Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “In vitro model”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 577 records · Page 32Linked to original sources
PubMed1998

Use of in vitro models of haemofiltration and haemodiafiltration to estimate dosage regimens for critically ill patients prescribed cefpirome.

BACKGROUND: The physico-chemical properties of cefpirome (low protein binding, high water solubility and low molecular weight) suggest that it may be lost readily from the extracorporeal circulation of intensive care unit patients during continuous renal replacement therapy. METHOD: In order to make informed dosage recommendations for patients receiving artificial renal support, cefpirome loss from human blood has been quantified using in vitro models of continuous haemofiltration and haemodiafiltration. Cefpirome clearance was measured using three membrane types at varying ultrafiltrate (UFR) and dialysis flow rates (Qd). RESULTS: During haemofiltration cefpirome was found to cross hollow fibre polyamide (PA) and polyacrylonitrile (PAN) membranes with equal efficiency. The mean sieving coefficients (S) of both PA and PAN membranes were consistently high (> 0.7) when two different ultrafiltration rates were used. Changing the ultrafiltration rate or membrane type had no significant effect on the sieving coefficient of cefpirome but did result in an increase in cefpirome filter clearance (Fcl). Using the haemodiafiltration model, cefpirome penetrated PAN membranes (flat plate AN69S) more efficiently than hollow fibre PA membranes (FH66D). In each case, increasing the dialysis flow rate reduced the S-value. However, although increasing Qd was associated with a greater Fcl of cefpirome when PAN membranes were employed, no such relationship was found for the PA hollow fibre membrane. CONCLUSION: The information generated can be used to estimate a dosing regimen for intensive care patients prescribed cefpirome and receiving continuous renal replacement therapy.

Cephalosporins↗
PubMed1997

Bactericidal activity of cefodizime on Enterobacteriaceae in an in-vitro model simulating plasma pharmacokinetics in humans.

An in-vitro dialysis model was employed to assess the feasibility of once-daily dosing of cefodizime in the treatment of infections caused by various Enterobacteriaceae: Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Serratia marcescens, Providencia stuartii and Enterobacter cloacae. This model simulated the concentrations of cefodizime detected in human blood after an intravenous (i.v.) bolus injection of 1 g or 2 g of the antibiotic. Validation of the model was undertaken to confirm its utility. Based on the data obtained with this model, once-daily dosing with 1 g cefodizime (i.v.) should be effective against infections due to the commonest Gram-negative bacteria (E. coli, K. pneumoniae, M. morganii). For infections caused by Enterobacteriaceae strains that produce large quantities of Class I beta-lactamases, twice-daily (P. stuartii or S. marcescens) or four times daily (E. cloacae) administration of 1 g cefodizime may be required.

Cefotaxime↗
PubMed1996

Tauroursodeoxycholic acid protects in vitro models of human colonic cancer cells from cytotoxic effects of hydrophobic bile acids.

Bile acids have been implicated as tumor promoters that enhance epithelial proliferation and the development of colonic tumors. This study investigated the effects of bile acids on the growth of in vitro models of human colonic epithelial cells. Cell lines with varying degrees of differentiation (Caco2, HT29, LS174T, and Lovo) were studied. Cell viability and number were measured by a tetrazolium (MTT) spectrophotometric assay. Enhanced cell growth was not observed with any bile acid over the range 10 nmol/L to 2.5 mmol/L. Cytotoxicity was consistently observed at concentrations of unconjugated bile acids greater than 0.1 mmol/L. The bile acid concentration at which 50% growth inhibition occurred was similar for all cell lines and increased in the following order: deoxycholic acid = chenodeoxycholic acid < taurodeoxycholic acid < ursodeoxycholic acid < taurochenodeoxycholic acid < cholic acid < tauroursodeoxycholic acid. Coincubation of tauroursodeoxycholic acid (TUDC) with taurodeoxycholic acid (TDC) or taurochenodeoxycholic acid (TDCD) reversed the short-term (30-minute) cytotoxicity and release of glycoprotein induced by TDC or TCDC regardless of differentiation status. In contrast, TUDC did not reverse the cytotoxicity of deoxycholic acid. Unconjugated ursodeoxycholic acid did not alter short-term cytotoxicity of any bile acid. These data indicate that bile acids do not stimulate cell growth in undifferentiated or differentiated colon cancer cell lines, in contrast to normal colonic epithelium in vivo. Bile acid cytotoxicity correlates with the relative hydrophobicity of the bile acid. Because tauroursodeoxycholic acid alters the cytotoxicity of hydrophobic bile acids in vitro, further understanding of bile acid interactions in the colon may have important implications in altering tumor promotion.

