, maximum systolic velocity, maximum diastolic velocity, end-diastolic velocity, reverse velocity, maximum time-averaged mean velocity, blood flow rate, resistance index and persistence index. The measurements did not differ among cows from the three farms. Maximum systolic velocity, vessel diameter and pulse rate did not differ but other variables differed significantly among blood flow profiles.
Conclusions
Differences in weight-bearing are thought to be responsible for the normal variability of blood flow profiles in healthy cows. The scanning technique used in this report for evaluation of blood flow in the interdigital artery appears suitable for further investigations in healthy and in lame cows.
... A dosage of 50 international units (I.E.; 1 I.E. = 1.68 μg) oxytocin per 700 kg cow is known to have a profound effect on the uterus in vivo (Magata et al., 2013) and corresponds to an oxytocin concentration of approximately 1.2 × 10 −4 mg/kg tissue or 1.2 × 10 −10 mol/L, which was the lowest concentration of oxytocin used in the present study. An analogous calculation applies to PGF (clinically effective dose: 25 mg/cow [ (Richter and Ungemach, 2014)]) with tissue concentrations of 0.036 mg/kg or 1.007 × 10 −7 mol/L. ...
... The inaugurating group was also able to correlate kidney perfusion measurements to MAG3 scintigraphy [5] and renal function represented by serum creatinine levels. The promising and broadly published Pixelflux 1 method was primarily developed in the environment of paediatric or veterinary medicine [7][8][9][10] and there is no information available about the stability of measurements in long-term investigational series of adult patients. Lubas et al. reported crosssectional DTPM data in 17 consecutive adult patients with CKD. ...
Dynamic tissue perfusion measurement (DTPM) is a pre-described and available method in pediatric ultrasound to quantify tissue perfusion in renal Doppler ultrasound by particular video analysis software. This study evaluates DTPM during single and between repeated visits after 6 months, calibrates repeated DTPM within different region of interest (ROI) and compares DTPM with kidney function markers in adult patients with early diabetic nephropathy (n = 17). During repeated measurements, no association of readings at the same patients in the same (n = 3 readings) as well as repeated visit (n = 2 visits) could be retrieved. No association between DTPM, MDRD-GFR, albuminuria, age and duration of diabetes was observed. These negative results are presumably related to inconsistency of DTPM due to non-fixed ROI position as could be shown in calibrating series. Further development of the method should be performed to enable reproducible DTPM readings in adults.
... This result may be attributed to the idea that the uterus becomes less sensitive to oxytocin during the early puerperium as the oxytocin receptors decline as compared with the values at parturition [42]. Additionally, blood flow volume decreases rapidly after oxytocin injection during the postpartum period [43]. However, oxytocin stimulates myometrial contractions for approximately 2 hours in early postpartum cows [41]. ...
Fifteen parturient camels given chlortetracycline (CTC) as intrauterine pessaries (3 g/head) were divided into the control group (n = 5), which remained untreated, oxytocin-treated group (50 IU, intramuscular; n = 5), and cloprostenol-treated group (Estrumate, 500 μg, intramuscular; n = 5). Serum samples were collected at 0, 1, 2, 4, 8, 24, 48, and 72 hours after treatment and CTC was determined. The CTC appeared in blood within 1 hour. The maximum concentration of CTC was detected in blood after 72 (543.58 ± 117.85 μg/L), 8 (520.48 ± 13.65 μg/L), and 1 hour (831.98 ± 111.01 μg/L) of administration in control, oxytocin-, and PGF2α-treated camels, respectively. There was a high significant effect of time (P < 0.001) and treatment-by-time interaction (P < 0.001) on serum CTC concentration. In the control group, there was a significant (P < 0.05) increase in CTC concentrations at 72 hours compared to the other times. In the oxytocin group, there was a significant (P < 0.05) decrease in CTC concentrations at 24, 48, and 72 hours compared to its level after 1 or 8 hours. In PGF2α, there was a significant (P < 0.001) decrease in CTC concentrations at 2, 4, 8, 24, 48, and 72 hours compared to its level after 1 hour. Treatment contrast at different time points showed a significant (P < 0.001) increase in CTC concentration after 1 hour in the PGF2α-treated group compared to oxytocin and control groups. By 72 hours, CTC concentrations were significantly (P < 0.05) lower in PGF2α and oxytocin groups than in the control group. In conclusion, serum CTC concentration in dromedary camels increases within 1 hour after intrauterine administration and remains elevated for at least 72 hours in control, oxytocin-, and PGF2α-treated animals.
Copyright © 2015 Elsevier Inc. All rights reserved.
Puerperium is a period post-partum characterized by physiological changes whereby the upper and lower reproductive tracts of the female genital system progressively tries to histologically and endocrinologically return to its pre-gravid state and the period is accompanied by adequate uterine tone for lochia elimination and epithelial regeneration (Voorwald and Tiosso, 2015). Normally, during puerperium the bitch exhibit initially greenish discharge (due to marginal haematoma), then serosanguinous vaginal discharge for 1–6 weeks being the time considered, as the time of normal uterine involution (Feldman and Nelson, 1986). In the first three weeks brownish, non-odorous lochia will be discharged from the vulva, gradually decreasing in volume after the first week (Von Heimendahl et al., 2009). In bitches, the normal uterine involution requires more and adequate time compared to other species due to its nature of the endothelial placentation and deep uterine wounds created at placentation sites after detachment (Al-Bassam et al., 1981). The duration of the puerperium/periparturient period in the bitch has been defined to be 12 weeks (Al-Bassam et al., 1981, Orfanou et al., 2009) or 15 weeks (Yeager et al., 1990). The Bitch, being a monoestrous, polytococcus, non-seasonal animal has a physiological anestrous stage that lasts between 15 to 30 weeks following either parturition (whelping) or diestrous which is characterized by normal quiescence of the gonads and the tubular reproductive tracts. The peripaturient period that occurs during the anaestrous stage of the reproductive/oestrous cycle of the bitch is very delicate and animals are usually susceptible to varying pathological conditions owing to stress and increased demands from the environment and the newborns. For this reason, follow-up of uterine involution is essential to ensure future reproductive capacity/fertility, since failure to complete reproductive organs regression can lead to endometritis, metritis and placental retention (Hirt et al., 2000; Magata et al., 2013). Many assumptions were raised due to lots of biological activities such as nursing of the puppies, uterine involution, milk production and hormonal changes that take place during postpartum period. Thus, bitches are supposed to be more susceptible to pathologic conditions and therefore, it is important to monitor vital functions, appetite and behaviour of postpartum bitches on a daily basis to enable early detection of illness (Grundy and Davidson, 2004). Increase demand in lactation/milk production may predispose the bitch to hypocalcaemia (puerperal tetany) during this period and also a few days post whelping the cervix is physiologically open, paving ways for ascending uterine infection by pyogenic microbes which may lead to septicemia. Thus, a good health surveillance by both the owners and veterinarians is of paramount significance.Infestation of the gastro-intestinal tract and other organs of the animal body by both the adult and immature stages of endo-parasitic helminths is well documented in dogs, especially in newly whelped or neonates and it constitute one of the main causes of pathologies of the intestinal tract in dogs (Blagburn et al., 1996). The life cycle of the many occurring canine helminth species usually involved a vertical transmission from the dam to her offspring. The route of vertical transmission can be: prenatal (e.g Toxocara canis), lactogenic (e.g Ancylostoma caninum, Strongyloides stercoralis) or via coprophagy (Echinococcus multilocularis, Filaroides hirthi, Oslems osleri). Hypobiosis or developmental arrest allows for certain and specific life-cycle stages of the helminthic parasites (mostly L3) to be temporary in-activated in the somatic tissues of the host until the condition for survival is conducive. Such occurs mostly during pregnancy or when the immunity of the host is severely compromised (Shoop, 1999). The L3 re-activates during gestation and is transmitted to the offspring or neonates via milk during puerperal period, the parasites then infest the intestinal tract of the neonates and cause pathologies such as protein loss, diarrhea, obstruction of lumen, iron-deficiency anaemia (especially hook worms) and mortality in unattended condition (Cromptom, 1989).
