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Biomedical subjects

X Zhou

Publications and source records attributed to X Zhou.

At least 505 records · Page 28Linked to original sources
PubMed1997

DNA strand exchange mediated by the Escherichia coli RecA protein initiates in the minor groove of double-stranded DNA.

The Escherichia coli RecA protein can recognize sequence homology between a single-stranded DNA (ssDNA) and homologous double-stranded DNA (dsDNA). One model for the homology recognition invokes a DNA triplex intermediate in which specific hydrogen bonds connect the ssDNA with groups in the major groove of dsDNA. Using photo-cross-linking methods, we have analyzed the arrangement of DNA strands after the local strand exchange. The results showed that the displaced strand sits in the major groove of the hybrid duplex product. This arrangement indicates that the ssDNA invades the minor groove of dsDNA and hence argues against the involvement of triplex intermediates. The results support an alternative model for the homology recognition that invokes melting of the dsDNA and annealing of the one strand to the invading ssDNA.

Base Sequence↗
PubMed1997

Suppression of natural killer cell activity in patients with fracture/soft tissue injury.

BACKGROUND: Natural killer cells (NKCs) participate in "innate" cell-mediated immunity. Fracture/soft tissue injuries are cytokine rich and may influence cell-mediated immunity. OBJECTIVE: To study the effects of fracture cytokines on NKC function. DESIGN: A case-control study. SETTING: A level I trauma center and laboratory in a university medical center. PARTICIPANTS: Patients requiring open fracture fixation and healthy volunteers. INTERVENTIONS: Fracture supernatants and peripheral plasma were collected during open fracture fixation. Volunteer mononuclear cells were used as effector (NKC) sources. Mononuclear cells were preincubated with fracture supernatants, paired peripheral plasma, or normal plasma under various conditions. MAIN OUTCOME MEASURES: Natural killer cell lysis of K562 target cells was assessed by chromium 51 release. RESULTS: Fracture supernatants suppressed NKC function more rapidly than peripheral plasma. Fracture supernatants from 1 to 4 days after injury were most suppressive. Inactivation of complement and reactive oxygen species failed to restore lysis. Neutralizing antibodies to interleukin 4 and interleukin 10 further suppressed lysis. Antibodies to transforming growth factor beta1 failed to restore lysis. The addition of interferon gamma did not restore lysis but the addition of interleukin 12 did. CONCLUSIONS: Fracture supernatants and peripheral plasma from patients with fractures suppress NKCs. The responsible mediators may be concentrated in fracture/soft tissue injuries. Responses to manipulation of the cytokine environment suggest that fracture cytokines may impair cooperation between NKCs and accessory cells.

Adult↗
PubMed1997

Tyrosine kinase inhibition decreases Muc-1 expression in mouse epithelial cells.

Mouse uterine epithelial cells (UEC) express high levels of both messenger RNA (mRNA) and protein encoding the polymorphic mucin glycoprotein, Muc-1, under most conditions in vivo and in vitro. Although steroid hormones modulate Muc-1 expression in vivo, it is not clear if these actions are mediated directly by steroid hormone receptors or indirectly by modulation of key intracellular signal transduction cascades. To address the latter issue, we examined the effects of a wide variety of modulators of signal transduction cascades on the expression of Muc-1 in primary cultures of polarized mouse UEC. Transient exposure of UEC to agents that inhibit tyrosine kinases by distinct mechanisms, i.e., tyrphostin, genistein, and staurosporine, consistently and significantly reduced Muc-1 expression. In contrast, a variety of agents that modulate protein kinase A- or C-dependent pathways had little or no effect on Muc-1. The effect of tyrphostin proved to be similar in magnitude at both the level of Muc-1 protein and mRNA expression. Transient transfection assays of mouse UEC and a murine mammary epithelial cell line, NMuMG, with mouse Muc-1 promoter-CAT reporter constructs demonstrated a similar (50-60%) degree of tyrphostin inhibition. These observations suggested an action at the level of Muc-1 gene expression. Levels of 100,000 g soluble tyrosine kinase activity in mouse UEC freshly isolated from estrous stage (high-level Muc-1 expression) and day 4 of pregnancy (low-level Muc-1 expression) correlated with Muc-1 expression. Furthermore, pretreatment of day 4 pregnant mice with the anti-progestin, RU486, an agent previously shown to restore or maintain high levels of Muc-1 expression, also restored soluble tyrosine kinase activity to levels similar to that observed in estrous stage mice. Collectively, these results indicate that tyrosine kinase activity is required to maintain high level Muc-1 expression in mice.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Synthesis and cytotoxic action of 3,5-isoxazolidinediones and 2-isoxazolin-5-ones in murine and human tumors.

