The Extracorporeal Perfusion of Swine Uterus as an Experimental Model: The Effect of Oxytocic Drugs

 

 Buy Article Permissions and Reprints

Abstract

The objective of this study was to establish an experimental model for extracorporeal perfusion of swine uterus. In order to validate this model, we examined some biochemical parameters and determined the effect of oxytocic drugs (Oxytoxin, Prostaglandin E₂) on extracorporeal perfused swine uteri. Thirty swine uteri were perfused with Krebs-Ringer bicarbonate-glucose buffer for a period up to eleven hours with the aim to preserve a viable organ, which should be responsive to hormones. The intrauterine pressure was recorded after administration of various concentrations of oxytocin and prostaglandin E₂. Perfusate pH, perfusate lactate, partial oxygen and carbon dioxide tensions, oxygen saturation, and hydrogencarbonate levels in the perfusate, all indicators of tissue ischemia or cell necrosis, showed good preservation of the organ for up to seven hours. We examined the relation of intrauterine pressure to oxytocin and prostaglandin E₂. Both were able to induce contractions of the uterus, whereas prostaglandin E₂ produced rhythmical contractions of smaller amplitude and a higher frequency. We could demonstrate that our perfusion system was able to preserve the swine uterus in a functional condition appropriate for the study of physiological questions.

