Biomedical subjects

C Bauer

Publications and source records attributed to C Bauer.

At least 91 records · Page 5Linked to original sources

PubMed1998

[Remifentanil in gynecologic laparoscopy. A comparison of consciousness and circulatory effects of a combination with desflurane and propofol].

OBJECTIVES: Rapid post-anaesthetic awakening and low hypnotic potency are two characteristic properties of the new opioid remifentanil. For clinical use remifentanil must be combined with another anaesthetic agent. Propofol is well-established for ambulatory anaesthesia, however, the properties of desflurane (low blood-gas solubility, rapid elimination) suggest this volatile anaesthetic to be a comparable alternative, particularly if rapid awakening is desired. The present study was designed to compare emergence times and haemodynamics for a combination of remifentanil wich hypnotic concentrations of either propofol or desflurane. METHODS: Gynaecological patients, scheduled for elective laparoscopy, were studied at random. After oral premedication with diazepam 0.08-0.12 mg/kg, anaesthesia was induced identically in both groups: remifentanil bolus (1 microgram/kg), start of remifentanil infusion (0.5 microgram/kg/min), followed by propofol (approx. 2 mg/kg) and cisatracurium (0.1 mg/kg). For maintenance of anaesthesia remifentanil (0.25 microgram/kg/min) was combined with either desflurane (0.5 MAC = 3.0 vol%) or propofol (6 mg/kg/h). With termination of surgery anaesthetic delivery was discontinued simultaneously and recovery times were recorded. Heart rate and non-invasive blood pressure were recorded at defined points of interest. RESULTS: In total, 40 patients (desflurane n = 20, propofol n = 20) were studied in comparable groups. For both regimens, emergence after remifentanil-based anaesthesia was remarkably rapid between unconsciousness and complete recovery: In mean only 60 s elapsed from the onset of spontaneous breathing to the moment when patients could clearly state their name. In comparison, recovery times were significantly shorter after remifentanil-desflurane than after remifentanil-propofol: time to spontaneous ventilation 6.4 +/- 2.8 vs. 9.6 +/- 3.9 min (mean +/- SD, p = 0.01); extubation 6.7 +/- 2.8 vs. 9.8 +/- 4.0 min (p = 0.02) and arrival at PACU 11.1 +/- 3.4 vs. 14.7 +/- 4.2 min (p = 0.005). The courses of heart rate (HR) and mean arterial pressure (MAP) were mostly similar in both groups with only minimal or moderate cardiocirculatory reactions during intubation or start of surgery. CONCLUSIONS: Remifentanil in combination with either desflurane or propofol, used for general anaesthesia during gynaecological laparoscopy, will facilitate a smooth haemodynamic course as well as a rapid emergence thereafter. Recovery times after remifentanil-based anaesthesia are significantly shorter with 3.0 vol% of desflurane than with 6 mg/kg/h propofol. Thus, desflurane appears to be a well-suited adjunct to remifentanil and an ideal alternative to propofol, if rapid recovery is required. Differences are best explained by the pharmacological properties of both coanaesthetics and their applied dosages.

Adult↗

PubMed1998

Optimized evaluation of a pulsed 2.09 microns holmium:YAG laser impact on the rat brain and 3 D-histomorphometry of the collateral damage.

Since more than 20 years CO2 and Nd:YAG lasers are established in the microsurgery of the nervous system. CO2 lasers can be used handheld, but may be focused on the target area by mirror optics and sideports of the operating microscope's micromanipulator. Nd:YAG lasers have the disadvantage of deep penetration into the brain and provocation of a large collateral damage. The need is for a fibre conducted solid system for surgery in delicate areas as for brain stem surgery. Fibre conduction of near infrared lasers allows better exposure of the target area compared to hollow wave guides or mirror equipment. Fibres can be tapered and modified according to the purpose. The holmium:YAG (Ho:YAG) laser has acquired interest by introducing the system into microsurgery of parenchymal tissue. They have not been proven yet sufficiently for neurosurgical tasks. The effort to minimalize the collateral tissue damage has to be maximalized in the surgery of nervous tissue and functional low redundant brain stem or spinal cord tissue. Volumetric data may be more precise in comparison to depth and width data of the laser lesion even when the different levels of the tissue interaction have to be analyzed for estimation of the real side effects in nervous tissue. We have used 50-800 ml delivered Ho:YAG single pulses in cortical areas of Sprague-Dawley rats and investigated the different lesion zones by volumetric data. The functional lesion zone was detected and measured by immunohistological staining of the heat shock protein HSP 72. For further reduction of the focus area, we have used tapered 400 to 200 microns fibres.

Animals↗

PubMed1998

Apoptosis in kidneys of endothelin-1 transgenic mice.