The 3,5-isoxazolidinediones and 2-isoxazolin-5-ones demonstrated potent cytotoxicity against the growth of human Tmolt3 T cell leukemia, murine P388 and L1210 leukemias, as well as human HeLa-S3 uterine carcinoma and glioma tumor cell growth. The specificity of the 3,5-isoxazolidinedione and 2-isoxazoline-5-one derivatives as cytotoxic agents varied with the histological type of tumor cell. Selected compounds were active against solid HeLa uterine. KB nasopharynx, skin A431, SW-480 adenocarcinoma, osteosarcoma and glioma growth. Selected compounds demonstrated in vivo antineoplastic activity against Ehrlich ascites carcinoma growth. In L-1210 leukemia cells, the agents blocked DNA and protein synthesis at 25, 50 and 100 microM over 60 min. The agents were effective in reducing rate limiting enzymes in the de novo purine and pyrimidine pathways. In addition they suppressed dihydrofolate reductase and ribonucleoside reductase activities with moderate inhibition of DNA and RNA polymerase activities. DNA itself was not a target of the agents.

Animals↗
PubMed1997

Biomass yield and composition of sweetpotato grown in a nutrient film technique system.

Sweetpotato cultivar TU-82-155 grown in a nutrient film technique system and separated into foliage, tips, fibrous, string and storage roots at harvest had a total dry biomass of 89.9 g per plant with 38.4% inedible portion. Tips and storage roots, the traditional edible parts, were analyzed for dry matter, protein, fat, ash, minerals (Ca, Fe, K, Mg, Na, Zn), vitamins (carotene, ascorbic acid, thiamin), oxalic and tannic acids, and trypsin and chymotrypsin inhibitors to determine their nutritional quality. Water soluble matter, minerals (Ca, Fe, K, Mg, Na, Zn), cellulose, hemicellulose and lignin concentrations in the edible and inedible parts were obtained to provide information needed for the selection of appropriate bioconversion processes of plant wastes into food or forms suitable for crop production in a controlled biological life support system.

Biomass↗
PubMed1997

The weight gain and ultimate adiposity in cafeteria diet-induced obesity is unrelated to the central serotoninergic tonus.

Early detection of subjects with a propensity to obesity might be of great help for setting up preventive intervention studies. In this study we tested whether the development of obesity in Wistar rats, given ad libitum cafeteria foods, could be predicted by a low prolactin (PRL) response to 5-hydroxytryptophan (5HTP), as an index of low hypothalamic serotoninergic tonus. Basal and 5HTP-stimulated (50 mg/kg body weight i.p.) PRL were measured by RIA in 15 young male Wistar rats, whose pelleted diet was afterwards supplemented with cafeteria foods. In the tested animals an increase of PRL between 4 and 56 times the basal value was observed 60 min after the 5HTP injection. After 2 months of feeding, marked inter-individual differences in weight gain between the cafeteria fed animals were observed. After 10 months of feeding, median body fat percentage, assessed by dual X-ray absorptiometry, of the overfed rats was significantly higher than that of control animals: median (range): 41.2% (28.9 - 51.5%) vs 25.1 (18.0 - 32.2%) (p < 0.0001). The PRL response at the start of the experiment was neither correlated with the monthly weight increases, nor with the fat mass percentage at the end of the experiment, suggesting that a pre-existing low hypothalamic serotoninergic tonus is probably not involved in the overeating and ultimate overweight of cafeteria diet fed animals.

