Contraction and relaxation of human uterine and placental smooth muscle. Endogenous control and calcium activation mechanisms.
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Adult↗
Biomedical subjects
S Maigaard
Publications and source records attributed to S Maigaard.
Rifampin and trimethoprim distribution in normal and hydronephrotic kidney and in prostate: an experimental study in dogs.
Concentrations of rifampin and trimethoprim, administered in the ratio 3.75:1 were measured in renal hilar lymph, renal interstitial fluid, prostatic interstitial fluid and prostatic secretion in dogs during constant infusion of the antibiotic combination. The lymph was obtained by direct cannulation of the lymphatics and the interstitial fluids from small plastic tissue chambers implanted 4 weeks before the experiments. Unilateral hydronephrosis was produced by ureteral ligation in dogs with tissue chambers in both kidneys to compare concentrations of the drug combination in renal interstitial fluid and urine from normal and hydronephrotic kidneys. Rifampin produced lower concentrations in both prostatic interstitial fluid and prostatic secretion than in plasma, while trimethoprim concentrations were much higher in prostatic secretion and prostatic interstitial fluid than in plasma. Renal lymph/plasma ratios and renal interstitial fluid/plasma ratios were significantly higher for trimethoprim than for rifampin, but only the lymph concentrations of trimethoprim exceeded the corresponding plasma concentrations. High urine concentrations were achieved for both drugs except in pelvises of hydronephrotic kidneys, where virtually no drug activity could be detected. Renal interstitial fluid concentrations of both drugs were similar in hydronephrotic and normal kidneys. The ratios between rifampin and trimethoprim concentrations varied considerably among plasma, various tissues and tissue fluids.
Animals↗
Inhibitory effects of nitrendipine on myometrial and vascular smooth muscle in human pregnant uterus and placenta.
Human myometrial visceral and vascular preparations and placental chorionic and stem villous vessels were dissected from myometrial and placental specimens obtained at term Caesarean section and after vaginal delivery. Vascular ring preparations and myometrial strips were mounted in organ bath and isometric tension recorded. Only myometrial preparations developed spontaneous contractile activity, which was effectively blocked by the calcium channel blocker nitrendipine (NTD) 10(-7) M. Pretreatment with calcium-depleted medium for 30 min. almost abolished myometrial responses to high K+ (124 mmol), oxytocin (OX) and prostaglandin F2 alpha (PGF2 alpha). Vascular responses to high K+ (124 mmol) were also nearly abolished by such treatment. However, noradrenaline (NA), vasopressin (VP) and PGF2 alpha in myometrial arteries and PGF2 alpha in chorionic vessels and stem villous arteries induced significant, but reduced contractions after calcium depletion. In all vascular preparations, exposed to calcium-depleted medium, NTD (10(-8) M) almost abolished contractions induced by calcium (0.1-4.0 mM) in the presence of K+ (124 mmol) and depressed responses to calcium in the presence of the other agonists tested. NTD (10(-10)-10(-7) M) depressed myometrial contractions induced by K+, OX and PGF2 alpha more effective than vascular responses to K+, NA, VP and PGF2 alpha in the myometrial arteries and K+ and PGF2 alpha in the placental arteries. It is concluded that activation of contraction in vessels from the human utero-placental unit implies multiple cellular sources of calcium, while in myometrial smooth muscle, influx of superficially bound calcium may be an important initial step in contractile activation. Treatment with calcium channel blockers during late human pregnancy might involve relaxation of the myometrium together with vasodilatation of the myometrial and foetal placental vascular beds.
Calcium↗
Effects of calcium channel blockers on the female genital tract.
Contractile activity and vascular resistance in the female genital tract are influenced by several smooth muscle tissues with individual mechanisms for control of mechanical activation. Calcium channel blockers have potent relaxant effects on preparations of human myometrium. The myometrial arteries utilize multiple sources of calcium for contractile activation, and excitation-contraction coupling in isolated vessels from non-pregnant uteri seems comparatively less sensitive to nifedipine than in corresponding myometrial preparations. Contractile activation of myometrial and placental arteries at term is inhibited by nitrendipine and nifedipine. Human oviductal smooth muscle depends on superficially bound calcium for mechanical activation, but only phasic contractions can be abolished by nifedipine, while tonic contractions induced by various agents are more resistant to the calcium channel blocker. Menstrual uterine contractions and pain are effectively counteracted by nifedipine in normal and dysmenorrhoeic women. Such therapy may represent an alternative principle in the treatment of dysmenorrhea. Nifedipine has potent relaxant effects on the mid-term pregnant and the post-partum uterus and calcium channel blockers may prove useful in the treatment of premature labor. Nifedipine and related compounds may further show effective in the treatment of pregnancy-associated hypertension. Whether such treatment in late pregnancy involves maintained or even improved placental perfusion could be assumed from in vitro data but needs further studies.