References

• 1 Toledo-Pareyra L H. Basic Concepts of Organ Procurement, Perfusion and Preservation for Transplantation. New York; Academic Press 1982
  Google Scholar
• 2 Bulletti C, Jasonni V M, Lubicz S, Flamigni C, Crurbide E. Extracorporeal perfusion of the human uterus.  Am J Obstet Gynecol. 1986;  154 683-688
  PubMedGoogle Scholar
• 3 Bulletti C, Jasonni V M, Tabanelli S, Gianaroli L, Ciotti P M, Ferraretti A P, Flamini C. Early human pregnancy in vitro utilizing an artificial perfused uterus.  Fertil Steril. 1988;  49 991-996
  PubMedGoogle Scholar
• 4 Bulletti C, Jasonni V M, Martinelli G, Govoni E, Tabanelli S, Ciotti P M, Flamigni C. A 48-hour preservation of an isolated human uterus: endometrial responses to sex steroids.  Fertil Steril. 1987;  47 122-129
  PubMedGoogle Scholar
• 5 Bulletti C, Jasonni V M, Ciotti P M, Tabanelli S, Naldi S, Flamigni C. Extraction of estrogens by human perfused uterus. Effects of membrane permeability and binding by serum proteins on differential influx into endometrium and myometrium.  Am J Obstet Gynecol. 1988;  159 509-515
  PubMedGoogle Scholar
• 6 Bulletti C, Prefetto R A, Bazzocchi G, Romero R, Mimmi P, Polli V, Lanfranchi G A, Labate A M, Flamigni C. Electromechanical activities of human uteri during extra-corporeal perfusion with ovarian steroids.  Hum Reprod. 1993;  8 1558-1563
  CrossrefPubMedGoogle Scholar
• 7 Bulletti C, de Ziegler D, Flamigni C, Giacommuci E, Polli V, Bolelli G, Franceschetti F. Targeted drug delivery in gynaecology: the first uterine pass effect.  Hum Reprod. 1997;  12 1073-1079
  CrossrefPubMedGoogle Scholar
• 8 Bulletti C, Flamigni C. Fisiopatologia dell' Endometrio. Endocrinologia 1997 I, Numero I
  Google Scholar
• 9 Bulletti C, de Ziegler D, Polli V, Diotallevi L, Del Ferro E, Flamigni C. Uterine Contractivity during the menstrual cycle.  Hum Reprod. 2000;  15 81-89
  PubMedGoogle Scholar
• 10 Swindle M M. Anesthesia and Experimental Techniques in Swine. Ames; Iowa State University Press 1998
  Google Scholar
• 11 Wiest D B, Swindle M M, Garner S S, Smith A C, Gillette P C. Pregnant Yucatan miniature swine as a model for investigating fetal drug therapy. In: Tumbleson M, Shook L (eds.) Advances in Swine in Biomedical Research. New York; Plenum Press 1996
  Google Scholar
• 12 Czekanowski R. In vitro studies into interdependence of volume and pressure in non-pregnant human uterus.  Zentralbl Gynakol. 1980;  102 129-137
  PubMedGoogle Scholar
• 13 Czekanowski R. Investigations of the human isolated nonpregnant uterus contractility in the course of the menstrual cycle by measuring intramyometrial Pressure.  Zentralbl Gynakol. 1977;  99 646-656
  PubMedGoogle Scholar
• 14 Czekanowski R, Mosler K H. The influence of drugs on perfusion pressure and contractility of the human uterus.  Arch Gynaek. 1973;  215 39-52
  PubMedGoogle Scholar
• 15 Richter O, Wardelmann E, Dombrowski F, Schneider C, Kiel R, Wilhelm K, Schmolling J, Kupka M, van der Ven H, Krebs D. Extracorporeal perfusion of the human uterus as an experimental model in gynaecology and reproductive medicine.  Hum Reprod. 2000;  15 1235-1240
  CrossrefPubMedGoogle Scholar
• 16 Tojo S, Mochizuki M, Nhya T, Kanazawa S, Sakai T, Tsuchiva K, Koga A, Yokohama S, Minva S, Anno G, Ono H. Studies on the new organ survive device for uterus and placenta.  Acta Obstet et Gynaecol Jap. 1970;  17 263-270
  PubMedGoogle Scholar
• 17 Tojo S, Fukunishu H, Tsuchihashi T, Shimura T, Mikami K, Kaku H. Electrical activity recorded from ovarian tissue in perfused human utero-tubo-ovarian unit.  J Reprod Fert. 1975;  44 587-589
  PubMedGoogle Scholar
• 18 Tojo S, Mochizuki M, Kunazawa S, Mikami K, Tsuchihashi T, Shimura T. In vitro perfusion of the human utero-tubo-ovarian unit.  Obstet Gynecol. 1974;  5 119-129
  PubMedGoogle Scholar
• 19 Tojo S, Fukunishi H. In vitro perfusion of human reproductive organs.  Thrombosis Research. 1976;  5 149-158
  PubMedGoogle Scholar
• 20 Boxall D K, Ford A P, Choppin A, Nahorski S R, Challiss R A, Eglen R M. Characterization of an atypical muscarinic cholinoceptor mediating contraction of the guinea pig isolated uterus.  Br J Pharmacol. 1998;  124 1615-1622
  CrossrefPubMedGoogle Scholar
• 21 Cantabrana B, Hidalgo A. Effects of nonsteroidal antiestrogens in vitro rat uterus.  Pharmacology. 1992;  45 329-337
  PubMedGoogle Scholar
• 22 Gallagher L A, Gantieri R F. Influence of a combination of ritodrine and nifetipine on the isolated rat uterus.  Res Commun Chem Pathol Pharmacol. 1992;  75 3-18
  PubMedGoogle Scholar
• 23 Dynarowicz I, Watkowski T, Dziegielewski M. Analysis of the effects of oxytocin, vasopressin, angiotensin, serotonin and histamine on the blood flow in the reproductive organs of swine during the estrous cycle.  Pol Arch Weter. 1988;  28 99-111
  PubMedGoogle Scholar
• 24 Dynarowicz I, Mortensen A, Watkowski T. The role of adrenergic receptors in the regulation of blood flow in the reproductive organs of swine during the estrous cycle.  Pol Arch Weter. 1988;  28 15-127
  PubMedGoogle Scholar
• 25 Dynarowicz I, Mortensen A. Effect of adrenomimetic drugs on the blood vessels of the genital organs of swine during the estrous cycle.  Pol Arch Weter. 1986;  26 75-86
  PubMedGoogle Scholar
• 26 Dynarowicz I, Dziegielewski M. The role of the cholinergic system in the regulation of blood flow through the reproductive organs of swine during the estrous cycle.  Pol Arch Weter. 1987;  27 69-83
  PubMedGoogle Scholar
• 27 Ritschel W A, Banerjee P S. Physiological pharmacokinetic models: principles, applications, limitations and outlook.  Methods Find Exp Clin Pharmacol.. 1986;  8 603-614
  PubMedGoogle Scholar
• 28 Scharl A, Beckmann M W, Arthwohl J E, Holt J A. Comparisons of radioiodoestradiol blood-tissue exchange after intravenous or intraarterial injection.  Int J Radiat Oncol Biol Phys. 1995;  32 137-146
  PubMedGoogle Scholar
• 29 Chernaeva L. Related articles, variations in the spontaneous activity of the uterine muscle in vitro and in situ and its response to oxytocin.  Acta Physiol Pharmacol Bulg. 1976;  2 54-62
  PubMedGoogle Scholar
• 30 Anderson N C. Physiologic basis of myometrial function.  Seminars in Perinatology. 1978;  2 211-222
  PubMedGoogle Scholar
• 31 Rath W, Winkler M. Medikamentöse Geburtseinleitung. Bremen; Uni-Med Verlag 2001
  Google Scholar

Dr. R. Dittrich

University of Erlangen/Nuremberg · Department of Obstetrics and Gynecology

Universitätsstr. 21 - 23 · 91054 Erlangen · Germany

Phone: +49(9131)8533481

Fax: +49(9131)8533552 ·

Email: ralf.dittrich@gyn.med.uni-erlangen