Poster 13: Altered Contractility of the Vaginal Muscularis in Prolapse

Abstract

OBJECTIVE: It is estimated that over 40% of women aged 40 years or more have some degree of pelvic organ prolapse. To elucidate the pathogenesis of pelvic organ prolapse, it is important to investigate the mechanism of support in the pelvis on both a structural and molecular level. The purpose of this study was to determine whether there are alterations in contractile properties of vaginal smooth muscle in patients with vaginal wall prolapse. METHODS: The study group consisted of 8 women diagnosed with apical prolapse and scheduled to undergo hysterectomy and prolapse repair. The control group consisted of one woman without prolapse undergoing hysterectomy for a benign condition. Patients with gynecologic malignancy were excluded. Biopsy pairs (anterior and posterior) from these 9 women were included in this study. Each biopsy pair consisted of anterior and posterior vaginal biopsies (approximately 1 × 2 cm) from the vaginal cuff. Biopsies were immersed and stored in Tyrode's buffer at 37oC and equilibrated with 95% oxygen 5% CO2. Longitudinal strips of vaginal muscularis (approximately 3 mm × 10 mM) were dissected from biopsy samples. One end of each muscle strip was attached to a force transducer and changes in muscle tension were measured on a Grass Model 7D Polygraph. At the end of each experiment, muscle strips were contracted by adding KCl (125 mM) to confirm a functional contractile apparatus. The smooth muscle content of the muscle strips used for force measurements was confirmed by histology and the force was expressed per gram of smooth muscle tissue. RESULTS: Both anterior and posterior prolapsed vaginal muscle strips contracted in response to KCl (125 mM)—an agonist that bypasses membrane dependent pathways. However, the addition of neither the α-1 agonist phenylephrine (250 μm) nor the cholinergic agonist carbachol (100 μm) elicited a contractile response in strips obtained from prolapsed vagina, whereas the anterior and posterior vaginal muscularis obtained from control tissue contracted in a dose-dependent manner to phenylephrine. Carbachol also induced a phasic contractile response in the muscle strips from the posterior vaginal wall of the control. CONCLUSIONS: Our data suggest differences in adrenergic and muscarinic receptor function in vaginal smooth muscle from patients diagnosed with prolapse compared with patients without prolapse. These findings highlight opportunities for further research for therapies and/or prevention of pelvic organ prolapse.