44 Term labor may be mediated by a decrease in the alpha 3 isoform of the sodium pump: A potential...

1
S90 SMFM Abstracts 44 TERM LABOR MAY BE MEDIATED BY A DECREASE 1N THE ALPHA 3 ISOo FORM OF THE SODIUM PUMP: A POTENTIAL MECHANISM FOR THE SWITCH FROM UTERINE CONTRACTURES TO CONTRACTIONS STEVEN GRAVES 1, MICHAEL ESPLIN ~, BARDETT FAUSETT 2, DAVID FAUX3; tBfigham Young University, Biochemistry, Provo, UT; 2University of Utah, Obstetrics and Gynecology, SLC, UT: "~Brigham Young University, Chemistry and Biochemistry, Provo, UT OBJECTIVE: The sodium pump (SP) occurs as three isoforms that regulate cell sodium and potassium and maintain the membrane potential. Reduced SP activity leads to membrane depolarization, increased cytosolic ionized cMcium, which when sufficient results in contraction of cardiac and vascular smooth muscle. We hypothesized that term labor may be anticipated by a reduction in one or more of the SP isoforms in the human myumetrium, leading to sustained contractions. STUDY DESIGN: Myometrial samples were collected from the lower uterine segment of laboring and non-laboring patients undergoing Caesarean section, Tissues were homogenized, separated by 7% SDS-PAGE and probed by SP isoform-specific monoclonal antibodies. Membranes were analyzed digitally to determine relative amounts of each SP isoform for every tissue. An unpaired Student's t test used to compare isoform abundance of laboring and non- laboring tissues. A Pvalue <.05 was considered statistically significant. RESULTS: MyometriM specimens were obtained fi'om 10 laboring and 30 non-laboring patients, Gestational age at delivex y was comparable between groups. We found no significant change in the abundance of the SP alpha 1 and 2 isoforms in women who had progressed to full labor. However, levels of the SP alpha 3 isoform were markedly lower in woumn who had progressed to labor compared to women r~ot experiencing active labor (Labor: 19.8 +- 1,6, No-labor: 52.3 +- 7.7 desity units, P = .0002). CONCLUSION: Sustained reduction in SP function leads initially to increased uterine smooth muscle sensitivity to agonists and later to direct sustained phasic contractions of uterus. Our results suggest that changes in SP Mpha 3 isoform abundance anticipate tabor and hence may increase contrac- tile force that constitutes the shift t-ore isolated contractures to coordinated contractions that describe the spontaneous onset of labor. 46 December 2001 AmJ Obstet Gynecol THE INTERDELIVERY INTERVAL AND THE RISK OF UTERINE RUP- TURE EMMANUEL BUJOLD t , NATHAN WAGSTAFF1 , CAMILLE BUJOLD 2, ANDREE SANSREGRET ~, FRANCOIS HAREL 2, ROBERT J. GAUTHIER2; 1Wayne State University, Obstetrics & Gynecology, Detroit, MI; 2Saiute-Justine Hospital, Ob/Gyn, Montreal, Quebec; ,~Universite de Montreal, Ob/Gyn, Montreal, Quebec OBJECTIVE: To determine the effect of the interval between the previous cesarean section and the subsequent trial of labor on the likelihood of successful VBAC and syinptomatic uterine rupture. STUDY DESIGN: The nmdical records of all women with a histmT of one prior cesarean were reviewed. Patients with a previous vaginal delivery or with more than one cesarean were excluded. Patients were divided in 4 groups according to the interval between their prior cesarean and their subsequent delivery: <12 months, 13-24 months, 25-36 months and >36 months. Rates of uterine rupture were compared for these 4 groups. Potential confounders were controlled using logistic regression analyses. RESULTS: 1527 patients were included. The rate of successful VBAC was comparable in each group: 13/21 (62%), 275/372 (74%), 310/436 (71%), 488/698 (70%), P = .43. The rate of uterine rapture was significantly higher in the first two groups. In a logistic regression analysis controlling for seven confounding variables, the odds ratio for uterine rupture in those patients with an interdelivery interval less than 24 months was 2.65 (95%CI = 1.08, 6.46). CONCLUSION: A short interdelivel T interval is associated with a increased risk of uterine rupture. This information can certainly be useful in counseling patients undergoing a subsequent trim of labor after a cesarean. Figure Rate of uterine rupture o 92 o .8o l l i ~3-24 2fiL38 ~30 Iotetdellv~ry inl'~r~el (~bhths) 45 CYCLOOXYGENASE AND LIPOXYGENASE INVOLVEMENT IN IN- CREASED UTERINE CONTRACTILITY DUE TO ENDOGENOUS