Bile Acids and Salts↗
PubMedDate not supplied

The Caco-2 cell monolayer system as an in vitro model for studying bacterial-enterocyte interactions and bacterial translocation.

Partly because of inherent limitations of in vivo models, the cellular mechanisms underlying the process of bacterial translocation across the intestinal epithelial barrier are incompletely understood. We therefore used the Caco-2 intestinal cell line as an in vitro model to examine the bacterial translocation process under controlled conditions. Caco-2 cells were grown on porous membranes in the upper compartment of a two-compartment system. Caco-2 cells were cultured for 7, 14, 21, or 28 days. Cellular confluence and tight junction integrity were verified by measurements of dextran permeability and transepithelial electrical resistance. Bacterial translocation was measured by culturing the bacteria (E. coli C25) that were able to cross the Caco-2 cell monolayer. The passage of E. coli C-25 and dextran across the Caco-2 monolayer was higher and the transepithelial electrical resistance lower after 7 days of culture than after 14 or 21 days of culture. The Caco-2 cells became impermeable to dextran blue after 14 days of culture with an average transepithelial electrical resistance of 173.1 +/- 9.24 ohms.cm2. When increasing doses of (10(2)-10(9) colony-forming units) of E. coli were tested in 14-day-old Caco-2 monolayers, bacterial translocation occurred in a time- and dose-dependent fashion. Once cellular confluence and tight junction integrity have been established, bacterial translocation across Caco-2 cells appears to be a time- and dose-dependent process.

Cell Movement↗
PubMed1988

The relationship between interictal and ictal paroxysms in an in vitro model of focal hippocampal epilepsy.

In studies of focal epilepsy it is frequently assumed that the interictal spike is the elementary form of epileptic activity and that seizure, or ictal, episodes evolve by temporal summation and spatial expansion of interictal paroxysms. We examined this hypothesis in an in vitro model of acute focal epilepsy produced by perfusing rat hippocampal slices with solutions containing moderately elevated concentrations of K+. Some of the preparations treated in this way displayed recurring electrical seizures in the CA1 field. Each seizure episode typically evolved by a seemingly smooth progression of brief interictal bursts into sustained ictal discharge. However, exposure of preparations showing electrical seizures to blockers of synaptic transmission or to cholinergic agonists abolished interictal spiking in all hippocampal fields but did not impede the initiation of ictal episodes in area CA1. Likewise, severing the connections between areas CA3 and CA1 abolished interictal spiking in area CA1 without disrupting the initiation of seizures in this region. These data clearly show that in this model, focal seizures arise independent of interictal spikes and through different cellular mechanisms. While interictal electrogenesis requires chemical synaptic excitation, ictal episodes can be initiated and maintained by nonsynaptic neuronal interactions.

Animals↗
PubMed1993

Plasma protein adsorption to hemodialysis membranes: studies in an in vitro model.

Upon interaction of whole blood with foreign materials, heterogeneous protein films are deposited onto the artificial surface (eg, hemodialysis membranes). The composition of these protein films subsequently affects various processes, eg, thrombogenesis or activation of the complement system. We developed an in vitro model with which we can identify and study proteins interacting with capillaries during hemodialysis. Using this model we studied the cuprophane dialyzer GFS 120 (CP) and the polymethylmetacrylate membrane Filtryzer B2-1.2 (PMMA). Heparinized whole blood from healthy young volunteers was dialyzed on an extracorporeal dialysis machine. After the dialysis procedure the adsorbed material was eluted from the hemodialysis membranes by different eluants and subsequently analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. A number of proteins could be identified in the eluates of both membrane types. Interestingly, platelet glycoproteins could only be found in PMMA eluates. Albumin, IgG, and antithrombin III were mainly present in the cuprophane eluates. Fibrinogen was demonstrable in all eluates, but in relatively low amounts, and the protein was significantly degraded. Degradation products of antithrombin III and complement factor 3 could also be identified. The process causing the degradation has not yet been identified, but may be due to proteases released from damaged cells.

