Biomedical subjects

T Satoh

Publications and source records attributed to T Satoh.

At least 109 records · Page 6Linked to original sources

PubMed2001

Neurotrophic actions of novel compounds designed from cyclopentenone prostaglandins.

Previously we found that some cyclopentenone prostaglandin derivatives promoted neurite outgrowth from PC12 cells and dorsal root ganglia explants in the presence of nerve growth factor; and so we referred to them as neurite outgrowth-promoting prostaglandins (NEPPs). In this study, NEPPs protected HT22 cells against oxidative glutamate toxicity. NEPP6, one of the most effective promoters of neurite outgrowth in PC12 cells, protected the cells most potently among NEPPs 1--10. Several derivatives, NEPPs 11--19, were newly synthesized based on the chemical structure of NEPP6. NEPP11 had a more potent neuroprotective effect than NEPP6. NEPP11 also prevented the death of cortical neurons induced by various stimuli and reduced ischemic brain damage in mice. Biotinylated compounds of NEPPs were synthesized to investigate their cellular accumulation. NEPP6-biotin protected the cells and emitted potent signals from the cells. In contrast, biotinylated non-neuroprotective derivatives emitted much weaker signals. These results suggest that NEPPs are novel types of neurotrophic compounds characterized by their dual biological activities of promoting neurite outgrowth and preventing neuronal death and that their accumulation in the cells is closely associated with their neuroprotective actions.

Animals↗

PubMed2001

Analysis of K-ras, APC, and beta-catenin in aberrant crypt foci in sporadic adenoma, cancer, and familial adenomatous polyposis.

BACKGROUND & AIMS: We have previously shown that aberrant crypt foci (ACF) are the putative precursor lesions of colorectal adenomas and subsequent cancer in humans using magnifying endoscopy. The present study was designed to investigate these genetic alterations in ACF biopsy specimens from normal subjects, familial adenomatous polyposis (FAP) or sporadic patients. METHODS: The non-FAP cases included 34 normal subjects, 35 colorectal adenoma patients, and 19 colorectal cancer patients; there were 4 FAP patients. Biopsies were performed on ACF by magnifying endoscopy. K-ras mutations were analyzed by 2-step polymerase chain reaction and restriction fragment length polymorphism, APC mutations by in vitro-synthesized protein assay, and beta-catenin mutations by direct sequencing. Full-length APC and beta-catenin were detected by immunofluorescence. RESULTS: In non-FAP cases, K-ras mutations were detected in 82% (89/106) of nondysplastic ACF and 63% (17/27) of dysplastic ACF. APC mutation and beta-catenin accumulation were not detected in non-FAP ACF, whereas in adenoma of these patients, positivity of APC mutation and beta-catenin accumulation were 78% (24/31), and that of K-ras mutation was 65% (20/31). FAP patients showed K-ras mutations in only 13% (1/8) of dysplastic ACF, which is the predominant form of ACF found in FAP. In FAP patients, somatic APC mutations were found in 100% of dysplastic ACF, as they are in adenoma. The frequency of K-ras mutations was 73% (8 of 11) in FAP adenoma. CONCLUSIONS: The data suggest that in sporadic colorectal carcinogenesis, assuming the biological implication of ACF as a precursor of adenomas, there is a route where K-ras mutation mainly occurs during the formation of ACF, which then become adenomas wherein APC mutation occurs. In FAP, however, somatic mutation of APC predominantly occurs during ACF formation, followed by K-ras mutation.

Adenomatous Polyposis Coli↗

PubMed2001

Critical role of type IV collagens in the growth of bile duct carcinoma. In vivo and in vitro studies.

Most extrahepatic bile duct carcinomas (EBDC) are characterized by a striking stromal response (desmoplasia). Our previous studies showed deposition of type IV collagen in the desmoplastic stroma beyond the basement membrane. Although type IV collagen is expressed in EBDC, little is known about the pattern of deposition in tumor stroma and how this matrix component influences the behavior of tumor cells. With the progression of desmoplasia in EBDC, different changes occurred in the quantity and localization of type IV collagen from that of type I collagen. Type I collagen was diffusely distributed in the stroma and appeared to be concentrated in the center of the tumors. In contrast, type IV collagen was deposited in the interstitium alongside carcinoma cells at the tumors' periphery. Weak or no type IV collagen deposition was detected in the more central portion of the tumors containing sclerotic collagens. To investigate the role of stromal type IV collagen in tumor cell proliferation, EBDC cell lines were cultured in a three-dimensional matrix containing varying compositions of type I collagen and type IV collagen. They were also assayed for cell adhesion and migration using in vitro models. Type IV collagen more extensively stimulated tumor cell proliferation, adhesion and migration in a dose-dependent manner than did type I collagen. All of these results suggest that modified tumor stroma with the presence of type IV collagen in EBDC provides a better environment for tumor growth and invasion.

