The effect of Xylocaine spray on suture material degradation.

OBJECTIVES: To compare the tensile strength of fast absorbable Polyglactin 910 suture material when impregnated with various agents for local anesthesia and to investigate whether the presence of ethanol in Xylocaine spray could explain a potential reduction in tensile strength after use of Xylocaine spray. METHODS: In all, 120 suture samples of Polyglactin 910 were divided into four groups of 30. These four groups were randomly impregnated with isotonic sodium chloride, isotonic sodium chloride plus Xylocaine spray, isotonic sodium chloride plus Xylocaine gel, or isotonic sodium chloride plus ethanol. After impregnation, the sutures were stored in sealed glass tubes in a heating cabinet at 37°C for 72 h. Thereafter, the tensile strength of these 120 samples was assessed by a universal tensile testing machine. The maximal force needed to break the suture material was recorded in newtons (N). RESULTS: Fast absorbable Polyglactin 910 suture material impregnated with Xylocaine spray or ethanol showed weakened tensile strength (mean values 11.40 and 11.86 N, respectively), whereas the specimens impregnated with Xylocaine gel or sodium chloride retained their tensile strength better (mean values 13.81 and 13.28 N, respectively; mean difference between Xylocaine gel and Xylocaine spray -2.41 N, P < 0.001). CONCLUSION: In this in vitro experiment, ethanol and Xylocaine spray weakened the tensile strength of fast absorbable Polyglactin 910 sutures. Use of Xylocaine spray, which contains ethanol, for local anesthesia might lead to early breakdown of the suture material and wound rupture. The authors suggest caution when using Xylocaine spray in combination with fast absorbable Polyglactin 910 suture.

Vaginal CO2 laser therapy for genitourinary syndrome in breast cancer survivors-VagLaser study protocol: a randomized blinded, placebo-controlled trial.

BACKGROUND: Vaginal CO2 laser therapy is a new treatment option for genitourinary syndrome of menopause. Its potential is particularly interesting in breast cancer survivors, where existing treatment options often are insufficient as hormonal treatment is problematic in these women. The objective of this study is to investigate the effectiveness of vaginal laser treatment for alleviation of genitourinary syndrome of menopause in breast cancer survivors treated with adjuvant endocrine therapy. The secondary objective is to explore the importance of repeated vaginal laser treatment and the long-term effects in this patient population. METHODS: VagLaser consist of three sub-studies; a dose response study, a randomized, participant blinded, placebo-controlled study and a follow-up study. All studies include breast cancer survivors in adjuvant endocrine therapy, and are conducted at the Department of Obstetrics and Gynecology, Randers Regional Hospital, Denmark. The first participant was recruited on 16th of February 2023. Primary outcome is vaginal dryness. Secondary subjective outcomes are vaginal pain, itching, soreness, urinary symptoms and sexual function. Secondary objective outcomes are change in vaginal histology (punch biopsy), change in vaginal and urine microbiota, and change in vaginal pH. DISCUSSION: More randomized controlled trials, with longer follow-up to explore the optimal treatment regimen and the number of repeat vaginal laser treatments for alleviation the symptoms of genitourinary syndrome of menopause in breast cancer survivors treated with endocrine adjuvant therapy, are needed. This study will be the first to investigate change in vaginal and urine microbiota during vaginal laser therapy in breast cancer survivors. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06007027 (registered 22 August, 2023). PROTOCOL VERSION: Version 1, Date 13.11.2023.

Treatment of apical vaginal prolapse with minimal mesh repair (Uphold): patient-reported long-term outcomes and mesh-related complications.