Adsorption↗
PubMed2002

Dioxin stimulates RANTES expression in an in-vitro model of endometriosis.

The industrial contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with inflammatory disorders in women and other mammals. The current studies were performed to investigate the effect of TCDD on RANTES expression in an in-vitro model of endometriosis. The biochemical effects of dioxins are mediated by binding to aryl hydrocarbon receptors (AhR). This study showed that both normal and endometriotic endometrial stromal cells express AhR protein, which was observed to be down-regulated by 40-60% after exposure to TCDD. Treatment with TCDD for 24 h increased the luciferase activity of the RANTES promoter by 2.5 +/- 1.0-fold in stromal cells derived from normal endometrium and endometriotic implants. When AhR were over-expressed in these cells, luciferase activity increased 6.1 +/- 1.4-fold, and RANTES protein secretion increased from undetectable to 31 +/- 10 pg/100,000 cells. TCDD failed to activate a RANTES construct with a mutated dioxin response element. Other AhR ligands had similar effects to TCDD on RANTES transcription and secretion. Control transfections using tumour necrosis factor (TNF)-alpha and nuclear factor (NF)-kappaB response element reporters indicated that these pathways are not activated by TCDD in endometrial stromal cells. This study has demonstrated that functional AhR are present in endometrial and endometriotic stromal cells and that TCDD up-regulates the expression of RANTES, providing a possible mechanistic link between dioxin exposure and chemokine expression in endometriosis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Tenocytes from ruptured and tendinopathic achilles tendons produce greater quantities of type III collagen than tenocytes from normal achilles tendons. An in vitro model of human tendon healing.

Type I collagen is the main collagen in tendons; type III collagen is present in small amounts. Ruptured Achilles tendons contain a significantly greater proportion of type Ill collagen, which predisposes them to rupture. We used an in vitro model to determine whether tenocytes from Achilles tendons that were ruptured (N = 22), nonruptured (N = 7), tendinopathic (N = 12), and fetal (N = 8) show different behavior. Samples of Achilles tendon were digested with collagenase and the released tenocytes were collected. Primary tenocyte cultures were established and subsequently cultured onto glass coverslips. Once a confluent monolayer was obtained, the cell populations were "wounded" by scraping a pipette tip along the surface. The cultures were further incubated for either 1, 4, 8, 12, 16, or 24 hours, and production of types I and II collagen was assessed by immunostaining. In cultures from ruptured and tendinopathic tendons, there was increased production of type Ill collagen. Athletic participation places excess stress on the Achilles tendon, which could potentially lead to areas of microtrauma within the tendon. These areas may heal by the production of type III collagen, which is an abnormal healing response. Accumulation of such episodes of microtrauma could resuit in a critical point where the resistance of the tissue to tensile forces is compromised and tendon rupture occurs.

Achilles Tendon↗
PubMedDate not supplied

Immunohistochemical study of collagen synthesis in an in-vitro model of scirrhous carcinoma of the stomach.

BACKGROUND/AIMS: The mechanisms involved in the unique stromal change that occurs upon cancer invasion are poorly understood in scirrhous carcinoma of the stomach. METHODOLOGY: Three different human gastric cancer cell lines (KATO-III, MKN-28, MKN-45) and human fibroblast cells (TIG-101) were co-cultured three-dimensionally in collagen gels. The gels, in vitro models of gastric cancer, were immunostained by monoclonal antibodies to human placental prolyl 4-hydroxylase (PH, a key enzyme of collagen synthesis) and then examined by light and electron microscopy. RESULTS: Under co-culture of cancer cells and fibroblasts, cytoplasmic staining for PH was observed in both the cancer cells (KATO-III, MKN-28, MKN-45) and fibroblasts. No significant difference in the expression patterns of the alpha- and beta-subunits of PH was observed not only among the KATO-III, MKN-28 and MKN-45 cell lines but also between cancer cells and fibroblasts. CONCLUSIONS: These findings indicate that both cancer cells and fibroblasts can synthesize collagen in gastric cancer models. Moreover, this property may not be a unique characteristic of scirrhous gastric cancer cells, but common to gastric cancer cells and fibroblasts in vitro.

Adenocarcinoma, Scirrhous↗
PubMed1995

Comparison of streptokinase, urokinase, and recombinant tissue plasminogen activator in an in vitro model of venous thrombolysis.

