Pathogenesis of amniotic fluid embolism

The reason for existant of amniotic fluid embolism is the disposition, which will be favoured by the overaction of the sympathic system, by age and the number of pregnancy. It happens especially by premature rupture of membrane, pathologic contents in the amniotic fluid, high pressure in the uterus, bad uterine muscel with laceration and with opened endymyometric veins. Pathophysiologic connection between the stages of amniotic fluid embolism are discussed in detail.     

Clinical aspects of amniotic fluid embolism

At the Clinic Obstetrics and Gynecology, Allgemeines Krankenhaus Celle, two cases of amniotic fluid embolism were observed. The first case showed the two characteristic phases of the disease (cardiopulmonary shock followed by severe disseminated intravascular coagulopathy). During the onset of the cardiorespiratory symptoms, the patient underwent cesarean section and a healthy infant was born. The mother survived. The other patient died of cardiopulmonary arrest. Cesarean section was carried out immediately. At first, the infant was heavily depressed, but further development was normal. Inspite of great advances in intensive care amniotic fluid embolism still is considered to be a very dangerous event with 86% maternal mortality.     

Acute hemodynamic and respiratory effects of amniotic fluid embolism in the pregnant goat model

OBJECTIVE: Our purpose was to determine the acute-phase central hemodynamic and respiratory effects of raw, filtered, filtered and boiled, and meconium-containing amniotic fluid. STUDY DESIGN: Pregnant goats (Capra hircus) in the last one third of pregnancy were given freshly collected autologous amniotic fluid in a volume of 2.5 ml/kg of body weight. Observations were then made at 10, 30, 60, 120, and 180 minutes after amniotic fluid embolism. Pulmonary artery catheters and femoral artery lung water catheters were placed for specimen and data collection. RESULTS: Marked pressor responses were observed in both the pulmonary and systemic circulations with all amniotic fluid infusions. The pressor response was similar with raw, filtered, and filtered and boiled amniotic fluid. The pressor response seen with amniotic fluid containing meconium was significantly greater than that seen with the other forms. No significant effects were observed on cardiac or respiratory function except in the meconium group, where transient left ventricular dysfunction was accompanied by an acute increase in extravascular lung water and dysoxia. CONCLUSIONS: The Capra hircus model is appropriate for the further study of amniotic fluid embolism. The acute pressor effects are transient and involve both the systemic and pulmonary circulations. Left ventricular dysfunction and dysoxia were observed only with embolism of amniotic fluid containing meconium.     

Fatal amniotic fluid embolism during induced abortion, 1972-1975

From 1972 to 1975, four women have died in the United States from documented amniotic fluid embolism during legal induced abortion. These women, whose pregnancies ranged from 14 to 35 menstrual weeks, had intra-amniotic saline instillation (three cases) and hystereotomy (one case). Performance of abortion in the first trimester and use of curettage technics could minimize the risks of this catastrophe.     

Oximetry for amniotic fluid embolism detection in mini-pigs: tail or snout?

The continuous, non-invasive real-time monitoring of arterial oxygenation (pulse oximetry) has become a standard of care in both human and veterinary medicine. It allows reliable, simple and inexpensive assessment of the arterial oxygenation status. In pigs, commonly used sites for oximetry-probe placement are the ear, snout or tongue, while more recently the 'pig-tail oximetry' has been suggested. In a study regarding the coagulation system during amniotic fluid embolism (AFE) in mini-pigs, we compared tail and snout for oximetry-probe placement and compared them with the 'gold standard': blood-gas analysis (BGA). In both the AFE group and the control group, the tail measurements were slightly lower and the snout measurements were slightly higher than the BGA results. In the experimental model used, both tail and snout measurements were able to detect a temporary desaturation immediately after amniotic fluid embolism (AFE). Blood-gas analysis (BGA) performed on blood drawn from a large artery missed the event. Clinically, there is no significant difference between snout and tail as oximetry-probe placement sites: both are reliable oximetry sites in mini-pigs.     

Expression of endothelin-1 immunoreactivity in breast cancer

This study performed immunohistochemical staining for human ET-1, utilizing avidinbiotin-peroxidase complex detection to examine 47 surgically resected primary breast cancers. Positive immunoreactivity was demonstrated in 19 of the 47 breast cancers (40.4%). There was no significant relationship between the expression of ET-1 and clinicopathological findings. A significant difference was found between ET-1 positive and negative groups in the incidence of recurrence and distant metastasis (P < 0.05). The 5-year overall survival rate was significantly poorer in patients with ET-1-positive cancer (84.2%), compared to 96.4% in patients with ET-1 negative cancer (P < 0.01). The 5-year disease-free survival rate was significantly poorer in patients with ET-1-positive cancer (73.7%) compared to 96.4% in patients with ET-1-negative cancer (P < 0.05). These results suggest that the expression of ET-1 could be used as a possible indicator for predicting the metastatic potential of breast cancer.     