In dairy cows, the efficacy of oxytocin treatment for preventing retained fetal membranes (RFM) is controversial. The physiological condition of cows associated with the calving process may affect the action of oxytocin. This study aimed to elucidate the difference in the efficacy of exogenous oxytocin treatment immediately after calving among cows that received various obstetric interventions. The calving ease was recorded using a score of 1–5, and assisted birth was defined as a score of 2 or more. Cows that required calving assistance (assisted, n = 28) due to delayed calving progression had a prolonged time from calving to expulsion of the fetal membrane (P < 0.01), and impaired reproductive performance compared to cows that did not receive calving assistance (unassisted, n = 78). The effect of oxytocin treatment was determined using cows that did not expel their fetal membrane within 3 h after calving. Cows were randomly divided into the control (unassisted, n = 41; assisted, n = 22) or oxytocin group (unassisted, n = 33; assisted, n = 10). Oxytocin (50 IU) was administered intramuscularly to the cows in the oxytocin group between 3 and 6 h after calving, while no treatment was administered in the control group. In cows with assisted birth, oxytocin administration accelerated placental expulsion (P < 0.05) and improved several reproductive parameters, such as the number of services until conception (P < 0.05) and the calving to conception intervals (P < 0.05) compared to the control group. On the other hand, oxytocin administration slightly accelerated placental expulsion (P < 0.05), but failed to improve fertility in cows with unassisted birth. The results indicate that the action of oxytocin varies depending on the calving situation of the cows. Oxytocin administration during the early postpartum period could prevent RFM and improve the decline in reproductive performance associated with calving assistance.
As parallel to technological innovations in the medical imaging, the ultrasonographic examinations in veterinary gynecology are getting diversified. In the past, genital organs could be examined with morphologically by only B-mode devices, today it can also be have knowledge of the hemodynamic structure and functional status of maternal/ fetal tissues by using Doppler ultra-sonography machines in different animal species. In this review, a brief summary of some Doppler studies carried out the field of veterinary obstetrics and gynecology is presented.
Transrectal color Doppler ultrasonography is a useful technique to get new information about physiologic and pathophysiologic alterations of the uterus and ovaries in female cattle. During all reproductive stages characteristic changes in uterine blood flow are observed. Cows with puerperal disturbances show delayed decrease in uterine blood flow in the first few weeks postparturition compared with healthy cows. Measurement of follicular blood flow is used to identify normally developing follicles and predict superovulatory response. Determination of luteal blood is more reliable than B-mode sonography to distinguish between functional and nonfunctional corpora lutea. Color Doppler ultrasonography is a promising tool to improve reproductive management in female cattle.
The aim of this study was to describe bidimensional and Doppler ultrasonographic changes of uterine involution during normal feline puerperium. Secondary, the postpartum vaginal discharge was described. Twelve pregnant female cats were included in this study. After queening, vulvar discharge was grossly and microscopically examined daily. Bidimensional and Doppler ultrasonographic examinations of the uterus were performed on Days -4 to -2, 4, 11, 18, and 25 from parturition. Total uterine diameter, uterine wall thickness, uterine lumen contents, peak systolic velocity, end diastolic velocity, and resistance index of uterine arteries were measured. The cats presented serosanguineous vulvar discharge for a mean of 3 ± 1 days after parturition, and the cytology revealed 70% to 80% of erythrocytes, which progressively decreased up to Day 13. Immediately after parturition, there were less than 20% neutrophils, and this percentage gradually diminished to 0% to 1% at the end of the study. Uterine total diameter diminished up to Day 25 (P < 0.01), when ultrasonographic uterine dimensions were similar to that of anestrus. A progressive decrease of uterine wall thickness (P < 0.05), uterine lumen contents (P < 0.01), peak systolic velocity (P < 0.01), and end diastolic velocity (P < 0.01) was found throughout the study period. Conversely, resistance index increased during the first week after parturition (P < 0.01). It is concluded that the uterine artery blood flow progressively decreased during the first 25 days after parturition, which was associated with the bidimensional ultrasonographic regression of the organ. Although lochial discharge disappeared far before ultrasonographic involution, cytologic findings further corroborated the duration of this regression process.
Copyright © 2015 Elsevier Inc. All rights reserved.
The objective of this study was to investigate the effects of puerperal uterine disease on uterine blood flow using trans-rectal Doppler sonography. Lactating Holstein Friesian cows (n=44) were divided into two groups based on whether they were healthy (UD-; n=23) or had uterine disease (UD+; n=21) defined as retained fetal membranes and/or metritis. General clinical examination, vaginoscopy, trans-rectal palpation, and trans-rectal B-Mode sonography were conducted on Days 8, 11, 18, 25 and then every 10 days until Day 65 after calving. Doppler sonography of the uterine arteries was conducted on Day 8, during diestrus after the second ovulation (Days 40-60 after calving) and during diestrus before breeding (Days 63-75 after calving). Cows with uterine disease had greater (P<0.05) uterine size as assessed trans-rectally compared with cows of the UD group. Sonographic measurements on Day 11 after parturition revealed a greater (P<0.05) horn diameter in cows of the UD+ than in the UD- group. Both uterine size and uterine horn diameter decreased more earlier following parturition (P<0.05) in cows of the UD- group. Blood flow volume (BFV) was greater and pulsatility index was less on Day 8 after calving in cows of UD+ than UD- group (P<0.05). In cows of the UD-, but not in those of the UD+ group, there was a further reduction in BFV subsequent to Day 45 after calving (P<0.05). The results of this study show that uterine blood flow measures by trans-rectal Doppler sonography are affected by puerperal uterine disease.
