Biomedical subjects

W Wuttke

Publications and source records attributed to W Wuttke.

At least 91 records · Page 5Linked to original sources

PubMed1995

Diagnosis of early ectopic pregnancy by measurement of the maternal serum to cul-de-sac fluid beta-hCG ratio.

In patients suspected of having an ectopic pregnancy, because of a positive beta-human chorionic gonadotropin (beta-hCG) test and a sonographically undetectable gestational sac, even laparoscopy cannot always achieve a precise diagnosis, when the gestational age is very early. This means that the patient has to be followed by repeated beta-hCG measurements and repeated laparoscopy, which are expensive and inconvenient for the patient. This paper reports on a method that is simple to perform and that will provide the clinician with valuable information about the strong likelihood of a tubal pregnancy when ultrasound and beta-hCG measurements raise the suspicion but are not diagnostic. A prerequisite for this approach is the availability of a minimal volume (1-2 ml) of peritoneal fluid in the pouch of Douglas. A total of 131 patients who had a positive beta-hCG test and an undetectable gestational sac within the uterine cavity and who had a small volume of cul-de-sac fluid were studied. The fluid was obtained transvaginally by means of an ultrasound-guided automatic puncture system. The beta-hCG level was determined in the cul-de-sac fluid and in the maternal serum, for comparison. In two cases with tubal pregnancy, concentrated viscous blood samples were aspirated and beta-hCG concentrations could not be measured for technical reasons. In 129 cases, the ratio of levels of beta-hCG between serum and cul-de-sac fluid could be measured. In 42 out of 44 patients with intrauterine pregnancy, the ratio was greater than unity; in 82 out of 85 patients with a tubal pregnancy, the ratio was less than unity. With this ratio used for detection of tubal pregnancy, the diagnostic sensitivity of the test was 95.4% and the specificity was 95.2%. The positive predictive value was 97.6% and the negative predictive value 91.3%. We conclude from these findings that the measurement of the maternal serum to cul-de-sac fluid beta-hCG ratio facilitated the early diagnosis of an ectopic pregnancy in the Fallopian tube.

Ascitic Fluid↗

PubMed1995

Enhanced cAMP production mediates the stimulatory action of pituitary adenylate cyclase activating polypeptide (PACAP) on in vitro catecholamine secretion from bovine adrenal chromaffin cells.

The 38 amino acid peptide pituitary adenylate cyclase activating polypeptide (PACAP) induced a dose dependent increase of catecholamine secretion in cultures of bovine chromaffin cells. This secretagogue activity of PACAP was strictly dependent on the presence of calcium in the culture medium. If calcium was omitted from the medium no effect of PACAP on catecholamine secretion could be detected during an incubation of 20 min. Preincubation of cells with 1 nM PACAP for 5 min facilitated the subsequent nicotine stimulated catecholamine secretion during a 20 min incubation without addition of the peptide. PACAP induced catecholamine secretion was clearly accompanied by a dose dependent increase of intracellular cAMP concentrations. The percentage of cells responding to PACAP with increased catecholamine secretion was assessed by immunocytochemistry of the transient appearance of dopamine-beta-hydroxylase, associated with the membranes of the chromaffin granules on the cell surface during the secretory process. About 70% of adrenal medullary cells responded to 100 nM PACAP with enhanced secretory activity. Though PACAP stimulated catecholamine secretion, we did not observed major effects on intracellular free calcium concentrations ([Ca2+]i) as determined with fura-2 by single cell fluorescence microscopy. In maximally 20% of the cells a rise in [Ca2+]i in response to a challenge with 500 nM PACAP was observed. Lower concentrations of PACAP were without an effect on [Ca2+]i. These data indicate that the stimulatory action of PACAP on in vitro catecholamine secretion from bovine chromaffin cells is linked to a rise of intracellular cAMP.

Adrenal Medulla↗

PubMed1995

The inhibitory effect of beta-endorphin on LH release in ovariectomized rats does not involve the preoptic GABAergic system.

