Spectroscopy and Directed Transport of Topological Solitons in Crystals of Trapped Ions.

We study experimentally and theoretically discrete solitons in crystalline structures consisting of several tens of laser-cooled ions confined in a radio frequency trap. Resonantly exciting localized, spectrally gapped vibrational modes of the soliton, a nonlinear mechanism leads to a nonequilibrium steady state of the continuously cooled crystal. We find that the propagation and the escape of the soliton out of its quasi-one-dimensional channel can be described as a thermal activation mechanism. We control the effective temperature of the soliton's collective coordinate by the amplitude of the external excitation. Furthermore, the global trapping potential permits controlling the soliton dynamics and realizing directed transport depending on its topological charge.

Hepatic stellate cells display a functional vascular smooth muscle cell phenotype in a three-dimensional co-culture model with endothelial cells.

Hepatic stellate cells (HSCs) are pericytes of liver sinusoidal endothelial cells (LSECs) and activation of HSC into a myofibroblast-like phenotype (called transdifferentiation) is involved in several hepatic disease processes including neovascularization during liver metastasis, chronic and acute liver injury. While early smooth muscle cell (SMC) differentiation markers including SM alpha-actin and SM22alpha are expressed in a variety of non-SMC, expression of late-stage markers is far more restricted. Here, we found that in addition to early SMC markers, activated rat HSC express a large panel of characteristic late vascular SMC markers including SM myosin heavy chain, h1-calponin and h-caldesmon. Furthermore, myocardin, which is present exclusively in SMCs and cardiomyocytes and controls the transcription of a subset of early and late SMC markers, is highly expressed in activated HSC. We further studied activated HSC in a functional three-dimensional spheroidal co-culture system together with endothelial cells (EC). Co-culture spheroids of EC and SMC differentiate spontaneously and organize into a core of SMC and a surface layer of EC representing an inside-outside model of the physiological assembly of blood vessels. Replacing SMC by in vitro activated HSC resulted in a similar organized spheroid with differentiated, von-Willebrand factor producing, surface lining quiescent human umbilical vein endothelial cell and a core of HSC. In an in vitro angiogenesis assay, activated HSC induced quiescence in vascular EC-the hallmark of vascular SMC function. Co-spheroids of LSEC and activated HSC formed capillary-like sprouts in gel angiogenesis assays expressing the vascular EC marker VE-cadherin. Our findings indicate that activated HSC are capable to adapt a functional SMC phenotype and to induce formation of tubular sprouts by LSEC and vascular endothelial cells. Since tumors and tumor metastasis induce HSC activation, HSC may take part in tumor-induced neoangiogenesis by adapting SMC-like functions.

Nucleolar association of fibroblast growth factor 3 via specific sequence motifs has inhibitory effects on cell growth.

The dual subcellular fate of fibroblast growth factor 3 (FGF3) is determined by the competing effects of amino-terminal signals for nuclear localization and secretion (P. Kiefer, P. Acland, D. Pappin, G. Peters, and C. Dickson, EMBO J. 13:4126-4136, 1994). Mutation analysis has implicated additional basic domains in the carboxy-terminal region of the protein as necessary for nuclear uptake and the association of FGF3 with the nucleoli. Immunogold electron microscopy shows that FGF3 is predominantly within the dense fibrillar component of the nucleolus. A form of FGF3 that localizes exclusively in the nucleus and nucleolus was generated by removing signals for secretion, and expression of this nonsecreted FGF3 in a mammary epithelial cell line resulted in slowly growing colonies of enlarged cells. Thus, nuclear import and nucleolar association of FGF3 are determined by the concerted interaction of several distinct motifs, and the exclusive production of the nuclear isoform can inhibit DNA synthesis and cell proliferation.

The Int-2/Fgf-3 oncogene product is secreted and associates with extracellular matrix: implications for cell transformation.

NIH3T3 cells transformed by mouse Int-2/Fgf-3 cDNA express a series of Int-2-related products representing discrete stages of processing and glycosylation. We confirm that in at least two highly transformed clonal lines, Int-2 products acquire further modifications and are efficiently secreted into the culture medium. Secreted proteins become associated with the cell surface and extracellular matrix and can be displaced by addition of soluble glycosaminoglycans, specifically heparin, heparan sulfate, and dermatan sulfate. Increasing concentrations of heparin not only compete for Int-2 binding in a dose-dependent manner but also inhibit the growth of these cells and revert the transformed phenotype. These findings reaffirm the notion that extracellular or surface-bound Int-2 protein is instrumental in the morphological transformation of these cells.