Adipose Tissue↗
PubMed1997

Cafeteria diet-induced obese rats have an increased somatostatin protein content and gene expression in the periventricular nucleus.

In human obesity, spontaneous and GRF stimulated growth hormone secretion have been shown to be blunted. We used cafeteria diet fed obese rats as a model to study the central mechanisms involved in growth hormone secretion changes which are observed in obesity. We analysed somatostatin messenger RNA and protein levels in the hypothalamic periventricular nucleus of the rats by non radioactive in situ hybridization and immunocytochemistry respectively. The optical density of somatostatin mRNA, measured by a computerized image system, was significantly higher in cafeteria diet fed rats (1014 +/- 87 vs 444 +/- 45; p < 0.05). The integrated optical density of somatostatin protein was also significantly higher in cafeteria rats compared to the control rats (222 +/- 36 vs 114 +/- 24; p < 0.05). In conclusion, cafeteria diet induced obese rats have a higher somatostatin biosynthesis in the periventricular nucleus. Further studies are needed to establish the possible link of this increased somatostatin gene expression with the decreased GH production.

Animals↗
PubMed1997

Identification and characterization of the Cecropin antibacterial protein gene locus in Drosophila virilis.

Cecropin is a type of antibacterial peptide that is synthesized in response to infection and has been characterized in many insect species and one mammal. The Cecropin locus of Drosophila melanogaster also contains the gene Andropin, which has been identified only in this species and encodes a male-specific antibacterial peptide. As a first step in studying the molecular evolution of the cecropin and andropin genes among Drosophila species, we have isolated genomic clones that cover the Cecropin locus in Drosophila virilis. The cloned region totals approximately 25 kb, within which a 9-kb fragment contains four cecropin genes and one pseudogene. All four genes have a high level of sequence homology to D. melanogaster Cecropin, about 80% identity in the coding regions, and the intron positions are conserved. As in D. melanogaster and other insects, kappa B-related cis-regulatory elements are found upstream of these cecropin genes. An Andropin-related sequence was not identified in D. virilis; however, genome Southern hybridizations suggest that Andropin-related sequences are present in at least the melanogaster species subgroup. Analysis of 19 insect cecropin genes identifies a common ancestral Cecropin before the divergence of Diptera and Lepidoptera. In addition, D. melanogaster and D. virilis can be identified by monophyletic clades for Cecropin. In contrast, the Lepidopteran species show polyphyletic relationships for duplicated cecropin genes.

Amino Acid Sequence↗
PubMed1997

Intravascular ultrasound assessment of regional aortic wall stiffness, distensibility, and compliance in patients with coarctation of the aorta.

BACKGROUND: Impaired aortic pulsatility has been demonstrated by angiography in children and in studies of experimental animals with coarctation of the aorta. OBJECTIVES: The purpose of this study was to assess regional aortic stiffness, distensibility, and compliance before and after balloon dilation in patients with coarctation of the aorta. METHODS AND RESULTS: Intravascular ultrasound examination was performed in 13 pediatric patients with the diagnosis of coarctation of the aorta to yield aortic diameter. Area transverse sections at both systolic and diastolic period were measured at three aortic levels: the proximal, distal, and coarctation segments. Balloon dilation was also performed in eight of 13 patients. By using pressures measured in the same areas, an aortic stiffness index (beta) was calculated as In(Ps/Pd)/(Ds-Dd), where In is natural logarithm, Ps is systolic pressure, Pd is diastolic pressure, Ds is systolic diameter, and Dd is diastolic diameter. Aortic distensibility and an estimation of aortic compliance were also calculated. The beta stiffness index of the coarctation and the proximal segments of the aorta were significantly greater than that of the distal segment of the aorta (p < 0.01). The aortic wall stiffness beta index did not acutely change after successful balloon dilation, but the distensibility and compliance of distal aorta were nonetheless significantly decreased after balloon dilation (p < 0.01, p < 0.05) as a function of changes of pulsatility of flow. CONCLUSIONS: Abnormal proximal aortic stiffness may be a strong contributing factor that promotes the genesis of hypertension in patients with coarctation even after successful repair or balloon angioplasty.