In rats, beta-endorphin (beta-END) and gamma-aminobutyric acid (GABA) suppress LH secretion by hypothalamic mechanisms involving the preoptic area (POA). Systemic injection of naloxone (NAL) increases LH secretion in male rats, an effect which can be prevented by coadministration of GABA agonists. Application of NAL into the POA of ovariectomized (ovx), progesterone substituted sheep modulates preoptic GABA release. These findings have been interpreted such that the endogenous opioids act via the preoptic GABAergic system to regulate LH release. To evaluate this hypothesis we implanted ovx rats with push pull cannula into the POA and measured GABA secretion prior to and during the preoptic application of either NAL or beta-END. Blood samples were collected to assess the effects of the drugs on LH secretion. In addition, ovx rats were substituted with estradiol (E2) to induce a negative feedback effect on LH release. Intrapreoptic application of beta-END caused a rapid decline of LH release in ovx rats which was completely reversible after termination of beta-END perfusion. Though LH levels were clearly suppressed, no change of GABA release in the POA was observed. During preoptic NAL perfusion both LH secretion and GABA release remained unaffected. Likewise, during beta-END perfusion into the POA of E2 treated rats neither LH nor GABA secretion changed. In contrast, NAL perfusion rapidly increased LH release but again this action of the opioidergic drug was not accompanied by alterations of GABA release. We conclude from these data: 1) Intrapreoptically applied beta-END inhibits LH release only in the absence of steroids. In turn, blockade of opioid receptors is effective only in the presence of steroids. Both findings indicate that in the POA opioidergic activity is low in ovx rats, but high during negative feedback of E2. 2) No changes of GABA secretion were observed during manipulations of the opioidergic tonus in the POA suggesting that both beta-END and GABA do not interact to regulate LH release. Thus, beta-END may directly inhibit the activity of GnRH neurons located in the POA or acts via a neurotransmitter other than GABA.

Animals↗

PubMed1995

Paracrine cell to cell interactions determine the effects of pituitary adenylate cyclase activating polypeptide (PACAP) on in vitro prolactin release from rat pituitary cells.

In static cultures of dispersed rat pituitary cells and in the reverse hemolytic plaque assay PACAP inhibits prolactin (Prl) secretion, while in vivo application of PACAP stimulates Prl release in rats. To elucidate the mechanism of this contradictory action, we compared the in vitro effects of PACAP on Prl secretion in cultures of dispersed or reaggregated cells and in pituitary fragments. While in monolayer cultures Prl release was inhibited by PACAP, in cultures of aggregated cells and in pituitary fragments Prl release was stimulated. Dopamine (DA) inhibited Prl release in either type of culture. PACAP also stimulated interleukin 6 (IL6) release under each of the experimental conditions. We conclude that PACAP has a direct inhibitory action on lactotropes. In addition, PACAP may induce the release of a paracrine acting factor within the pituitary which stimulates Prl release and which may be IL6. In the intact pituitary tissue and in reaggregated cells this paracrine factor stimulates Prl release more potently than PACAP directly inhibits Prl secretion resulting in a net effect of enhanced hormone release. In monolayer cultures, however, the direct inhibition is dominant, because the stimulatory paracrine factor is diluted in the culture medium. Therefore we suggest that paracrine cell to cell communication is crucial for the action of PACAP on Prl release.

Animals↗

PubMed1995

Activation of central GABAA-but not of GABAB-receptors rapidly reduces pituitary LH release and GnRH gene expression in the preoptic/anterior hypothalamic area of ovariectomized rats.