Retention of fibroblast growth factor 3 in the Golgi complex may regulate its export from cells.

The fibroblast growth factors (FGFs) fall into two distinct groups with respect to their mode of release from cells. Whereas FGF1 and FGF2 lack conventional signal peptides, the remaining members have typical features of secreted proteins. However, the behavior of mouse FGF3 is anomalous, since, despite entering the secretory pathway and undergoing primary glycosylation, its release from transfected COS-1 cells is very inefficient compared with that of FGF4 and FGF5. To investigate the unusual properties of FGF3, we analyzed the processing, secretion, and intracellular localization of a series of site-directed mutants as well as chimeras produced by fusing parts of FGF3, FGF4, and FGF5. Wild-type FGF3 was shown to accumulate in an immature form in the Golgi complex, from where it is slowly released into the extracellular matrix. Removing or relocating the Asn-linked glycosylation site further impaired its release, and exchanging the signal peptide or carboxy terminus had little effect. In contrast, a chimeric protein with an amino terminus from FGF5 was efficiently secreted and biologically active in cell transformation assays. The data suggest that a structural feature of FGF3 involving the amino-terminal region and glycosylation site has a significant bearing on its passage through the Golgi complex and may regulate the secretion of the ligand.

NoBP, a nuclear fibroblast growth factor 3 binding protein, is cell cycle regulated and promotes cell growth.

Secreted and nuclear forms of fibroblast growth factor 3 (FGF3) have opposing effects on cells. The secreted form stimulates cell growth and transformation, while the nuclear form inhibits DNA synthesis and cell proliferation. By using the yeast two-hybrid system we have identified a nucleolar FGF3 binding protein (NoBP) which coimmunoprecipitated and colocalized with FGF3 in transfected COS-1 cells. Characterization of the NoBP binding domain of FGF3 exactly matched the sequence requirements of FGF3 for its translocation into the nucleoli, suggesting that NoBP might be the nucleolar binding partner of FGF3 essential for its nucleolus localization. Carboxyl-terminal domains of NoBP contain linear nuclear and nucleolar targeting motifs which are capable of directing a heterologous protein beta-galactosidase to the nucleus and the nucleoli. While NoBP expression was detected in all analyzed proliferating established cell lines, NoBP transcription was rapidly downregulated in the promyelocytic leukemia cell line HL60 when induced to differentiate. Analysis on the expression pattern of NoBP mRNA throughout the cell cycle in HeLa cells synchronized by lovastatin demonstrated a substantial upregulation during the late G(1)/early S phase. NoBP overexpression conferred a proliferating effect onto NIH 3T3 cells and can counteract the inhibitory effect of nuclear FGF3, suggesting a role of NoBP in controlling proliferation in cells. We propose that NoBP is the functional target of nuclear FGF3 action.

Stable and radioiodine concentrations in cow milk: dependence on iodine intake.

For testing the potential use of stable iodine as a countermeasure to reduce radioiodine transfer to milk, concentrations of stable iodine and radioiodine in the milk of dairy cows fed different amounts of stable iodine were measured. The results indicated that, compared to a normal average stable iodine intake of about 20 mg d(-1) for cows, low iodine dietary intake (<1.5 mg d(-1)) resulted in a reduced transfer of radioiodine to milk by 25%, varying stable iodine intakes in the range of 10-500 mg d(-1) did have no significant effect; at stable iodine intake rates above 1000 mg I d(-1), a reduction by a factor of approximately two was achieved. The high dietary iodine intakes--being about 100 times the normal iodine supply--required to reduce the radioiodine transfer significantly, will result in stable iodine concentrations in milk in excess of advised or legal limits for human consumption. Nevertheless, the provision of stable iodine via the milk pathway might be considered for emergency situations when stable iodine is used as a preventative measure for dose reduction to humans.

Amplification and expression of protooncogenes in human small cell lung cancer cell lines.