Animals↗
Differential effects of angiotensin, vasopressin and oxytocin on various smooth muscle tissues within the human uteroplacental unit.
Tissue specimens from various parts of the uteroplacental unit were obtained from women undergoing caesarean section, and placental tissue from women with normal deliveries. Strips of myometrial tissue, and segments of intramyometrial arteries were dissected together with segments of chorionic plate arteries and veins, and stem villous arteries. The preparations were mounted in organ baths, isometric tension recorded, and the responses to angiotensin II, vasopressin, and oxytocin were studied. In myometrial preparations, angiotensin caused a slight, transient increase in the frequency of spontaneous contractions, but no changes in amplitude. In all vascular preparations angiotensin produced concentration-related contractions. The responsiveness of the preparations was myometrial artery greater than villous artery greater than chorionic plate artery = chorionic plate vein. All responses were transient and tachyphylaxis was pronounced in all tissues. Tachyphylaxis was not influenced by pretreatment with indomethacin. Vasopressin increased transiently frequency and amplitude of contractions in myometrial strips. Myometrial arteries responded with a sustained contraction, as did chorionic plate arteries and veins but the latter vessels were less responsive. Villous arteries did not respond to vasopressin. Oxytocin preferentially stimulated myometrial strips, but also had a weak concentration-related contractant effect on chorionic plate arteries and veins. Villous arteries did not respond to oxytocin. At a higher concentration, causing a pronounced increase in the frequency and amplitude of contractions of myometrial strips, oxytocin abruptly caused a marked contraction of myometrial arteries. Lower concentrations of the peptide had almost no effects. The results suggest that various smooth muscle tissues of the human uterus and placenta are highly differentiated as regards responses to angiotensin II, vasopressin, and oxytocin. The physiological and possible clinical importance of the present findings deserve further investigation.
Adult↗
Relaxant and contractile effects of some amines and prostanoids in myometrial and vascular smooth muscle within the human uteroplacental unit.
Tissue specimens of human myometrium and placenta were obtained at caesarean section and normal vaginal deliveries. Strips of myometrial tissue, and segments of intramyometrial arteries, chorionic plate arteries and veins, and stem villous arteries were dissected. The preparations were mounted in organ baths, and isometric tension was recorded. In myometrial preparations, prostaglandin F2 alpha (PGF2 alpha), prostaglandin E2 (PGE2), noradrenaline (NA) and serotonin (5-HT) all caused concentration-related contractions. In vascular preparations, the maximum contractant or relaxant effect, Emax or Imax, and the drug concentrations causing half maximum responses, EC50 or IC50 were determined. In intramyometrial arteries no significant differences between Emax or EC50 values were found for NA, 5-HT and PGF2 alpha. The Imax values (relaxation of vessels contracted by vasopressin) ranged prostacyclin (PGI2) greater than PGF2 alpha = PGE2, and the IC50 values PGF2 alpha = PGE2 = PGI2 (PGF2 alpha less than PGI2). Thus, PGF2 alpha showed dual effects. Only PGI2 relaxed placental vessels contracted by PGF2 alpha. In chorionic arteries, Emax values ranged PGE2 = PGF2 alpha greater than 5-HT greater than NA, and IC50 values 5-HT less than NA = PGF2 alpha = PGE2. In stem villous arteries, Emax ranged PGE2 = PGF2 alpha greater than 5-HT = NA, and EC50 5-HT = NA = PGE2 = PGF2 alpha. In chorionic veins the order of Emax values was PGF2 alpha = PGE2 greater than 5-HT greater than NA, and that of the EC50 values 5-HT less than NA = PGF2 alpha = PGE2. Smooth muscle tissues from the human uteroplacental unit show individual responses to prostanoids and amines, probably reflecting individual mechanisms for control of contractile activity and blood flow.
Adult↗
Different responses to prostaglandin F2 alpha and E2 in human extra- and intramyometrial arteries.