PURPOSE: Presumed differences in the thrombolytic activity and fibrinolytic specificity of the three commonly used thrombolytic agents, streptokinase, urokinase, and recombinant tissue plasminogen activator (rt-PA), are based on clinical study results, where variability renders meaningful comparisons difficult. An in vitro model of catheter-directed venous thrombolysis was used to compare the three agents. METHODS: Retracted iodine 125-radiolabeled clots that simulate those observed in the venous system were infused with thrombolytic agents at doses analogous to those used clinically. Perfusion with heparinized, whole human blood was undertaken for 60 minutes, measuring the efficacy of thrombolysis through serial quantification of radio tracer released into the circuit. Fibrinolytic specificity was determined by following decrements in perfusate fibrinogen concentration. RESULTS: Streptokinase was the agent associated with the slowest rate of clot lysis (p = 0.01 vs urokinase and rt-PA). Urokinase was associated with an intermediate rate of lysis but appeared to be the agent with the greatest degree of fibrinolytic specificity (p = 0.02 vs streptokinase, p = 0.05 vs rt-PA). Although rt-PA was associated with improved efficacy early in the perfusions, the differences between rt-PA and urokinase dissipated after 30 minutes. CONCLUSIONS: These laboratory observations suggest that urokinase may be the most appropriate agent for catheter-directed venous thrombolysis, offering an advantageous compromise between fibrinolytic specificity and thrombolytic speed.

Analysis of Variance↗
PubMed2001

Glycation during human dermal intrinsic and actinic ageing: an in vivo and in vitro model study.

BACKGROUND: Non-enzymatic glycation occurring in normal human skin plays an important part in ageing. OBJECTIVES To visualize and quantify, in human subjects, the extent of glycation during human dermal intrinsic and actinic ageing, and to develop a reliable reproducible in vitro model for evaluating the efficacy of potential inhibitors of glycation. METHODS: By immunohistochemistry using a monoclonal antibody recognizing carboxymethyl lysine, an advanced glycation end-product (AGE) (first objective), and by incubating dead de-epidermized dermis (DED) with glucose to simulate ageing-induced glycation in a human dermal equivalent model (second objective). RESULTS: We found that glycation of the dermis generally arises after 35 years, then increases rapidly with intrinsic ageing. We also noticed an enhancement of glycation by solar irradiation that occurred via glycation of the elastic fibre network or solar elastosis tissue. In the model, production of AGEs appeared in a time-dependent way, mimicking glycation observed in vivo during chronological ageing. Irradiation of DED before incubation with glucose strongly enhanced induction of AGEs, corresponding to the effect of solar irradiation on AGEs observed in vivo. CONCLUSIONS: These results confirm a marked increase of AGEs during intrinsic ageing in normal human skin and also suggest that glycation is enhanced in photoaged skin.

Adult↗
PubMed2004

An in vitro model for the lepromatous leprosy granuloma: fate of Mycobacterium leprae from target macrophages after interaction with normal and activated effector macrophages.

The lepromatous leprosy granuloma is a dynamic entity requiring a steady influx of macrophages (Mphi) for its maintenance. We have developed an in vitro model to study the fate of Mycobacterium leprae in a LL lesion, with and without immunotherapeutic intervention. Target cells, consisting of granuloma Mphi harvested from the footpads of M. leprae-infected athymic nu/nu mice, were cocultured with normal or IFN-gamma-activated (ACT) effector Mphi. The bacilli were recovered and assessed for viability by radiorespirometry. M. leprae recovered from target Mphi possessed high metabolic activity, indicating a viable state in this uncultivable organism. M. leprae recovered from target Mphi incubated with normal effector Mphi exhibited significantly higher metabolism. In contrast, bacilli recovered from target Mphi cocultured with ACT effector Mphi displayed a markedly decreased metabolic activity. Inhibition by ACT Mphi required an E:T ratio of at least 5:1, a coculture incubation period of 3-5 days, and the production of reactive nitrogen intermediates, but not reactive oxygen intermediates. Neither IFN-gamma nor TNF-alpha were required during the cocultivation period. However, cell-to-cell contact between the target and effector Mphi was necessary for augmentation of M. leprae metabolism by normal effector Mphi as well as for inhibition of M. leprae by ACT effector Mphi. Conventional fluorescence microscopy and confocal fluorescence microscopy revealed that the bacilli from the target Mphi were acquired by the effector Mphi. Thus, the state of Mphi infiltrating the granuloma may markedly affect the viability of M. leprae residing in Mphi in the lepromatous lesion.