The objective was to determine the effect of oxytocin treatments after calving on the incidence of RFM and reproductive performance in dual purpose cows under tropical conditions. Five hundred thirty six pluriparous, crossbred Zebu cows were randomly assigned to two groups: Oxy (n = 280): cows were given 30 IU of oxytocin im immediately after normal unassisted calving, and again 6 h later; C (n = 256): control. Expulsion of fetal membranes was evaluated 24 h after delivery. After a 30-d voluntary waiting period, AI was done 12 h after cows were detected in estrus. Oxytocin had no effect on the incidence of RFM (4.6 vs. 3.1% for Oxy and C, respectively, P > 0.05). Cows in Oxy and C had similar first service and overall pregnancy rates (54.0 vs. 47.8% and 75.4 vs. 73.4%; respectively, P > 0.05). There were no differences between Oxy and C for calving to first estrus (83.6 ± 3.7 vs. 77.2 ± 3.8 d) and calving to conception intervals (113.6 ± 5.0 vs. 110.5 ± 5.2 d), as well as rates of anestrus (13.6 vs. 13.7%), repeat breeding (21.8 vs. 20.7%), and culling (15.7 vs. 16.4%). In conclusion, oxytocin treatment after normal unassisted calving did not significantly reduce the incidence of RFM or improve reproductive performance in crossbred Zebu cows under tropical conditions.
The aim of the study was to compare the effect of two acute puerperal metritis (APM) treatment protocols on uterine condition during the late puerperal period (5th to 7th week). Late gestation healthy cows (n = 21) were divided randomly in three equal groups. Parturitions were induced. Treatments of APM were started on the third day postpartum (PP). Group A was treated with an oxytocin analogue carbetocin for three days and intrauterine administration of cephapirin between days 15 and 17. Group B was given intramuscular injection of ceftiofur for five days followed by two injections of prostaglandin F2alpha, at an interval of 12 h, on the eighth day PP. Group C served as the control group with no treatment. Body temperature was recorded daily for 14 days PP. Uterine biopsies for bacteriology, and uterobrush samples for cytology, were taken once a week from the 5th to 7th week postpartum. No differences were found in body temperature on day 14 PP, presence of bacteriological infections and disappearance of uterine inflammatory signs diagnosed by cytological examination between experimental groups.
Retained fetal membranes (RFM) in cattle have adverse effects on fertility and production. Understanding the pathophysiology and causes of RFM is important for managing this disease. The hormonal processes that lead to normal placental separation are multifactorial and begin before parturition. A variety of risk factors, including early or induced parturition, dystocia, hormonal imbalances, and immunosuppression, can interrupt these normal processes and result in retention of the placenta. Current research does not support the efficacy of many commonly practiced treatments for RFM. Systemic administration of antibiotics can be beneficial for treating metritis after RFM, but antibiotic administration has not been shown to significantly improve future reproduction in cows with RFM. Collagenase injected into the umbilical arteries of retained placentas specifically targets the lack of placentome proteolysis and might enhance placental release. However, such therapy is costly and its benefits in terms of improving subsequent reproductive function have not been evaluated.
Oxytocin receptors were measured in myometrium and intercaruncular endometrium of cows during pregnancy and parturition. Concentrations of estradiol-17 beta, estrone, and progesterone in peripheral blood were also measured. Receptor concentrations in the endometrium rose almost 200-fold from Day 20 to term (p < 0.0001, ANOVA), from 40 +/- 11 to 7300 +/- 1430 fmol/mg protein. Myometrial receptor concentrations increased 10-fold from 180 +/- 36 fmol/mg on Day 20 to 1850 +/- 360 fmol/mg protein at term (p < 0.0001, ANOVA). During labor, endometrial receptors (6600 +/- 1300 fmol/mg) remained at prelabor values, whereas myometrial receptor concentrations had decreased to 1190 +/- 316 fmol/mg (not significant) and declined further postpartum. Plasma concentrations of progesterone declined from 4-5 ng/ml to about 2 ng/ml between Days 250 and 282 and dropped to < 0.2 ng/ml shortly before delivery. Plasma concentrations of estrone and estradiol-17 beta were below 10-20 pg/ml until Day 230. Estrone concentrations were significantly (p < 0.05) increased by Day 250 and estradiol-17 beta by Day 270, and then both rose rapidly. During labor, plasma estrone was 1135 +/- 245 pg/ml and plasma estradiol-17 beta was 226 +/- 131 pg/ml. The molar ratio of estrone and estradiol-17 beta to progesterone rose from less than 0.01 to 4.4 during labor, and was correlated with oxytocin receptor concentrations in endometrium (r = 0.5160, p < 0.001), but not those in myometrium (r = 0.0122). The regulation of oxytocin receptors by ovarian hormones in the two tissues may therefore differ.(ABSTRACT TRUNCATED AT 250 WORDS)
At the end of pregnancy, the myometrium becomes extremely sensitive to oxytocin (OT) as result of a dramatic increase in the number of OT receptors (OTR), indicating an important role for OTR in the process of labor. There are no studies in sheep in which the physical properties and histological distribution of OTR are evaluated in relation to parturition. Also, no studies have been performed in any species to simultaneously examine the distribution of OTR at the messenger RNA (mRNA) as well as the protein levels in the same tissues and correlate those changes with the patterns of myometrial activity that occur at labor. In the present studies, we have used a polyclonal anti-OTR antibody and Western blot analysis to determine the apparent molecular mass of ovine OTR in late pregnant sheep myometrium and endometrium. We also examined the distribution of OTR mRNA and protein expression in the intact myometrium and endometrium and in individual cultured cells using in situ hybridization and immunocytochemistry. The expression of OTR and its mRNA has been correlated with the patterns of activity observed in the pregnant sheep myometrium. Western blot analysis of myometrial and endometrial extracts revealed a major form of OTR with an approximate molecular mass of 66 kDa. Both immunocytochemistry and in situ hybridization localized OTR and its mRNA in myometrial cells and glandular cells of the endometrium. Increased OTR and its mRNA expression in the myometrium and endometrium were correlated with the occurrence of myometrial contractions. OTR was also demonstrated by immunocytochemistry in the smooth muscle of myometrial blood vessels. Localization of OTR and its mRNA in pregnant sheep myometrial cells is consistent with the hypothesis that OTR plays an important role in regulating myometrial contractility. Positive staining of OTR in endometrial glandular cells supports the view that OT is involved in PG production by the endometrium in late pregnancy. Increased expression of OTR and its mRNA in the myometrium during labor further indicates that changes in tissue OTR play a significant role in the mechanism of parturition. Increased expression of OTR and its mRNA in endometrium may relate to the role of OT in regulating PG production by the endometrium during labor.