gamma-Aminobutyric acid (GABA) exerts an inhibitory action on gonadotropin-releasing hormone (GnRH) release from the hypothalamus. In vivo, this inhibitory action appears to be mediated via the GABAA receptor since in ovariectomized (ovx) rats and sheep direct application of muscimol (MUS), a GABAA agonist, into the preoptic area (POA), the site were the GnRH cell bodies are located, caused an immediate reduction of LH release. This effect may be the result of an inhibition of GnRH release but also GnRH biosynthesis may be affected. Using competitive reverse transcription-polymerase chain reaction (RT-PCR) we now addressed the question, whether an acute inhibition of the GnRH pulse generator in ovx rats by GABA involves reduction of GnRH biosynthesis as determined by GnRH mRNA levels in micropunches of the POA. To activate either the GABAA or GABAB receptor, we injected intraventricularly (icv) MUS or baclofen (BAC). Intracerebroventricular injection of 10 nmol MUS caused a rapid and lasting inhibition of LH release from about 7.5 ng/ml (pretreatment value) to approximately 1.5 ng/ml. Neither application of BAC or saline (control injections) affected LH secretion. Two hours after icv injections, rats were decapitated and GnRH mRNA levels were determined. MUS induced a pronounced decrease of GnRH levels in the POA (control rats: 2.26 pg GnRH mRNA; MUS-treated rats: 0.85 pg, n = 10/group). BAC was without any effect on GnRH mRNA levels. Thus, we confirm the inhibitory action of GABA on LH release in vivo which is exerted via the A-subtype of the receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Preoptic rather than mediobasal hypothalamic amino acid neurotransmitter release regulates GnRH secretion during the estrogen-induced LH surge in the ovariectomized rat.

Inhibitory and excitatory amino acid neurotransmitters have been suggested to participate in the feedback actions of estradiol (E2) on LH secretion. In the rat estrogen-receptive neurons have been demonstrated in the preoptic/anterior hypothalamic area (POA) and mediobasal hypothalamus/median eminence (MBH) and many of these neurons utilize gamma-aminobutyric acid (GABA) as neurotransmitter. The actions of excitatory amino acids (EAA) differ in ovariectomized (ovx) and ovx E2-substituted rats indicating that EAAs also participate in the positive feedback action of E2 on LH release. However, little information is available as to whether in vivo these transmitters exert their effects in the POA, where most of the GnRH perikarya are located, or in the MBH, i.e. at the nerve terminals. Therefore we conducted push pull cannula perfusions to compare the release rates of GABA, aspartate (ASP) and glutamate (GLU) in the MBH and POA. A subcutaneous implant of a silastic tube containing E2 resulted in LH surges in the afternoon of all treated animals. Prior to and during this LH surge the MBH release rates of neither GABA nor ASP nor GLU were significantly altered. In contrast, a conspicuous drop in preoptic GABA release occurred prior to and during the time of estrogen-induced LH surges and this was accompanied by enhanced preoptic secretion of ASP and GLU. In conclusion, we present the first data about amino acid release in the MBH during the E2-induced LH surge. Since only in the POA the LH surge is associated with changes in amino acid release, it appears that both inhibitory and excitatory amino acids act at the level of the GnRH cell bodies and/or dendrites and not on GnRH nerve terminals to mediate the feedback mechanism of E2 on LH release.

Animals↗

PubMed1995

[Increased serum level of c-erbB-2-coded protein p105 in patients with pre-eclampsia].

OBJECTIVE: This study investigated p105 serum levels in normal pregnancies and in preeclamptic women. PATIENTS AND METHODS: The p105 serum level was determined in 65 women with normal pregnancy and 25 preeclamptic women. RESULTS: The mean p105 serum level for the control group was 102-333 fmol/ml (median 163 fmol/ml). Preeclamptic women had significant higher serum levels (97-368 fmol/ml, median 202 fmol/ml, p < 0,005). CONCLUSION: Elevated serum levels of the c-erbB-2-encoded protein p105 in preeclamptic women could be the result of endothelial dysfunction in preeclampsia.

Adult↗

PubMed1995

Effect of GABAergic compounds on gonadotropin-releasing hormone receptor gene expression in the rat.

Using a competitive reverse transcription-polymerase chain reaction (RT-PCR), the amounts of GnRH receptor (GnRHR) transcript in a discrete nucleus micropunched from rat brain slices were determined. GnRHR transcript was highly expressed in anterior pituitary >> median eminence > posterior mediobasal hypothalamus (pMBH) > preoptic area (POA) but not in cortex and posterior pituitary, which were used as control tissues. To examine the effect of GABA on GnRHR transcript level, 10 nmol of muscimol, a GABA-A receptor agonist, or baclofen, a GABA-B receptor agonist, was microinjected into the lateral ventricle of ovariectomized rats. Two hours after an intraventricular injection, rats were decapitated. Blood was collected 1 h before and after drug administration and used for LH determination. Serum LH levels were significantly reduced by muscimol but not by baclofen within 2 h. The activation of GABA-A receptors with muscimol resulted in a significant inhibition in GnRHR transcript level in both the pMBH and POA but not in the pituitary. The activation of GABA-B receptors with baclofen, however, did not produce any effect on GnRHR transcript level in the pMBH and POA, as well as the pituitary. This experiment demonstrates for the first time that GABAergic neurotransmission, through GABA-A receptors, is involved in the regulation of GnRHR transcript level in the rat hypothalamus. This suggests that GABAergic neurotransmission regulates GnRHR gene expression in a coordinated, yet complex, fashion in the control of the neuroendocrine function of GnRH-LH axis.

