Effects of bupivacaine and calcium antagonists on human uterine arteries in pregnant and non-pregnant women.

Bupivacaine is a local anesthetic commonly used in obstetrical practice. Although not generally constrictive, it has a constricting effect on blood vessels in clinically used doses, and when administered close to the uterine vasculature, as in a paracervical blockade, it can induce severe fetal bradycardia and thus be hazardous to the fetus. The bupivacaine-induced vasoconstriction on uterine arteries from pregnant and non-pregnant women was effectively reduced by two different calcium antagonists, verapamil and nifedipine. In non-pregnant women, nifedipine (2.9 x 10(-7) mol.l-1) administered simultaneously with bupivacaine (5.8 x 10(-4) mol.l-1) caused a 96% and verapamil (10(-5) mol.l-1) an 84% reduction as compared with the control vessel where only bupivacaine (5.8 x 10(-4) mol.l-1) was administered. In pregnant women, nifedipine 2.9 x 10(-7) mol.l-1 and 2.9 x 10(-6) mol.l-1 produced 66% and 79% reductions, respectively. It is possible that calcium antagonists administered together with bupivacaine in paracervical blockade could reduce the risk of fetal bradycardia.

Adhesion formation after laparoscopic surgery in tubal pregnancy: a randomized trial versus laparotomy.

OBJECTIVE: Women with ectopic pregnancy (EP) who have been operated on by laparoscopy are thought to have improved subsequent fertility, probably because of less adhesion formation. We aimed to evaluate the adhesion formation after laparoscopy as compared with laparotomy in a randomized trial. DESIGN: One hundred five patients with tubal pregnancy were stratified with regard to age and risk factors and randomized to surgery by laparoscopy or laparotomy. To evaluate adhesion formation and tubal status, 73 patients with strong desire of pregnancy underwent a second-look laparoscopy. The adhesion status at the ipsilateral and contralateral side at primary surgery was compared with the status at second-look laparoscopy. RESULTS: Patients operated on by laparotomy developed significantly more adhesions at the operated side than patients operated on by laparoscopy (P less than 0.001). Substantially more patients in the laparotomy group underwent adhesiolysis at second-look laparoscopy than did patients in the laparoscopy group. Tubal patency did not differ between the groups. CONCLUSIONS: Laparoscopic treatment of EP results in less impairment of the pelvic status compared with conventional conservative surgery.

Effects of bupivacaine and calcium antagonists on the rat uterine artery.

Bupivacaine is a commonly used local anesthetic in obstetrical practice, but since this compound also has a constrictor action on vascular smooth muscle it can be hazardous to the fetus. The aim of the present study was to analyze the effect of bupivacaine on the uterine vasculature using the rat uterine artery as a model. Small arterial segments were mounted in tissue chambers for isometric recording of vascular tension using a specially designed teflon-steel gauge. Bupivacaine induced marked vasoconstriction and this vasoconstriction was reduced considerably by two different Ca antagonists, verapamil and nifedipine. Verapamil (10(-5) mol.l-1) reduced bupivacaine-produced arterial contraction by a mean of 78% and nifedipine (2.9 x 10(-7) mol.l-1) reduced arterial contraction by a mean of 57%.

Laparoscopic surgery in ectopic pregnancy. A randomized trial versus laparotomy.

A randomized, prospective clinical trial was conducted to compare the efficacy of laparoscopic treatment with conventional conservative abdominal surgery for tubal pregnancy. Entry criteria were: size of the ectopic gestation less than 4 cm, hemodynamic stability, accessibility for laparoscopic treatment and a trained laparoscopist on duty. There was no difference between the groups regarding gestational duration, size and location of the ectopic gestation, or the mean preoperative hCG values. The groups differed with respect to total operation time (73 min for the laparoscopy group vs. 88 min for the laparotomy group), hospital stay (2.2 vs. 5.4 days) and convalescence period (11 vs. 24 days). The rates of elimination of hCG was similar in the groups, and there were no statistical difference in the rate of second intervention.

Influence of bupivacaine and morphine on human umbilical arteries and veins in vitro.

Strips from human umbilical arteries and veins were prepared by microdissection. The vessel strips were mounted in tissue baths for isometric recording of contractile activity. The local anesthetic drug bupivacaine induced a concentration-dependent increase of tone in both artery and vein, whereas morphine had no effect. Nor did morphine influence the increase in vessel tone induced by bupivacaine. If applicable in vivo, the results suggest that morphine has little influence on umbilical vessel tone, whereas bupivacaine may reduce the umbilical blood flow, at least when the local concentration of bupivacaine exceeds a certain critical level. The addition of morphine to local anesthetics did not increase any adverse effects on the umbilical vessels in this study.

Local prostaglandin F2 alpha injection for termination of ectopic pregnancy.

In nine women with unruptured ectopic pregnancy, prostaglandin F2 alpha was injected under laparoscopic control into the affected oviduct and in eight patients also into the ovary containing the corpus luteum. Termination of the pregnancy was achieved in all cases (in one at the second attempt), without complications. Fertility after this procedure needs to be compared with that after conventional surgery.