MAST CELL DEGRANULATION EGLE BYTAUTIENE 1, YURI VEDERNIKOV 2, GEORGE SAADE2, ROBERTO ROMERO 3, ROBERT GARFIELD2; 1University of Texas Medical Branch, ObsTetrics & Gynecology, Galveston, TX; 2University of Texas Medical Branch, Obstetrics and Gynecology, Galveston, TX; ~NICHD, Perinatology Research Branch, Bethesda, MD OBJECTIVE: To determine the roles of cyclooxygenase and lipoxygenase in the increase in uterine contractility in response to endogenous mast cell (MC) degranulation in pregnant mice. STUDY DESIGN: Uterine rings obtained from pregnant day 14 and day ] 8 (term) 5-1ipoxygenase knockout mice (KO, 129-Alox5tmlFun) and their corresponding wild-type control (WT, 129S3/SvlmJ) (n 5-7 in each group) were mounted for isometric tension recording in organ chambers filled with Krebs' solution and bubbled with 5% CO2 in air. Responses of uterine tissues to the MC degranulating agent, compound 48/80 (100 g/ml), were determined in the absence or presence of ibuprofen (10-5 M; cyclooxygenase inhibitor), nordihydroguaretic acid (NDGA, 10-5 M; cyclooxygenase and lipoxygenase inhibitor), linoleyl hydroxamic acid (LHA, 10-5 M: lipoxygenase inhibitor), BW-B 70C (10-5 M; specific 5-1ipoxygenase inhibitor). Changes in integral activity tor 10 rain were expressed as % of the reference contraction to 60 mM KCI. For statistical analysis Student's t test, One Way ANOVA were used as appropriate (significance: P < .05). RESULTS: Ibuprofen, NDGA and BW-B 70C inhibited contractions induced by compound 48/80 in day 18 pregnant WT mice. Ibuprofen inhibited contractions induced by compound 48/80 in d~ty 14 pregnant KO mice. NDGA and LHA were more effective in day 18 compared with day 14 KO mice. Ibuprofen, NDGA and BW-B 70C were more effective in 18 compared with day 14 ~rr mice. ffiuprofen inhibited contractions induced by compound 48/80 significantly more in day 14 KO compared to day 14 WT mice. CONCLUSION: Mast cell degranulation results in increased uterine contractility. Both lipoxygenase and cyclooxygenase products are involved in modulating the increase in uterine contractility evoked by endogenous mast cell degranulation. 47 INTERNATIONAL EDUCATIONAL OUTREACH: MODULAR TEACHING AS AN APPROACH TO DECREASING MATERNAL AND NEONATAL MOR- TALITY IN LITHUANIA DAVID SCHRIMMER 1, ARUNAS LIUBSYS2; 1Uni- versity of California, San Diego, Reproductive Medicine, San Diego, CA; 2Vilnius Universi~' Children's Hospital, Neonatology, Vilnius OBJECTIVE: To provide updated clinical information and skill sets to both perinatologists and neonatologists to decrease maternal and infant morbidity/mortality in Lithuania. In addition, emphasis was placed on the practice of evidence based medicine instead of time-honored, Soviet protocols. STUDY DESIGN: Coordinated through International Relief Teams, over a 5-year period, U.S. trained reaching teams have traveled to Lithuania biyearly for nine teaching modules. A Perinatologist and Neonatologist lead each module. Additional team nmmbers have been selected from tile specialties of general obstetrics, perinatal pathology, obstetrical anesthesia, dysmorphology, biostatistics, and specialty rmrsing. After an initial needs assessment module, a comprehensive curriculum was developed in collaboration with the national perinatal/neonatal society in Lithuania. A total of forty-eight obstetricians, neonatologists and specialty nurses were selected from 12 leading hospitals in Lithuania. These individuals attend all nine modules, and receive a translated copy of all lecture rnateriMs at the end of each module for secondaL~ teaching. The initial modules were primarily didactic sessions, while the finn module is a six-week, side-by-side clinical module. RESULTS: See Table. CONCLUSION: The overall reduction in maternal and neonatal mortMity rates is clearly multifactoriaL Nonetheless, the continuing decline suggests that organized, modular teaching may provide an efficient approach m improving maternal and neonatal outcome in countries where infant and maternal mortality rates remain hNh. Table Mortality rates 1992" 1993 1994 1995 1996 1997 1998 1999 Neonates 11.8 10.3 9.0 7.9 5.9 6.0 4.9 4.7 (0-27 days)** Inf~mts 16.5 15.4 14.0 12.4 10.0 10.2 9.2 8.6 (0-1 yr.)** Maternal*** 44.0 30.0 21.3 29.3 17.9 23.8 18.9 16.6 *First full year of independence from Russia. **Per 1,000 live births. ***Per 100.000 live births.