No quantitative or qualitative Doppler velocimetry classification of vascular flow resistance covering all stages of forward and reversed flows exists. The objective of this study was to characterize uterine artery (UtA) flow velocity waveforms (FVWs) obtained during an oxytocin challenge test (OCT) and compare them to FVWs in spontaneous normal labor.
Uterine artery Doppler velocimetry was performed during and between uterine contractions in 61 high-risk pregnancies subjected to an OCT and in 20 normal pregnancies undergoing spontaneous labor. FVWs were classified relative to the presence of forward/absent/reversed flow during systole and diastole, and the time-averaged flow velocity over the heart cycle.
Eleven different FVW classes were identified. No relationship between FVWs recorded during uterine inertia and contractions was found (P >/= 0.2). In both groups, only forward FVWs were recorded between contractions, whereas during contractions flow reversal was more common in the OCT group (P </= 0.002). In cases of predominantly reversed flow, a reciprocal relationship to FVW classes recorded in the contralateral artery was found.
UtA FVW patterns recorded during uterine contractions were not predicted by flow patterns recorded during uterine inertia. Reversal of flow direction was more common during oxytocin-induced uterine contractions than during spontaneous contractions. In cases of predominantly reversed flow, domains of the uterus may be supplied by blood from the contralateral UtA. These observations give new insights into the circulatory dynamics of the uterus during labor, and also point to a possible vasoconstrictory effect in the UtAs of oxytocin at high concentrations.
In experiment I, the effect of i.m. oxytocin (OT) injection (50 IU) on OT blood pattern was tested. Blood samples from 6 cows were collected for 2 h after OT injection either with or without milking. To test the effect of i.m. OT injection (50 IU) on milk ejection efficiency, intramammary pressure (IMP) was measured in 13 cows (experiment II). Milk ejection was induced by manual teat stimulation. After IMP increased and reached a plateau, OT was injected. In experiment III, the effect of chronic OT treatment on mammary gland sensitivity and endogenous OT release was tested. For 19 d, cows were i.m. injected at each milking with 50 IU OT (n = 13) or 5 mL of NaCl 0.9% (n = 14) 1 min before the start of udder preparation. To test mammary gland sensitivity, IMP recording was performed after a long (11 h, 7 OT cows, and 7 NaCl cows) and a short (3 h, 6 OT cows, and 7 NaCl cows) milking interval at d -1 and d 18. To test the effect of withdrawal of chronic i.m. treatment on OT release, blood sample collection was performed during evening milking at d 0 and d 19. Intramuscular oxytocin injection (experiment I) caused elevated OT blood levels observed at least for 2 h and showed an even more pronounced effect when milking was also performed. Intramuscular OT injection after teat stimulation (experiment II) caused additional milk ejection but only in 6 out of 13 cows. Withdrawal of chronic OT treatment (experiment III) did not reduce OT release during milking. However, ejection time was prolonged during OT infusion after a long milking interval. Ejection pressure tended to be lower after a short milking interval. It seems that the reduction of spontaneous milk removal after chronic OT treatment was due to reduced contractibility of myoepithelial cells in the mammary gland at a physiological range of OT concentrations.
To determine whether, in a group of high-risk pregnancies undergoing an oxytocin challenge test (OCT), uterine artery Doppler velocimetry will identify fetuses at risk of distress during the provoked contractions.
Bilateral uterine artery Doppler velocimetry was performed simultaneously with electronic fetal heart rate (FHR) recordings in 67 high-risk pregnancies subjected to an OCT. Flow velocity waveforms (FVWs) were classified according to pulsatility index (PI), presence of diastolic notching and a novel classification of FVW shapes. The OCT was classified as negative (normal) or positive (late FHR decelerations). Only OCT-negative cases were allowed a trial of vaginal delivery. Non-parametric statistical methods were used to test for differences between the OCT groups.
There was no difference in prevalence of high PI or diastolic notching in OCT-positive (n = 10) and OCT-negative (n = 57) cases at basal (resting) measurements or between uterine contractions in either uterine artery (P > or = 0.3). During contractions the PI could not be used for assessment due to the biphasic shape of the FVWs, but there was no difference in distribution of FVW classes between the groups in either the placental side (P > or = 0.3) or contraplacental side (P > or = 0.6) uterine artery. No significant associations between PI or FVW class distribution and birth asphyxia or operative delivery for fetal distress in labor were found (P > or = 0.1).
During uterine contractions there is no difference in uterine artery FVW pattern between OCT-positive and OCT-negative cases. Recording of uterine artery FVWs during the OCT seems to be of limited clinical relevance.
Reproductive diseases after parturition are a serious problem in dairy cattle. It is important to predict postpartum reproductive diseases early and to develop prophylaxis. The objectives of this study were to demonstrate changes in the peripheral blood concentration of interleukin-6 (IL-6) before parturition, which was mainly produced by T helper 2 type (Th2) cells, and to investigate a correlation between the IL-6 concentration and the occurrence of the postpartum retained placenta, endometritis and/or follicular cyst in dairy cattle. Twenty-seven Holstein-Friesian cows were used for this study. Thirteen had no clinical disease, 8 had retained placenta, 4 were diagnosed with endometritis by vaginal inspection, and 2 were diagnosed with follicular cyst by rectal palpation at 1 and 2 months after parturition. Blood samples were collected 60 days pre- and post-partum. They used for IL-6, progesterone (P(4)) and estradiol-17beta (E(2)) concentration determination. This study showed that the IL-6 concentration prepartum was higher than postpartum. Low levels of IL-6 and P(4) in peripheral blood prepartum tended to affect retained placenta and a high level of IL-6 prepartum tended to affect endometritis. These results indicate that measurement of change in the IL-6 concentration during pregnancy is one useful tool for predicting crisis in postpartum reproductive diseases in dairy cattle.