Adenocarcinoma↗

PubMed2001

Cooperativity of alpha-naphthoflavone in cytochrome P450 3A-dependent drug oxidation activities in hepatic and intestinal microsomes from mouse and human.

1. The effects of several CYP3A substrates (alpha-naphthoflavone (alphaNF), terfenadine, midazolam, erythromycin) on nifedipine oxidation and testosterone 6beta-hydroxylation activities were investigated in hepatic and intestinal microsomes from mouse and human. 2. alphaNF (10 microM) and terfenadine (100 microM) inhibited nifedipine oxidation activities (at substrate concentration of 100 microM) in mouse hepatic microsomes to approximately 50%, but not in mouse intestinal microsomes. alphaNF (30 microM) stimulated nifedipine oxidation activities in mouse and human intestinal microsomes and in human hepatic microsomes to approximately 1.3-1.8-fold. Inhibitory potencies (50% inhibition concentration, IC50) of midazolam and erythromycin for nifedipine oxidations were calculated to be approximately 90 microM in human intestinal microsomes. In contrast, testosterone (100 microM) stimulated the nifedipine oxidation activities approximately 1.5-fold in hepatic and intestinal microsomes from mouse and human. 3. alphaNF showed different effects on the kinetic parameters including the Hill coefficients of nifedipine oxidation and testosterone 6beta-hydroxylation catalysed by hepatic and intestinal microsomes from mouse and human. Cooperativity in nifedipine oxidation was increased by the addition of alphaNF to pooled human hepatic microsomes, but little effects of alphaNF could be observed in individual human intestinal microsomes. 4. These results suggest that CYP3A enzymes in liver and intestine might have different characteristics and that observations from hepatic microsomes should not be directly applicable to intestine metabolism in some cases. Studies of drug-drug interactions of CYP3A substrates are recommended to be performed using intestinal samples.

Animals↗

PubMed2001

Antitumor effect of bcl-2 antisense phosphorothioate oligodeoxynucleotides on human renal-cell carcinoma cells in vitro and in mice.

BACKGROUND AND PURPOSE: Programmed cell death is a genetically regulated pathway that is altered in many cancers. This process is, in part, regulated by the bcl-2 oncogene. Antisense oligodeoxynucleotides (ODNs) targeted to specific oncogenes have been used with some therapeutic success in animal models of leukemia and melanoma cells and human Hodgkin's lymphoma. We evaluated the effects of antisense ODNs targeted to the bcl-2 oncogene on the proliferation of human renal-cell carcinoma (RCC) cells in vitro and on the growth of human RCC xenografts in BALBc nude (nu/nu) mice. MATERIALS AND METHODS: Expression bcl-2 mRNA in five RCC cell lines (ACHN, Caki-1, RCZ, RCW, and OS-RC-2) was analyzed by reverse transcriptase-polymerase chain reaction. The effects of phosphorothioated ODNs containing human bcl-2 sense and bcl-2 antisense sequences that were transfected with Lipofectin on the proliferation and viability of cultures of established human RCC cell lines were determined by MTS assay. The expression of Bcl-2 protein in ACHN tumor cells following antisense bcl-2 (AS2) ODN treatment was evaluated by Western blot analysis, and the extent of apoptosis in these cells was determined by fluorescence-activated cell sorter (FACS) analysis. The antitumor activity in ACHN xenografts in nu/nu mice was monitored by measuring differences in tumor weight in treated and control mice. RESULTS: Expression of bcl-2 mRNA was detected in all five RCC lines. Treatment with antisense bcl-2 ODNs inhibited the growth of all tested RCC cells and decreased Bcl-2 protein expression in ACHN cells. The AS2 antisense ODN complementary to the coding region of bcl-2 mRNA showed a superior antiproliferative effect compared with AS1 ODN complementary to the translation initiation region. Inhibition by antisense bcl-2 ODNs of ACHN cells was dose dependent. The FACS analysis revealed that growth inhibition was associated with the induction of programmed cell death. In vivo, AS2 ODN antitumor activity was noted in locally injected groups. CONCLUSIONS: Treatment of human RCC with antisense ODNs targeted to bcl-2 inhibits growth and is associated with the induction of programmed cell death. These results suggest therapeutic use of antisense bcl2 in the treatment of RCC.