Transcript of 44 Term labor may be mediated by a decrease in the alpha 3 isoform of the sodium pump: A potential...

Page 1: 44 Term labor may be mediated by a decrease in the alpha 3 isoform of the sodium pump: A potential mechanism for the switch from uterine contractures to contractions

S90 SMFM Abstracts

44 TERM LABOR MAY BE MEDIATED BY A DECREASE 1N THE ALPHA 3 ISOo FORM OF THE SODIUM PUMP: A POTENTIAL MECHANISM FOR THE SWITCH FROM UTERINE CONTRACTURES TO CONTRACTIONS STEVEN GRAVES 1, MICHAEL ESPLIN ~, BARDETT FAUSETT 2, DAVID FAUX3; tBfigham Young University, Biochemistry, Provo, UT; 2University of Utah, Obstetr ics and Gynecology, SLC, UT: "~Brigham Young University, Chemistry and Biochemistry, Provo, UT

OBJECTIVE: The sodium p u m p (SP) occurs as three isoforms that regulate cell sodium and potassium and maintain the membrane potential. Reduced SP activity leads to membrane depolarization, increased cytosolic ionized cMcium, which when sufficient results in contraction of cardiac and vascular smooth muscle. We hypothesized that term labor may be anticipated by a reduction in one or more of the SP isoforms in the h u m a n myumetrium, leading to sustained contractions.

STUDY DESIGN: Myometrial samples were collected f rom the lower uterine segment of laboring and non-laboring patients undergo ing Caesarean section, Tissues were homogenized, separated by 7% SDS-PAGE and probed by SP isoform-specific monoclonal antibodies. Membranes were analyzed digitally to determine relative amounts of each SP isoform for every tissue. An unpaired Student 's t test used to compare isoform abundance of labor ing and non- laboring tissues. A Pvalue <.05 was considered statistically significant.

RESULTS: MyometriM specimens were obtained fi'om 10 laboring and 30 non- labor ing patients, Gestational age at delivex y was comparable between groups. We found no significant change in the abundance of the SP alpha 1 and 2 isoforms in women who had progressed to full labor. However, levels of the SP alpha 3 isoform were markedly lower in woumn who had progressed to labor compared to women r~ot experiencing active labor (Labor: 19.8 +- 1,6, No-labor: 52.3 +- 7.7 desity units, P = .0002).