Prenatal diagnosis of Smith-Lemli-Opitz syndrome is possible by measurement of 7-dehydrocholesterol in amniotic fluid

Amniocentesis was performed at 17.3 weeks in a pregnancy with severe intrauterine growth retardation. Cytogenetic studies on amniocytes were normal, 46,XX, and the pregnancy was continued. The diagnosis of Smith-Lemli-Opitz syndrome was suspected in the neonatal period and confirmed by the presence of 7-dehydrocholesterol (7-DHC) in the plasma (0.4 mmol/l, normal = not detectable) associated with a low total cholesterol concentration (0.4 mmol/l, normal = 2.56 +/- 0.23). Retrospective analysis of the amniotic fluid sample revealed an elevated level of 7-DHC (0.022 mmol/l; normal = undetectable). Therefore measurement of 7-DHC levels in amniotic fluid during the second trimester of pregnancy is useful for the prenatal diagnosis of Smith-Lemli-Opitz syndrome in families at risk and should be considered in cases of severe growth retardation of unknown aetiology for which amniotic fluid is available and in which a normal chromosomal pattern in amniocytes is present.     

The mechanism of myometrial contractions induced by endothelin-1 in rat

Experiments were performed to characterize endothelin-1-induced contractions and the role of endothelin (ET) receptor subtypes in rat myometrium. The binding sites of [(125)I]-ET-1 were saturable with high affinity. Scatchard plot analysis revealed that ET-1 binding sites in the myometrium constituted a single population. The dissociation equilibrium constant (Kd) and the maximum binding sites (Bmax) were determined to be 48.9+/-3.0 pM and 1364.0+/-210.3 fmol/mg protein respectively. Specific [(125)I]-ET-1 binding was inhibited completely by unlabelled ET-1 and Ro 46-2005 (mixed-type ET receptor antagonist), but not fully (90.7+/-1.4%) by BQ 123 (a selective ETA receptor antagonist), and not at all by RES 701-1 (a selective ETB receptor antagonist). ET-1 induced myometrial contractions were composed of two types, an increase in resting tone and rhythmic contractions. These contractions were inhibited by BQ 123 and Ro 46-2005, but not by RES 701-1. ET-1-induced contractions were greatly reduced in Ca2+-free Krebs' solution. Nifedipine abolished the rhythmic contractions without affecting the increase in resting tone. These results suggest that ETA receptors are predominantly localized in rat myometrium and that excitation of ETA receptors evokes two types of contractions by increasing the cytoplasmic Ca2+ concentration.     

Collagen degradation products in amniotic fluid

It was found that amniotic fluid (38-42 Hbd) contains hydroxyproline in concentration about 10 micrograms/ml. Gel filtration and dialysis demonstrated that most of hydroxyproline exists in a form of low molecular weight products. Furthermore, it was found that amniotic fluid contains a protein which eluates during gel filtration in void volume of the column. It gives a positive reaction for hydroxyproline but the absorption spectrum of such product is not characteristic for this amino acid. Furthermore, it is not digested by bacterial collagenase. It allows to conclude that amniotic fluid (38-42 Hbd) does not contain collagenous proteins. Only low molecular weight degradation products were found. Only part of them is susceptible on the action of bacterial collagenase.     

Expression of endothelin-1 in the lungs of patients with pulmonary hypertension

BACKGROUND: Pulmonary hypertension is characterized by an increase in vascular tone or an abnormal proliferation of muscle cells in the walls of small pulmonary arteries. Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide with important mitogenic properties. It has therefore been suggested that endothelin-1 may contribute to increases in pulmonary arterial tone or smooth-muscle proliferation in patients with pulmonary hypertension. We studied the sites and magnitude of endothelin-1 production in the lungs of patients with various causes of pulmonary hypertension. METHODS: We studied the distribution of endothelin-1-like immunoreactivity (by immunocytochemical analysis) and endothelin-1 messenger RNA (by in situ hybridization) in lung specimens from 15 control subjects, 11 patients with plexogenic pulmonary arteriopathy (grades 4 through 6), and 17 patients with secondary pulmonary hypertension and pulmonary arteriopathy of grades 1 through 3. RESULTS: In the controls, endothelin-1-like immunoreactivity was rarely seen in vascular endothelial cells. In the patients with pulmonary hypertension, endothelin-1-like immunoreactivity was abundant, predominantly in endothelial cells of pulmonary arteries with medial thickening and intimal fibrosis. Likewise, endothelin-1 messenger RNA was increased in the patients with pulmonary hypertension and was expressed primarily at sites of endothelin-1-like immunoreactivity. There was a strong correlation between the intensity of endothelin-1-like immunoreactivity and pulmonary vascular resistance in the patients with plexogenic pulmonary arteriopathy, but not in those with secondary pulmonary hypertension. CONCLUSIONS: Pulmonary hypertension is associated with the increased expression of endothelin-1 in vascular endothelial cells, suggesting that the local production of endothelin-1 may contribute to the vascular abnormalities associated with this disorder.     