Amplification and expression of 16 protooncogenes were examined in 12 established small cell lung cancer (SCLC) cell lines. Seven of 12 cell lines showed a 20- to 35-fold amplification of the c-myc oncogene, 3 cell lines showed an 80- to 130-fold amplification of N-myc oncogene, and one cell line had a simultaneous amplification of the c-myb and N-myc oncogene. In this cell line both oncogenes were transcriptionally highly active at the same time. A variant subpopulation of SCLC expressed an 8.5-kilobase v-fms homologous transcript at high levels but without amplification of the c-fms gene. All cell lines examined had similar RNA levels of the N-ras, Ki-ras, Ha-ras, and c-raf1 oncogenes. DNA amplification, however, was undetectable. The protooncogenes c-fes, c-fos, and c-erbB were expressed very weakly and the transcripts of the oncogenes c-mos, c-sis, c-erbA, c-src, and c-abl were not observed in any of the 12 SCLC-cell lines. From these data we conclude that beyond the oncogenes myc and myb, oncogenes whose gene products are GTP binding proteins and phosphokinases may also be necessary to develop and keep the malignant state of SCLC. The v-fms homologous transcript found may be involved in the transition of the classic cell type to the variant cell type of SCLC.

Secretion and mitogenic activity of zebrafish FGF3 reveal intermediate properties relative to mouse and Xenopus homologues.

Zebrafish (Brachyodanio rerio) Fgf-3 cDNAs expressed in COS-1 cells give rise to the heterogeneous set of secreted proteins with relative molecular masses in the range of 29-30.5 kDa. These proteins associate strongly with the extracellular matrix but are quantitatively released into the culture medium in the presence of heparin (5 micrograms/ml). Extracellular zebrafish FGF3 (ZFGF3) also contains a smaller sized component that appears to result from an amino-terminal proteolytic cleavage. These properties are similar to those described for Xenopus FGF3 (XFGF3). Receptor binding experiments indicate that ZFGF3 has a higher affinity for the IIIb rather than the IIIc isoform of FGFR2; properties that are more reminiscent of the mouse than the Xenopus homologue. Consistent with the FGF receptor binding properties, ZFGF3 shows a restricted mitogenic potential and a reduced transforming activity on NIH3T3 cells compared to XFGF3. Hybrid proteins made between Xenopus and zebrafish FGF3 implicate the C-terminal region in determining the differences in receptor potential affinities, mitogenic potency and transforming activity. Thus, ZFGF3 shows the structural and secretory properties of XFGF3, but has biological properties more akin to those of the mouse homologue.

Expression of p64c-myc and neuroendocrine properties define three subclasses of small cell lung cancer.

Twelve human small cell lung cancer (SCLC) cell lines and 6 non-SCLC cell lines were analysed with respect to expression of the c-myc, c-myb, and c-raf1 protooncogenes at the protein level. Analysis of p64c-myc protein expression in 12 SCLC cell lines resulted in the observation that it is present at high levels not only in cells with low, but also in those with moderate neuroendocrine differentiation. Neuroendocrine differentiation was based on parameters such as growth rate, colony formation, L-Dopa decarboxylase (DDC) activity, bombesin, and neurotensin described before. Surprisingly, in two cell lines with low neuroendocrine differentiation but without c-myc protein expression (SCLC-86M1 and NCI-H526) p75c-myb expression was observed which may therefore be able to substitute for the p64c-myc protein. Analysis of p74c-raf1 expression did not result in correlation with any growth or differentiation parameter since it was expressed at low levels in 11 out of 12 cases. We conclude that SCLC in vitro can be classified in three rather than two previously defined subclasses. In addition to the classic subclass with slow growth, high neuroendocrine differentiation, and absent or very low p64c-myc expression and the variant subclass with fast growth, absent to very low neuroendocrine differentiation, and high p64c-myc expression, we suggest a third subclass designated as transitional with moderate growth, moderate neuroendocrine differentiation, and high p64c-myc expression. Data on a small number of non-SCLC cell lines tested showed that high levels of p64c-myc correlate with high in vitro growth rates. This indicates that high p64c-myc levels may be associated with high proliferative activity, and lack of differentiation in lung cancer in general. The p74c-raf1 protein was found in all non-SCLC cell lines. Whether this classification of SCLC cell lines is applicable to SCLC in vivo remains to be determined.

Isolation, characterization and expression of the Xenopus laevis ribosomal protein S6 gene.