CONCLUSION: Sustained reduc t ion in SP func t ion leads initially to increased uter ine smooth muscle sensitivity to agonists and later to direct sustained phasic contractions of uterus. Our results suggest that changes in SP Mpha 3 isoform abundance anticipate tabor and hence may increase contrac- tile force that constitutes the shift t -ore isolated contractures to coordinated contractions that describe the spontaneous onset of labor.

46

December 2001 A m J Obstet Gynecol

THE INTERDELIVERY INTERVAL AND THE RISK OF UTERINE RUP- TURE EMMANUEL BUJOLD t , NATHAN WAGSTAFF 1 , CAMILLE BUJOLD 2, ANDREE SANSREGRET ~, FRANCOIS HAREL 2, ROBERT J. GAUTHIER2; 1Wayne State University, Obstetrics & Gynecology, Detroit, MI; 2Saiute-Justine Hospital , O b / G y n , Montreal , Quebec; ,~Universite de Montreal , O b / G y n , Montreal, Quebec

OBJECTIVE: To determine the effect of the interval between the previous cesarean section and the subsequent trial of labor on the l ikel ihood of successful VBAC and syinptomatic uterine rupture.

STUDY DESIGN: The nmdical records of all women with a histm T of one prior cesarean were reviewed. Patients with a previous vaginal delivery or with more than one cesarean were excluded. Patients were divided in 4 groups according to the interval between their pr ior cesarean and their subsequent delivery: <12 months, 13-24 months, 25-36 months and >36 months. Rates of uter ine rup ture were compared for these 4 groups. Potential confounders were controlled using logistic regression analyses.

RESULTS: 1527 patients were included. The rate of successful VBAC was comparable in each group: 13/21 (62%), 275/372 (74%), 310/436 (71%), 488/698 (70%), P = .43. The rate of uterine rap ture was significantly higher in the first two groups. In a logistic regression analysis control l ing for seven confounding variables, the odds ratio for uterine rupture in those patients with an interdelivery interval less than 24 months was 2.65 (95%CI = 1.08, 6.46).

CONCLUSION: A shor t interdelivel T interval is associated with a increased risk of uterine rupture. This information can certainly be useful in counseling patients undergo ing a subsequent trim of labor after a cesarean.

Figure Rate of uterine rupture

o 92 o .8o

l l i

~3-24 2fiL38 ~30

Iotetdellv~ry inl '~r~el (~bhths)

45 CYCLOOXYGENASE AND LIPOXYGENASE INVOLVEMENT IN IN- CREASED UTERINE CONTRACTILITY DUE T O ENDOGENOUS MAST CELL DEGRANULATION EGLE BYTAUTIENE 1, YURI VEDERNIKOV 2, GEORGE SAADE 2, ROBERTO ROMERO 3, ROBERT GARFIELD2; 1University of Texas Medical Branch, ObsTetrics & Gynecology, Galveston, TX; 2University of Texas Medical Branch, Obstetrics and Gynecology, Galveston, TX; ~NICHD, Perinatology Research Branch, Bethesda, MD

OBJECTIVE: To determine the roles of cyclooxygenase and lipoxygenase in the increase in uterine contractility in response to endogenous mast cell (MC) degranulat ion in pregnant mice.