Animals↗

PubMed1995

Regulation of luteal function by luteinizing hormone and prolactin at different times of the luteal phase.

In 54 healthy women luteal function was assessed by sequential withdrawals of blood samples at 10-min intervals for 8-10 h. Subgroups of the women were studied during the early and late ovulatory period and during the early, mid- and late luteal phase. Bio- and immunoreactive luteinizing hormone (LH), prolactin, testosterone, estradiol and progesterone levels were determined in each sample. While the bio- and immunoreactivity of LH pulses correlated fairly well, a number of bio- or immunoreactive LH pulses were observed that were not detected by the respective other method. Responsivity of the corpus luteum to LH episodes developed during the second half of the luteal phase and was most marked in cases where LH episodes were accompanied by prolactin episodes. In the absence of prolactin episodes. LH episodes did not stimulate progesterone or estradiol secretion. The highest incidence of coincident LH and prolactin pulses was observed during the mid- and late luteal phase. Serum testosterone levels showed also some fluctuations but these were independent of immuno- or bioactive LH episodes and therefore most likely not of luteal origin. Prior to menstruation LH episodes were not any more stimulatory to progesterone secretion, indicating that it is not the withdrawal of LH but, rather, another possibly intraovarian mechanism that results in luteolysis. In a number of women, increased estradiol and progesterone secretion was strictly related to the prior occurrence of LH and prolactin pulses. In other subjects, both gonadal steroids fluctuated largely with no discernible correlation to LH fluctuations. This may indicate that in these subjects the corpora lutea have some degree of autonomous regulation.

Adolescent↗

PubMed1995

Luteotropic and luteolytic effects of oxytocin in the porcine corpus luteum.

The presence and the release of oxytocin (OT) by corpora lutea (CL) of a number of species (Wathes et al. 1986, Watkins and Choy 1988) including ruminants (Ivell and Richter 1984, Hirst et al. 1986, Rodgers et al. 1983, Sawyer et al. 1986), primates (Dawood and Khan-Dawood 1986, Khan-Dawood 1987, Maas et al. 1992, Khan-Dawood et al. 1993), and the pig (Pitzel et al. 1984, Einspanier et al. 1991, Jarry et al. 1992) have been amply verified. Conflicting results concerning the effects of OT on steroidogenesis have been published; the peptide has been shown to be luteotrophic (Sawyer et al. 1986, Maas et al. 1992, Jarry et al. 1990), to have no effects (Rodgers et al. 1985) or to be luteolytic (Auletta et al. 1984, Auletta et al. 1988, Pitzel et al. 1988) and it appears that this confusion is only in part due to species differences but also the age of the luteal tissue seems to be of crucial importance for the understanding of the effects of OT (Schams et al. 1983, Wuttke et al. 1993, 1994). In the present contribution we will focus largely on our results obtained in the pig and where applicable, compare them with those obtained in other species. We will thus demonstrate that OT is released by luteal cells (Jarry et al. 1990, Einspanier et al. 1991, Jarry et al. 1992) and that luteal cells have OT receptors (Sernia et al. 1989, Pitzel et al. 1993a) which mediate the effects of the peptide on steroidogenesis. Finally, we will address the question whether OT is inhibitory or stimulatory to progesterone (P) and estradiol (E2) release, and we will come to the conclusion that OT is both luteotropic and luteolytic (Wuttke et al. 1993, 1994). The CL of all species investigated so far consists of two steroidogenic cell types. The so-called large luteal cells stem from follicular granulosa cells and they appear to be barely responsive to luteinizing hormone (LH)/human chorionic gonadotrophin (hCG) but they are highly receptive to prostaglandin F2 alpha (PGF2 alpha) (Hansel and Dowd 1986, Pitzel et al. 1990). Furthermore, they appear to produce OT (Rodgers et al. 1983, Theodosis et al. 1986). The small luteal cells are believed to derive from the follicular theca cells (Hansel and Dowd 1986, Pitzel et al. 1990). They are LH-receptive but synthesize few, if any, regulatory peptides. In the last few years it has become increasingly evident that cells deriving from the white blood cell line are involved in processes such as ovulation and luteolysis. Of crucial importance for the understanding of luteolysis is the morphological observation that macrophages invade the CL at the time of luteal regression (Adashi 1990, Paavola 1977, Kirsch et al. 1981).

