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G Ahlborg

Publications and source records attributed to G Ahlborg.

At least 19 recordsLinked to original sources

Contribution of endogenous endothelin-1 to basal vascular tone during normal pregnancy and preeclampsia.

OBJECTIVE: The aim of this study was to determine the physiologic role for endogenous endothelin in the regulation of vascular tone during normal pregnancy and preeclampsia. The vascular sensitivity to endothelin-1 during pregnancy was studied also. STUDY DESIGN: Forearm blood flow was measured by venous occlusion plethysmography during intra-arterial infusion of phosphoramidon, an endothelin-converting enzyme inhibitor, for 60 minutes, which was followed by co-infusion with endothelin-1 for 30 minutes. Three groups were studied: healthy nonpregnant women, normal pregnant women, and women with preeclampsia. RESULTS: There was a significant increase in forearm blood flow in the nonpregnant group after phosphoramidon infusion alone (73%+/-37%; P<.05). Phosphoramidon did not change forearm blood flow in pregnant subjects. Co-infusion with endothelin-1 significantly decreased forearm blood flow in both the nonpregnant and normal pregnant women (53%+/-7% and 40%+/-11%, respectively; P<.01). No response to endothelin-1 was found among women with preeclampsia. CONCLUSION: The vascular sensitivity to endothelin-1 is not altered during normal pregnancy in contrast to preeclamptic pregnancy, where no effect of endothelin-1 was seen. Reduced endothelin dependence during pregnancy might be one mechanism behind the fall in peripheral vascular resistance.

Adult↗

Endothelin-1: increased plasma clearance, pulmonary affinity and renal vasoconstriction in young smokers.

Pulmonary and renal haemodynamics and elimination of endothelin-1 (ET-1) were studied in six young smokers in response to 20 min intravenous infusion of ET-1 (4 pmol kg(-1) min(-1)) after smoking. At 20 min of ET-1 infusion fractional ET-1 extractions in the lungs and kidneys were 60 +/- 2 and 60 +/- 7%, respectively. Cardiac output and renal blood flow (RBF) fell by 18 +/- 4% (P<0.05) and 34 +/- 5% (P<0.01). Mean systemic arterial pressure increased (P<0.05) whereas pulmonary pressures were unchanged. Compared with previously published data in non-smokers (Weitzberg et al., 1991, 1993) basal arterial ET-1 and ET-1-values during ET-1 infusion were lower with a more rapid return to basal value. Smokers had higher pulmonary extraction of ET-1 at the same pulmonary arterial concentration (P<0.05). RBF reduction was more pronounced (P<0.05). Systemic vascular resistance increased while pulmonary vascular resistance did not increase as in non-smokers. Increased plasma clearance and more efficient pulmonary elimination of ET-1 lowers the arterial level in young smokers. In addition ET-1 evokes more pronounced renal vasoconstriction in these individuals.

Adult↗

Occupational and environmental medicine in Sweden.

Great changes have taken place in the fields of occupational and environmental medicine in Sweden during the past decade. Unemployment, work stress, and indoor climate problems have become increasingly common. Chemical exposures in industry and serious work accidents have continued to decrease. State subsidies to occupational health services have been withdrawn and the legislation concerning, for example, occupational diseases has been changed in order to decrease state expenditure. Research has focused on, for instance, ergonomic and psycho-social factors, electromagnetic fields and exposures causing allergy. There is a growing awareness of the need for more emphasis on prevention, which should act in favour of both hospital-based occupational and environmental medicine and the occupational health services sector.

Education, Medical, Graduate↗

The association of shift work and nitrous oxide exposure in pregnancy with birth weight and gestational age.

We examined the relation between shift work and occupational nitrous oxide exposure in the second trimester of pregnancy and birth weight and gestational age at delivery among the members of the Swedish Midwives Association. Eighty-four per cent of members who were registered in 1989 responded to a postal questionnaire concerning occupational exposures, including work schedule and the use of nitrous oxide, in relation to each of their pregnancies. We obtained information on births from the Swedish Medical Birth Register. We used models with allowance for dependence between births for the same woman and found that night work was associated with preterm birth (<37 weeks) [odds ratio (OR) = 5.6; 95% confidence limits (CL) = 1.9, 16.4] and to a lesser extent with low birth weight [OR = 1.9 (95% CL = 0.6, 5.8)]. Three-shift work schedule (day, evening, and night rotation) showed a possible association with preterm birth [OR = 2.3 (95% CL = 0.7, 7.3)]. Exposure to nitrous oxide use was associated with reduced birth weight (-77 gm; 95% CL = -129, -24) and an increase in the odds of infants being small for gestational age (< or = 10th percentile of weight for gestational week) (OR = 1.8; 95% CL = 1.1, 2.8).