Adolescent↗
PubMed1997

A transforming growth factor beta 1 receptor type II mutation in ulcerative colitis-associated neoplasms.

BACKGROUND & AIMS: Numerous gastrointestinal tumors, notably sporadic and ulcerative colitis (UC)-associated colorectal carcinomas and dysplasias, gastric cancers, and esophageal carcinomas, manifest microsatellite instability. Recently, a transforming growth factor beta 1 type II receptor (TGF-beta 1RII) mutation in a coding microsatellite was described in colorectal carcinomas showing instability. One hundred thirty-eight human neoplasms (61 UC-associated, 35 gastric, 26 esophageal, and 16 sporadic colorectal) were evaluated for this TGF-beta 1RII mutation. METHODS: Whether instability was present at other chromosomal loci in these lesions was determined. In lesions manifesting or lacking instability, the TGF-beta 1RII coding region polydeoxyadenine (poly A) microsatellite tract was polymerase chain reaction amplified with 32P-labeled deoxycytidine triphosphate. Polymerase chain reaction products were electrophoresed on denaturing gels and exposed to radiographic film. RESULTS: Three of 18 UC specimens with instability at other chromosomal loci (17%) showed TGF-beta 1RII poly A tract mutation, including 2 cancers and 1 dysplasia; moreover, 2% of UC specimens without instability (1 of 43) (1 cancer), 81% of unstable sporadic colorectal cancers (13 of 16), and none of the 61 stable or unstable gastric or esophageal cancers contained TGF-beta 1RII mutations. CONCLUSIONS: Mutational inactivation of the poly A microsatellite tract within TGF-beta 1RII occurs early and in a subset of unstable UC neoplasms and commonly in sporadic colorectal cancers but may be rare in unstable gastric and esophageal tumors.

Activin Receptors, Type I↗
PubMed1997

Efficacy and safety of one year of growth hormone therapy in steroid-dependent nephrotic syndrome.

OBJECTIVES: To study the efficacy and safety of 1 year of growth hormone (GH) therapy in children with steroid-dependent nephrotic syndrome. STUDY DESIGN: A prospective pilot, open study in which GH (mean dose 0.32 mg/kg per week) was administered for 1 year to 8 children with steroid-dependent nephrotic syndrome requiring prednisolone (mean dose 0.46 mg/kg per day) to maintain remission. Steroid dependence was defined as recurrence of proteinuria within 2 weeks of discontinuation of prednisolone, or when the dose was lowered below a critical level. At entry, all patients had been steroid dependent for at least 1 year. Anthropometric and bone mineral density measurements after treatment were compared with 1-year pretreatment data. RESULTS: Pretreatment mean (+/-SD) chronologic age was 12.6 (+/-3.1) years, with a mean bone age of 9.1 (+/-2.0) years, with delayed puberty in five patients. The mean height velocity increased from 3.7 (+/-1.4) to 9.4 (+/-2.1) cm/yr after 1 year of treatment (p < 0.05). The mean height standard deviation score increased from -1.4 (+/-1.6) to -0.3 (+/-1.1), (p < 0.05). In the spine, the mean bone mineral density increased from 0.50 to 0.64 gm/cm2 (p < 0.05), and in the femoral neck, from 0.55 to 0.64 gm/cm2 (p < 0.05) after 1 year of treatment. Mean lean body mass increased from 58.1% to 62.6% (p < 0.01). There were no significant changes in creatinine clearance, fasting glucose, fasting insulin, or glycosylated hemoglobin levels. The mean bone age increased to 11.4 (+/-2.4) years, and pubertal stage advanced in 2 patients. CONCLUSIONS: One year of GH therapy is effective in improving the height standard deviation score, height velocity, bone mineral density, and lean body mass of children with steroid-dependent nephrotic syndrome. There were no significant adverse effects. However, the bone age accelerated at a greater pace than the height age, and further studies are required to define the role of GH therapy in steroid-dependent nephrotic syndrome.