Animals↗

PubMed2001

Halothane potentiates the effect of methamphetamine and nomifensine on extracellular dopamine levels in rat striatum: a microdialysis study.

Brain microdialysis was used to study the in vivo release and metabolism of dopamine (DA) in the rat striatum during halothane anaesthesia. Concentrations were measured in microdialysates collected every 20 min and applied directly to an on-line high-performance liquid chromatograph. Halothane was administered at concentrations of 0.5, 1.0, 1.5 and 2.0%. In another series of experiments, rats were treated intraperitoneally or locally with methamphetamine, a drug of abuse, or with nomifensine, a dopamine uptake blocker and antidepressant, in combination with 0.5 or 1.5% halothane. Halothane anaesthesia did not affect the dialysate (extracellular) concentration of DA at 2.0%. By contrast, the concentrations of DA metabolites [3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] increased during inhaled halothane anaesthesia in a dose-dependent manner and recovered after anaesthesia. Halothane potentiated the ability of methamphetamine to increase the extracellular concentration of DA when administered systemically, whereas only a small increase in DA accumulation was seen when methamphetamine was administered locally via the perfusate. Similarly, the increase in extracellular DA was accentuated by systemic nomifensine during halothane anaesthesia, but no obvious enhancement was observed when it was applied locally. It has been shown that the neurotoxic effect of methamphetamine is mediated by the suboxidation of DA released from the cytoplasm into the extracellular space and transformed into highly reactive free radicals. On the basis of our results, it is suggested that care should be exercised when halothane anaesthesia is used in patients abusing phenylethylamines (amphetamines) or being treated with DA uptake blockers (nomifensine).

Analysis of Variance↗

PubMed2001

Comprehensive gene expression profile of human activated T(h)1- and T(h)2-polarized cells.

In response to antigen stimulation, T(h) cells differentiate into two types of effector cells, T(h)1 and T(h)2. T(h)1 cells predominantly mediate cellular immunity, whereas T(h)2 cells induce humoral allergic responses. We have conducted here serial analysis of gene expression (SAGE) in human activated T(h)1- and T(h)2-polarized cells from cord blood. SAGE analysis of 64,510 tags (32,219 and 32,291 tags from T(h)1 and T(h)2 cells respectively) allowed identification of 22,096 different transcripts. In activated T(h)1 cells, many of the known genes (12 genes, P: < 0.01; 56 genes, P: < 0.05), including genes encoding IFN-gamma, lymphotactin, osteopontin, MIP-1alpha, MIP-1beta, perforin, beta-catenin and CD55, are highly expressed. On the other hand, in activated T(h)2 cells rather limited numbers of known genes (four genes, P: < 0.01; 10 genes; P: < 0.05), such as genes encoding FUS, ILF-2, IL-13 and E2-EPF, are found to be selectively expressed. The comprehensive identification of genes selectively expressed in human activated T(h)1 or T(h)2 cells should contribute to our understanding of the molecular basis of T(h)1/T(h)2-dominated human diseases and may provide genetic information to diagnose these diseases.

Cells, Cultured↗

PubMed2001

Characterization of cDNA of the liverwort phytochrome gene, and phytochrome involvement in the light-dependent and light-independent protochlorophyllide oxidoreductase gene expression in Marchantia paleacea var. diptera.

The cDNA of the phytochrome gene in the liverwort Marchantia paleacea var. diptera (MpdPHY1) was isolated. MpdPHY1 encoded a conventional phytochrome apoprotein. The MpdPHY1 transcript was accumulated in the dark and suppressed in the light. The degradation of the MpdPHY1 transcript by red light irradiation had red/far-red reversibility, suggesting that the liverwort phytochrome gene expression was regulated by a phytochrome. Northern blot analysis of the transcripts in cells irradiated by red/far-red light revealed that the liverwort phytochrome was involved in the expressions of chlB, chlL, chlN, or por, which encode subunits of light-independent and light-dependent protochlorophyllide oxidoreductase, respectively.