Adult↗

Hemodynamic effects of endothelin-1 and big endothelin-1 in chronic hemodialysis patients.

Increased plasma concentrations of endothelin-1 (ET-1) and big endothelin-1 (big ET-1) have been reported in patients with end-stage renal failure (ESRD). In the present study, which included hemodialysis (HD) patients with (n = 21) and without (n = 32) ischemic heart disease, the putative association between plasma levels of ET-1 and big ET-1 and ischemic heart disease and the influence of the dialysis procedure on ET concentrations was investigated. This study also examined in an additional five HD patients without cardiac disease whether intravenously infused ET-1 and big ET-1 (0.2, 1, and 4 pmol/kg per min, each dose for 20 min) preserve their vasoactive potency and whether exogenous big ET-1, which in healthy humans is converted in the kidney, is still converted to ET-1 in ESRD. HD patients with ischemic heart disease demonstrated higher plasma levels of ET-1 and big ET-1 than HD patients without this disorder, and HD reduced plasma ET-1 and big ET-1 concentrations. In HD patients, the big ET-1 infusion, resulting in a 1.5-fold increase in plasma ET-1, caused a more marked and prolonged rise in mean arterial BP than ET-1 (20% versus 13%, P = 0.0001) and a slightly smaller but more prolonged decrease in estimated splanchnic blood flow than ET-1 (37% versus 44%, P = 0.02). Furthermore, big ET-1 lowered heart rate by 9% (P = 0.01) but ET-1 did not. Plasma half-lives of ET-1 and big ET-1 were longer in HD patients than in healthy humans. Thus, ET-1 and big ET-1 preserve their vasoactive potency, and circulating big ET-1 is still converted to active ET-1 in ESRD. Consequently, the increased plasma levels of ET-1 and big ET-1 noted in HD patients, especially in patients with ischemic heart disease, might play a role in the development of uremic cardiovascular complications.

Adult↗

The C-terminal fragment of big endothelin-1 does not potentiate the vasoactive effects of endothelin-1.

The aim was to study the cardiovascular effects of the C-terminal (22-38) fragment of big endothelin-1, which is produced by the cleavage of big endothelin-1 (big ET-1) to endothelin-1 (ET-1). An intravenous infusion of the (22-38) fragment (4, 8 and 12 pmol kg-1 min-1, each dose for 10 min) was given to 10 healthy subjects. Four control subjects received 0.9% saline. Two additional subjects received ET-1 1 (0.2 and 4 pmol kg-1 min-1, each dose for 20 min) alone or combined with an equimolar infusion of the (22-38) fragment on two separate occasions. The fragment infusion did not alter heart rate, mean arterial blood pressure, cardiac output, systemic or pulmonary vascular resistance, splanchnic, cerebral or forearm blood flow. Renal blood flow showed a slight fall (11%, P < 0.001) in the fragment group of the same magnitude as in a previous control study. After the fragment infusion, a decrease in mean pulmonary arterial pressure (MPAP) by 12% (P < 0.01) and in pulmonary capillary wedge pressure (PCWP) by 31% (P < 0.001) was noted, which did not differ from the pulmonary pressures in the saline-infused control group. The (22-38) fragment, when combined with ET-1, was not able to modify the effects of ET-1 on heart rate, mean arterial blood pressure, splanchnic and renal blood flow. Consequently, the exogenous (22-38) fragment does not seem to cause any significant cardiovascular effects in healthy humans.

Adult↗

Cyclooxygenase inhibition potentiates the renal vascular response to endothelin-1 in humans.