INTRODUCTION: To evaluate patient-reported outcomes and clinical findings after surgery for apical prolapse with the transvaginal Uphold mesh technique. Moreover, to evaluate the rate of mesh-related complications. MATERIAL AND METHODS: A historical cohort study of patients who underwent surgery from January 1, 2012 to April 30, 2019, at Aarhus University Hospital, Denmark. Pelvic examination and patient completion of questionnaires were performed in 2018-2019. Information on adverse events and reoperations was obtained from medical records. RESULTS: A total of 240 patients were operated on using the Uphold mesh, 89% due to recurrent prolapse. Follow-up was attended by 192 patients (80%). Median follow-up time was 30 months, interquartile range 19-52. During follow-up, 29 patients (15%) underwent reoperation due to prolapse and are considered failures. Among the remaining, patient satisfaction was high. Thus, average score for pelvic symptoms affecting daily life was 2, on a scale of 0-10, where 0 represents no symptoms. The Patient Global Impression of Improvement (PGI-I) had an average score of 6.4 (1: very much worse; 7 very much better). Preoperatively, 89.5% of the women had grade 2 or more apical prolapse, whereas at follow-up, this was only 6.1%. Perioperative heavy bleeding needing embolization was observed in one patient (0.5%). Two patients had serious constriction of the ureter and needed re-operation. Postoperative complications, primarily temporary voiding problems, were observed in 15 patients (8%). Complications during the follow-up period were registered in 23 patients (12%); eight of these were mesh erosions. Due to complications, 11 patients (6%) needed re-operation. CONCLUSIONS: The study confirms that the Uphold procedure in a centralized set-up is a procedure with high patient-reported satisfaction even in a population characterized by a high proportion of recurrent prolapse. Moreover, the procedure seems safe with acceptable complication rates.

Fast track sacrospinous ligament fixation: subjective and objective outcomes at 6 months.

BACKGROUND: Sacrospinous ligament fixation (SSLF) is a widely used vaginal procedure for correction of apical vaginal prolapse. The objective of this study was to evaluate subjective and objective outcomes of SSLF performed in a fast-track setting. METHODS: This was a prospective cohort study of sacrospinous ligament fixation performed using local anesthesia and light sedation in a fast-track setting at Aarhus University Hospital between April 2016 and December 2017. Objective signs of prolapse were assessed by gynecological examination preoperatively and at 6 months after the operation. Subjective symptoms were evaluated by questionnaires (the Pelvic Floor Distress Inventory (PFDI 20), and the Patient Global Impression of Improvement (PGI-I) supplemented with individual questions from the ICIQ-vaginal Symptoms (ICIQ-VS) and Sexual Questionnaire-IR (PISQ-12) questionnaires). RESULTS: One hundred and three women with a median age of 65 (36-84) years were included. Previous hysterectomy had been performed in 40% of the women, and 43% had a history of previous prolapse operations. At follow-up, 75% of the women had apical descent less than stage 2. However, 18% had anterior vaginal wall prolapse beyond the hymen, and 25% had recurrence of the apical prolapse stage 2 or more and were offered reoperation. Bladder and anal symptoms improved in most women after the operation, and the number of women reporting dyspareunia was halved. In the overall assessment by Patient Global Impression of Improvement (PGI-I) questionnaire, 76% reported improvement. No serious operative complications were reported, and 81% of the patients were discharged on the day of the surgery. CONCLUSION: In this cohort with a high rate of previous prolapse surgery, sacrospinous ligament fixation performed in a fast-track setting showed subjective and objective results comparable to the results of apical native tissue repair reported in the literature. Furthermore, the complication rate was low. Trial registration This study was notified to The Central Denmark Region Committees on Health Research Ethics on July 7, 2015, and was approved by The Danish Data Protection Agency (1-16-02-442-15). All methods were performed in accordance with the relevant guidelines and regulations. An informed consent for participation in the study and acceptance of using data for scientific purposes and publication was signed by all patients.

Can ultrasound 10 days after obstetric anal sphincter injury predict anal incontinence at long-term follow-up?