Animals↗
PubMed1997

Distribution of adhesion molecules on HeLa cells, platelets and endothelium in an in vitro model mimicking the early phase of metastasis. An immunogold electron microscopic study.

The aim of the present study was to obtain information about the distribution of various adhesion molecules within and on the surface of HeLa cells, platelets and endothelial cells in an in vitro model mimicking the early phase of metastasis. Suspensions of HeLa cells and human platelets, added to a medium of cultured human umbilical-vein endothelial cells, were stimulated by the addition of thrombin. Hirudin was added before thrombin in some experiments, and in other experiments the endothelium was pretreated with 0.5 mM acetylsalicylic acid (ASA). The distribution of platelet-endothelial cell adhesion molecule (PECAM), P-selectin, von Willebrand factor (vWf), fibrinogen (FG) and thrombospondin (TSP) was investigated on fixed material from the three experimental settings by using an immunogold electron-microscopic technique on frozen thin sections. Cells that had not been exposed to thrombin or any other type of stimulation were used as controls. PECAM was the only adhesion molecule detected on HeLa cells. It outlined the membrane on tumour cells that were not adherent to platelets in both basic and hirudin experiments. However, tumour cells in close proximity to activated platelets were unlabelled. In contrast, PECAM was detected on both platelets and endothelium in all experimental settings and in controls. P-selectin was only demonstrable on platelets in basic experiments. vWf was found both in endothelium and in platelets in controls and in all experimental settings. FG and TSP were found on platelets only, in a manner similar to that seen with vWf. Thus, among the adhesive factors examined in our experimental model, PECAM is the only one demonstrated on HeLa cells. This suggests that PECAM on tumour cells may play a role as adhesion molecule in the early stage of metastasis. P-selectin, vWf, FG and TSP were also consistently expressed. Therefore, these factors may contribute to the adhesive reactions involved in early metastasis.

Aspirin↗
PubMed2000

Effects of transforming growth factor-beta and mechanical strain on osteoblast cell counts: an in vitro model for distraction osteogenesis.

Factors known to regulate bone production during distraction osteogenesis include mechanical strain on bone forming cells and up-regulation of transforming growth factor-beta (TGF-beta) during the distraction, or strain phase of distraction osteogenesis. In the present study, an in vitro model was used to evaluate the functional effect of exogenous TGF-beta1 on mitogenesis in murine-derived MC3T3 osteoblasts during the period of active mechanical strain. The first hypothesis to be tested was that mitogenic suppression of MC3T3 osteoblasts by TGF-beta1 is further enhanced when these cells are also subjected to mechanical strain. To test this hypothesis, MC3T3 osteoblasts were seeded on flexible and rigid membranes. These were subjected to cyclic, vacuum-induced strain, simulating physiologic stress loads. After 24 hours, all cells were transferred to media containing TGF-beta1, and strain was continued for an additional 48 hours. The study was repeated by using two doses of TGF-beta1. This study demonstrated that final cell counts were significantly decreased in the presence of TGF-beta1 in both the nonstrained and strained groups (p < 0.0001). The final cell count in the strained group was significantly less than that in the nonstrained group (p < 0.0001) for both concentrations of TGF-beta1 tested, confirming the initial hypothesis. The second hypothesis to be tested was that alteration in the mitogenic response of MC3T3 osteoblasts after strain is not directly due to autocrine factors produced by the strained osteoblasts. To test this hypothesis, a proliferation assay was performed on nonconfluent MC3T3 osteoblasts by using conditioned media collected from strained and nonstrained osteoblasts. This study demonstrated no significant differences in cell counts after addition of conditioned media collected from strained versus nonstrained cells, confirming the latter hypothesis. The present study demonstrates the functional significance of mechanical strain on osteoblast cell counts. Furthermore, this may help to explain the temporal relationship observed during the early distraction (strain) phase of distraction osteogenesis in rodent models in which peak up-regulation of TGF-beta1 gene expression correlates with peak suppression of osteoblast function as measured by gene expression of extracellular matrix proteins.