Amino Acid Sequence↗

PubMed2001

Mutational analysis of regulatory cis-acting elements for the transcriptional activation of the dmsCBA operon in Rhodobacter sphaeroides f. sp. denitrificans.

Four direct repeats of a 10-nt sequence, called dms boxes, are located upstream of the dmsCBA operon encoding dimethyl sulfoxide (DMSO) reductase in Rhodobacter sphaeroides f. sp. denitrificans IL106. Two dms boxes 1 and 2 have been shown to be binding sites of DmsR protein, a response regulator of a two-component system involved in the anaerobic induction by DMSO of DMSO reductase synthesis. In this study, functions of four dms boxes in the transcriptional regulation of the dmsCBA operon were investigated. The transcription start site of the dmsCBA genes was identified at the distance of 23 nt downstream of the closest dms box 4. Expression of the dmsC-lacZ gene fusion which included the dmsCBA promoter region containing the dms boxes was examined and its anaerobic induction by DMSO and DmsR-dependency were demonstrated in the phototroph. The examination with nucleotide substitutions in the four respective dms boxes showed that the set of four dms boxes is required for the dmsCBA operon activation. Moreover, the importance of the nucleotide sequence of TTCAC in dms box 4 and of A at the center in dms box 1 was significantly shown. These facts suggest that the pentad nucleotides TTCAC and TTAAC in the dms boxes serve as cis-acting elements in the transcriptional activation of the dmsCBA operon.

Anaerobiosis↗

PubMed2001

Profile soft-seal cuff, a new endotracheal tube, effectively inhibits an increase in the cuff pressure through high compliance rather than low diffusion of nitrous oxide.

We assessed the nitrous oxide (N(2)O) gas-barrier properties of a new endotracheal tube cuff, the Profile Soft-Seal Cuff (PSSC) (Sims Portex, Kent, UK). The tracheas of randomly selected patients were intubated with the Trachelon (Terumo, Tokyo, Japan), Profile Cuff (PC) (Sims Portex), or PSSC (n = 15 for each) endotracheal tube. Cuffs were inflated with air, and intracuff pressure was measured during anesthesia with 67% N(2)O. The concentration of N(2)O in cuffs was measured at the end of anesthesia. Postoperative sore throat was assessed. The volume-pressure relationship and thickness of the cuff were also measured. Cuff pressure, which increased gradually during anesthesia, was significantly less in the PSSC and PC groups than in the Trachelon group. The PSSC had smaller pressure than the PC 120 min after the start of anesthesia (P < 0.05). There were no significant differences in the N(2)O concentration in cuffs among the groups, although the PSSC had the thinnest cuff with the highest compliance. The incidence of postoperative sore throat in the Trachelon group was significantly higher than in the other two groups. In summary, the PSSC effectively inhibits an increase in cuff pressure during anesthesia with N(2)O. The underlying mechanism is probably the higher compliance of the thinner cuff, rather than a reduction in N(2)O diffusion into the cuff.

Adult↗

PubMed2001

Deflationary phenomenon of the nitrous oxide-filled endotracheal tube cuff after cessation of nitrous oxide administration.

UNLABELLED: After cessation of nitrous oxide (N(2)O) administration, intracuff pressure of the endotracheal tube may decrease through rediffusion of N(2)O. There may then be an increased risk for air leaks, aspiration of gastric contents, or both. In this study, the time required for intracuff pressure to decrease by 50% (T(1/2)) after substituting oxygen for N(2)O inspired was estimated with the least-squares method. Fifty patients were randomly assigned to five groups, and their tracheas were intubated with the Hi-Contour, Sheridan, Rush, Reinforce, or Profile Soft-Seal Cuff endotracheal tubes. Cuffs were inflated with 40% N(2)O, and cuff pressure was measured during anesthesia with 67% N(2)O. After 120 min, N(2)O inspired was replaced with 100% oxygen, and cuff pressure was measured until the cuff pressure decreased by about 30%. In the five groups, stable cuff pressures were achieved during 120 min of anesthesia with N(2)O. The cuff pressures at 120 min were not different among groups (P = 0.098). After cessation of N(2)O administration, the intracuff pressure decreased exponentially. T(1/2) in the Hi-Contour group was 27.8 +/- 8.5 min, which was significantly shorter than in the Profile Soft-Seal Cuff group (49.7 +/- 18.5 min; P < 0.01). Therefore, our results demonstrate that pressure of the N(2)O-filled cuff decreases quickly when N(2)O-inspired concentrations are reduced, and we suggest that intracuff pressure should be checked frequently to avoid air leaks or aspiration of gastric contents during delayed extubation or transportation of patients with tracheal intubations. IMPLICATIONS: A recently developed method for maintaining stable cuff pressure (N(2)O-filled cuffs) enables us to assess the decrease in cuff pressure after cessation of N(2)O administration. Our results confirm the limitations of N(2)O-filled cuffs when N(2)O-inspired concentrations are reduced.