Vascular endothelin-receptor stimulation results in vasoconstriction and concomitant production of the vasodilators prostaglandin I2 and nitric oxide. The vascular effects of cyclooxygenase (COx) blockade (diclofenac intravenously) and the subsequent vasoconstrictor response to endothelin-1 (ET-1) infusion 30 min after diclofenac were studied in healthy men. With COx blockade, cardiac output (7%) and splanchnic (14%) and renal (12%) blood flows fell (all P < 0.001). Splanchnic blood flow returned to basal value within 30 min. Mean arterial blood pressure increased (4%, P < 0.001). Splanchnic glucose output fell (22%, P < 0.01). Subsequent ET-1 infusion caused, compared with previous ET-1 infusion without COx blockade (G. Ahlborg, E. Weitzberg, and J. M. Lundberg. J. Appl. Physiol. 77: 121-126, 1994; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Biochem. Biophys. Res. Commun. 180: 1298-1303, 1991; E. Weitzberg, G. Ahlborg, and J. M. Lundberg. Clin. Physiol. (Colch.) 13: 653-662, 1993), the same increase in mean arterial blood pressure (4%), decreases in cardiac output (13%) and splanchnic blood flow (38%), but no significant change in splanchnic glucose output. Renal blood flow reduction was potentiated (33 +/- 3 vs. 23 +/- 2%, P < 0.02), with a total reduction corresponding to 43 +/- 3% (P < 0.01 vs. 23 +/- 3%). We conclude that COx inhibition induces renal and splanchnic vasoconstriction. The selectively increased renal vascular responsiveness to ET-1 emphasizes the importance of endogenous arachidonic acid metabolites (i.e., prostaglandin I2) to counteract ET-1-mediated renal vasoconstriction.

Adult↗

Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation.

We have previously demonstrated that the brain contains about 80% of the 24S-hydroxycholesterol in the human body and that there is a net flux of this steroid from the brain into the circulation (Lütjohann, D. et al. 1996. Proc. Natl. Acad. Sci. USA. 93: 9799-9804). Combining previous data with new data on 12 healthy volunteers, the arteriovenous difference between levels of this oxysterol in the internal jugular vein and in a peripheral artery was found to be -10.2 +/- 2.8 ng/ml (mean +/- SEM) corresponding to a net flux of 24S-hydroxycholesterol from the brain of about 6.4 mg/24 h. The arteriovenous difference between levels of 24S-hydroxycholesterol in the hepatic vein and a peripheral artery of 12 other volunteers was found to be 7.4 +/- 2.2 ng/ml, corresponding to a hepatic uptake of about 7.6 mg/24 h. The concentrations of 24S-hydroxycholesterol in the renal vein were about the same as those in a peripheral artery, indicating that a renal elimination is not of importance. Intravenously injected deuterium-labeled racemic 24-hydroxycholesterol was eliminated from the circulation of two human volunteers with half-lives of 10 h and 14 h, respectively. A positive correlation was found between the levels of circulating cholesterol and 24S-hydroxycholesterol. The results are consistent with a cerebral origin of most of the circulating 24S-hydroxycholesterol and suggest that the liver is the major eliminating organ. It is concluded that conversion into 24S-hydroxycholesterol is a quantitatively important mechanism for elimination of cholesterol from human brain. The possibility is discussed that circulating levels of 24S-hydroxycholesterol can be used as a marker for pathological and/or developmental changes in the brain.

Adult↗

A comparison of skeletal stability after mandibular advancement and use of two rigid internal fixation techniques.

