-
[show abstract]
[hide abstract]
ABSTRACT: We evaluated a new, ultra-fast response continuous cardiac output monitor in 34 adult patients undergoing off-pump coronary artery bypass graft surgery. Cardiac output was measured with the TruCCOMS continuous cardiac output monitor (Aortech International plc, Lanarkshire, UK), using triplicate cold bolus thermodilution as the criterion standard, at fixed time points during surgery and during dobutamine infusion. The two techniques were compared using linear regression and Bland-Altman analysis. Overall, the study device displayed a bias of 0.4 l.min(-1) with limits of agreement of +2.5 l.min(-1) and -1.7 l.min(-1). The study device failed to detect the change in cardiac output caused by dobutamine accurately (y = 0.18x + 0.45; r(2) = 0.13), with an error linearly related to the magnitude of the change measured. We conclude that the device's failure to detect changes in cardiac output could be a major limitation in its clinical use in its current form.
Anaesthesia 05/2004; 59(4):385-9. · 2.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: 1. Of the melanocortin peptides, gamma(2)-melanocyte-stimulating hormone (MSH) has been attributed a cardiovascular effect, inducing an increase in blood pressure and heart rate. Although still controversial, this effect, based on pharmacological blockade experiments, is supposed to be mediated through sympathetic activation. 2. The aims of the present study were to identify the N-terminal pro-opiomelanocortin (N-POMC) fragments and melanocortins that influence blood pressure and heart rate and to investigate the real-time changes in baroreflex sensitivity and in sympathetic and vagal modulation underlying cardiovascular effects in conscious rats without the use of pharmacological blockade. 3. Intracerebroventricular administration of different melanocortins and N-POMC induced a long-lasting dose- dependent pressor response from 1 nmol onwards, with only a small initial bradycardic response with the highest dose. 4. Coinciding with this pressor response, an elicitation of the low-frequency (LF) component was observed in spectral analysis of both blood pressure variability (BPV) and heart rate variability (HRV), followed by the high-frequency (HF) component in at least BPV. Baroreflex sensitivity remained unchanged. 5. After intravenous administration, gamma(2)-MSH produced a short-lasting dose-dependent pressor and cardioaccelerator response with very rapid onset with concentrations from 1 nmol onwards. 6. Continuous infusion of gamma(2)-MSH depressed baroreflex sensitivity and simultaneously increased both components of BPV, with a radical reduction of the LF component and a preserved vagal HF component in HRV. 7. Of all the intravenously administered melanocortins, only gamma(2)-MSH was active. The central effect is likely to depend on an increase of (alpha-)sympathetic outflow. 8. For the peripheral effect, gamma(2)-MSH appeared to act as a baroreceptor reflex-blocking agent, being compatible with a role in the acute stress response.
Clinical and Experimental Pharmacology and Physiology 08/2002; 29(7):549-58. · 1.85 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We report the production of biologically active recombinant rat Gly-2-Ser-1-POMC1-74 (rrPOMC1-74) in a prokaryotic expression system. The polypeptide was produced as a fusion protein with glutathione-S-transferase (GST), using the pGEX-4T-1 vector and subsequently cleaved by thrombin. Amino acid sequencing, up to residue 45, showed a correct primary structure including the two additional amino acids at the N-terminus, Gly and Ser, derived from the thrombin cleavage site. Electrospray ionization mass spectrometry showed a Mr of 8358.5 Da which was 14-16 Da heavier (oxidation or methylation) than the calculated mass. Combined digestion with trypsin and endoproteinase Glu-C followed by MALDI-TOF mass spectrometry and N-terminal sequencing of the separated fragments showed a correct disulphide bridge configuration. In reaggregate cell cultures of immature rat pituitary, rrPOMC1-74 displayed biological activity similar to that of natural human (h) POMC1-76 or rat POMC1-74: it stimulated DNA replication in lactotrophs but not in other pituitary cell types. However, its efficacy was significantly lower than that of the natural product. Gamma3-MSH, a peptide that can be generated from POMC1-74 and a typical ligand of the melanocortin-3 (MC-3) receptor, also stimulated DNA replication in lactotrophs and, in contrast to rrPOMC1-74, also in somatotrophs and thyrotrophs. rrPOMC1-74 increased cAMP levels in 293HEK cells stably transfected with the MC-3 receptor with an intrinsic activity and potency similar to that of gamma3-MSH. However, natural hPOMC1-76 was inactive in the latter test system. These data show that rrPOMC1-74 mimics the selective mitogenic action of natural POMC1-74 on lactotrophs. Since natural POMC1-74 is N- and O-glycosylated and rrPOMC1-74 is not, glycosylation does not seem to determine the selectivity for lactotrophs. In spite of the feature that rrPOMC1-74 is an agonist at the MC-3 receptor and the reported evidence that the MC-3 receptor is expressed in the anterior pituitary, the mitogenic action of rrPOMC1-74 on lactotrophs does not seem to be mediated by the MC-3 receptor.
Molecular and Cellular Endocrinology 09/1999; 154(1-2):111-22. · 4.19 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: A pituitary cell population of 14-day-old female rats, containing lactotropes and somatotropes but deprived of gonadotropes, was prepared by unit gravity sedimentation through a serum albumin gradient and allowed to reaggregate either as such or after mixing this population with cells of the gonadotropic alpha T3-1 cell line. In a perifusion system gonadotropin-releasing hormone (GnRH) had no effect on prolactin (PRL) and growth hormone (GH) release in the former aggregates but stimulated PRL release in the latter. In the alpha T3-1 cell-containing aggregates GnRH showed a biphasic effect on GH release: inhibition during exposure to GnRH followed by a rebound secretion upon removal of the peptide. The aggregation capacity of alpha T3-1 cells with the normal pituitary cells was demonstrated by using an alpha T3-1 cell clone stably transfected with the reporter gene beta-galactosidase. Perifusion of the gonadotrope-deprived aggregates with medium conditioned by alpha T3-1 cell provoked a rapid stimulation of PRL release and a biphasic effect on GH release. Medium conditioned by the corticotropic cell line AtT20 also stimulated PRL release but had no concomitant effect on GH release. Medium conditioned by alpha T3-1 cells, when added for 40 h to aggregates of 14-day-old rat pituitary, provoked an increase in the number of 3H-thymidine (3H-T)-labelled lactotropes and a decreased in the number of 3H-T-labelled somatotropes. The conditioned medium was concentrated on Sep-Pak C18 and ultrafiltrated through an Amicon membrane with 3-kD molecular weight cut-off and the retained molecules separated by reversed-phase HPLC. The material stimulating 3H-T labelling of lactotropes eluted from the column with a different retention time than material inhibiting 3H-T labelling of somatotropes, suggesting that the effect on lactotropes is mediated by (a) molecule(s) different from that affecting somatotropes. The effects of alpha T3-1 cells and their secretion products on lactotropes and somatotropes were comparable to those we previously observed using enriched populations of normal gonadotropes. The HPLC elution profiles of the substances affecting 3H-T incorporation as well as the specificity of these effects were also similar to that of the substances isolated previously from gonadotrope-conditioned medium. The present data, therefore, support previous conclusions on the paracrine control of the lactotrope/somatotrope lineage by the gonadotropes. Further purification and chemical characterization of the growth factors with selective action on lactotropes and somatotropes may lead to a better understanding of the development of the latter lineage.
Neuroendocrinology 04/1995; 61(3):326-36. · 2.38 Impact Factor
