Low molecular weight heparin stimulates myometrial contractility and cervical remodeling in vitro.
OBJECTIVE
The low molecular weight heparin, Dalteparin, shortens human labor time. The aim of this study was to investigate if the mechanism behind this effect involves myometrial contractility and cervical ripening and if the anticoagulative activity is necessary for its effect.


METHODS
Experimental in vitro study.


METHODS
Lund University and Karolinska Institute, Sweden.


METHODS
The effect of low molecular weight heparins with or without anticoagulative properties on myometrial contractility was measured in vitro on smooth muscle strips from biopsies obtained at elective cesarean sections. The effects on cervical ripening were assessed in cervical fibroblasts cultured from explants of cervical biopsies obtained at delivery.


METHODS
Mean force and number of contractions in uterine smooth muscle strips and interleukin-8 (IL-8) secretion in cervical fibroblasts.


RESULTS
Myometrial smooth muscle strips pretreated with low molecular weight heparins showed increased contractile activity compared to untreated smooth muscle strips. Secretion of IL-8 from cultured cervical fibroblasts was significantly increased after treatment with low molecular weight heparin. Both these effects were independent of anticoagulative activity of the low molecular weight heparin.


CONCLUSIONS
A possible underlying mechanism for the shortened labor time after low molecular weight heparin treatment is enhanced myometrial contractility and an increased IL-8 secretion in cervical fibroblast, mimicking the final cervical ripening in vivo. Our data support the notion that anticoagulant activity is not required to promote labor.
Ekman-Ordeberg
Gunvor
G
Department of Women and Child Health, Division of Obstetrics and Gynecology, Karolinska Institutet, Stockholm, Sweden. Gunvor.Ekman-Ordeberg@ki.se
Hellgren
Margareta
M
Akerud
Anna
A
Andersson
Eva
E
Dubicke
Aurelija
A
Sennstrom
Maria
M
Byström
Birgitta
B
Tzortzatos
Gerasimos
G
Gomez
Maria F
MF
Edlund
Måns
M
Lindahl
Ulf
U
Malmström
Anders
A
D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D018929:Cell Culture Techniques; D020070:Cervical Ripening / Q000187:drug effects; D002584:Cervix Uteri / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D017985:Dalteparin / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D011247:Pregnancy; D046509:Tissue Culture Techniques; D014590:Uterine Contraction / Q000187:drug effects*
D000925:Anticoagulants; D016209:Interleukin-8; D017985:Dalteparin