Adult↗

PubMed2001

The effects of low-flow sevoflurane and isoflurane anesthesia on renal function in patients with stable moderate renal insufficiency.

UNLABELLED: Sevoflurane degrades to Compound A, which is nephrotoxic in rats. Therefore, the renal effects of Compound A is an area of intense debate. We investigated the effects of low-flow sevoflurane and isoflurane anesthesia on renal function in patients with stable renal insufficiency. Seventeen patients with a serum creatinine level of more than 1.5 mg/dL were anesthetized with sevoflurane or isoflurane at a total flow of 1 L/min. Serum creatinine and blood urea nitrogen were measured before anesthesia and again 1, 2, 3, 5, 7, and 14 days after anesthesia. The 24-h creatinine clearance was measured before anesthesia and 7 days after anesthesia. There were no significant differences in the blood urea nitrogen levels, serum creatinine concentrations, or creatinine clearance before and after anesthesia within each group. These results suggest that sevoflurane and isoflurane have similar effects on renal function in patients with moderately impaired renal function. Further study of the effects of low-flow sevoflurane anesthesia on impaired renal function with a larger sample size than ours is required to resolve the issue of sevoflurane safety in patients with renal insufficiency. IMPLICATIONS: The serum creatinine and blood urea nitrogen data indicate that, for exposures of <130 ppm/h in Compound A inspired area under the curve, renal effects of low-flow sevoflurane are similar to those of isoflurane in patients with stable renal insufficiency.

Aged↗

PubMed2001

The determinants of propofol induction of anesthesia dose.

UNLABELLED: Recently it was reported that the pharmacokinetics of propofol are modified by changes in cardiac output. The objective of this study was to evaluate the effects of cardiac output and other factors on the hypnotic dose of propofol. One-hundred surgical patients were administered indocyanine green immediately before the induction of anesthesia to measure their cardiac outputs and blood volumes. Propofol (250 microg. kg(-1). min(-1)) was infused IV for 8 min, and the hypnotic dose of propofol and the time to hypnosis were recorded. The plasma concentration of propofol immediately after 2 mg/kg infusion was measured. Multiple regression analysis showed that, in addition to age and weight, cardiac output was a small but significant factor for predicting the hypnotic dose of propofol (R(2) = 0.468, P < 0.001), the time to hypnosis (R(2) = 0.454, P < 0.001), and the plasma concentration of propofol (R(2) = 0.248, P < 0.01). Cardiac output, age, and weight showed similar partial coefficients for the hypnotic dose (0.128, 0.137, and 0.140, respectively). IMPLICATIONS: This study demonstrates a significant relationship between cardiac output and the hypnotic dose of propofol. We suggest that anesthesiologists should include cardiac output, as well as age and weight, in calculating the induction dose of propofol.

Adolescent↗

PubMed2001

The carbon dioxide absorption capacity of Amsorb is half that of soda lime.