Oxytocin receptors were measured in myometrium and intercaruncular endometrium of cows during pregnancy and parturition. Concentrations of estradiol-17 beta, estrone, and progesterone in peripheral blood were also measured. Receptor concentrations in the endometrium rose almost 200-fold from Day 20 to term (p < 0.0001, ANOVA), from 40 +/- 11 to 7300 +/- 1430 fmol/mg protein. Myometrial receptor concentrations increased 10-fold from 180 +/- 36 fmol/mg on Day 20 to 1850 +/- 360 fmol/mg protein at term (p < 0.0001, ANOVA). During labor, endometrial receptors (6600 +/- 1300 fmol/mg) remained at prelabor values, whereas myometrial receptor concentrations had decreased to 1190 +/- 316 fmol/mg (not significant) and declined further postpartum. Plasma concentrations of progesterone declined from 4-5 ng/ml to about 2 ng/ml between Days 250 and 282 and dropped to < 0.2 ng/ml shortly before delivery. Plasma concentrations of estrone and estradiol-17 beta were below 10-20 pg/ml until Day 230. Estrone concentrations were significantly (p < 0.05) increased by Day 250 and estradiol-17 beta by Day 270, and then both rose rapidly. During labor, plasma estrone was 1135 +/- 245 pg/ml and plasma estradiol-17 beta was 226 +/- 131 pg/ml. The molar ratio of estrone and estradiol-17 beta to progesterone rose from less than 0.01 to 4.4 during labor, and was correlated with oxytocin receptor concentrations in endometrium (r = 0.5160, p < 0.001), but not those in myometrium (r = 0.0122). The regulation of oxytocin receptors by ovarian hormones in the two tissues may therefore differ.(ABSTRACT TRUNCATED AT 250 WORDS)
. Doppler recordings from branches of the uterine artery were made simultaneously with intrauterine pressure measurements in eight women in labour. Blood velocities fell and pulsatility index (PI) increased during all 22 contractions studied. Velocities were reduced almost linearly by up to 60% when pressure increased from 0 to 50 mmHg. To study the effect of uterine contractions before labour on uterine blood flow, simultaneous Doppler recordings from branches of the uterine artery and external tocodynamometry were made in seven women during the last trimester. Velocities fell during 18 of the 20 contractions studied (median 35%, range 19–71%). Extrapolating from labour contractions, this corresponds to a pressure increase of 30–40 mmHg. Fetal heart rate (FHR) recordings were normal during all contractions.
Transrectal Doppler ultrasound was used for the noninvasive investigation of uterine blood flow in cows. Both the left and right Aa.uterinae were scanned to obtain blood flow velocity waveforms over 2 consecutive estrous cycles. Blood flow was reflected by the resistance index (RI) and the time-averaged maximum velocity (TAMV). Intra-observer reproducibility of Doppler measurements was evaluated. The intra-class correlation coefficient (Intra-CC) was 0.97 for the RI and 0.95 for TAMV. While RI values did not differ between the left and right A.uterina (P > 0.05), differences in TAMV occurred between both vessels in 2 cows. These differences were not related to the ovary bearing the dominant follicle or to the corpus luteum (P < 0.001). As in all cows, changes of RI and TAMV values between the left and right artery during the estrous cycle were correlated (correlation coefficient r > 0.72; P < 0.0001); the mean values of both sides were used for subsequent analyses. Variance component estimates for the effect of cow on RI and TAMV were 8 and 13% and for the influence of day of estrous cycle they were 70 and 47%, respectively (P < 0.0001). Between estrous cycles no significant differences could be measured within cows (P > 0.05). The highest RI and lowest TAMV values occurred on Day 0 (= day of ovulation) and Day 1, while the lowest RI and highest TAMV values were measured between Days -3 and -1 of the estrous cycle, respectively. There was a positive correlation between TAMV and estrogen concentrations and a negative correlation between RI and plasma estrogen levels. Plasma progesterone levels and TAMV were negatively correlated, but no correlation could be measured (P > 0.05) between RI values and plasma progesterone concentrations. While there were no differences in plasma concentrations of estrogens and progesterone between estrous cycles within cows, the levels of these hormones differed between cows. The results show that transrectal Doppler sonography is a useful, noninvasive method for examining uterine blood flows in cows. If there is an influence of uterine perfusion on fertility in cows its role needs further investigation.
PROBLEM: Intra-uterine infection results in the production of inflammatory cytokines, including interleukin-6 (IL-6). Increased oxytocin-receptor (OTR) concentrations are associated with the onset of preterm labor. We hypothesize that infection up-regulates OTR expression through IL-6-induced transcription factors. METHOD OF STUDY: Primary cultures of human myometrium were treated for various time periods or with different concentrations of IL-6 and OTR mRNA as well as OTR binding were measured by means of reverse transcription polymerase chain reaction and
I-ornithine-vasotocin-binding assay. To study underlying mechanisms of OTR changes with IL-6 treated, cells were also incubated with genistein or H7 (tyrosine and serine phosphorylation inhibitors), respectively. RESULTS: OTR mRNA increased 2.5-fold after 4 hr of IL-6 treatment and OTR binding 1.4-fold after 8 hr of cytokine stimulation. The IL-6-induced increase in binding was blocked by genistein and H7. CONCLUSIONS: IL-6 up-regulates uterine OTR mRNA expression and binding capacity in cultured human myocytes most likely through tyrosine and serine phosphorylation pathways involving the nuclear factor STAT-3.
The objective of the study was to determine uterine motility during the postpartum period in cattle. In the present study spontaneous uterine activity was recorded during postpartum period using electrodes which were surgically implanted into the myometrium 4-6 weeks before parturition. After the placenta has been released 4-8 hours post part, spontaneous uterine motility drastically decreased until the second week post part. The effects of oxytocin, depotocin, prostaglandin, ergometrin, detomidin on the uterine contractility, during postpartum period were investigated. Oxytocin and carbotocin given intravenously always provoked strong uterine contractions. Prostaglandin F2alpha and detomidinum HC1 stimulated uterine activity in the early puerperium. Following administration of ergometrin unequal response was recorded. Ultrasonographic examinations were performed daily with real time B-mode scanner equipped with a 5.0 MHz linear-array transducer (Aloka 210, Pie Medical). 10 muciparous Black-White-Holstein cows between 2 and 4 years old and 550-650 kg b.w. were used. A 6-min scan of the longitudinal view of the uterine body was recorded using video cassette recorder connected to the ultrasound scanner. A scoring system was used to determines uterine motility. Contractility scores were higher just after parturition then in the following times. Blood samples were collected daily from jugular vein for plasma progesterone and estrogen concentrations. Changes in uterine activity were associated with plasma progesterone and estrogen level.
The aim of this study was to evaluate the relationship between the occurrence of retention of the fetal membranes (RFM) and the hormonal concentrations of progesterone, estradiol-17beta, prostaglandin E(2) (PGE(2)), prostaglandin F(2alpha) (PGF(2alpha)), oxytocin (OT), oxytocin receptor (OT-R), endothelin-1 and angiotensin II (Ang II) in the placental tissues of cattle. Parturition was induced in nine Holstein cows by a single injection of PGF(2alpha) on Day 274 of gestation. Six out of nine cows in the induced group did not release the fetal membranes within 12 h after parturition and served as the RFM group, and the remaining three cows in that group, which released their fetal membranes within 12 h, served as the non-RFM group. Five other cows calved spontaneously and served as controls. The placental tissues were collected immediately (0 h) and at 6 h after parturition. The hormonal concentrations were measured by enzyme immunoassay in maternal and fetal placental tissues from RFM, non-RFM and control cows. There were no differences in P4 and E2 concentrations among the RFM, non-RFM and control groups. The mean PGF(2alpha) concentration of the RFM group was lower than those of the non-RFM and control groups in the maternal part of the placenta. In maternal tissues, the OT and OT-R concentrations in the RFM group were lower than those at 0 and 6 h after parturition in the non-RFM group. Additionally, the Ang II concentration of the RFM group in both the maternal and fetal parts of placental tissues tended to be higher than those of the other groups. In conclusion, the present results suggest that ET-1 and Ang II may play differential tissue-specific roles in the placental unit that may amplify the local endocrinological cascade involving OT, OT-R and PGF(2alpha) interactions which are necessary for normal placental separation in the cow.