Adolescent↗
PubMed1997

Mesangial cell actin disassembly in high glucose mediated by protein kinase C and the polyol pathway.

High glucose alters mesangial cell cytoskeletal structure and function. We postulated that high glucose causes mesangial cell filamentous (F) actin disassembly through a protein kinase C (PKC) mechanism involving the polyol pathway. Rat mesangial cells (passage < 10, N = 60/group) were growth-arrested and then cultured in glucose 5.6 mM (NG), 15 mM (MG) or 30 mM (HG) for 48 hours, with or without the aldose reductase inhibitor Tolrestat 0.3 mM. F and globular (G) actin were labeled with rhodamine-phalloidin and FTTC-DNase-1, respectively. Both fluorescence probes were imaged simultaneously in each cell using dual-channel confocal laser microscopy. In HG, F-actin disassembly was observed and measured by a 40% decrease in F-/G-actin fluorescence intensity ratio (no change in NG + mannitol 24.4 mM). In separate experiments, cells were labeled with BODIPY FL-bisindolylmaleimide, specific for most PKC isoforms, and fluorescence intensity/cell was measured. In NG, exposure to phorbol 12-myristate 13-acetate (PMA) 0.1 microM for 15 minutes caused perinuclear and nuclear translocation of PKC, and F-actin disassembly identical to observations in HG alone. In HG, total PKC fluorescence increased by 50% and PMA exposure for 24 hours normalized both the total PKC and F-/G-actin fluorescence ratio. In NG and HG, exposure (15 min) to PMA 0.1 microM increased PKC activity three to four times, measured by in situ 32P-phosphorylation of EGF-receptor substrate. By immunofluorescence and confocal imaging, diacylglycerol-sensitive PKC-delta was localized to the cytosol in NG, and after 15 minutes exposure to PMA, translocated to the perinuclear region and plasma membrane. In HG. PKC-delta immunofluorescence was significantly increased/cell, distributed in a cytoskeletal pattern and the intensity was glucose-concentration dependent (30 > 15 > 5.6 mM). In HG, exposure to PMA for 24 hours returned the PKC-delta fluorescence to the intensity and cytosolic pattern observed in NG, and simultaneously prevented F-actin disassembly. Tolrestat significantly reduced the total PKC and PKC-delta fluorescence intensity and F-actin disassembly observed in HG. Immunoblot confirmed increased PKC-delta in HG, which was normalized by Tolrestat. The immunofluorescence pattern of diacylglycerol-insensitive PKC-delta was unchanged in HG, with PMA or Tolrestat. We conclude that mesangial cell F-actin disassembly in high glucose is likely mediated through diacylglycerol-sensitive PKC isoforms, including PKC-delta and involves the polyol pathway.

Actins↗
PubMed1997

MHC class I presentation of live and heat-inactivated Sendai virus antigen in T2Kb cells depends on an intracellular compartment with endosomal characteristics.