Tubal segments of the ascending uterine arteries and of intramyometrial arteries were obtained from 18 women who underwent hysterectomy at various phases of the menstrual cycle. Ring preparations of the vessels were mounted in organ baths and isometric tension was recorded. In extramyometrial arteries (outer diameter 2-3 mm) prostaglandin (PG) F2 alpha most potently, but also PGE2 caused concentration-related contractions. In contrast, the contractant effects of both PGs on intramyometrial arteries (outer diameter 0.5-0.6 mm) were negligible. Both extra- and intramyometrial vessels were relaxed to a moderate degree (10-25%) by low concentrations of PGF2 alpha and PGE2. No significant differences between the responses to vasopressin and noradrenaline were found between the vessel preparations. Thus human uterine arteries seem to change their responses to PGF2 alpha and PGE2 as they enter the myometrium and decrease in diameter, and the results raise doubt about the view that direct vasoconstrictor effects of these PGs contribute to the regulation of myometrial blood flow. Such effects of vasopressin and noradrenaline cannot be excluded.
Adolescent↗
Concentrations and contractile effects of substance P in the human ampullary-isthmic junction.
From 20 women undergoing hysterectomy, strip preparations were isolated from the outer, longitudinal and the inner, circular smooth muscle layer of the ampullary-isthmic junction (AIJ), together with small arterial segments dissected as ring preparations from the root of the mesosalpinx. The specimens were mounted in organ baths and isometric tension was recorded. In addition, tissue concentrations of substance P (SP) in the ampulla, AIJ and utero-tubal junction were determined by radioimmunoassay. Tissue concentrations of SP expressed as pmol X g tissue-1 (wet weight, +/- SE) amounted to 3.09 +/- 1.40 in the utero-tubal junction, 1.08 +/- 0.299 in the AIJ and 0.742 +/- 0.299 in the ampulla. In strips of circular muscle, SP at concentrations of 10(-7) -3 X 10(-6) mol X l-1 elicited a combined phasic and tonic response and in longitudinal muscle a mainly tonic contraction was produced. In both tissues, contractions elicited by SP were rapidly abolished in calcium-free medium. Nifedipine abolished the phasic contraction elicited in circular muscle by SP while the tonic response was resistant. The contraction in longitudinal muscle was reduced by 20-30%. Vasoactive intestinal polypeptide (VIP) decreased tension in preparations contracted by SP, prostaglandin F2 alpha and K+-depolarization (124 mmol X l(-1). In unstimulated oviductal arterial preparations, SP had no effect, while the peptide induced a transient relaxation of noradrenaline contracted preparations, and slightly decreased tension of K+-depolarized vessels. The results suggest that SP may be involved in the control of motility of the human AIJ.
Adult↗
Differences in contractile activation between human myometrium and intramyometrial arteries.
Small intramyometrial arteries and pieces of adjacent myometrial tissue were obtained from 25 non-pregnant women undergoing hysterectomy. Vascular and myometrial preparations were dissected, mounted in organ baths and isometric tension was recorded. Myometrial strips, but no vascular preparation, developed spontaneous contractile activity. Noradrenaline (NA) and vasopressin (VP) contracted both vessels and myometrium. Prostaglandin F2 alpha (PGF 2 alpha) contracted the myometrial tissue, but had only a minor effect on the vessels. Removal of extracellular calcium almost abolished the myometrial responses to high K+ (124 mM)-solution, PGF 2 alpha, NA and VP. The vascular responses remaining after this treatment were 18% (K+), 34% (NA) and 25% (VP) of control contractions induced by high K+ (124 mM). Nifedipine potently depressed myometrial contractions induced by NA and VP, but was less active against the vascular responses to these agents. In preparations exposed to calcium-free medium, nifedipine (10(-7) M) almost abolished myometrial contractions induced by calcium in the presence of K+ (124 mM), NA or VP. It also effectively depressed vascular responses to calcium in the presence of K+, but was less active if NA and VP were present. It is suggested that PGF2 alpha has almost no contractant effect on intramyometrial arteries, and that the activation process in these vessels is much less dependent on extracellular calcium than that of the myometrium.
Adult↗
Course and treatment of milk stasis, noninfectious inflammation of the breast, and infectious mastitis in nursing women.