We report the isolation and characterization of genomic DNA clones encoding Xenopus ribosomal protein (rp) S6. A human rpS6 cDNA was used to screen a genomic DNA library, and this led to the isolation of a genomic clone encompassing the complete rpS6 gene locus. DNA sequencing and primer extension analysis indicate that Xenopus rpS6 is structurally analogous to the mammalian rpS6 genes, and its transcription starts at two sites within the same polypyrimidine tract of 10 bases. A series of deletions of the 5' region of the Xenopus rpS6 gene were fused to the chloramphenicol acetyltransferasereporter gene and transfected into COS-1 cells. The results suggest that the regulatory regions of the Xenopus rpS6 gene are clearly distinct from those earlier reported for the human rpS6 gene. Northern blot analysis of stage-specific embryonic RNA demonstrated an uniform rpS6 transcription during embryogenesis. Southern blot and PCR analyses indicate that the Xenopus rpS6 gene is pseudotetraploid in the Xenopus genome.

The zebrafish Fgf-3 gene: cDNA sequence, transcript structure and genomic organization.

We report the isolation and characterization of genomic and cDNA clones encoding zebrafish fibroblast growth factor 3 (FGF3). An initial cDNA clone was generated by PCR amplification using degenerate oligo primers corresponding to a conserved region of protein found in the mouse and human homologues. Screening a cDNA library made from 30-33-h-old zebrafish embryos with this PCR product led to the isolation of two cDNA clones. Sequence analysis of the longest cDNA insert (1810 bp) revealed a 256-amino-acid (aa) orf. The central region, composed of approx. 155 aa, shares 78% identity with the analogous region of Xenopus laevis FGF3 and 72% identity with the product of the more distantly related human gene. However, the N-and C-terminal domains of zebrafish FGF3 are very different from those of other known homologues. The cDNA was used as a probe on genomic DNA to create a physical map of the locus and to isolate a genomic clone encompassing the entire coding region and 5' sequences. DNA sequencing and RNase protection analyses indicate that zebrafish Fgf-3 (ZFgf-3) is structurally analogous to the mouse gene and regulated through two different promoters. The transcription start point of the proximal promoter aligns to that of mouse promoter P3 and lies within a conserved region of sequence.

Differential expression of insulin-like growth factor binding proteins in human non-small cell lung cancer cell lines.

The possible expression and secretion of insulin-like growth factor binding proteins (IGFBPs) by non-small cell lung cancer (NSCLC) cell lines was investigated and compared with possible IGFBP expression by primary NSCLC tumours. Cells growing under serum-free conditions released binding proteins with apparent molecular masses of 26-43 kD when analysed by a ligand blotting method under non-reducing conditions. Additionally, northern blot analysis of total RNA from NSCLC cell lines and tumours was performed using cDNAs coding for each of IGFBP-1, IGFBP-2, and IGFBP-3. This analysis revealed expression of all three mRNAs to varying degrees by all cell lines. In contrast all primary tumours analysed expressed predominantly IGFBP-2 and IGFBP-3 and none showed any evident expression of IGFBP-1. Both NSCLC cell lines and tumours synthesise IGFBPs but the pattern of expression differs significantly between cell lines and primary tumours.

Molecular cloning of IGFBP-5 from SCLC cell lines and expression of IGFBP-4, IGFBP-5 and IGFBP-6 in lung cancer cell lines and primary tumours.

We showed recently that insulin-like growth factor binding protein (IGFBP)-1, -2 and -3 are differentially expressed in lung cancer and permanent lung cancer cell lines. Elevated levels of IGF binding capacity in serum of lung cancer patients were also reported. The function and tissue specificity of IGFBP are still obscure but they are probably local regulators of IGF action. Here we show the expression of IGFBP-4 transcripts in 11/11 small cell lung cancer (SCLC) cell lines, in nine out of 11 non-small cell lung cancer (NSCLC) cell lines, in 11/11 lung tumour specimens (10 derived from patients with NSCLC and one from SCLC origin) and in normal lung. In addition we isolated IGFBP-5 cDNA from lambda gt10 libraries of SCLC cell lines. With this IGFBP-5 cDNA we detected transcripts of different lengths in seven out of 11 SCLC cell lines, in 11/11 lung cancer specimens but only in one out of 11 NSCLC cell lines and in normal lung. IGFBP-6 was not detected in northern analysis of any tested SCLC cell line but it was expressed in nine out of 11 NSCLC cell lines and in nine out of 11 human lung cancer specimens and in normal lung.