PURPOSE: Two different methods of rigid fixation were compared for postoperative stability 6 months after mandibular advancement for treatment of Class II malocclusion. MATERIAL AND METHODS: Sixty (30 + 30) patients from two different oral and maxillofacial units treated for a Class II malocclusion by bilateral saggital split osteotomy (BSSO), and two different methods of internal rigid fixation were prospectively investigated. Two groups (S1, n = 15; S2, n = 15) had bicortical noncompressive screws inserted in the gonial area through a transcutaneous approach, and the other two groups (P1, n = 15; P2, n = 15) had the bone segments fixed with unicortical screws and miniplates on the lateral surface of the mandibular body. Cephalograms were taken preoperatively, 2 days postoperatively and 6 months after the operation. A computer program was used to superimpose the three cephalograms and to register the mandibular advancement and postoperative change both sagittally and vertically. RESULTS: These were minor differences in the advancement and postoperative changes between the four groups, but statistically no significant difference was shown in either sagittal or vertical directions. However, statistically verified differences proved that increasing age was associated with a smaller amount of postsurgical relapse. Low-angle cases (ML/NSL < 25 degrees) had a bigger amount of surgical (P = .0008) and postsurgical (P = .0195) movement compared with the patients in the high-angle group (ML/NSL < 38 degrees). Using a multiple regression test, a positive correlation was also shown between the amount of surgical advancement and the amount of postsurgical instability (P = .018). CONCLUSIONS: This prospective dual-center study indicates that the two different methods of internal rigid fixation after surgical advancement of the mandible by BSSO did not significantly differ from each other, and it is up to the individual operator to choose the method for internal rigid fixation.

Adolescent↗

Exogenous endothelin-1 causes peripheral insulin resistance in healthy humans.

In states of insulin resistance, increased plasma levels of endothelin-1 and a disturbed vascular reactivity have been reported. In order to investigate the effects of endothelin-1 on peripheral insulin sensitivity and the vasoactive interactions between insulin and endothelin-1, six healthy subjects were studied on two different occasions with the euglycaemic hyperinsulinaemic clamp technique combined with an intravenous infusion of either endothelin-1 (4 pmol kg-1 min-1) or 0.9% sodium chloride. During the endothelin-1 infusion, arterial plasma endothelin-1 levels rose 10-fold. The endothelin-1 infusion reduced insulin sensitivity as demonstrated by a 31 +/- 7% decrease in whole-body glucose uptake (P < 0.05) and a 26 +/- 11% fall in leg glucose uptake (P < 0.05) compared with the control protocol. During the state of hyperinsulinaemia, exogenous endothelin-1 increased mean arterial blood pressure by 8 +/- 1% (P < 0.05) and decreased splanchnic and renal blood flow by 30 +/- 6% (P < 0.001) and 20 +/- 4% (P < 0.001), respectively. However, the endothelin-1 infusion did not lower skeletal muscle blood flow measured as leg and forearm blood flow. In summary, exogenous endothelin-1 induced insulin resistance in healthy humans by reducing insulin-dependent glucose uptake in skeletal muscle without decreasing skeletal muscle blood flow. Furthermore, endothelin-1 also preserved its vasoactive potency in the presence of hyperinsulinaemia.

Adult↗

Long-lasting coronary vasoconstrictor effects and myocardial uptake of endothelin-1 in humans.

The effect of intravenous administration of the endothelium derived vasoconstrictor peptide endothelin-1 (ET-1 0.2. 1 and 8 pmol kg-1 min-1) on coronary blood flow in relation to plasma ET-1 as well as blood lactate and glucose levels were investigated in six healthy volunteers. Coronary sinus blood flow was measured by thermodilution. Administration of ET-1 elevated arterial plasma ET 35-fold, dose-dependently increased mean arterial blood pressure from 95 +/- 5 mmHg to 110 +/- 6 mmHg (P < 0.01) and reduced heart rate from 64 +/- 4 beats min-1 to 58 +/- 4 beats min-1 (P < 0.05) at 8 pmol kg-1 min-1. Coronary sinus blood flow was reduced maximally by 23 +/- 4% (P < 0.01) and coronary vascular resistance increased by 48 +/- 11% (P < 0.01). Coronary sinus oxygen saturation decreased from 35 +/- 1% to 22 +/- 2% at 2 min after the infusion (P < 0.01). A coronary constrictor response was observed at a 4-fold elevation in plasma ET. The reduction is coronary sinus blood flow lasted 20 min and coronary sinus oxygen saturation was still reduced 60 min after the infusion. Myocardial oxygen uptake or arterial oxygen saturation were not affected by ET-1. Myocardial lactate net uptake decreased by 40% whereas glucose uptake was unaffected. At the highest infusion rate there was a net removal of plasma ET by 24 +/- 3% over the myocardium (P < 0.05). The results show that ET-1 induces long-lasting reduction in coronary sinus blood flow via a direct coronary vasoconstrictor effect in healthy humans observable at a 4-fold elevation in plasma ET-1. Furthermore, there is a net removal of circulating ET-1 by the myocardium.