INTRODUCTION AND HYPOTHESIS: The objective was to investigate whether endoanal ultrasound (EAUS) performed 10 days after a primary repaired obstetric anal sphincter injury (OASIS) can predict the severity of anal incontinence (AI) in the long term. METHODS: This prospective cohort study included women with a primary repaired 3b-degree tear, 3c-degree tear or fourth-degree tear at Aarhus University Hospital, Denmark, from 1 September 2010 to 31 May 2011. Clinical assessment and EAUS were performed on day 2, day 10, and day 20 after delivery. Functional outcomes were assessed using a questionnaire at the time of all clinical visits and at the long-term follow-up, 7 years after delivery. AI was graded according to the Wexner score and EAUS defects were graded according to the Starck score. RESULTS: Ninety-six out of 99 women consented to participate. Five women had a secondary sphincter repair and were subsequently excluded from follow-up. Fifty-seven women underwent both EAUS 10 days after delivery and answered the long-term follow-up questionnaire. Median follow-up time was 7.7 years (IQR 7.4-7.8). Mean Wexner score was 4.4 ± 4.8 10 days after delivery and 2.5 ± 2.8 at follow-up; thus, the Wexner score improved over time (p = 0.01). Ultrasound sphincter defects were found in 82.6% of the women. Mean Starck score was 3.0 ± 1.8. The risk of AI was 0% (95% CI 0.0-30.8) if the Starck score was 0. No correlation was found between the Starck score and the Wexner score at follow-up. CONCLUSIONS: We found that performing EAUS in the puerperium following OASIS has limited value in predicting long-term AI.

Clinical relevance of routine transvaginal ultrasound in women referred with pelvic organ prolapse.

BACKGROUND: The aim of this study was to investigate the prevalence of incidental findings on transvaginal ultrasound scan in women referred with pelvic organ prolapse by a general practitioner and to investigate which further examinations and treatments were performed as a result of these findings. METHODS: This was a retrospective cohort study that investigated women with pelvic organ prolapse referred to the outpatient urogynaecological clinics at Randers Regional Hospital and Aarhus University Hospital, Denmark. RESULTS: A total of 521 women were included and all of them were examined with a routine transvaginal ultrasound scan and a gynaecological examination. Prolapse symptoms only and no specific indication for transvaginal ultrasound scan were seen in 507 women (97.3%), while 14 women (2.7%) received scans on indication. Among the latter women, five (35.7%) had cancer. In the women with solely prolapse symptoms, 59 (11.6%) had incidental findings on transvaginal ultrasound scan, but all were benign. However, two patients were later diagnosed with cancer unrelated to the initial ultrasound findings. The treatment was extended with further examinations not related to POP in 19 of the women (32.2%) with incidental ultrasound findings. CONCLUSION: The prevalence of incidental ultrasound findings was not high in the women referred with pelvic organ prolapse and no additional symptoms, and all these findings were benign. However, it should be considered that these findings resulted in further investigations and changes to the patients' initial treatment plans. A meticulous anamnesis and digital vaginal examination are crucial to rule out the need for vaginal ultrasound.

[Abdominal ectopic pregnancy].

This review summarises the knowledge of abdominal ectopic pregnancy (AEP), which is a rare condition with higher morbidity and mortalilty than other types of ectopic pregnancies. The condition can be primary, if the pregnancy implants directly on to an abdominal site, or it can be secondary after a tubar abortion. AEP differs from tubal pregnancies by a normal level of human chorionic gonadotropin and rare vaginal bleeding, which causes a diagnostic delay. In an early pregnancy the treatment is laparoscopic removal, but in second and third trimester pregnancies laparotomy is preferred, if possible preceded by MRI for mapping of vascular involvement and location of placenta.

High Patient Satisfaction With Local Anesthesia and Light Sedation in a Novel Fast-Track Setup for Sacrospinous Fixation.

