Magda Erik-Soussi

Oxytocin pretreatment attenuates oxytocin-induced contractions in human myometrium in vitro.

Background:Oxytocin receptor desensitization has been shown to occur in humans at biomolecular level and in isolated rat myometrium; however, its effect on human myometrial contractility has not been demonstrated. The objective of this in vitro study was to investigate the contractile response of human pregnant myometrium to oxytocin after pretreatment with different concentrations of oxytocin for variable durations. Methods:Myometrial samples were obtained from 62 women undergoing elective cesarean deliveries under regional anesthesia. The strips were pretreated with oxytocin 10−10, 10−8, 10−5 M, or physiological salt solution (control) for 2, 4, 6, or 12 h, followed by a dose–response testing with oxytocin 10−10 to 10−5 M. Amplitude and frequency of contractions, motility index, and area under the curve during the dose–response period were recorded, analyzed with linear regression models, and compared among groups. Results:Pretreatment with oxytocin 10−5 and 10−8 M significantly reduced motility index (estimate [standard error]: −0.771 [0.270] square root units, P = 0.005 and −0.697 [0.293], P = 0.02, respectively) and area under the curve (−3.947 [1.909], P = 0.04 and −4.241 [2.189], P = 0.05, respectively) compared with control group, whereas pretreatment with oxytocin 10−10 M did not significantly attenuate contractions. Increase in duration of oxytocin pretreatment from 2 to 12 h significantly decreased amplitude (type 3 generalized estimating equation analysis: chi-square = 14.0; df = 3; P = 0.003), motility index (chi-square = 9.3; df = 3; P = 0.03), and area under the curve (chi-square = 10.5; df = 3; P = 0.02), but not the frequency of oxytocin-induced contractions. Conclusion:Pretreatment with oxytocin decreases oxytocin-induced myometrial contractions in a concentration and time-dependent manner, likely as a function of the oxytocin receptor desensitization phenomenon.

The Contractile Effects of Oxytocin, Ergonovine, and Carboprost and Their Combinations: an In Vitro Study on Human Myometrial Strips.

BACKGROUND:The objective of this study was to compare the in vitro contractile effects of the combination of oxytocin (low dose and high dose) with either ergonovine or carboprost in myometrial strips from women undergoing cesarean delivery (CD), and to study the effect of oxytocin pretreatment on these contractions. We hypothesized that the use of ergonovine or carboprost in combination with oxytocin would improve contractility compared with oxytocin alone. METHODS:Myometrial samples obtained from women undergoing elective CD were pretreated in organ bath chambers with either oxytocin 10−5 M (experimental) or physiological salt solution (control) for 2 hours. They were then washed and subjected to dose-response testing with oxytocin, ergonovine, or carboprost (10−10 to 10−5 M), either alone or in combination with a fixed low-dose (10−10 M) (LDOx) or high-dose (10−6 M) (HDOx) oxytocin. The amplitude, frequency, area under the curve, and motility index (amplitude × frequency) of contractions during the dose-response period were analyzed with linear regression models, and compared among the groups. The primary outcome was the motility index across the study groups. RESULTS:One hundred sixty-nine experiments were done in samples obtained from 56 women. The mean square root of the motility index [standard error] (√g·contractions/10 min) of oxytocin was significantly higher in the control (3.40 [0.24]) versus experimental group (2.02 [0.15]) (P < 0.001). When all control groups were compared, the motility index of oxytocin (3.21 [0.25]) was higher than that of ergonovine (2.13 [0.30], P < 0.001 [multiple comparisons adjusted P value, P < 0.001]), carboprost (1.88 [0.10], P < 0.001 [P < 0.001]), ergonovine + LDOx (2.07 [0.15], P < 0.001 [P < 0.001]), and carboprost + LDOx (1.82 [0.15], P < 0.001 [P < 0.001]) and was not different than that of ergonovine + HDOx (3.39 [0.32], P = 0.68 [P = 0.99]) and carboprost + HDOx (2.68 [0.30], P = 0.20 [P = 0.60]). However, in oxytocin-pretreated groups, carboprost + LDOx (motility index: 2.53 [0.08], P = 0.001 [multiple comparisons adjusted P value, P = 0.002]) and ergonovine + HDOx (2.82 [0.15], P < 0.001 [P < 0.001]) exhibited significantly superior contractility response compared with oxytocin alone, while ergonovine + LDOx (2.47 [0.13], P = 0.01 [P = 0.08]) and carboprost + HDOx (2.51 [0.20], P = 0.05 [P = 0.24]) showed higher mean contractility response compared with oxytocin alone but failed to reach statistical significance in adjusted analyses. CONCLUSIONS:The attenuation of oxytocin-induced contractility in oxytocin-pretreated myometrial strips is in keeping with the previously established oxytocin-receptor desensitization phenomenon. Oxytocin is the most effective of the uterotonics tested if the myometrium is not preexposed to oxytocin. However, in the oxytocin-pretreated myometrium, a synergistic response is evident, and the combination of oxytocin with either ergonovine or carboprost produces superior response compared with oxytocin alone. Further in vivo studies in humans are necessary to determine whether these differences identified in vitro are clinically significant.