Animals↗
PubMed1998

An in vitro model of human red blood cell production from hematopoietic progenitor cells.

Hemoglobinopathies, such as beta-thalassemias and sickle cell anemia (SCA), are among the most common inherited gene defects. Novel models of human erythropoiesis that result in terminally differentiated red blood cells (RBCs) would be able to address the pathophysiological abnormalities in erythrocytes in congenital RBC disorders and to test the potential of reversing these problems by gene therapy. We have developed an in vitro model of production of human RBCs from normal CD34(+) hematopoietic progenitor cells, using recombinant growth factors to promote terminal RBC differentiation. Enucleated RBCs were then isolated to a pure population by flow cytometry in sufficient numbers for physiological studies. Morphologically, the RBCs derived in vitro ranged from early polylobulated forms, resembling normal reticulocytes to smooth biconcave discocytes. The hemoglobin pattern in the in vitro-derived RBCs mimicked the in vivo adult or postnatal pattern of beta-globin production, with negligible gamma-globin synthesis. To test the gene therapy potential using this model, CD34(+) cells were genetically marked with a retroviral vector carrying a cell-surface reporter. Gene transfer into CD34(+) cells followed by erythroid differentiation resulted in expression of the marker gene on the surface of the enucleated RBC progeny. This model of human erythropoiesis will allow studies on pathophysiology of congenital RBC disorders and test effective therapeutic strategies.

Adult↗
PubMed1989

Role of oxygen free radical species in in vitro models of proximal tubular ischemia.

Lipid peroxidation (LP) of cell membranes by oxygen free radical species (OFRS) during reflow may be a mechanism for progressive proximal tubule injury after ischemia. We examined the relationship between tubule function and an endproduct of LP, malondialdehyde (MDA), in two in vitro models using a suspension of rat proximal tubule segments (PTS). Exposure of PTS to tert-butyl hydroperoxide (tBHP), a potent oxidant, induced dose-dependent decrements in the PTS respiration (QO2) but was associated with a progressive increase in MDA. The relationship between increasing doses of tBHP, QO2, and MDA content, as well as that between MDA and QO2 were highly correlated (r greater than or equal to 0.89, n = 6). Dithiothreitol (1 mM), a sulfhydryl reagent, prevented the tBHP-induced changes in both QO2 and LP. In the second model, 45-min O2 deprivation followed by 30 min of reoxygenation produced similar decrements in QO2 as did 0.75 mM tBHP but without a rise in MDA (n = 9). Mitochondria isolated from ischemic PTS had a 49 +/- 8.2% decrement in state III respiration (P less than 0.006, n = 4) but their MDA content was unchanged. Furthermore, allopurinol, superoxide dismutase, and catalase, agents that reduce tissue OFRS, did not attenuate ischemic tubular injury (n = 9). These results suggest that OFRS do not mediate transient O2 deprivation injury to the proximal tubule.

Adenosine Triphosphate↗
PubMed2006

The effect of fibrinogen substitution on reversal of dilutional coagulopathy: an in vitro model.

Colloids and crystalloids are usually administered as treatment for hypovolemia in severely injured patients. However, dilution of clotting factors and platelets together with impaired fibrinogen polymerization are associated with fluid therapy and may aggravate hemorrhage, thus worsening final outcome of these patients. We investigated, in an in vitro model, whether the addition of fibrinogen to diluted blood samples can reverse dilutional coagulopathy. Blood from 5 healthy male volunteers was diluted by 60% using lactated Ringer's solution, 4% modified gelatin solution, or 6% hydroxyethyl starch 130/0.4, as well as the combination of lactated Ringer's solution with either of the 2 colloid solutions. Thereafter, aliquots of diluted blood samples were incubated with 3 different concentrations of fibrinogen (0.75, 1.5, and 3.0 mg/mL). Measurements were performed by modified thrombelastography (ROTEM; Pentapharm, Munich, Germany). After 60% dilution, clotting times increased, whereas clot firmness and fibrin polymerization decreased significantly. After administration of fibrinogen, clotting times decreased and clot firmness, as well as fibrin polymerization, increased in all diluted blood samples. The effect of in vitro fibrinogen substitution on ROTEM variables was dependent on the fibrinogen dosage and the type of solution used to dilute the blood samples.

Adult↗