Animals↗

PubMed1994

Porcine luteal cells express monocyte chemoattractant protein-2 (MCP-2): analysis by cDNA cloning and northern analysis.

From an expression library in lambda UniZAP, derived from porcine corpus luteum (CL), a clone lambda MCP9 was detected by hybridization with a porcine MCP-1 specific probe. A pBluescriptSK-derivative pMCP9 was generated from lambda MCP9 by in vivo excision and was shown to contain an open reading frame (ORF) encoding a protein highly homologous to bovine monocyte chemoattractant protein-2 (MCP-2). Comparison of amino acid sequences of known MCPs identified the protein encoded by pMCP9 as porcine MPC-2. The 3' untranslated region of pMCP9 was completed by 3' RACE. Northern analysis using RNA from porcine luteal cells and probes specific for porcine MCP-1 and MCP-2 revealed that porcine luteal cells express both MCPs. According to Southern analysis MCP-2, like MCP-1, is specified by a single copy gene.

Amino Acid Sequence↗

PubMed1994

Porcine luteal cells express monocyte chemoattractant protein-1 (MCP-1): analysis by polymerase chain reaction and cDNA cloning.

RT PCR employing poly(A+)RNA from porcine luteal cells and a combination of primers designed from the known bovine MCP-1 cDNA identified the luteal cells as a source of MCP-1. This finding is corroborated by results from Northern analysis using total RNA from luteal cells. To characterize the complete porcine MCP-1 cDNA, poly (A+)RNA was isolated from porcine corpus luteum, transcribed into cDNA and the latter cloned into the expression vector lambda Uni-ZapXR. A digoxigenin-labeled DNA probe of 375 bp was obtained by PCR and employed to screen the library. From the positive clones pMCP5, pMCP7 and pMCP10, the clone pMCP5 was selected and both strands of the cDNA insert were sequenced. The cDNA insert was 742 bp long, with an open reading frame (ORF) encoding a protein of 99 amino acid residues which by comparison with known amino acid sequences of MCPs yielded highest identities with MCP-1 sequences. We therefore assume that pMCP5 encodes the amino acid sequence for porcine MCP-1.

Amino Acid Sequence↗

PubMed1994

Ontogenic changes in the hypothalamic levels of amino acid neurotransmitters in the female rat.

In order to evaluate the participation of several amino acid neurotransmitters (AANT) in sexual maturation we measured the hypothalamic concentrations of aspartate (Asp), glutamate (Glu), homocysteic acid (HCA), glycine (Gly), taurine (Tau) and gamma-aminobutyric acid (GABA) in female rats at different ages of sexual development. Animals (15-, 20-, 25-, 30-, 35- and 40-day-old female rats, as well as adult diestrous rats, n = 8-10/group) were decapitated at noon; each brain was rapidly removed and frozen on dry ice. Preoptic area (POA) and mediobasal hypothalamic (MBH) needle punch samples were obtained from 500-600 microns thick coronal slices, homogenized and centrifuged. AANT concentrations were measured in the supernatants following derivatization with phenyl isothiocyanate and reverse-phase HPLC separation by UV detection. Significant (P < 0.05) changes in hypothalamic AANT concentrations can be summarized as follows: POA Glu, HCA and Gly levels rose transiently at day 20 and then increased steadily in 35- and 40-day-old rats. Asp concentrations rose in 35- and 40-day-old rats. Tau concentrations decreased markedly from day 30 onwards. GABA levels were lowest in 15-day-old rats, as compared to the other age groups. Asp, Glu, Gly and GABA concentrations were highest in adult diestrous rats. Changes in MBH AANT levels were not as relevant: only Gly concentrations rose significantly at day 40; Asp, Glu, HCA, Gly and GABA concentrations increased in adult diestrous rats and Tau concentrations were lower from day 35 onwards.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