Fate of receptor-bound human chorionic gonadotrophin in pseudopregnant rat ovaries perfused in vitro.

Pseudopregnant rats were injected with [125I] hCG, anaesthesized 1 h later and after cannulation of the aorta the ovaries were isolated and perfused with Gey & Gey buffer containing 0.2% BSA. The release of radioactivity was monitored for 2 h and analyzed by gel filtration. Five to ten per cent of the radioactivity was released within 2 h and represented small molecular weight peptides and iodotyrosine and [125I]hCG. Analysis of the ovarian radioactivity prior to and after perfusion revealed that virtually all hCG was receptor-bound. Loading the medium with unlabelled hCG displaced [125I]hCG from the receptor but did not enhance its degradation. Histological examination showed that the ovarian tissues were still intact after the 2 h perfusion. Immunohistochemical studies revealed a localization of the hCG at the cell periphery both prior to and after perfusion. These results provide evidence showing that the rate of internalization of receptor-hCG complexes in rat luteal cells is slow in vivo.

Studies on the morphology of the isolated perfused rabbit ovary. II. Ovulation in vitro after HCG-treatment in vivo.

Ovulation was induced in rabbits by intravenous administration of human chorionic gonadotrophin (HCG), and 4-5 h later the ovaries were isolated and introduced into an in-vitro perfusion system containing synthetic medium with albumin. Rupture of follicles occurred in vitro within the physiological time range (mean 11.3 h after injection of HCG), although with a reduced frequency. Preovulatory and ruptured follicles were studied in detail by light and electron microscopy. In the granulosa layer of ruptured or preovulatory follicles cytoplasmic blebbing activity, disappearance of Call-Exner bodies and differentiation toward luteinized cells were found. Perhaps the most important sign of normal preovulatory development in vitro was that the basement membrane surrounding the granulosa layer was penetrated by projections of granulosa cells. In the absence of this penetration phenomenon the granulosa layer prolapsed out of the follicle. Immediately before rupture, follicles showed marked degeneration, restricted to the outer layers of the apical wall, which is compatible with the hypothesis that degradative enzymes are released close to the surface of preovulatory follicles. Although the majority of follicles that ovulated under in-vitro conditions showed the same kind of morphological alterations as can be seen in vivo, occasional atypical ruptures occurred without any overt signs during perfusion. Also technical manipulations of the perfusion system, e.g., nonphysiological increase of perfusion pressure, could force follicles to rupture. This illustrates the importance of careful morphological study of all ovaries perfused in vitro before conclusions are drawn.

Studies on the morphology of the isolated perfused rabbit ovary. I. Effect of long-term perfusion.

Isolated ovaries from untreated, sexually mature rabbits were introduced into an in vitro perfusion system and perfused with a chemically defined medium containing albumin. The ovaries were perfused for up to 15 h (mean 11.5 h) and then processed for morphological investigation. Both at the light- and electron-microscopical levels, most of the ovaries exhibited a normal structure comparable with ovaries in situ. In two cases, however, marked accumulations of bacteria were found, although not inside the follicles. Since ovulation in the rabbit normally occurs between 9.5-13 h after mating or human chorionic gonadotrophin treatment, this model seems adequate for studies of ovulation in vitro. It is, however, important to study the ovaries microscopically after the perfusion to detect artifacts, e.g., bacterial infection, that may have influence on the process of ovulation.

Effects of PGF2 alpha and indomethacin on ovulation and steroid production in the isolated perfused rabbit ovary.

Both ovaries of 31 rabbits were perfused with a chemically defined medium in vitro in a recirculation system. In one series of experiments, hCG (100 IU) was injected iv 5-6 h prior to anaesthesia and surgery. Approximately 1 h later the perfusion was started. One ovary was perfused as control while the other ovary was perfused with 5 micrograms/ml indomethacin or with indomethacin and 1 micrograms/ml PGF2 alpha. In another series of experiments the rabbits received no pretreatment prior to operation. Instead, bovine LH was added to the perfusion medium of both control and experimental ovaries. The experimental side also received either indomethacin or indomethacin and PGF2 alpha. Finally, the effect of PGF2 alpha in the absence of LH was compared to the control ovary receiving only LH. After injection of hCG in vivo, ovulations occurred in 4 of 5 control ovaries. Indomethacin completely blocked ovulation in 4 of the 5 ovaries treated, while PGF2 alpha restored ovulations in all the experimental ovaries. In the group of experiments where LH was added in vitro, ovulations were induced in all ovaries treated with varying LH doses. Furthermore, indomethacin blocked ovulation in 5 out of 7 ovaries, and PGF2 alpha restored ovulation in all ovaries. Fifty per cent of the ovaries treated only with PGF2 alpha (in the absence of LH) also ovulated. The pattern of steroid release did not differ between control ovaries, indomethacin treated ovaries, and indomethacin + PGF2 alpha treated ovaries. Ovaries treated in perfusion with PGF2 alpha alone had very low steroid levels compared to the ovaries treated with LH.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible adrenergic effects on heart protein metabolism.