OBJECTIVES: Simple prolapse operations can be performed using local anesthesia. However, this has not been the case for advanced pelvic organ prolapse operations. The aim of this study was to investigate the patient-reported feasibility and acceptability of local anesthesia and light sedation for sacrospinous fixation (SSF). METHODS: This is a prospective observational study on 105 women who underwent SSF in a public outpatient setting from April 2016 to October 2017. They received infiltration anesthesia with mepivacaine or lidocaine together with a pudendal nerve block with Marcaine. Local anesthesia was supplemented by intravenous light sedation and pain reliever. A Local Anesthetic Intraoperative Experience Questionnaire was used to evaluate patient experience. RESULTS: One patient was converted to general anesthesia. Eighty-eight women answered the questionnaires. Ninety-nine percent defined themselves as satisfied or very satisfied with the anesthesia. Little or no pain during the operation was reported by 92% and 92% would choose the same type of anesthesia again. No adverse effect of the anesthetic procedure was observed. The median (range) admission time was 12 (4.5-48) hours, and 81% of the patients could be discharged on the day of surgery. At follow-up after 8 weeks and 6 months, no patients reported adverse events to the anesthesia. CONCLUSIONS: The SSF can be performed using local anesthesia and light sedation with high degree of patient satisfaction. These preliminary data indicate that the concept of ambulatory surgery might be implemented more widely if the use of local anesthesia is also applied to more advanced surgical procedures.

Recurrent apical prolapse after high uterosacral ligament suspension - in a heterogenous cohort characterised by a high prevalence of previous pelvic operations.

BACKGROUND: The apical prolapse is probably the most complex form of pelvic organ prolapse (POP). Adequate apical support is essential in the treatment of POP, as it contributes to the support in all vaginal compartments. This study aimed to evaluate the rate of symptomatic recurrent apical prolapse after high uterosacral ligament suspension (HUSLS), in a cohort of women characterised by a high prevalence of previous pelvic operations and a significant degree of prolapse. METHODS: This is a retrospective chart review of 95 women who underwent HUSLS for symptomatic apical prolapse from 2002 to 2009 at Aarhus University Hospital, Denmark. Of these women, 97% attended a six-month clinical control. Recurrence was defined as symptomatic vaginal vault prolapse stage 2 or more (according to the International Continence Society (ICS) quantification system). Medical charts were reviewed for a mean period of 7.2 years. Any new contacts due to prolapse were noted. RESULTS: Before the operation, 73% of the women were hysterectomised, and 52% had previous prolapse surgery. Stage 2 apical prolapse was reported in 71% of the women, whereas 26% had stage 3 or 4. At six-month follow-up, 19% of the women had recurrent symptomatic apical prolapse, and 9% of the women had symptomatic recurrent prolapse in other compartments 6 months after operation. In all, 35% of the women had a renewed prolapse operation during the long-term follow-up period. Perioperative adverse events were seen in 7%. Two women were re-operated due to postoperative complications. CONCLUSIONS: This retrospective study of 95 women with a significant degree of prolapse and a high prevalence of previous pelvic operations demonstrates that the rate of recurrent prolapse associated with HUSLS might be higher than originally described. In conclusion, HUSLS may not be the optimal first choice of operation in this group of patients.

Prospective evaluation of paravaginal defect repair with and without apical suspension: a 6-month postoperative follow-up with MRI, clinical examination, and questionnaires.