PubMed1994

Effects of taurine on basal and stimulated luteinizing hormone (LH) and LH-releasing hormone secretion in ovariectomized rats: in vitro studies.

Taurine (Tau), a putative inhibitory amino acid neurotransmitter, has been shown to inhibit luteinizing hormone (LH) release in vivo. We investigated the effect of this amino acid on LH secretion by cultured anterior pituitary cells. A 5-h incubation with Tau (10(-3)-10(-8) M) did not affect basal or LH-releasing hormone (LHRH)-stimulated LH release. Basal LHRH release from superfused mediobasal hypothalamic fragments was not affected by Tau (10(-3) M). However, this substance clearly diminished LHRH release after stimulation with KCl (50 mM) or N-methyl-D-aspartate (10(-4) M). It is concluded that Tau may exert an inhibitory effect on LH secretion acting at the hypothalamic level.

Animals↗

PubMed1994

Elevated serum levels of a c-erbB-2 oncogene product in ovarian cancer patients and in pregnancy.

Amplification of the proto-oncogene c-erbB-2 (HER-2/neu) has been shown to be a prognostic marker in ovarian cancer. In order to obtain further information on the biological role of the c-erbB-2 gene product p185 it is necessary to quantify expression levels. In this study we evaluated an enzyme-linked immunosorbent assay (ELISA) for the extracellular domain of p185 to determine whether a soluble oncoprotein fragment can be detected in the serum of ovarian cancer patients and in the serum of pregnant women. Sera from 199 women (57 previously untreated ovarian cancer patients, 62 pregnant women and 80 healthy controls) were assayed in a sandwich ELISA utilizing two mouse monoclonal antibodies. To study c-erbB-2 overexpression in ovarian cancer tissue samples we have used an immunohistochemical technique involving a monoclonal antibody specifically reactive with the external domain of the protein p185. The mean serum value for the normal controls was 1203 HNU/ml with a standard deviation (SD) of 279 HNU/ml and a range of 595-1947 HNU/ml. We chose a level of 1761 HNU/ml (2 SD above the mean) as a cut-off to distinguish individuals with elevated levels. The ovarian cancer patients' serum values ranged from 526 to 16,332 HNU/ml. Immunohistochemically detectable p185 was noted in 8 of 57 ovarian cancer patients. The oncoprotein fragment levels in the sera from these 8 patients ranged from 878 to 16,332 HNU/ml. Of 8 patients with p185 overexpression in their tumors, 4 had elevated serum levels. In the sera from the 49 cancer patients without overexpression the values were distributed in the range 526-2892 HNU/ml. There was no association between serum oncoprotein fragment levels and tumor stage, histological type or grading. Serum concentrations of the p185 fragment in pregnancy ranged from 612 to 3265 HNU/ml. The highest levels were found in the third trimester. The results of the present study raise the possibility that the soluble c-erbB-2 protein level in serum is an indicator for cell proliferation and therefore deserves further evaluation as a diagnostic tool in ovarian cancer patients and pregnancy.

Adult↗

PubMed1994

[Total intravenous anesthesia with methohexital-alfentanil or propofol-alfentanil in hypogastric laparotomy. Clinical aspects and the effects of stress reaction].