T2Kb cells, which do not express TAP1/2 peptide transporters or the low molecular weight protein 2/7 (LMP2/7) proteasomal subunits, can still process and present both live and heat-inactivated Sendai virus (SV). As this operation may also reflect the existence of an alternative processing pathway in normal antigen-presenting cells (APC), the authors have characterized it using intracellular inhibitors and anti-Kb monoclonal antibodies (MoAbs). From the results with lipophilic amines (ammonium chloride, methylamine and chloroquine), cytoskeletal inhibitors (cytochalasin B and vinblastine), and an endoprotease inhibitor (phenylmethylsulfonyl fluoride, PMSF), the authors conclude that the processing of SV antigen in T2Kb cells has endosomal characteristics depending on cellular activities such as uptake, vesicular transport and intracellular-vesicular proteolysis. In addition, internalized 'empty' Kb molecules derived from the T2Kb cell surface appeared to be involved in the presentation of SV antigen, as demonstrated by a protocol using a combination of the Golgi inhibitor brefeldin A(BFA) and anti-Kb antibodies. The results thus indicate that T2Kb cells process SV antigen in an endosomal-like compartment which contain recycling 'empty' Kb molecules.

Amines↗
PubMed1997

Changes in rat corneal matrix metalloproteinases and serine proteinases under vitamin A deficiency.

PURPOSE: Vitamin A deficiency alters the transparency of the cornea due to epithelial cell keratinization and increases the susceptibility of the cornea to ulceration. The purpose of this study was to determine the effect of vitamin A deficiency on rat corneal matrix metalloproteinases and serine proteinases. METHODS: Four dietary groups of male WAG/RijMCW rats were prepared: (1) Vitamin A deficient rats were raised on a casein-based retinoid deficient diet; (2) Retinol repleted rats were raised on the retinoid deficient diet. On the eighty-sixth day on this diet, the rats were fed retinyl palmitate and then given free access to the retinyl palmitate-supplemented control diet; (3) The weight-matched, pair-fed rats were restricted in their intake of the retinyl palmitate-supplemented diet so that their weight gain matched that of the A-rats; (4) The non-restricted rats were given free access to the retinyl palmitate-supplemented diet. The animals were killed at the late plateau stage for weight of the deficiency (102-106 days). Zymography was used to study proteinases in the corneal extracts. RESULTS: Vitamin A deficient and control rat corneas contain multiple matrix metalloproteinases and serine proteinases. The matrix metalloproteinases at 90/92 kDa (gelatinase B) and 66/63/57 kDa (gelatinase A) were significantly decreased in the corneas of the vitamin A deficient rats relative to the control corneas. Corneas from the four groups of rats contained 76, 45, 38, 28 and 22 kDa proteinases that cleaved casein. Only the vitamin A deficient corneas contained a 50 kDa casein cleaving enzyme. The 76, 45, 38 and 28 kDa serine proteinases were significantly lower in the vitamin A deficient corneas. The major 22 kDa enzyme was not altered by the deficiency. All casein cleaving proteinases were inhibited by phenylmethylsulfonyl fluoride and chymostatin except for a minor 76 kDa band. The activity of this band was not altered by inhibitors for the other classes of proteinases, ethylenediaminetetraacetic acid, E-64 or pepstatin. The concentrations of the 61, 52 and 40 kDa plasminogen activators were not altered by the deficiency. CONCLUSIONS: Alterations in corneal proteinases under vitamin A deficiency conditions may be involved in the characteristic changes observed in the cornea under vitamin A deficiency conditions: decreased exfoliation of epithelial cells, increased levels of keratofibrils in the corneal keratocytes, increased stromal keratocyte degradation and increased susceptibility towards ulceration.

Animals↗
PubMed1997

First trial of home ECG and blood pressure telemonitoring system in Macau.

OBJECTIVE: To determine the feasibility of home monitoring of patients with cardiac disease or hypertension. METHODS: An improved home electrocardiographic and blood pressure telemonitoring system linked to a central workstation was tested in 10 patients in Macau for 3 months. RESULTS: The total number of connections was 1377. Of the automatic alarm connections, 32.5% were false positive, with the percentage of false positives ranging from 7.6 to 54.6 for different patients. Both patients and physicians found the system easy to use. CONCLUSIONS: Further investigation is required to match the number of patients with the system capacity. A more robust dysrhythmia detection algorithm is needed to reduce the number of false alarms. Nevertheless, the results were sufficiently good that the trial is being expanded.