In Vitro Comparative Effect of Carbetocin and Oxytocin in Pregnant Human Myometrium with and without Oxytocin Pretreatment.

Background:The purpose of this study was to compare in vitro contractile effects of oxytocin and carbetocin on human term pregnant myometrium with and without oxytocin pretreatment. Methods:This laboratory investigation was conducted on myometrial samples from women undergoing elective cesarean deliveries. The samples were dissected into four strips and suspended in individual organ bath chambers containing physiologic salt solution. After equilibration, they were pretreated with oxytocin 10−5 M (experimental group) or physiologic salt solution (control group) for 2 h and then subjected to dose–response testing with increasing concentrations of oxytocin or carbetocin (10−10 to 10−5 M). The amplitude, frequency, motility index (amplitude × frequency), and area under the curve of contractions were recorded and analyzed during the equilibration and dose–response periods. Comparisons were made between oxytocin-induced and carbetocin-induced contractions in control and oxytocin-pretreated groups. Motility index was the primary outcome measure. Results:Sixty-three experiments were performed (carbetocin, n = 31; oxytocin, n = 32) on samples from 18 women. The motility index of contractions (√g.contractions/10 min) produced by oxytocin was significantly higher than carbetocin in both control (regression-estimated difference, 0.857; 95% CI, 0.290 to 1.425; P = 0.003) and oxytocin-pretreated (0.813; 0.328 to 1.299; P = 0.001) groups. The motility index was significantly lower in oxytocin-pretreated groups than their respective controls for both oxytocin (−1.040; −1.998 to −0.082; P = 0.03) and carbetocin (−0.996; −1.392 to −0.560; P < 0.001). Conclusions:In vitro contractions produced by oxytocin are superior to carbetocin in human myometrium with or without oxytocin pretreatment. Oxytocin pretreatment results in attenuation of contractions induced by both oxytocin and carbetocin.

Contractile Efficacy of Various Prostaglandins in Pregnant Rat Myometrium Pretreated With Oxytocin

Oxytocin pretreatment of pregnant rat myometrium has been shown to reduce the contractions produced by further administration of oxytocin, as a function of the desensitization phenomenon. It is unclear whether this phenomenon affects the contractions produced by various prostaglandins that are used in the management of postpartum hemorrhage. The objective of this study was to investigate the contractile effects of various prostaglandins after oxytocin pretreatment and to compare their relative efficacies in vitro on pregnant rat myometrial strips. Myometrial samples from 29 pregnant Wistar rats at term were isolated and pretreated with oxytocin (10−8 mol/L, experimental group) or physiological salt solution (control group) for 1 hour. They were then subjected to dose–response testing with oxytocin (n = 32), PGF2α (n = 16), dinoprostone (n = 14), alprostadil (n = 14), or misoprostol (n = 15) with cumulative increases in the organ bath concentrations from 10−10 to 10−5 mol/L. The contractile efficacies of various prostaglandins and oxytocin during the dose response were analyzed using mixed linear modeling and compared between the groups. There was no significant difference in the amplitude, frequency, motility index (amplitude × frequency), or area under the curve of all prostaglandins between the groups pretreated with oxytocin and the control group. However, there was a significant decrease in the frequency (P = .02) and motility index (P = .05) in the dose–response curves of oxytocin in the groups pretreated with oxytocin compared with the control groups. Overall, oxytocin produced superior contractions compared with all other prostaglandins, while dinoprostone and misoprostol produced the weakest contractions. The uterotonic effects of various prostaglandins are not affected by oxytocin desensitization; and despite desensitization, oxytocin provides superior contractions compared with the prostaglandins.

Management of Simulated Maternal Cardiac Arrest by Residents: Didactic Teaching Versus Electronic Learning

Purpose Successful resuscitation of a pregnant woman undergoing cardiac arrest and survival of the fetus require prompt, high-quality cardiopulmonary resuscitation. The objective of this observational study was to assess management of maternal cardiac arrest by anesthesia residents using high-fidelity simulation and compare subsequent performance following either didactic teaching or electronic learning (e-learning). Methods Twenty anesthesia residents were randomized to receive either didactic teaching (Didactic group, n = 10) or e-learning (Electronic group, n = 10) on maternal cardiac arrest. Baseline management skills were tested using high-fidelity simulation, with repeat simulation testing one month after their teaching intervention. The time from cardiac arrest to start of perimortem Cesarean delivery (PMCD) was measured, and the technical and nontechnical skills scores between the two teaching groups were compared. Results The median [interquartile range] time to PMCD decreased after teaching, from 4.5 min [3.4 to 5.1 min] to 3.5 min [2.5 to 4.0 min] (P = 0.03), although the change within each group was not statistically significant (Didactic group 4.9 to 3.8 min, P = 0.2; Electronic group 3.9 to 2.5 min, P = 0.07; Didactic group vs Electronic group, P = 1.0). Even after teaching, only 65% of participants started PMCD within four minutes. Technical and nontechnical skills scores improved after teaching in both groups, and there were no differences between the groups. Conclusion There are gaps in the knowledge and implementation of resuscitation protocols and the recommended modifications for pregnancy among residents. Teaching can improve performance during management of maternal cardiac arrest. Electronic learning and didactic teaching offer similar benefits.