Adult↗

Nitric oxide-endothelin-1 interaction in humans.

Healthy men received NG-monomethyl-L-arginine (L-NMMA) intravenously to study cardiovascular and metabolic effects of nitric oxide synthase blockade and whether this alters the response to endothelin-1 (ET-1) infusion. Controls only received ET-1. L-NMMA effects were that heart rate (17%) cardiac output (17%), and splanchnic and renal blood flow (both 33%) fell promptly (all P < 0.01). Mean arterial blood pressure (6%), and systemic (28%) and pulmonary (40%) vascular resistance increased (P < 0.05 to 0.001). Arterial ET-1 levels (21%) increased due to a pulmonary net ET-1 release (P < 0.05 to 0.01). Splanchnic glucose output (SGO) fell (26%, P < 0.01). Arterial insulin and glucagon were unchanged. Subsequent ET-1 infusion caused no change in mean arterial pressure, heart rate, or cardiac output, as found in the present controls, or in splanchnic and renal blood flow or splanchnic glucose output as previously found with ET-1 (G. Ahlborg, E. Weitzberg, and J. M. Lundberg. J. Appl. Physiol. 79: 141-145, 1995). In conclusion, L-NMMA like ET-1, induces prolonged cardiovascular effects and suppresses SGO. L-NMMA causes pulmonary ET-1 release and blocks responses to ET-1 infusion. The results indicate that nitric oxide inhibits ET-1 production and thereby interacts with ET-1 regarding increase in vascular tone and reduction of SGO in humans.

Adult↗

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.

Adult↗

Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation.

We have investigated whether side chain-hydroxylated cholesterol species are important for elimination of cholesterol from the brain. Plasma concentrations of 24-hydroxycholesterol (24-OH-Chol) in the internal jugular vein and the brachial artery in healthy volunteers were consistent with a net flux of this steroid from the brain into the circulation, corresponding to elimination of approximately 4 mg cholesterol during a 24-h period in adults. Results of experiments with rats exposed to 18O2 were also consistent with a flux of 24-OH-Chol from the brain into the circulation. No other oxysterol measured showed a similar behavior as 24-OH-Chol. These results and the finding that the concentration of 24-OH-Chol was 30- to 1500-fold higher in the brain than in any other organ except the adrenals indicate that the major part of 24-OH-Chol present in the circulation originates from the brain. Both the 24-OH-Chol present in the brain and in the circulation were the 24S-stereoisomer. In contrast to other oxysterols, levels of plasma 24-OH-Chol were found to be markedly dependent upon age. The ratio between 24-OH-Chol and cholesterol in plasma was approximately 5 times higher during the first decade of life than during the sixth decade. There was a high correlation between levels of 24-OH-Chol in plasma and cerebrospinal fluid. It is suggested that the flux of 24-OH-Chol from the brain is important for cholesterol homeostasis in this organ.

Adolescent↗

Shift work, nitrous oxide exposure and subfertility among Swedish midwives.

BACKGROUND: Shift work and nitrous oxide exposure have both been suspected of having adverse influence on the reproductive performance of health workers. Time to pregnancy has been suggested as a sensitive measure of fecundity in occupationally exposed groups. We investigated the effects of shift work and nitrous oxide exposure on the fertility of Swedish midwives. METHODS: A questionnaire was mailed to all members of the Swedish Midwives Association who were born 1940 or thereafter, 3985 in all. Eighty-four per cent responded. Detailed information on the number of menstrual cycles required to achieve pregnancy and the working conditions during that period were obtained concerning the most recent, planned pregnancy occurring after 1983. The per cycle probability of becoming pregnant was calculated for each exposure category, and the relation to the unexposed was expressed as fecundability ratios. RESULTS: Midwives who worked two-shift, three-shift rotas, or only nights had reduced fertility compared to those working in the day time. The fecundability ratios were 0.78 (95% confidence interval [CI]: 0.65-0.94), 0.77 (95% CI: 0.60-0.98), and 0.82 (95% CI: 0.64-1.03), respectively, after adjustment for covariates. No effect of nitrous oxide exposure was noted except in the small group reporting that they assisted at more than 30 deliveries per month when nitrous oxide was used (fecundability ratio = 0.64; 95% CI: 0.44-0.95). CONCLUSION: Shift work and frequent, high occupational exposure to nitrous oxide may have a negative influence on the ability of women to become pregnant.