Total intravenous anaesthesia (TIVA) using a combination of a hypnotic and an analgesic agent is gaining increasing popularity as an alternative to balanced anaesthesia with volatile anaesthetics for abdominal surgery. Among the required characteristics of the drugs used in this technique are a good correlation between dose, plasma concentrations, and effect as well as rapid elimination from the circulation, allowing close control of anaesthetic depth. Two hypnotic drugs with similar pharmacokinetic and pharmacodynamic profiles are propofol and methohexitone, both of which can be employed as a component of a TIVA technique. Two TIVA combinations utilising either of these drugs with alfentanil were tested against isoflurane-nitrous oxide in a balanced regimen. METHODS. Twenty-seven healthy women undergoing hysterectomy for non-malignant diseases participated in the study after having given written consent. They were randomly allocated to receive either isoflurane (Iso), methohexital-alfentanil (M-A), or propofol-alfentanil (P-A). Blood samples for determination of cortisol, prolactin, catecholamines, glucose, lactate, non-esterified fatty acids, and pharmacon concentrations were drawn repeatedly from before induction until 360 min after surgery. Anaesthesia was induced in group Iso with fentanyl 0.1 mg and M 1.5 mg.kg-1 and maintained with Iso-N2O. In the TIVA groups M or P was given in a two-step infusion to load peripheral compartments and then maintain plasma concentrations within the hypnotic range. A was given as a continuous infusion in an identical dose (0.1 mg.kg-1 initial, 0.125 mg.kg-1.h-1 maintenance) in both groups. If signs of insufficient depth of anaesthesia occurred (heart rate or systolic blood pressure > 25% above baseline), then first A (0.5-1 mg), and if that was ineffective, then 50 mg hypnotic was administered. The A infusion was stopped 30 min before the end of surgery, and Iso or the hypnotic was stopped at skin closure. Recovery time was the time until the patients were able to give their birth date after stopping the Iso or hypnotic. RESULTS. The three groups were comparable with regard to age, weight, and duration of surgery. The total doses of M and P were 1,357 +/- 125 mg (mean +/- SEM) and 1,315 +/- 121 mg, respectively, and the total A doses were 20.7 +/- 2.5 mg (M-A) and 23.4 +/- 3.5 (P-A). The peak plasma concentrations were P 10.6 +/- 1.5 micrograms.ml-1 and M 12.4 +/- 2.6 micrograms.ml-1. At the end of surgery the P concentrations were in the projected range while those of M were somewhat lower than expected (P 3.7 +/- 0.4 microgram.ml-1; M 3.5 +/- 0.6 microgram.ml-1). Three patients each in the P-A and M-A groups required supplementary A injections. Five patients in the P-A group required additional bolus injections of the hypnotic as compared to 2 in the M-A group. The median recovery times were Iso 15 min, M-A 50 min, and P-A 25 min (P < 0.05). The incidence of shivering was Iso 3/9, M-A 5/9, and P-A 0/9 (P < 0.05); vomiting occurred with equal frequency in all groups (Iso 33%, M-A 33%, P-A 22%). The patients were somewhat more restless in group M-A. Systolic blood pressure dropped in a similar manner in all groups after induction of anaesthesia (Iso -31%, M-A -37%, P-A -36%) but recovered during surgery. The intraoperative response of cortisol (Iso + 216%, M-A +92%, P-A +43%) and catecholamines (noradrenaline Iso +56%, M-A +30%, P-A -21%) was lower in the TIVA groups, whereas prolactin increased after induction in all groups. Plasma concentrations of glucose, lactate, and fatty acids were lower in the TIVA groups than in the Iso group intraoperatively, but increased to comparable postoperative levels. CONCLUSIONS. Both TIVA regimens are acceptable alternatives to balanced anaesthesia with Iso N2O. (ABSTRACT TRUNCATED)

Adult↗

PubMed1994

[TIVA with etomidate-fentanyl versus midazolam-fentanyl. The perioperative stress of coronary surgery overcomes the inhibition of cortisol synthesis caused by etomidate-fentanyl anesthesia].