To clarify the effects on uterine arterial flow velocity waveforms of uterine contractions following oxytocin infusion and during spontaneous labor.
Uterine arterial flow velocity waveforms were obtained by pulsed Doppler methods from 22 women during an oxytocin challenge test (OCT), 26 women during oxytocin-induced labor, and 40 women during spontaneous labor. Mean resistance index (RI) for bilateral arteries was used for analyses. After the onset of labor, flow velocity waveforms were assessed according to cervical dilatation. During OCT, Doppler flow velocimetry was performed when three uterine contractions occurred per 10-min period.
RI values did not differ significantly between induced and spontaneous labor during relaxations at any level of cervical dilatation. However, during contractions, RI was significantly higher for induced labor than for spontaneous labor. Absence or reversal of flow was more frequent in the OCT group than in the induced labor group (P < 0.0001). However, no significant differences were found between spontaneous and induced labor groups.
Interactions between the contracting uterine body and the relaxing lower segment in oxytocin-induced labor might be associated with differences in uterine arterial flow during contraction between oxytocin-induced and spontaneous labor. However, changes in the intensity of uterine contractions during labor progression might differ between oxytocin-induced and spontaneous labor.
The aim of this study was to determine if transrectal colour Doppler sonography of uterine arteries is a useful method to quantify uterine changes during the first 12 weeks after parturition in cows. Examinations were carried out on days 1, 7, 14, 28, 56 and 86 after parturition (day 0) in 42 Holstein-Friesian multiparous dairy cows (mean lactation number: 2.63+/-0.73). Findings obtained by transrectal manual palpation were quantified using scores for uterine size (SUS) graded from 1 to 6. The mean diameter of intrauterine fluid accumulation within the uterine body and the presence of a dominant follicle and/or a corpus luteum were examined using B-mode sonography. Blood flow was measured by determining blood flow volume (BFV) and pulsatility index (PI) of the uterine arteries. Clinical uterine involution was complete on day 28 as demonstrated by transrectal palpation and B-mode sonography. BFV declined (P<0.05) steeply between days 1 and 7 from 4312 ml/min to 1443 ml/min and moderately (P<0.05) to 230 ml/min on day 28. From this time on there were no significant changes (P>0.05) of BFV until the end of the study. The pulsatility index rose from 1.54 on day 1 reaching a peak value of 5.56 on day 28 and decreased (P<0.05) linearly to 3.13 on day 86. The results show that transrectal colour Doppler sonography is an additional tool for examining uterine changes during the first 12 weeks after parturition in cows. While uterine blood flow changes were only demonstrated during the first 4 weeks of the puerperium, the pulsatility index was also suitable to investigate alterations in uterine perfusion during the next 8 weeks after parturition.
Recordings of electrical activity of the oviduct and uterus were obtained during three oestrous cycles in cows fitted with an extra-cellular multi-electrode assembly. The stages of the cycle were identified by the appearance of the cervico-vaginal secretions and changes in the peripheral plasma level of progesterone were determined by radioimmunoassay. A gradual transition from local non-propagating electrical activity to propagating electrical activity with increase in the duration of contractions and then of their amplitude occurred 48 hr before the onset of oestrus. The transition coincided with a rapid decrease in progesterone level from 5 to 10 ng/ml to less than 0-1 to 0-4 ng/ml. This phenomenon was recorded from all uterine electrode sites, but was most marked at the uterotubal junction. Two days before oestrus, trains of potentials and bursts of activity became progressively grouped, apparently randomly, into prolonged phases in the distal portion of the oviduct and over the entire myometrium. During oestrus, the phases of activity became synchronized at these sites and both their amplitude and frequency reached a maximum. The strength but not the frequency of the phases diminished progressively 3 days after oestrus, followed by relative inactivity. The last remaining zone of activity was the uterotubal junction. During oestrus, the activities of the oviduct and the uterus were modified by oxytocin and adrenaline, the effect of the former being more marked on the uterus and that of the latter on the oviduct.
The uterine effects of oxytocin, the prostaglandins dinoprost and cloprostenol as well as clenbuterol, ergometrin, xylazine and Utrorale were investigated in 8 cows during late pregnancy, parturition and early puerperium (until 4th day p. p.). Uterine motility was measured by means of pressure microsensors and electrodes which were surgically implanted 3 to 4 weeks before parturition. Hysterograms were characterized by means of pressure amplitude, frequency and duration of uterine contractions and also by electromyography. Oxytocin (2-5 IE) given intravenously always provoked strong uterine contractions until the 4th day p.p. From the prostaglandins examined during early puerperium only dinoprost (15 mg i.v.) produced uterotonic effects, while the synthetic analogue cloprostenol (0.25 mg i.v.) had a weak stimulatory activity only on day 1 p.p. Both prostaglandins were ineffective when injected intramuscularly. Clenbuterol (0.3 mg i.v.) a beta 2-mimetic compound effectively induced long lasting tocolysis during parturition, which could be abolished by oxytocin. Xylazine (10 mg i.v.) was able to significantly increase uterine motility during late gestation. Following intravenous administration of ergometrin (1 and 10 mg), bunitrolol (1-16 mg) and Utrorale (0.1-4 ml) including its compounds oleum sabinae, oleum terebinthinae, balsamum copaivale and Styrax no uterokinetic activity was recorded at any time.
Twelve normal parturients were studied with a continuous wave Doppler unit to assess changes in uterine and umbilical velocity waveforms during labor. The analysis of these waveforms included the peak systolic/end-diastolic ratio and the evaluation of a diastolic notch. Each woman served as her own control, and all fetal heart rate tracings were normal. In latent phase labor and intact membranes, the umbilical artery systolic/end diastolic ratios before, during, and after a contraction were 2 +/- 0.2, 2 +/- 0.3 and 1.95 +/- 0.3 (N.S.). Similar results were obtained in the active phase, after rupture of membranes, or during oxytocin stimulation. This stability of the fetal cardiovascular system ensures an uninterrupted gas exchange process during the contractions (on the fetal side), enabling the great majority of term fetuses to tolerate labor with minimal if any metabolic changes. The uterine artery end-diastolic velocity fell progressively during the contraction, reaching 0 when the intrauterine pressure exceeded 35 mm Hg. Despite intrauterine pressure of greater than 60 mm Hg, the diastolic notch did not appear. Thus at term, the umbilical artery velocity waveform does not change over a wide range of uterine pressures. The changes seen in the uterine artery waveforms suggest that the end-diastolic component is primarily determined by changes in the arcuate and spiral arteries, both of which are affected during the uterine contraction.