INTRODUCTION AND HYPOTHESIS: Paravaginal defect (PVD) has been suggested as one of the main contributors to the development of prolapse in the anterior vaginal wall (AVW). We aimed to evaluate the descent of pelvic organs, presence of vaginal H configuration, and pubococcygeus (PC) muscle defect by pelvic magnetic resonance imaging (MRI), together with subjective symptoms of prolapse, before and 6 months after PVD repair. We also aimed to evaluate risk factors of recurrence. METHODS: Fifty women with PVD diagnosed by gynecological examination and scheduled for vaginal PVD repair were planned for enrollment. Preoperatively and 6 months postoperatively, subjective symptoms were evaluated using the International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS) together with MRI of the pelvis to evaluate defects in the PC muscle, vaginal shape, and pelvic organ descent. RESULTS: Forty-six women completed the study. Twenty had PVD repair alone, whereas 26 also had concomitant surgery performed. Prolapse grade, subjective symptoms, sexual problems, and quality of life (QoL) were significantly improved at follow-up. Missing vaginal H configuration was observed in 21 women before operation and was correlated with PC muscle defect. Recurrence rate was 39%, and significantly more women with recurrence had PC muscle defects and missing H configuration. CONCLUSION: Vaginal PVD repair alone or combined with concomitant surgery significantly reduces objective prolapse and subjective symptoms. We could not demonstrate MRI findings of missing H configuration to be a sign of PVD but, rather, a sign of defect in the PC muscle. Risk of recurrence is significantly higher in women with major PC muscle defects and missing H configuration.

Translation and validation of the International Consultation on Incontinence Questionnaire Vaginal Symptoms (ICIQ-VS): the Danish version.

INTRODUCTION: In the clinical evaluation of women with pelvic organ prolapse (POP), it is important to evaluate both objective and subjective presentations. The objective evaluation is done by gynecological examination, but the subjective presentation is more complex. The International Consultation on Incontinence Questionnaire-Vaginal Symptoms (ICIQ-VS) is an important tool for subjective evaluation, and a Danish version was developed. MATERIALS AND METHODS: The English version was translated into Danish in accordance with guidelines. Eight women underwent a semistructured interview showing no misunderstandings. Women with and without prolapse completed the questionnaire and underwent a Pelvic Organ Prolapse Quantification (POP-Q) examination. Three weeks later a retest was done. Women undergoing prolapse surgery completed the questionnaire 3 months postoperatively. RESULTS: Ninety-four women with and 98 without prolapse were included; 52 underwent surgery. Retest response rate was 88-95%. Mean time between test and retest was 24.5 and 92.2 days, respectively. Missing data ranged between 0 and 1%. Test-retest reliability was good to excellent (ICC 0.61-0.88) and internal consistency was acceptable (Cronbach's alpha 0.79-0.84). The questionnaire was excellent when distinguishing between women with and without prolapse (p < 0.001). Criterion validity (correlation between POP-Q stage and the questionnaire) was perfect (p < 0.001). Sensitivity to change was excellent for vaginal symptom score and quality of life (p < 0.001) but not for sexual matters (p = 0.059). CONCLUSIONS: The Danish version of ICIQ-VS was successfully translated and can be a valuable tool for prolapse research and daily evaluation of patients.

Early secondary repair of labial tears, 1st and 2nd degree perineal lacerations and mediolateral episiotomies in a midwifery-led clinic. A retrospective evaluation of cases based on photo documentation.

OBJECTIVES: To examine whether early secondary repair of labial tears, 1st and 2nd degree perineal lacerations and episiotomies provided an anatomically acceptable result. STUDY DESIGN: A retrospective analysis of 126 women undergoing an early secondary repair of birth lacerations not involving the sphincter complex within 21 days postpartum. Patients were included from 1 January 2014 to 11 August 2017 at Aarhus University Hospital, Denmark. Photo documentation of the wound was available just before the early secondary repair and at the follow-up visit after the repair. Photos were evaluated by two trained Urogynaecological Consultants. MAIN OUTCOME MEASURES: Whether the anatomic result of the early secondary repair was acceptable based on photo documentation. RESULTS: Early secondary repair was performed by a specialised team of midwives in 94.4% and by doctors in 5.6% of the cases. In all, 72.2% were 2nd degree perineal lacerations. The most common indications for early secondary repair were wound dehiscence (55.3%) and suboptimal primary repair (34.1%). At the follow-up clinical examination seven days after the early secondary repair, the result was considered anatomically acceptable in 67.5% of the cases, not optimal in 22.2% and not possible to evaluate in 10.3% of the cases. In 7.9% of the cases, wound infection was suspected after the early secondary repair. CONCLUSIONS: Based on photo documentation, early secondary repair of birth lacerations not involving the sphincter complex provides an anatomically acceptable result in the majority of cases without risk of serious complications.