STUDY DESIGN: Uterine rings obtained f rom pregnant day 14 and day ] 8 (term) 5-1ipoxygenase knockou t mice (KO, 129-Alox5tmlFun) and their corresponding wild-type control (WT, 129S3/SvlmJ) (n 5-7 in each group) were mounted for isometric tension recording in organ chambers filled with Krebs' solution and bubbled with 5% CO2 in air. Responses of uterine tissues to the MC degranu la t ing agent , c o m p o u n d 4 8 / 8 0 (100 g / m l ) , were determined in the absence or presence of ibuprofen (10-5 M; cyclooxygenase inhibi tor) , nord ihydroguare t i c acid (NDGA, 10-5 M; cyclooxygenase and lipoxygenase inhibitor), linoleyl hydroxamic acid (LHA, 10-5 M: lipoxygenase inhibitor), BW-B 70C (10-5 M; specific 5-1ipoxygenase inhibitor). Changes in integral activity tor 10 rain were expressed as % of the reference contraction to 60 mM KCI. For statistical analysis Student's t test, One Way ANOVA were used as appropriate (significance: P < .05).

RESULTS: Ibuprofen , NDGA and BW-B 70C inhibi ted contrac t ions induced by c o m p o u n d 4 8 / 8 0 in day 18 p r e g n a n t WT mice. Ibuprofen inhibited contractions induced by compound 48/80 in d~ty 14 p regnan t KO mice. NDGA and LHA were more effective in day 18 compared with day 14 KO mice. Ibuprofen, NDGA and BW-B 70C were more effective in 18 compared with day 14 ~ r r mice. ffiuprofen inhibited contractions induced by compound 48 /80 significantly more in day 14 KO compared to day 14 WT mice.

CONCLUSION: Mast cell degranu la t ion results in increased u ter ine contractility. Both lipoxygenase and cyclooxygenase products are involved in modulat ing the increase in uterine contractility evoked by endogenous mast cell degranulation.

47 INTERNATIONAL EDUCATIONAL OUTREACH: MODULAR TEACHING AS AN APPROACH TO DECREASING MATERNAL AND NEONATAL MOR- TALITY IN LITHUANIA DAVID SCHRIMMER 1, ARUNAS LIUBSYS2; 1Uni- versity of California, San Diego, Reproduct ive Medicine, San Diego, CA; 2Vilnius Universi~' Children's Hospital, Neonatology, Vilnius

OBJECTIVE: To provide upda ted clinical informat ion and skill sets to bo th perinatologists and neonatologis ts to decrease materna l and infant morbidi ty/morta l i ty in Lithuania. In addition, emphasis was placed on the practice of evidence based medicine instead of t ime-honored, Soviet protocols.

STUDY DESIGN: Coordinated th rough International Relief Teams, over a 5-year period, U.S. trained reaching teams have traveled to Lithuania biyearly for n ine teaching modules. A Perinatologist and Neonatologis t lead each module. Additional team nmmbers have been selected f rom tile specialties of general obstetrics, perinatal pathology, obstetrical anesthesia, dysmorphology, biostatistics, and specialty rmrsing. After an initial needs assessment module, a comprehensive curriculum was developed in collaboration with the national per ina ta l /neona ta l society in Lithuania. A total of forty-eight obstetricians, neonatologists and specialty nurses were selected from 12 leading hospitals in Lithuania. These individuals at tend all nine modules, and receive a translated copy of all lecture rnateriMs at the end of each module for secondaL~ teaching. The initial modules were primarily didactic sessions, while the f inn module is a six-week, side-by-side clinical module.

RESULTS: See Table. CONCLUSION: The overall reduction in maternal and neonatal mortMity

rates is clearly multifactoriaL Nonetheless, the continuing decline suggests that organized, modular teaching may provide an efficient approach m improving materna l a n d neonata l ou tcome in countr ies where infant a n d maternal mortality rates remain hNh.

Table Mortality rates

1992" 1993 1994 1995 1996 1997 1998 1999

Neonates 11.8 10.3 9.0 7.9 5.9 6.0 4.9 4.7 (0-27 days)**

Inf~mts 16.5 15.4 14.0 12.4 10.0 10.2 9.2 8.6 (0-1 yr.)**

Maternal*** 44.0 30.0 21.3 29.3 17.9 23.8 18.9 16.6

*First full year of independence from Russia. **Per 1,000 live births. ***Per 100.000 live births.