A double blind randomised clinical trial was performed to assess the effects of oxytocin on the duration of placental retention following dystocia. If the placenta remained attached to the uterus immediately following assisted delivery of a calf, and was not expelled in the period taken to complete the protocol, an intramuscular injection of either 3 ml (60 USP units) of oxytocin or 3 ml of 0.9 per cent physiological saline was given to the cow. Each farmer was asked to observe the cow to determine the time of placental expulsion. In 55 cases available for analysis there was no significant difference between the treatment and control groups for percentage of placental retention at days 1, 2 or 3 post partum.
To evaluate the effects of treatment at parturition with dinoprost tromethamine, fenprostalene, or oxytocin on postpartum disease and reproductive performance during the subsequent breeding season in dairy cows.
Prospective study.
1,400 Holstein cows from 5 commercial dairies.
Cows were assigned within 2 hours after calving to serve as untreated control cows or to be treated with 1 mg of fenprostalene, SC; 25 mg of dinoprost tromethamine, IM; or 20 IU of oxytocin, IM. Cows were confined to treatment pens and monitored daily until fetal membranes were expelled. Cows with retained fetal membranes (RFM) were treated according to existing treatment protocols for the dairy, with the provision that intrauterine infusions were not allowed. All other disease conditions were recorded, and appropriate treatment was administered. Postpartum reproductive examinations were performed 28 to 56 days after parturition Breeding records were maintained for all cows until pregnancy was confirmed or the cow was removed from the herd.
Fetal membranes were retained in 12.1% of all cows, and this outcome was unaffected by treatment. Compared with cows without RFM, cows with RFM had longer intervals to first insemination (76.4 vs 82.0 days), reduced first insemination conception rates (46.8 vs 28.0%), and increased number of days not pregnant (103.2 vs 127.4 days). Farm, as a variable, significantly affected development of RFM and postpartum disease conditions as well as reproductive performance during the subsequent breeding season. Fetal membranes were retained in 12.4, 15.2, 8.7, 6.3, and 16.9% of cows on farms 1, 2, 3, 4, and 5, respectively. Mean days to first insemination varied from 64.5 days (farm 3) to 91.5 days (farm 1). Mean number of days not pregnant varied from 94.8 days (farm 3) to 15.9 days (farm 4).
Administration of prostaglandins or oxytocin at the time of calving does not reduce the incidence of RFM or improve reproductive performance. Farm management practices have the greatest impact on dairy cow performance.
Oxytocin was administered to reduce incidence of retained placenta and uterine infections that could delay subsequent conception. Three hundred and fifty multiparous Friesian cows, each with spontaneous delivery of a single calf were divided randomly into two groups. Some (n = 175) were injected with 30 IU of oxytocin immediately after delivery and again 2-4 h later, while the remainder formed an untreated control group. The placental retention 24 h after parturition was 24.6% and 10.9% in control and treated animals respectively (P < 0.01). Endometritis occurred in 51.6% of the animals following placental retention as compared to 10.4% of those with normal expulsion of the fetal membranes (P < 0.001). A comparison of reproductive indices showed a statistically significant improvement of fertility in treated cows with the average interval from calving to conception being reduced from 124.4 d to 93.7 d (P < 0.0001).
An epidemiological study of risk factors for postpartal ovarian disturbances was carried out on 334 high-yielding dairy cows in 6 well-managed Belgian herds. Ovarian activity was closely monitored using progesterone profiles, based on twice weekly RIA-analysis for progesterone in milk fat, starting at 10 d after calving and continuing until the confirmation of a new pregnancy. Attention was focused on abnormal cyclicity during the preservice, postpartum period; cows were divided into 6 different categories. Three of these categories (normal profile, delayed cyclicity, and prolonged luteal phase) were of major importance and were analyzed using a multiple variable logistic regression model. Season of calving (stable vs pasture, odds ratio (OR)=5.7), an extended length of the previous dry period (> 77 vs < or = 63 d, OR=2.9), problem calvings (OR=3.6), abnormal vaginal discharge (OR=4.5), health problems during the first month of lactation (clinical disease, OR=5.4; ketosis, OR=11.3), and clinical parameters illustrating the appearance of a severe negative energy balance significantly increased the risk for delayed cyclicity before service. Parity (> or = 4 vs 1, OR=2.5), problem calvings (OR=2.9), occurrence of puerperal disturbances (OR ranged from 3.5 to 11.0), health problems during the first month of lactation (OR=3.1), and an early resumption of ovarian cyclicity after calving (< 19 d vs > 32 d, OR=2.8) increased the risk for prolonged luteal cycles before service.
Transrectal Doppler ultrasound was used for the noninvasive investigation of uterine blood flow in cows. Both the left and right Aa. uterinae were scanned to obtain blood flow velocity waveforms over 2 consecutive estrous cycles. Blood flow was reflected by the resistance index (RI) and the time-averaged maximum velocity (TAMV). Intra-observer reproducibility of Doppler measurements was evaluated. The intra-class correlation coefficient (Intra-CC) was 0.97 for the RI and 0.95 for TAMV. While RI values did not differ between the left and right A. uterina (P > 0.05), differences in TAMV occurred between both vessels in 2 cows. These differences were not related to the ovary bearing the dominant follicle or to the corpus luteum (P < 0.001). As in all cows, changes of RI and TAMV values between the left and right artery during the estrous cycle were correlated (correlation coefficient r > 0.72; P < 0.0001); the mean values of both sides were used for subsequent analyses. Variance component estimates for the effect of cow on RI and TAMV were 8 and 13% and for the influence of day of estrous cycle they were 70 and 47%, respectively (P <0.0001). Between estrous cycles no significant differences could be measured within cows (P > 0.05). The highest RI and lowest TAMV values occurred on Day 0 (= day of ovulation) and Day 1, while the lowest RI and highest TAMV values were measured between Days -3 and -1 of the estrous cycle, respectively. There was a positive correlation between TAMV and estrogen concentrations and a negative correlation between RI and plasma estrogen levels. Plasma progesterone levels and TAMV were negatively correlated, but no correlation could be measured (P > 0.05) between RI values and plasma progesterone concentrations. While there were no differences in plasma concentrations of estrogens and progesterone between estrous cycles within cows, the levels of these hormones differed between cows. The results show that transrectal Doppler sonography is a useful, noninvasive method for examining uterine blood flows in cows. If there is an influence of uterine perfusion on fertility in cows its role needs further investigation.
Intra-uterine infection results in the production of inflammatory cytokines, including interleukin-6 (IL-6). Increased oxytocin-receptor (OTR) concentrations are associated with the onset of preterm labor. We hypothesize that infection up-regulates OTR expression through IL-6-induced transcription factors.