Heterogeneity and underlying mechanism for inotropic action of endothelin-1 in rat ventricular myocytes

1. To clarify the mechanisms underlying the positive inotropic action of endothelin-1 (ET-1), we investigated the effect of ET-1 on twitch cell shortening and the Ca2+ transient in rat isolated ventricular myocytes loaded with a fluorescent Ca2+ indicator indo-1. 2. There was a cell-to-cell heterogeneity in response to ET-1. ET-1 (100 nM) increased twitch cell shortening in only 6 of 14 cells (44%) and the increase in twitch cell shortening was always accompanied by an increase in the amplitude of the Ca2+ transient. 3. The ET(A)- and ET(B)-receptors antagonist TAK-044 (100 nM) almost reversed both the ET-1-induced increases in twitch cell shortening and in the Ca2+ transient. In the ET-1 non-responding cells, the amplitude of the Ca2+ transient never increased. 4. Intracellular pH slightly increased (approximately 0.08 unit) after 30 min perfusion of ET-1 in rat ventricular myocytes. However, ET-1 did not change the myofilament responsiveness to Ca2+, which was assessed by (1) the relationship between the Ca2+ transient amplitude and twitch cell shortening, and by (2) the Ca2+ transient-cell shortening phase plane diagram during negative staircase. 5. We concluded that there was a cell-to-cell heterogeneity in the positive inotropic effect of ET-1, and that the ET-receptor-mediated positive inotropic effect was mainly due to an increase in the Ca2+ transient amplitude rather than to an increase in myofilament responsiveness to Ca2+.     

Fibrinolytic components in fetal membranes and amniotic fluid

OBJECTIVE: We evaluated fibrinolytic components in plasma and amniotic fluid of pregnant women and in postpartum fetal membranes. STUDY DESIGN: Fibrinolytic parameters in amniotic fluid and plasma were measured by means of enzyme-linked immunosorbent assays. Fetal membranes collected after spontaneous labor at term were analyzed by immunohistochemical methods with immunospecific antibodies against fibrinolytic components. RESULTS: Amniotic fluid contained high plasminogen activator inhibitor-1 concentrations but had low activity. Strong staining for plasminogen activator inhibitor-1 and vitronectin was observed in chorionic trophoblasts and moderate staining in decidual connective tissue. Strong staining for plasminogen activator inhibitor-2 was seen in decidual cells. Although prominent staining of plasminogen activators and plasminogen were observed in the amniotic epithelium, virtually no plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, or alpha 2-plasmin inhibitor staining was detected. CONCLUSION: The delicate balance of fibrinolytic activators and inhibitors in fetal membranes and amniotic fluid may contribute to the triggering of membrane rupture at term.     

Comparable potent coronary constrictor effects of endothelin-1 and big endothelin-1 in humans

BACKGROUND: Endothelin-1 (ET-1) is a potent vasoconstrictor produced from the precursor big ET-1 in endothelial cells. The coronary effects of these peptides in humans in vivo are unknown. Therefore, the effects of ET-1 and big ET-1 on coronary blood flow in relation to plasma ET-1 and big ET-1 levels were compared in healthy subjects. METHODS AND RESULTS: The peptides were infused intravenously at the rates of 0.2, 1, and 8 pmol/kg per minute. Each dose administered for 20 minutes except the highest dose of ET-1, which was administered for 10 minutes. ET-1 and big ET-1 evoked dose-related increases in mean arterial blood pressure from 93 +/- 4 to 107 +/- 4 mm Hg and from 89 +/- 2 to 122 +/- 5 mm Hg, respectively, at the highest dose. ET-1 and big ET-1 reduced coronary sinus blood flow, measured with thermodilution by a maximum of 25 +/- 4% and 28 +/- 8% and increased coronary vascular resistance by 50 +/- 9% and 107 +/- 26%, respectively. Coronary sinus, but not arterial, oxygen saturation was reduced in parallel with the coronary sinus blood flow. The effects of ET-1 and big ET-1 were similar at corresponding time points. During infusion of ET-1, a 19 +/- 5% extraction of ET-1 was observed over the coronary vascular bed (P < .05). Administration of big ET-1 elevated arterial plasma ET-1 levels by 2.4-fold, and after correction for the local extraction of ET-1, a myocardial production of ET-1 was observed. CONCLUSIONS: ET-1 and big ET-1 induce comparable increases in blood pressure and coronary constriction in humans in vivo. The results also suggest a net local removal of circulating ET-1 and big ET-1 and a local conversion of big ET-1 into ET-1 within the coronary vascular bed.     