Paravaginal defect: anatomy, clinical findings, and imaging.

INTRODUCTION AND HYPOTHESIS: The paravaginal defect has been a topic of active discussion concerning what it is, how to diagnose it, its role in anterior vaginal wall prolapse, and if and how to repair it. The aim of this article was to review the existing literature on paravaginal defect and discuss its role in the anterior vaginal wall support system, with an emphasis on anatomy and imaging. METHODS: Articles related to paravaginal defects were identified through a PubMed search ending 1 July 2015. RESULTS: Support of the anterior vaginal wall is a complex system involving levator ani muscle, arcus tendineus fascia pelvis (ATFP), pubocervical fascia, and uterosacral/cardinal ligaments. Studies conclude that physical examination is inconsistent in detecting paravaginal defects. Ultrasound (US) and magnetic resonance imaging (MRI) have been used to describe patterns in the appearance of the vagina and bladder when a paravaginal defect is suspected. Different terms have been used (e.g., sagging of bladder base, loss of tenting), which all represent changes in pelvic floor support but that could be due to both paravaginal and levator ani defects. CONCLUSION: Paravaginal support plays a role in supporting the anterior vaginal wall, but we still do not know the degree to which it contributes to the development of prolapse. Both MRI and US are useful in the diagnosis of paravaginal defects, but further studies are needed to evaluate their use.

Native-tissue repair of isolated primary rectocele compared with nonabsorbable mesh: patient-reported outcomes.

INTRODUCTION: We evaluated patient-reported outcomes and complications after treatment of isolated primary rectocele in routine health-care settings using native-tissue repair or nonabsorbable mesh. METHODS: We used prospective data from the Swedish National Register for Gynaecological Surgery and included 3988 women with a primary operation for rectocele between 2006 and 2014: 3908 women had native-tissue repair, 80 were operated with nonabsorbable mesh. No concurrent operations were performed. Pre- and perioperative data were collected from doctors and patients. Patient-reported outcomes were evaluated 2 and 12 months after the operation. Only validated questionnaires were used. RESULTS: One year after native-tissue repair, 77.8 % (76.4-79.6) felt they were cured, which was defined as never or hardly ever feeling genital protrusion; 74.0 % (72.2-75.7) were very satisfied or satisfied, and 84 % (82.8-85.9) reported improvement of symptoms. After mesh repair, 89.8 % (77.8-96.6) felt cured, 69.2 % (54.9-81.3) were very satisfied or satisfied, and 86.0 % (72.1-94.7) felt improvement. No significant differences were found between groups. Organ damage was found in 16 (0.4 %) patients in the native-tissue repair group compared with one (1.3 %) patient in the mesh group [odds ratio (OR) 3.08; 95 % confidence interval (CI) 0.07-20.30]. The rate of de novo dyspareunia after native-tissue repair was 33.1 % (30.4-35.8), comparable with that after mesh repair. The reoperation rate was 1.1 % (0.8-1.5) in both groups. CONCLUSION: Most patients were cured and satisfied after native-tissue repair of the posterior vaginal wall, and the patient-reported outcomes were comparable with results after mesh repair. The risk of serious complications and reoperation were comparable between groups.