Primary cultures of human myometrium were treated for various time periods or with different concentrations of IL-6 and OTR mRNA as well as OTR binding were measured by means of reverse transcription polymerase chain reaction and 125I-ornithine-vasotocin-binding assay. To study underlying mechanisms of OTR changes with IL-6 treated, cells were also incubated with genistein or H7 (tyrosine and serine phosphorylation inhibitors), respectively.
OTR mRNA increased 2.5-fold after 4 hr of IL-6 treatment and OTR binding 1.4-fold after 8 hr of cytokine stimulation. The IL-6-induced increase in binding was blocked by genistein and H7.
IL-6 up-regulates uterine OTR mRNA expression and binding capacity in cultured human myocytes most likely through tyrosine and serine phosphorylation pathways involving the nuclear factor STAT-3.
It is now well-accepted that attention to dry cow nutrition can markedly reduce the incidence of postpartum problems. Little is known about the pathophysiology of the diseased postpartum uterus, and there is no scientifically proven therapy for toxic metritis other than supportive care (systemic antibiotics, anti-inflammatory medication, and fluid therapy). There is no scientific evidence that an IM injection of prostaglandin or estrogen will stimulate the type of rhythmic tubocervical contractions required to empty an atonic postpartum uterus. It is noteworthy that the increased frequency of uterine contractions following oxytocin administration in the postpartum cow is exactly the same phenomenon as that seen when Stage II of labor commences. The presence of the fetus in the vaginal canal is known to stimulate endogenous oxytocin release (Ferguson re.ex) [96,228]. The research by scientists such as Burton, Gajewski, Kundig, and Thun and their coworkers [16,20,24,25,90,227,232] has refuted the often-quoted view that oxytocin is only uterotonic during the first 1 to 2 days postpartum. It is unfortunate that these studies of Burton, Kundig, and Gajewski and their coauthors were not conducted using the more typical IM route of oxytocin administration. Burton [16] did confirm, however, that the myometrial response following injection of 20 to 30 USP units of oxytocin is similar following administration via the IV, IM, or SQ routes. Because a low dose of oxytocin (20 USP units) is uterotonic up to 9 days postpartum, it has the most scientific validity as a therapeutic agent. Estrogen priming is not indicated. Repeated low-dose oxytocin therapy (20 USP units every 3 hours) would ensure that the uterus remains under the influence of rhythmic contractions although this protocol may be impractical under field conditions. Farmers should be educated to adopt early intervention practices before the cow succumbs to the systemic effects of endotoxin. Although daily monitoring of rectal temperatures in the first 7 to 10 days postpartum can help to identify high-risk animals, nothing replaces close observation that permits early recognition of a cow's changing appearance and behavior.
Literature pertaining to retained fetal membranes and postpartum uterine infections of cows was reviewed. Many therapeutic failures are explained by the effects of the uterine environment on antibacterials, the effects of therapy on the uterine defense mechanism, bacterial resistance patterns and the failure to recognize normal physiological processes in the postpartum period. Prostaglandin F(2)alpha and its analogues provide effective alternatives to antibiotic and antibacterial therapy for most postpartum disorders.
Postpartum uterine contraction variables were measured in 15 parturient Holstein dairy cows and heifers: 8 assigned to dexamethasone (DEX) treatment and 7 to control (CON) treatment. The DEX animals were induced to calve early with an injection of dexamethasone and estradiol benzoate, administered on days 270 to 274 of gestation. At this time, the CON animals were injected with sterile saline and allowed to calve at term. Six of the eight DEX animals and one of the seven CON animals retained their fetal membranes longer than 12 hours postpartum. The uterine contraction variables determined were: the number of contractions over a 10 minute period (C/10), the average amplitude of contractions (AMP), the average duration of contractions (DUR), Montevideo units (MONT) and Alexandria units (ALEX). Recordings were taken at 1 hour, 6 hours and 48 hours postpartum, for a period of 20 minutes each. The contraction variables were measured using a catheter which was fluid-filled and inserted into the pregnant horn and connected to a pressure transducer, amplifier and recorder. The data were analyzed in terms of DEX vs. CON animals and animals with retained fetal membranes (RET) vs. animals with a normal release (NRET). Treatment with dexamethasone and estradiol benzoate resulted in an increase in C/10 at 48 hours (P<.05). The AMP, MONT and ALEX variables were also higher in the DEX animals, as compared to controls at that time. Significant differences (P<.01) were observed at 48 hours postpartum between the RET and NRET animals in terms of AMP, MONT and ALEX variables, and at that time the RET animals had a higher rate of uterine contractility than the NRET animals. No significant differences in the amount of uterine work between either the DEX and CON animals or the RET and NRET animals were observed, at 1 and 6 hours postpartum. The treatment with dexamethasone and estradiol benzoate prolonged uterine motility up to 48 hours postpartum, and the retention of the fetal membranes was not a result of the lack of uterine contractility during the early stages postpartum.
The development of Doppler processing extended the scope of sonographic imaging from an anatomical to a physiological basis. This technique became established as a clinical tool in human gynaecology. For example, it has been discussed that the implantation of an embryo is influenced by the uterine blood flow. In cows, this uterine blood flow was investigated, using surgically implanted Doppler ultrasonic or electromagnetic blood flow probes prior to the introduction of colour Doppler sonography in bovine medicine. Therefore, the aims of our studies were to use transrectal Doppler sonography for the non-invasive measurement of uterine and ovarian blood flow in cows and to determine changes in genital perfusion during the oestrous cycle, pregnancy and puerperium, respectively. The results of our studies show that transrectal flow imaging can be used to obtain blood flow velocity waveforms from the uterine arteries at any time during the oestrous cycle, pregnancy and puerperium. During all these phases, characteristic changes in the uterine blood flow could be observed. This uterine blood flow was low during diestrus and high during proestrus and oestrus. During pregnancy, an exponential rise in uterine blood supply could be detected. There was a positive relationship between the uterine blood flow volume (BFV) at the end of gestation and the birth weight of calves. During puerperium, the uterine BFV declined tremendously, especially during the first week after birth. In cows, with pathological disturbances of the pueperium a delayed decrease in the uterine BFV was observed. Characteristic alterations occurred also in the luteal blood flow during the oestrous cycle, which were highly related to those of the progesterone levels. Furthermore, it has been detected by the colour Doppler technique that there is no decrease, but an increase of the luteal blood flow at the beginning of luteolysis in cows. Another group has found that there are close relationships between the LH-surge and the follicular blood flow before ovulation. In conclusion, these studies show that transrectal colour Doppler sonography is a useful technique for the investigation of the genital blood flow and provides new information about physiological changes of the genital organs during, all reproductive phases. The influence of the genital blood flow on fertility in cows needs to be examined further in future studies.
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