Effect of dopexamine on hepatic metabolic activity in patients with septic shock.

Hepato-splanchnic metabolic activity is seen to be related to regional blood flow and oxygen/substrate availability in patients with sepsis. Catecholamines, which may modulate metabolic activity perse, are common to stabilize hemodynamics. We studied the effect of a dopexamine-induced increase in splanchnic blood flow (Qspl) on regional metabolic rate in 10 patients with septic shock requiring norepinephrine to maintain mean arterial pressure (>60 mmHg). Splanchnic blood flow was determined using the indocyanine-green method with hepatic venous sampling. We determined the hepato-splanchnic lactate, pyruvate, alanine, and glutamine turnover and the lactate/pyruvate and ketone body ratio as well as the endogenous glucose production (EGP) using the stable isotope approach. Qspl increased from 0.86 (0.79-1.15) to 0.96 (0.92-1.33) L/min/m2, not influencing any parameter of metabolic activity. We speculate that this finding is due to altered beta-adrenoreceptor-mediated thermogenic effects due to the interplay of different beta-sympathomimetics at the receptor site.

Different pattern of expression of cellular oncogenes in human non-small-cell lung cancer cell lines.

Altered and deregulated cellular oncogenes were found in many human solid tumors. Except for a few types of tumors that consistently exhibited specific altered proto-oncogenes, the majority of tumors are associated with a number of transcriptionally activated cellular oncogenes. In the heterologous group of non-small-cell lung cancer (NSCLC), nothing about a specific pattern of proto-oncogene expression is known. Therefore, we investigated the expression of a panel of cellular oncogenes in NSCLC cell lines. DNA and RNA from 11 established NSCLC cell lines (4 adenocarcinoma cell lines, 3 squamous cell carcinoma cell lines, 3 large-cell carcinoma cell lines and 1 mesothelioma cell line) were isolated and analysed using the Southern, dot blot and Northern hybridization technique. c-myc RNA expression was found in all NSCLC cell line, L-myc expression only in 1 adenocarcinoma cell line, N-myc and c-myb expression in none of the 11 cell lines examined. No c-myc amplification could be detected in the DNAs. v-sis-related mRNA was observed in 5/11 cell lines without association to a specific NSCLC subtype. v-src-related mRNA, found in all tested cells, exhibited increased levels in 1 adenocarcinoma cell line (A-549) compared to the other cell lines. Binding sites for epidermal growth factor (EGF) had been described previously in NSCL, therefore we found erbB homologue transcripts coding for the EGF receptor in all NSCLC cell lines. Also, c-raf1-, N-ras-, Ki-ras-, and H-ras-related RNA expression was observed in all lines. We conclude that L-myc, N-myc, and c-myb expression does occur less frequently in NSCLC than in SCLC. Also amplification does not appear to be an important mechanism by which the c-myc proto-oncogene is activated in NSCLC. A specific pattern of oncogene expression could not be detected in NSCLC cells; each cell line examined showed its own pattern. However, transcriptional activation of a proto-oncogene like erbB, ras, raf, src, and c-myc, which are all involved in the progression pathway of EGF, may be a common feature of NSCLC.

Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects.

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional, and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-alpha were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3-30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.

Effect of an acute increase in PCO2 on splanchnic perfusion and metabolism.

OBJECTIVES: To evaluate the acute effects of an increase in PCO2 on splanchnic tissue perfusion and metabolism. DESIGN: Clinical prospective study in the intensive care unit in a university clinic. PATIENTS: Six patients with severe acute lung injury requiring mechanical ventilation. All patients had bilateral infiltrates on chest radiography, a PaO2/FIO2 ratio less than 200 mmHg, and stable hemodynamics without vasoactive drugs. INTERVENTIONS: PCO2 was increased 5-20% by an added dead space from baseline, followed by a return to baseline. MEASUREMENTS AND RESULTS: Splanchnic blood flow was measured using primed continuous infusion of indocyanine green dye with hepatic venous sampling and systemic hemodynamics by routine monitoring; we also determined the gastric mucosal-arterial PCO2 difference and splanchnic lactate/pyruvate exchange. PCO2 was increased by an added dead space; after 60 min all measurements were repeated; after return to baseline a third measurement followed. The increase in PCO2 had no significant effect on splanchnic blood flow or indices of perfusion and metabolism. CONCLUSION: Our results suggest that acute moderate changes in PCO2 have no major effect on splanchnic perfusion and metabolism.