Etomidate is a hypnotic with only minor effects on haemodynamics. Although its rapid elimination kinetics would suggest its use in total intravenous anaesthesia (TIVA) and sedation, its administration in higher doses or for a prolonged period has been discouraged due to its inhibitory effects on corticosteroid synthesis. Newer evidence that the suppression of cortisol synthesis might not be total requires a re-evaluation of this drug as a component of a TIVA technique. The effects of high-dose etomidate with fentanyl on spontaneous and stimulated corticosteroid levels as a measure of the magnitude and duration of adrenocortical suppression, as well as on plasma concentrations of adrenocorticotropic hormone (ACTH) beta-endorphin, and catecholamines during cardiac surgery were investigated in a prospective, randomised study and compared to those following the administration of midazolam-fentanyl. PATIENTS AND METHODS. Nineteen patients undergoing myocardial revascularisation were assigned to two groups: group 1: etomidate-fentanyl (n = 9) and group 2: midazolam-fentanyl (n = 10). Anaesthesia was induced with fentanyl 0.5 mg and either etomidate 0.3 mg/kg or midazolam 0.2 mg/kg. Relaxation was achieved with pancuronium 0.1 mg/kg. Anaesthesia was maintained during extracorporeal circulation (ECC) with an infusion of etomidate (0.36 mg.kg-1.h-1) or midazolam (0.16 mg.kg-1.h-1) and fentanyl 10 micrograms.kg-1.h-1. Blood samples were drawn before induction, before ECC, and 1, 6, and 20 h after surgery. Cortisol secretion was stimulated with 0.25 mg ACTH1-24 IV at 6 and 20 h postoperatively. RESULTS. The total drug doses were etomidate 87 +/- 3 mg and midazolam 46 +/- 2 mg. Plasma cortisol concentrations decreased in the etomidate group from 20 (10-31) to 10 (6-31) micrograms.dl-1 (median and range) before ECC, but had returned to baseline at 1 h and were significantly increased at 6 h [29 (15-47) micrograms.dl-1] and 20 h [46 (29-62) micrograms.dl-1]. There was no difference between the groups except at 20 h, when cortisol levels were higher in the etomidate group. The stimulated cortisol increase was markedly impaired in this group at both measuring points. ACTH and beta-endorphin were markedly increased in the etomidate group and ACTH concentrations were eight times greater than the corresponding values in the midazolam group after surgery (ACTH 141 vs. 18 pmol.l-1). Plasma catecholamine concentrations increased significantly in both groups. Noradrenaline concentrations were greater in the etomidate group at 6 h after surgery. Two patients in the midazolam group and none in the etomidate group required circulatory support with exogenous catecholamines. DISCUSSION. It is concluded that the stress of cardiac surgery can overcome the block in cortisol synthesis caused by the administration of high-dose etomidate by substantially increasing ACTH secretion. The administration of high-dose etomidate was not associated with cardiovascular instability. The use of etomidate as a component of TIVA can therefore not be ruled out on the grounds of insufficient cortisol secretion.

Adrenocorticotropic Hormone↗

PubMed1994

In vivo-effect of intraadrenal nicotine and substance P application on rat adrenal medullary catecholamine secretion.

The present study was conducted to characterize in vivo the intraadrenal catecholamine (CA) secretion in rats. This was possible by using a microdialysis system (MDS) which mimics some properties of an artificial capillary. One end of this system was connected to a peristaltic pump, from the other end fractions were sampled at 5 min intervals. Concentrations of epinephrine (E) and norepinephrine (NE) in adrenal dialysate fractions were determined by HPLC electrochemical detection. Through this MDS nicotine was administered directly into the adrenal medulla of freely moving rats and the response of catecholamine release was determined. In the second part of the study the effect of exogenous substance P (SP) on spontaneous as well as on nicotine-stimulated CA release was investigated. Like nicotine, SP was administered directly into the adrenal medulla. At a flow rate of 25 microliter/min the transfer rates of CA and nicotine were approximately 1% whereas SP passed at a rate of 01.-0.2%. Under resting conditions CA release remained constant. In response to 2 x 10(-7) M nicotine (which resulted in local concentration of 2 x 10(-7) M), E and NE secretion increased 2.9 and 5.4-fold, respectively. However, due to an increased E response this difference attenuated with a later onset of the first stimulus. The higher concentrations of 10(-4) M resulted in 8.1 and 10.8-fold increases for E and NE. This latter response is clearly supraphysiologic and therefore the 2 x 10(-5) M concentration was used for further experimentation. CA secretion was stimulated with nicotine four times at 30 min intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