Female↗

Exercise-induced changes in neuropeptide Y, noradrenaline and endothelin-1 levels in young people with type I diabetes.

In search of early signs of autonomic and vascular dysfunction in diabetic subjects, six young men with type I diabetes and six healthy subjects were investigated regarding arterial levels of noradrenaline (NA), neuropeptide Y- (NPY) and endothelin-1-(ET-1) like immunoreactivity (Li) during and after 1 h of exercise at 70% of peak oxygen uptake. Basal NA, NPY-Li and ET-1-Li levels did not differ between groups. NA and NPY-Li rose during exercise in diabetic subjects to only 60% of the control values (P < 0.05, interaction group x time P < 0.001). Disappearance rates for NA and NPY-Li did not differ between groups. Plasma ET-1-Li did not differ between groups during exercise. Values returned to basal levels within 5 min in the diabetic but not in the control group. In conclusion, diabetic subjects show lower NPY-Li and NA levels than control subjects during exercise but similar disappearance rates after exercise, indicating lower releases. Furthermore, plasma ET-1 levels did not differ between groups during exercise.

Adult↗

Shift work, nitrous oxide exposure, and spontaneous abortion among Swedish midwives.

OBJECTIVES: To study the relation between irregular work hours, nitrous oxide (N2O) exposure, and the risk of spontaneous abortion. METHODS: All 3985 female members of the Swedish Midwives Association in 1989, born in 1940 or later, received a questionnaire on exposure before and during all of their pregnancies. Questions on work conditions covered occupation, extent of employment, workplace, work schedules, use of anaesthetics, and work load. The association between exposure variables and spontaneous abortion was analysed by logistic regression models. RESULTS: Night work and three shift schedules among midwives showed increased odds ratios (ORs) (95% confidence intervals (95% CI)) 1.63 (0.95-2.81) and 1.49 (0.86-2.59), respectively. The ORs of late spontaneous abortions (after the 12th week of pregnancy) was increased for night work 3.33 (1.13-9.87). Use of N2O (> 50% of the deliveries) was not associated with increased risk of spontaneous abortion OR 0.95 (0.62-1.47). Frequent or permanent shortage of staff was related to an increased risk of spontaneous abortions before the 13th week of pregnancy. CONCLUSIONS: The results support the hypothesis that night work and high work load increase the risk of spontaneous abortion.

Abortion, Spontaneous↗

Central and regional hemodynamic effects during infusion of Big endothelin-1 in healthy humans.

Big endothelin-1 (Big ET-1) was given intravenously to six healthy men to study uptakes and vascular effects. Blood samples were taken from systemic and pulmonary arterial and internal jugular and deep forearm venous catheters. Arterial Big ET-1-like immunoreactivity (Big ET-1-LI) increased from 5.43 +/- 0.60 to 756 +/- 27 pmol/l, and ET-1-LI increased from 4.67 +/- 0.08 to 6.67 +/- 0.52 pmol/l (P < 0.001). Skeletal muscle fractional extraction of Big ET-1-LI was 15 +/- 4%. ET-1-LI release did not increase in the studied vascular beds. Heart rate fell by 17% (P < 0.001), cardiac output fell by 26% (P < 0.001), and stroke volume fell by 11% (P < 0.05). Mean arterial blood pressure increased 18%, systemic vascular resistance increased 65%, and pulmonary vascular resistance increased 57% (P < 0.01-0.001). Pulmonary blood pressures, forearm blood flow, arterial pH, arterial PCO2, and systemic arterial-internal jugular venous O2 difference remained unchanged. No specific Big ET-1 receptors were found in human pulmonary membranes. The half-maximal inhibitory concentration for the receptor antagonist bosentan was 181 nM. In summary, circulating Big ET-1 elicits greater increases in mean arterial blood pressure and systemic vascular resistance and decreases in heart rate and cardiac output compared with an equimolar ET-1 infusion (26).

Adult↗