In nursing women with inflammatory symptoms of the breast, it has been possible on the basis of leukocyte counts of the milk and quantitative cultivation for bacteria to classify these cases into milk stasis (counts of less than 10(6) leukocytes and less than 10(3) bacteria per milliliter of milk), noninfectious inflammation (counts of greater than 10(6) leukocytes and less than 10(3) bacteria), and infectious mastitis (counts of greater than 10(6) leukocytes and greater than 10(3) bacteria). In the present study the duration and outcome of these cases were observed, and those without intervention were compared to those with treatment that consisted of systematic and intensive emptying of the breast, supplemented in some cases by antibiotic therapy as directed by susceptibility tests of the bacteria. The course of milk stasis was of short duration and the outcome was good independent of treatment. In cases of noninfectious inflammation the symptoms persisted for several days without treatment, and half of the patients developed infectious mastitis. Emptying of the breast resulted in a significant decrease in the duration of symptoms and a significantly improved outcome. Infectious mastitis without treatment was followed by a good result in only 15% of the cases, and 11% developed abscesses. Emptying of the breast increased the rate of a good outcome to 50% and significantly decreased the duration of symptoms. The addition of antibiotic therapy resulted in a good outcome in 96% of the cases and a further significant reduction of the persistence of symptoms.
Abscess↗
Effects of nifedipine on human placental arteries.
Small chorionic plate arteries (outer diameter 600-700 micron) and umbilical arteries were obtained from human placentas following normal vaginal delivery. Tubal vascular preparations were dissected, mounted in organ baths, and isometric tension was recorded. None of the preparations developed spontaneous contractile activity. The course of potassium-induced contractions differed between chorionic and umbilical arteries. The chorionic arteries showed decreased response to 5-hydroxytryptamine (5-HT) as compared to the umbilical arteries, whereas the contractile response to prostaglandin F2 alpha (PGF2 alpha) was equal. In the chorionic arteries, nifedipine effectively inhibited potassium-induced contractions and, at concentrations of 10(-8)-10(-6) M, decreased responses to 5-HT and PGF2 alpha. Removal of extracellular calcium almost abolished the response to high potassium and reduced the response to both PGF2 alpha and 5-HT by 65%. Nifedipine (10(-8) M) significantly reduced, and nifedipine (10(-7) M) almost abolished, the contractile response induced by calcium after K+ (124 mM) depolarization, and in the presence of PGF2 alpha and 5-HT, nifedipine (10(-8)-10(-7) M) effectively depressed the responses to calcium. The results show decreased response to 5-HT with decreasing dimensions of the placental vessels, and suggest that small placental vessels utilize multiple sources of calcium for contractile responses. Nifedipine seems to interfere with some of these mechanisms and clinical use of the drug may imply a decreased fetal placental vascular resistance.
Arteries↗
Comparison of the effects of nicardipine and nifedipine on isolated human myometrium.
The effects of nicardipine, a calcium-entry blocker which also has a potent phosphodiesterase inhibitory action, were investigated on isolated human term-pregnant and nonpregnant myometrium, and compared with those of nifedipine. Both drugs relaxed pregnant and nonpregnant myometrial preparations contracted by potassium (127 mM), and also reduced or abolished contractions occurring spontaneously, or induced by prostaglandin F2 alpha, oxytocin and vasopressin. However, the effect of nicardipine had a slower onset of action than that of nifedipine, and the drug was significantly more potent than nifedipine is at least as effective as nifedipine. If the differences between the drugs can be reproduced also in vivo, nicardipine offers an interesting alternative to nifedipine for inhibition of undesired uterine activity.
Adult↗
Low dose i.v. infusion of prostaglandin F2 alpha for induction of labor at term.
In 100 pregnant women at term, labor was induced for medical reasons by i.v. infusion of a low dose of prostaglandin F2 alpha (PGF2 alpha). With a dose not exceeding 6 micrograms PGF2 alpha/min, all patients were induced into labor. The mean induction-delivery time was 6.6 hours and the overall proportion of instrumental deliveries was 19%, including 6% cesarean sections. Very few side effects were observed. It is concluded that i.v. infusion of prostaglandin F2 alpha in a low dose regimen might be considered as an alternative to existing methods for the induction of labor at term.
Adolescent↗
Transcutaneous PO2 monitoring in routine observation of newborns.