It is known that the heart will adapt to actual demand by increasing or decreasing its size through different mechanisms. In this presentation, the possible role of catecholamines in regulating heart protein synthesis and developing cardiac hypertrophy and cardiomyopathy is discussed. Injecting animals with catecholamines has been found to induce cardiac hypertrophy. In vitro perfusion of rat heart in the presence of catecholamines has been found to induce a time-dependent and dose-dependent stimulation of amino acid transport and incorporation into proteins. Acute haemodynamic effects of catecholamines increase cardiac performance while long-term treatment seems to cause depression of cardiac function, especially during ischaemic conditions. Chronic beta-blockade in patients with primary congestive cardiomyopathy improved both cardiac function and clinical condition in more than half the patients. Furthermore, a beneficial effect on survival was also found, when compared with a matched control group. It is hypothesised that catecholamines may play a role in developing cardiac hypertrophy as well as congestive cardiomyopathy.

The preovulatory decline in follicular oestradiol is not required for ovulation in the rabbit.

Using a method of in vitro perfusion of the rabbit ovary with a chemically defined medium in a recirculation system, normal appearing follicular ruptures occurred following exposure of the ovaries to hCG in vivo (100 IU) or following addition of LH (0.25 microgram/ml of NIH B9) to the perfusate. The addition of oestradiol-17 beta (10 micrograms/ml) to the perfusate did not inhibit these follicular ruptures, although the follicular fluid oestradiol contents were increased more than 100-fold as compared to the control side not receiving the addition of oestradiol. These data suggest that the physiological decline of follicular oestrogen, normally observed in vivo prior to ovulation in the rabbit, is not required as part of the mechanism of ovulation and that normal appearing ovulations can occur even though follicular oestrogen levels are kept artificially elevated.

The study of ovulation in the isolated perfused rabbit ovary. 1. Methodology and pattern of steroidogenesis.

A previously described technique for perfusion of the isolated rabbit ovary in a recirculating system (Ahrén et al., 1975) was modified for studies of preovulatory follicular development and ovulation. Follicular ruptures were induced either by injection of human chorionic gonadotropin (hCG) to the animal 5-6 h prior to perfusion or by adding luteinizing hormone (LH) directly to the medium during perfusion. Ovulation occurred 9-14 h after hCG injection in vivo and 7-13 h after the addition of LH in vitro. Ovulations did not occur unless the ovaries were stimulated by gonadotropin in vivo or in vitro. The patterns of release of estradiol-17 beta and progesterone into the medium are consistent with the measurements reported by others on these steroids in ovarian venous blood in vivo. This experimental model is likely to be useful in further exploration of the physiology, biochemistry and anatomy of ovulation.

The study of ovulation in the isolated perfused rabbit ovary. II. Photographic and cinematographic observation.

Using the model of in vitro perfusion of the isolated rabbit ovary, in which follicular ruptures can be observed, in this paper we report on the photographic and cinematographic recording of the gross anatomy of ovulation. The observed sequence of events and their timing were very similar to that which has been reported for ovulation observed in vivo. In addition, the use of infrared film made it possible to visualize intrafollicular events prior to rupture.

The isolated perfused rabbit ovary-a model for studies of ovarian function. Ultrastructure after perfusion with different media.

In the present investigation the ultrastructure of isolated rabbit ovaries, perfused with different media for various time periods, was studied. The steroid hormone production by the perfused ovary was also determined. Perfusion with Medium 199 results in prominent interstitial ovarian oedema which increases with perfusion time. Even after the addition of 6-10% Dextran T40, oedema appears in the interstitial tissue of the ovary. Perfusion solutions with osmotically active colloid particles of large molecular size (Dextran T70; average molecular weight 70,000 and bovine serum albumin), cause less distortion in the ovarian structure, and ultrastructurally the ovarian tissues appear essentially the same as in the control ovaries. The results indicate that the perfused rabbit ovary, under strictly controlled conditions, can be used as an experimental model for studies of various aspects of ovarian function, including follicular rupture.

A luteolytic effect of a prostaglandin F2 alpha analogue in non-pregnant women?

Four healthy non-pregnant volunteers with regular cycles were exposed to vaginal suppositories containing a PGF2 alpha analogue (ICI 81.008, 500-600 microgram) twice at 24-hour intervals in the early or mid-luteal phase. In comparison to serum progesterone levels of ovulatory control cycles, this treatment caused a significant decrease of serum progesterone combined with a shortening of the length of the luteal phase by 1.4 days. No gastrointestinal or other adverse effects were noticed during this treatment. Administration of ICI 81.008 in the follicular phase interfered neither with ovulation nor with the length or shape of the following luteal phase. Although limited, these data suggest a luteolytic effect of ICI 81.008 in women.