A comparison of the effects of lindane and FeCl3/ADP on spontaneous contractions in isolated rat or human term myometrium.

Oxidative stress affects the contractile behavior of smooth muscle resulting in complications during labor. Toxicants such as lindane and ferric chloride (FeCl3)/adenosine diphosphate (ADP) cause oxidative stress and have previously been shown to inhibit smooth muscle contraction. In this study we examined the effects of the oxygen species scavengers, ascorbic acid and N-acetylcysteine on lindane and FeCl3/ADP's inhibition of spontaneous myometrial contractions in rat and human myometrium. Lindane and FeCl3/ADP gave rise to concentration-dependent reductions in rat (EC50 11.8×10-6M and 0.9×10-3M) and human myometrial contractions (EC50 16.3×10-6M and 1.1×10-3M, respectively). Pre-treatment with N-acetylcysteine significantly increased the EC50 for the effects of lindane on motility index of human tissue and reduced the maximum inhibitory effect of FeCl3/ADP on contractions in both rat and human myometrium. Ascorbic acid reduced the effects of FeCl3/ADP in rat tissue only. In conclusion pre-treatment with specific antioxidants may protect both rat and human myometrium from the inhibitory effects of lindane and FeCl3/ADP.

A Role for Adrenergic Receptors in the Uterotonic Effects of Ergometrine in Isolated Human Term Nonlaboring Myometrium.

BACKGROUND: Ergometrine is a uterotonic agent that is recommended in the prevention and management of postpartum hemorrhage. Despite its long-standing use, the mechanism by which it acts in humans has never been elucidated fully. The objective of this study was to investigate the role of adrenoreceptors in ergometrine's mechanism of action in human myometrium. The study examined the hypothesis that α-adrenoreceptor antagonism would result in the reversal of the uterotonic effects of ergometrine. METHODS: Myometrial samples were obtained from women undergoing elective cesarean delivery. The samples were then dissected into strips and mounted in organ bath chambers. After the generation of an ergometrine concentration-response curve (10 to 10 M), strips were treated with increasing concentrations of ergometrine (10 to 10 M) alone and ergometrine (10 to 10 M) in the presence of phentolamine (10 M), prazosin (10 M), propranolol (10 M), or yohimbine (10 M). The effects of adding ergometrine and the effect of drug combinations were analyzed using linear mixed effects models with measures of amplitude (g), frequency (contractions/10 min), and motility index (g×contractions/10 min). RESULTS: A total of 157 experiments were completed on samples obtained from 33 women. There was a significant increase in the motility index (adding 0.342 g × counts/10 min/µM; 95% confidence interval [CI], 0.253-0.431, P < .001), amplitude (0.078 g/µM; 95% CI, 0.0344-0.121, P = 5e-04), and frequency (0.051 counts/10 min/µM; 95% CI, 0.038-0.063, P < .001) in the presence of ergometrine. The α-adrenergic antagonist phentolamine and the more selective α1-adrenergic antagonist prazosin inhibited the ergometrine mediated increase in motility index, amplitude, and frequency (-1.63 g × counts/10 min/µM and -16.70 g × counts/10 min/µM for motility index, respectively). CONCLUSIONS: These results provide novel evidence for a role for α-adrenergic signaling mechanisms in the action of ergometrine on human myometrial smooth muscle in the in vitro setting. Information that sheds light on the mechanism of action of ergometrine may have implications for the development of further uterotonic agents.

Evaluation of point-of-care maternal venous lactate testing in normal pregnancy.

OBJECTIVE: There is little information about whether the established non-pregnant adult venous lactate reference range is appropriate for pregnancy. This prospective observational study examined whether the non-pregnant adult reference range is appropriate during pregnancy. METHODS: Women attending for routine prenatal appointments or elective cesarean delivery in a tertiary hospital were recruited. Clinical details were recorded and venous lactate concentration was measured using a point-of-care (POC) device. RESULTS: Of the 246 women, 199 were 6-18 weeks' gestation and 47 were 36-42 weeks' gestation. Mean lactate concentration was within the non-pregnant reference range in early and late pregnancy (0.86 SD ± 0.46 mmol/L and 1.15 SD ± 0.40 mmol/L, respectively). The mean time between phlebotomy and result was 6.1 SD ± 1.7 min. There was no correlation between lactate levels and either maternal age or time interval from tourniquet placement to lactate measurement. In women of 6-18 weeks' gestation positive bivariate relationships were found between lactate and BMI (p = 0.03, r = 0.158), earlier gestational age (p = 0.04, r = -0.145), and smoking (p = 0.01, r = 0.183), but these were not found in late pregnancy. CONCLUSIONS: The venous lactate reference range for the non-pregnant adult may be applied in pregnancy. Further studies should examine lactate dynamics in labor and postpartum.

Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium.

The existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [d-Ala 2, d-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA, respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1 × 10(-7)M-1 × 10(-4)M; 54% reduction in contractile activity, P<0.001 at 1 × 10(-4)M concentration). Mu and delta opioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-labouring myometrium in vitro.

Epidural analgesia practices for labour: results of a 2005 national survey in Ireland.

BACKGROUND AND OBJECTIVE: The last 25 years have seen changes in the management of epidural analgesia for labour, including the advent of low-dose epidural analgesia, the development of new local anaesthetic agents, various regimes for maintaining epidural analgesia and the practice of combined spinal-epidural analgesia. We conducted a survey of Irish obstetric anaesthetists to obtain information regarding the conduct and management of obstetric epidural analgesia in Ireland in 2005. The specific objective of this survey was to discover whether new developments in obstetric anaesthesia have been incorporated into clinical practice. METHODS: A postal survey was sent to all anaesthetists with a clinical commitment for obstetric anaesthesia in the sites approved for training by the College of Anaesthetists, Ireland. RESULTS: Fifty-three per cent of anaesthetists surveyed responded. The majority of anaesthetists (98%) use low-dose epidural analgesia for the maintenance of analgesia. Only 11% use it for test-dosing and 32% for the induction of analgesia. The combined spinal-epidural analgesia method is used by 49%, but two-thirds of those who use it perform fewer than five per month. Patient-controlled epidural analgesia was in use at only one site. CONCLUSION: It appears that Irish obstetric anaesthetists have adopted the low-dose epidural analgesia trend for the maintenance of labour analgesia. This practice is not as widespread, however, for test dosing, the induction of analgesia dose or in the administration of intermittent epidural boluses to maintain analgesia when higher concentrations are used. Since its introduction in 2000, levobupivacaine has become the most popular local anaesthetic agent.

A comparison of the inhibitory effects of bupivacaine and levobupivacaine on isolated human pregnant myometrium contractility.

BACKGROUND: Epidural analgesia with levobupivacaine and bupivacaine is a common and effective method of labor pain relief. However, its use is associated with an increased instrumental delivery rate. One of the mechanisms postulated to account for this unwanted effect is the direct effect of local anesthetics on myometrial contractility. We determined the effects of bupivacaine and levobupivacaine on the amplitude and frequency of contractions of human term myometrium. METHODS: Uterine specimens were obtained from nonlaboring parturients scheduled for elective lower-segment cesarean delivery at term. Longitudinal muscle strips were prepared and mounted vertically in tissue chambers, and changes in the amplitude (peak force) and the frequency of contractions were recorded. Spontaneous contractions commenced after a period of application of 1 g (9.81 mN) of tension to the myometrial strips. No uterotonic drugs were used. The muscle strips were then exposed to cumulative concentrations of bupivacaine and levobupivacaine and dose-response curves were generated. RESULTS: Both bupivacaine and levobupivacaine decreased the amplitude of contractions in human myometrium in a concentration-dependent manner, reaching significance at 1x10(-4) M for both bupivacaine and levobupivacaine compared with the internal control amplitude. With both drugs, the decrease in amplitude was accompanied by an increase in the frequency of contractions reaching significance at 3x10(-5) M for both bupivacaine and levobupivacaine compared with the internal control frequency. CONCLUSIONS: The concentrations required for the effects on amplitude are much higher (33 fold) than the clinically relevant plasma concentrations of these drugs after epidural administration, and are unlikely to be significant in the setting of low-dose epidural analgesia in labor.