UNLABELLED: A new CO(2) absorbent, Amsorb (A), which does not contain monovalent bases, is ideal because it does not degrade volatile anesthetics to either Compound A (from sevoflurane) or carbon monoxide (from desflurane, enflurane, or isoflurane). The CO(2) absorption capacity of A, however, has not been investigated under clinical conditions. In this study, we compared the longevity (time to exhaustion) and CO(2) absorption capacity (the volume of CO(2) absorbed before CO(2) rebreathing occurs) of A under low-flow anesthesia (1 L/min) with those of two soda lime absorbents-Medisorb (M) and Sodasorb (S)-by using a 750-mL ADU canister and a 1350-mL Aestiva 3000 canister. In the study with the ADU canister, the longevity of A was 213 +/- 71 min, significantly less than those of M (445 +/- 125; P < 0.01) and S (503 +/- 89; P < 0.001). The CO(2) absorption capacity (L/100 g absorbent) of A was 5.5 +/- 1.2, significantly less than those of M (10.7 +/- 1.7) and S (12.1 +/- 1.8; P < 0.001). In the study with the Aestiva 3000 canister, the longevity of A was 218 +/- 61 min, significantly less than those of M (538 +/- 136) and S (528 +/- 103; P < 0.001). The CO(2) absorption capacity (L/100 g absorbent) of A was 7.6 +/- 1.6, significantly less than those of M (14.4 +/- 1.8) and S (14.8 +/- 2.3; P < 0.001). These results indicate that the CO(2) absorption capacity of A is half that of M or S and that the difference in the CO(2) absorption capacity between A and M or S is almost constant, regardless of the canister design. IMPLICATIONS: The CO(2) absorption capacity of Amsorb is half that of Medisorb and Sodasorb under clinical low-flow (1 L/min) anesthesia with either a 750-mL Ohmeda ADU compact or a 1350-mL Ohmeda Aestiva 3000 canister.

Absorption↗

PubMed2001

Early pregnancy does not reduce the C(50) of propofol for loss of consciousness.

UNLABELLED: Requirements for inhaled anesthetics decrease during pregnancy. There are no published data, however, regarding propofol requirements in these patients. Because propofol is often used for induction of general anesthesia when surgery is necessary in early pregnancy, we investigated whether early pregnancy reduces the requirement of propofol for loss of consciousness using a computer-assisted target-controlled infusion (TCI). Propofol was administered using TCI to provide stable concentrations and to allow equilibration between blood and effect-site (central compartment) concentrations. Randomly selected target concentrations of propofol (1.5-4.5 microg/mL) were administered to both pregnant women (n = 36) who were scheduled for pregnancy termination and nonpregnant women (n = 36) who were scheduled for elective orthopedic or otorhinolaryngologic surgery. The median gestation of the pregnant women was 8 wk (range, 6-12 wk). Venous blood samples for analysis of the serum propofol concentration were taken at 3 min and 8 min after equilibration of the propofol concentration. After a 10-min equilibration period of the predetermined propofol blood concentration, a verbal command to open their eyes was given to the patients twice, accompanied by rubbing of their shoulders. Serum propofol concentrations at which 50% of the patients did not respond to verbal commands (C(50) for loss of consciousness) were determined by logistic regression. There was no significant difference in C(50) +/- SE of propofol for loss of consciousness between the Nonpregnant (2.1 +/- 0.2 microg/mL) and Pregnant (2.0 +/- 0.2 microg/mL) groups. These results indicate that early pregnancy does not decrease the concentration of propofol required for loss of consciousness. IMPLICATIONS: The C(50) of propofol for loss of consciousness in early pregnancy did not differ from that in nonpregnant women, indicating that there is no need to decrease the propofol concentration for loss of consciousness when inducing general anesthesia for termination of pregnancy.

Abortion, Induced↗

PubMed2001

Effects of probenecid on renal function in surgical patients anesthetized with low-flow sevoflurane.

BACKGROUND: Dehydrofluorination of sevoflurane by carbon dioxide absorbents in anesthesia machines produces compound A, which is nephrotoxic in rats. Several clinical studies indicate that prolonged low-flow sevoflurane anesthesia is associated with an increased urinary excretion of biochemical markers, such as protein. Probenecid, a competitive inhibitor of organic anion transport, diminishes compound A nephrotoxicity in rats. The purpose of the present study was to examine the effects of low- and high-flow sevoflurane anesthesia on urinary excretion of biochemical markers in humans and to examine the effects of probenecid on urinary excretion of these markers. METHODS: Elective surgical patients (n = 64) were assigned to four groups (n = 16 each): low-flow sevoflurane plus probenecid (LSP), low-flow sevoflurane (LS), high-flow sevoflurane plus probenecid (HSP), and high-flow sevoflurane (HS). Probenecid (2.0 g) was administered orally 2 h before the induction of anesthesia in both the LSP and HSP groups. Nothing was administered orally 2 h before the induction of anesthesia in either the LS or HS groups. All patients underwent prolonged low-flow (1 l/min) or high-flow (6 l/min) sevoflurane anesthesia. Urinary excretion of protein, albumin, beta(2)-microglobulin, glucose, and N-acetyl-beta-d-glucosaminidase was measured for up to 7 days postoperatively. RESULTS: Sevoflurane doses were similar in all four groups. There were no differences in blood urea nitrogen, creatinine, or creatinine clearance among the four groups after anesthesia. Average values for urinary excretion of protein, beta(2)-microglobulin, and N-acetyl-beta-d-glucosaminidase in the LS group were significantly higher than those in the other groups (LSP, HSP, HS; P < 0.05). There was no significant difference between the LS and LSP groups in average values for urinary excretion of albumin and glucose, although there were significant differences between the LS and both high-flow sevoflurane groups (HSP, HS). CONCLUSIONS: Low-flow sevoflurane, which produces a sevenfold higher compound A exposure than high-flow sevoflurane, resulted in significant increases of several biochemical markers in half of the patients. Probenecid appears to provide protection against these renal effects.