TcPO2 was monitored in 209 of 814 infants admitted to the premature ward connected to our obstetric department. The majority of the infants were monitored less than 14 h. Approximately 77% of the infants were treated with up to 40% O2, while for a period the remaining infants were treated with more than 40% O2. TcPO2 values were generally controlled to the desirable range of 7-12 kPa (50-90 mm Hg). The daily handling of the equipment was performed by the nursing staff, who found good correlation between the TcPO2 measurement and clinical observations. The importance of application of the electrode in the preductal area is stressed to avoid hyperoxemia in the retinal vessels.
Carbon Dioxide↗
Nitroimidazoles in the canine prostate, vagina, and urethra.
Diffusion of metronidazole and tinidazole in canine prostatic secretion was studied and compared to the diffusion of metronidazole into the canine vagina. This particular comparison was made because prostatic secretion represents an acidic environment in contrast to the canine vagina which has a basic pH. Metronidazole reached significantly higher concentrations in the prostatic secretion (PS) than in plasma (P). No differences were found in the concentrations of tinidazole in P and PS. Plasma and prostatic interstitial fluid (PIF) concentrations of both drugs showed no differences either. However, the PS/P and PIF/P ratios of metronidazole were significantly higher than the corresponding ratios of tinidazole. Metronidazole concentrations in the canine vagina and urethra were significantly lower than the plasma concentrations, possibly because of the basic pH environment. These findings suggest a possible advantage in using metronidazole over tinidazole in aerobic and Trichomonas vaginalis prostatitis and vaginitis in acidic environments. However, clinical studies comparing the two drugs should be carried out in order to establish if this is of clinical importance.
Animals↗
Cinoxacin in urinary tract infections. Theoretical and practical considerations.
In dogs we found that cinoxacin concentrations in prostatic tissue, secretion, and interstitial fluid always were lower than the simultaneous serum concentrations, during constant infusion experiments. The cinoxacin concentrations in urethral and vaginal secretions were similar to those found in prostatic interstitial fluid, approximately one third to one fourth of the simultaneous serum concentrations. The concentrations of cinoxacin in human prostatic tissue after single or multiple doses of 500 mg. were found to be in the range of minimum inhibitory concentrations for most microorganisms found in urinary tract infections. Cinoxacin was found to have a half-life of 2.7 hours in patients with normal renal function, but increased to 8.5 hours in patients with impaired renal function. We found little or no drug accumulation during a seven-day treatment of patients with impaired renal function.
Animals↗
Prophylactic antibiotics in transurethral prostatectomy.
There were 110 patients with preoperative sterile urine who underwent transurethral resection of the prostate and were included in a prospective, randomized, double-blind study that compared the effects of cefoxitin, a cephalosporin, to a placebo. The 2 treatment groups were comparable in age, weight of patient, general condition, diagnosis, preoperative instrumentation, operating time, weight of resected tissue and blood loss. Cefoxitin significantly lowered the incidence of infection, as indicated 3 and 7 days postoperatively, from 26.4 to 3.9 per cent and from 42 to 6.5 per cent, respectively. We were not able to correlate infection to age, general condition, diagnosis, operating time, preoperative instrumentation, weight of resected tissue or blood loss. No statistical difference was found between the 2 treatment groups in the incidence and degree of postoperative fever. These data suggest that prophylactic antibiotics should be administered preoperatively to uninfected patients who undergo transurethral resection of the prostate to prevent postoperative urinary tract infection.
Aged↗
Effect of urine concentration versus tissue concentration of ampicillin and mecillinam on bacterial adherence in the rat bladder.
We investigated the effect of tissue and urine concentrations of ampicillin and mecillinam on bacterial bladder wall adherence in rats. Escherichia coli 02 labeled with 3H-1-leucine was inoculated into the bladder for 2 hr. With the ureters transected bilaterally, antibiotic was instilled into the bladder lumen or administered intravenously only. No bacteria survived after the presence of antibiotic in the bladder lumen for 1.5 hr. After intravenous administration of ampicillin, with no antibiotic in the bladder lumen, measured by viable counts, decreased significantly as compared to controls. Adherence, measured by radioactive counts, decreased significantly after intravenous administration of mecillinam, possibly indicating prevention of tissue invasion. This finding was explained by entrapment of bacterial debris in the bladder lumen and invasion of bacteria into the bladder wall. Our results support the importance of tissue concentrations in the treatment of urinary tract infections.
Amdinocillin↗