Immunoreactive endothelin-1, endothelin-2 and big endothelin-1 in follicular fluids of women undergoing ovulation induction for in-vitro fertilization

Atlantic cod (Gadus morhua) transferrin cDNAs were isolated from a liver cDNA library using a cod transferrin-derived polymerase chain reaction product as a hybridization probe. The composite nucleotide sequence of two overlapping clones was 2223 bp in length excluding the poly(A) sequence and was equivalent to 87% of the 3' end of the Atlantic salmon transferrin cDNA sequence. Comparison of the deduced amino acid sequence of cod, salmon, Xenopus and several mammalian transferrins revealed that the two fish sequences are more similar with respect to their amino acid sequence and the position of additions/deletions than to other vertebrate transferrins. Conservation of the iron-binding domains and cysteine residues involved in disulphide bridges indicates that all transferrins share similar tertiary structure and support the hypothesis that extant vertebrate transferrin genes were derived from a gene duplication before the divergence of fish, frogs and mammals. Cod transferrin mRNA was detected in both brain and liver RNA and to a much lesser extent in RNA isolated from kidney and heart in contrast to salmon and several other vertebrates in which the transferrin gene is not expressed in brain.     

The role of endothelin-1 as a mediator of the pressure response after air embolism in blood perfused lungs

BACKGROUND: Irritable bowel syndrome is a common cause of abdominal pain and discomfort and may be related to disordered gastrointestinal motility. Our aim was to assess the effects of long-term treatment with a prokinetic agent, cisapride, on postprandial jejunal motility and symptoms in the irritable bowel syndrome (IBS). METHODS: Thirty-eight patients with IBS (constipation-predominant, n = 17; diarrhoea-predominant, n = 21) underwent 24-h ambulatory jejunal manometry before and after 12 week's treatment [cisapride, 5 mg three times daily (n = 19) or placebo (n = 19)]. RESULTS: In diarrhoea-predominant patients significant differences in contraction characteristics were observed between the cisapride and placebo groups. In cisapride-treated diarrhoea-predominant patients the mean contraction amplitude was higher (29.3 +/- 3.2 versus 24.9 +/- 2.6 mm Hg, cisapride versus placebo (P < 0.001); pretreatment, 25.7 +/- 6.0 mm Hg), the mean contraction duration longer (3.4 +/- 0.2 versus 3.0 +/- 0.2 sec, cisapride versus placebo (P < 0.001); pretreatment, 3.1 +/- 0.5 sec), and the mean contraction frequency lower (2.0 +/- 0.2 versus 2.5 +/- 0.4 cont./min, cisapride versus placebo (P < 0.001); pretreatment, 2.5 +/- 1.1 cont./min] than patients treated with placebo. No significant differences in jejunal motility were found in the constipation-predominant IBS group. Symptoms were assessed by using a visual analogue scale before and after treatment. Symptom scores relating to the severity of constipation were lower in cisapride-treated constipation-predominant IBS patients [score, 54 +/- 5 versus 67 +/- 14 mm, cisapride versus placebo (P < 0.05); pretreatment, 62 +/- 19 mm]. Diarrhoea-predominant IBS patients had a higher pain score after cisapride therapy [score, 55 +/- 15 versus 34 +/- 12 mm, cisapride versus placebo (P < 0.05); pretreatment, 67 +/- 19 mm]. CONCLUSION: Cisapride affects jejunal contraction characteristics and some symptoms in IBS.     

Clinical utility of amniotic fluid volume assessment

Abnormal amniotic fluid volume is associated with increased maternal risk and perinatal morbidity and mortality. Until the advent of ultrasonography, the invasive nature of amniotic fluid volume assessment limited its clinical utility. Refinements in quantifying the noninvasive sonographic assessment of oligohydramnios and hydramnios have improved the ability of clinicians to identify at-risk pregnancies. This article reviews the available methods of amniotic fluid volume assessment and outlines a comprehensive approach to sonographic screening and monitoring.