Blood Pressure Determination↗
PubMed1997

Soluble amylose cornstarch is more digestible than soluble amylopectin potato starch in rats.

In liquid enteral formulations, high molecular weight soluble starches may be able to replace glucose and low molecular weight glucose polymers that have high glycemic indices. Male rats were fed either commercial cornstarch, dextrose, modified soluble potato (70-75% amylopectin) starch, or modified soluble amylomaize-7 (70% amylose) starch for 4 wk. Body weights did not differ among the groups. Food consumption was significantly higher in the two modified starch-fed groups than in the two control groups. Commercial cornstarch, dextrose, modified potato starch and modified amylomaize-7 starch were 100 +/- 0, 100 +/- 0, 69.0 +/- 1.0 and 91.5 +/- 0.8% digestible, respectively (n = 9, mean +/- SEM). The modified potato starch-fed group deposited the least fat, protein and energy. In both modified starch-fed groups, liver weights were significantly greater than in the two control groups. In food-deprived rats, serum free fatty acid concentrations in the modified potato starch-fed group were significantly higher than in the two control groups, and serum glucose concentrations were significantly higher in the two modified starch-fed groups than in the controls. The insulin to glucagon ratios were significantly lower in the modified potato starch-fed and amylomaize-7 starch-fed groups than in the dextrose-fed control group. Serum protein concentrations, measured after food deprivation, were significantly lower in the modified potato starch-fed group than in the other three groups. Gluconeogenesis from fermentation products might account for the high serum glucose concentrations in the two experimental groups. These data indicate that only the modified amylomaize-7 starch may be useful in the development of food products for liquid nutritional supplements because of the high digestibility and the low resultant insulin levels.

Adipose Tissue↗
PubMed1997

Role of adenosine triphosphate-sensitive potassium channels in coronary vasodilation by halothane, isoflurane, and enflurane.

BACKGROUND: Halothane, isoflurane, and enflurane cause coronary vasodilation and cardiac depression. This study was performed to assess the role of adenosine triphosphate (ATP)-sensitive potassium channels (KATP channels) in these effects. METHODS: Twenty-five thoracotomized dogs were anesthetized with fentanyl and midazolam. The left anterior descending coronary artery was perfused via either of two pressurized (80 mmHg) reservoirs. One reservoir was supplied with arterial blood free of a volatile anesthetic, and the second reservoir was supplied with arterial blood equilibrated in an oxygenator with a 1 minimum alveolar concentration of either halothane (0.9%, n = 10), isoflurane (1.4%, n = 8), or enflurane (2.2%, n = 7). Coronary blood flow (CBF) was measured using a Doppler flow transducer, and segmental shortening (SS) was measured with ultrasonic crystals. Responses to the volatile anesthetics were assessed under control conditions, during intracoronary infusion of the KATP channel inhibitor glibenclamide (100 micrograms/min), and after cessation of glibenclamide (recovery). The effectiveness of glibenclamide was verified from inhibition of coronary vasodilator responses to the KATP channel opener cromakalim without effect on those to the KATP channel-independent vasodilators, sodium nitroprusside and acetylcholine. RESULTS: Under control conditions, the volatile anesthetics caused pronounced increases in CBF (isoflurane > halothane = enflurane), and decreases in SS (enflurane > halothane = isoflurane). Glibenclamide blunted significantly (and reversibly) the increases in CBF, but it had no effect on the decreases in SS. CONCLUSIONS: The KATP channels play an important role in coronary vasodilation but apparently are not involved in cardiac depression caused by halothane, isoflurane, and enflurane in canine hearts in situ.

Adenosine Triphosphate↗