Operation for recurrent cystocele with anterior colporrhaphy or non-absorbable mesh: patient reported outcomes.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare patient reported outcomes and complications after repair of recurrent anterior vaginal wall prolapse in routine health care settings using standard anterior colporrhaphy or non-absorbable mesh. METHODS: The study is based on prospective data from the Swedish National Register for Gynaecological Surgery. 286 women were operated on for recurrent anterior vaginal wall prolapse in 2008-2010; 157 women had an anterior colporrhaphy and 129 were operated on with a non-absorbable mesh. Pre-, and perioperative data were collected from doctors and patients. Patient reported outcomes were evaluated 2 months and 12 months after the operation. RESULTS: After 12 months, the odds ratio (OR) of patient reported cure was 2.90 (1.34-6.31) after mesh implants compared with anterior colporrhaphy. Both patient- and doctor-reported complications were found more often in the mesh group. However, no differences in serious complications were found. Thus, an organ lesion was found in 2.3% after mesh implant compared with 2.5% after anterior colporrhaphy (p = 0.58). Two patients in the mesh group (1.2%) were re-operated compared with 1 patient (0.6%) in the anterior colporrhaphy group (p = 0.58). The infection rate was higher after mesh (8.5%) than after anterior colporrhaphy (2.5%; OR 3.19 ; 1.07-14.25). CONCLUSION: Implantation of synthetic mesh during operation for recurrent cystocele more than doubled the cure rate, whereas no differences in serious complications were found between the groups. However, mesh increased the risk of infection.

One or two day mifepristone-misoprostol interval for second trimester abortion.

METHODS: A retrospective 2-year cohort study of 127 women, with gestation between 13 and 24 weeks and a live fetus, seeking induced abortion. The aim was to compare the effect of a 1-day and a 2-day interval between oral mifepristone (200 mg) and vaginal misoprostol (400 microg) every 3 h. RESULTS: The time to fetal expulsion was longer (9.8 versus 7.5 h; p<0.01) in the 1-day than in the 2-day group, but the median number of applications were identical and abortion occurred in 98% within 24 h in both groups The time to abortion was longer in women with a gestation of 17-22 weeks compared to women with lower gestation (10.2 versus 6.8 h; p<0.001), and longer in nulliparae than in parous women (10.0 versus 6.7 h; p<0.001). CONCLUSION: The combined regimen of mifepristone and misoprostol is effective in the second trimester, and the interval between the drugs can be reduced allowing individualised patient care.

KATP-channel-induced vasodilation is modulated by the Na,K-pump activity in rabbit coronary small arteries.

The purpose of the study was to evaluate the importance of the Na,K-pump in relaxations induced by K(ATP)-channel openers in rabbit coronary small arteries. Arterial segments were mounted in myographs for recording of isometric tension. Whole-cell patch clamp was used to assess K(ATP)-channel currents in isolated smooth muscle cells from the arteries. In arteries preconstricted with the thromboxane A(2) analogue U46619 pinacidil and cromakalim induced concentration-dependent relaxations. In arteries preconstricted with potassium (124 mM) only high concentrations of pinacidil had a small relaxant effect. In arteries preconstricted with U46619 pinacidil-induced relaxations were unaffected by pretreatment with N(omega)-nitro-L-arginine (L-NNA) and only slightly reduced after mechanical removal of the endothelium. Pinacidil induced relaxations were not significantly affected by 1 microM glibenclamide. However, the relaxations were partly inhibited in potassium-free media and by 1 microM ouabain. In contrast, the concentration-dependent relaxation to cromakalim was partly blocked by 1 microM glibenclamide and partly by 1 microM ouabain and when both drugs were present the inhibition increased. Ouabain (1 microM) and glibenclamide (1 microM) each partly inhibited an ATP-sensitive current induced by pinacidil and cromakalim. In the presence of both inhibitors a greater inhibition was seen. When the solution in the patch pipette was sodium-free the current was reduced and ouabain had no effect. The study suggests that the relaxation to cromakalim and most likely pinacidil is mediated through opening of K(ATP) channels. Inhibition of the Na,K-pump, however, may change the local environment for the K(ATP) channels (i.e. increases the ATP/ADPratio and/or decreases the transmembrane potassium gradient), which partly prevents the activation of the K(ATP)-channel current.