Effect of positive end-expiratory pressure on splanchnic perfusion in acute lung injury.

OBJECTIVE: To evaluate the acute effects of an increased positive end-expiratory pressure (PEEP) on splanchnic tissue perfusion. DESIGN: Clinical prospective study. SETTING: Intensive care unit in a university clinic. PATIENTS: Six patients with severe acute lung injury (ALI) requiring mechanical ventilation. All patients had bilateral infiltrates in chest X-ray, PaO2/FiO2 < 200 mmHg and stable hemodynamics without vasoactive drugs. INTERVENTIONS: PEEP was increased by 5 cmH2O from a clinically selected PEEP level (8/6-11 cmH2O) up to (13/10-14 cmH2O) followed by a return to baseline. MEASUREMENTS AND MAIN RESULTS: Splanchnic blood flow was measured using primed continuous infusion of indocyanine green dye with hepatic venous sampling and systemic hemodynamics by routine monitoring. In addition, we estimated gastric mucosal-arterial PCO2 difference and splanchnic lactate/pyruvate exchange. After a baseline measurement, PEEP was increased. After 60 min all measurements were repeated. PEEP was returned to the baseline level and a third measurement followed. PEEP had no effect on cardiac index (baseline I: 3.2/6.1-2.5 l/min/m2; PEEP: 3.3/5.7-2.3 l/min/m2; baseline II: 3.4/6.0-2.5 l/min/m2); neither did PEEP have any effect on splanchnic blood flow (baseline I: 0.91/1.39-0.62 l/min/m2; PEEP: 1.04/1.75-0.54 l/min/m2; baseline II: 1.07/1.42-0.68 l/min/m2, respectively) or perfusion (gastric mucosal-arterial PCO2 difference baseline I: 2.1/12.8-0.6 kPa; PEEP: 1.7/14.5-0.7 kPa; baseline II: 1.7/8.8-0.1 kPa; lactate uptake baseline I: 0.5/1.1-0.3 mmol/min/m2; PEEP: 0.4/1.0-0.3 mmol/min/m2; baseline II: 0.5/0.9-0.3 mmol/min/m2; hepatic venous lactate/pyruvate baseline I: 9.7/10.6-5.7; PEEP: 9.7/14.2-6.4; baseline II: 8.4/12.4-7.3; respectively). CONCLUSION: PEEP by itself does not have a consistent effect on splanchnic blood flow and metabolism when cardiac index is stable and patients are ventilated within the linear part of the pv curve.

Influence of prone position on gastric mucosal-arterial PCO2 gradients.

OBJECTIVE: To evaluate the effects of mechanical ventilation in the prone position on gastric mucosal-arterial PCO2 gradients. DESIGN: Prospective clinical study. SETTING: Intensive care unit in a university clinic. PATIENTS: Twenty-five patients requiring mechanical ventilation. The physician in charge indicated the turning manoeuver for the individual patient. MEASUREMENTS/RESULTS: In addition to routine measurements of global hemodynamics and gas exchange we determined: 1) intragastric pressure; and 2) gastric mucosal-arterial PCO2 difference. After a baseline measurement in the supine position patients were turned to the prone position. After 60', 120', a median of 6.5 h (2-10 h) in the prone position, and again after 60' in the supine position, all measurements were repeated. Global hemodynamics remained unaltered throughout the study. While gastric mucosal-arterial PCO2 gradients did not change significantly during the first 60 min in the prone position, they significantly increased during the following 60 min [median/percentile: baseline: 6 (1 to -3); 60': 7 (15-5); 120': 13 (20-8) mmHg]. The median intragastric pressure was not significantly affected [baseline: 10 (13-5); 60': 12 (16-8); 120': 11 (13-7) mmHg], but 9 of the 11 patients in whom intragastric pressure increased during the first 60 min in the prone position also showed significantly increased PCO2 gradients (P < 0.01). CONCLUSION: Mechanical ventilation in the prone position may be affiliated with increased tonometric gastric mucosal-arterial PCO2 gradients depending on the effect on intraabdominal pressure. Measuring intraabdominal pressure and/or gastric mucosal PCO2 via a nasogastric tube therefore may help to detect adverse effects of this ventilatory strategy.