Adult↗

PubMed2001

Epidural anesthesia retards intestinal acidosis and reduces portal vein endotoxin concentrations during progressive hypoxia in rabbits.

BACKGROUND: Because it is postulated that gut is important via bacterial translocation in the development of the systemic inflammatory response and multiple organ dysfunction, the preservation of gut integrity is a therapeutic goal for physicians who care for critically ill patients. The aim of the current study was to evaluate whether epidural anesthesia prevented gut injury and subsequent translocation of endotoxin during acute progressive hypoxia in rabbits. METHODS: After the placement of an epidural catheter, 18 male rabbits, anesthetized with buprenorphine-midazolam, were allocated randomly to two groups: 0.5% lidocaine (group E) and saline (group C) groups. The solutions (0.4 ml/kg) were injected epidurally, followed by continuous infusion (0.1 ml x kg(-1) x h(-1)) during the study period. Portal blood flow, portal endotoxin concentrations, and intramucosal pH (pHi) of the ileum were measured at baseline and during two stages of progressive hypoxia (fraction of inspired oxygen [Fio2] = 0.15 and 0.10). RESULTS: In both study groups, the portal blood flow was preserved to a similar extent during acute hypoxia. However, pHi was reduced to a lesser extent in group E (7.33 +/- 0.12 versus 7.22 +/- 0.12 at an Fio2 of 0.15 and 7.13 +/- 0.15 versus 7.03 +/- 0.12 at an Fio2 of 0.10; mean +/- SD, P < 0.01), concurrently with lower portal endotoxin concentrations (P < 0.05) compared with group C. CONCLUSIONS: The current study showed that epidural anesthesia slowed the progression of intestinal ischemia during acute hypoxia, subsequently preventing translocation of endotoxin through the gut mucosa.

Acidosis↗

PubMed2001

Relation between exercise capacity and left ventricular systolic versus diastolic function during exercise in patients after myocardial infarction.

BACKGROUND: It is known that left ventricular systolic function at rest does not correlate well with exercise capacity of patients with heart failure. However, the contribution of left ventricular diastolic dysfunction, especially during exercise, to exercise capacity of cardiac patients remains to be determined. OBJECTIVE: To determine the impact of left ventricular systolic and diastolic function during exercise on exercise capacity of patients with left ventricular dysfunction after myocardial infarction. METHODS: A symptom-limited exercise test was performed with measurements for hemodynamics and uptake of oxygen (Vo2) of 26 men who had previously suffered myocardial infarction. These patients were divided into two groups according to their peak Vo2 (group 1 with peak Vo2 > or = 16 ml/kg per min, n= 13; and group 2 with peak Vo2 < 16 ml/kg per min, n= 13). Pulmonary arterial pressure, left ventricular and systemic arterial pressure, and cardiac output were measured at rest and during exercise. RESULTS: At rest, there was no difference between the two groups in terms of hemodynamic parameters except for minimal dP/dt, minimal left ventricular pressure (LVP) and time constant for decay of left ventricular pressure (tau). During peak exercise, cardiac output, left ventricular end-diastolic pressure (EDP), minimal dP/dt, minimal LVP, and tau for the two groups were significantly different. Furthermore, peak Vo2 was significantly correlated with T, minimal LVP, minimal dP/dt, EDP, and maximal dP/dt during peak exercise for the whole group of patients. CONCLUSION: Left ventricular diastolic function during exercise, i.e. diastolic reserve, may be an important determinant of exercise capacity of patients with left ventricular dysfunction after myocardial infarction.

Adult↗