Endothelin-1 (ET-1) transgenic mice are characterized by age-dependent development of renal cysts and renal fibrosis (interstitial fibrosis and glomerulosclerosis), leading to a progressive decrease in glomerular filtration rate. The mechanism causing the loss of functionally and morphologically normal renal tissue is unknown. An imbalance between cell proliferation and apoptosis in the kidneys of ET-1 transgenic mice might contribute to this process. We identified apoptotic cells in kidney sections by in situ end-labeling and by the typical nuclear chromatin morphology after propidium iodide (PI) staining. Cell proliferation was measured by estimating the proliferating cell nuclear antigen (PCNA)-positive cells. The numbers of apoptotic cells were significantly increased (p < 0.001) in the kidneys of 14-month-old ET-1 transgenic mice, whereas cell proliferation was not enhanced. Apoptotic cells were detected in the glomeruli, tubular cells, and renal interstitial cells in ET-1 transgenic mice. In conclusion, apoptotic loss of functional renal tissue appears to be associated with the progression of cyst formation and renal fibrosis. Therefore, an imbalance between cell proliferation and apoptosis could be an important cellular mechanism in ET-1 transgenic mice leading to end-stage kidney disease.

Animals↗

PubMed1998

High-resolution emboli detection and differentiation by characteristic postembolic spectral patterns.

BACKGROUND AND PURPOSE: High-intensity transient signals (HITS) detected by transcranial Doppler ultrasonography correspond to microemboli in intracranial arteries. The purpose of this study was to develop new diagnostic criteria for the differentiation of these microembolic signals from artifact, based on a high-resolution analysis of Doppler power spectra in an in vitro model. METHODS: Two hundred seventy-six formed emboli, consisting of different biological and nonbiological materials and as air bubbles, were injected into a flow phantom with artificial blood vessels and perfused in a steady or a pulsatile way. Embolic passage was assessed with a modified 2.5-MHz pulsed Duplex machine and a commercial 2-MHz Doppler system. Embolic HITS were analyzed using internationally accepted criteria for the audiovisual characteristics of HITS. Doppler spectra changes associated with HITS were evaluated by means of a specially developed high-resolution analysis of Doppler raw data. RESULTS: Seventy-seven percent of all embolic events could be identified using conventional audiovisual criteria for embolic HITS. Analysis of Doppler spectra showed that all injected emboli generated high-amplitude signals with a minimum of at least 3 dB above background level. In addition, using high-resolution processing, specific changes in Doppler spectral patterns could be identified after all embolic HITS caused by solid particles. These postembolic spectral patterns were always characterized by a Doppler frequency shift decreasing in time and resembling the letter lambda (lambda). Duration and appearance of the postembolic spectral patterns were mainly influenced by the size and velocity of the embolus. Similar phenomena could not be found in case of embolism by either small air bubbles or in case of provoked artifact registration. Using a commercial Doppler system specific, we documented postembolic spectral patterns in 47% of injected emboli. CONCLUSIONS: In this study, highly specific changes in Doppler spectral patterns associated with microembolic HITS could be characterized, resulting in further criteria for the differentiation between microembolic signals and artifact in Doppler emboli detection. The sensitivity of the detection of these signals can be increased by high-resolution analysis of raw Doppler data.

Animals↗

PubMed1998

Renal endothelin system in polycystic kidney disease.

Polycystic kidney disease (PKD) is characterized by interstitial fibrosis and formation of renal cysts. Interestingly, interstitial fibrosis and renal cyst formation were also seen in human endothelin-1 (ET-1) transgenic mice. This study, therefore, analyzes the tissue distribution of ET-1, the tissue concentrations of ET-1, as well as the expression of ET receptor subtypes in the kidneys of a rat model of PKD: Han:SPRD rats. Six-week-old heterozygous (cy/+) and homozygous (cy/cy), as well as 6-mo-old heterozygous (cy/+) Han:SPRD rats and the corresponding age-matched Sprague Dawley littermates (SD) (+/+) were analyzed. Furthermore, the acute effects of the mixed (A/B) endothelin receptor antagonist bosentan on hemodynamic and renal function were investigated in 6-mo-old, conscious, chronically instrumented (cy/+) rats. The kidneys of affected rats showed significantly elevated tissue levels of ET-1 compared with age-matched controls (3.5 +/- 0.3-fold in young cy/cy rats, P < 0.01; 1.4 +/- 0.2-fold in young cy/+ rats, P < 0.01; 6.2 +/- 0.4-fold in old cy/+ rats, P < 0.001) due to a highly increased ET-1 synthesis within the epithelial cells of the cysts. Analyzing tissue sections from patients with typical autosomal dominant PKD demonstrated a high ET-1 expression within the epithelial cells of the cysts as well. Scatchard analysis revealed a markedly decreased ETA and ETB receptor density in all groups of affected rats. The acute blockade of both endothelin receptor subtypes using bosentan in 6-mo-old heterozygous PKD rats led to a significant decrease in mean arterial BP (MAP) (-19.7 +/- 2.1 mmHg, P < 0.05) and GFR (-41 +/- 5%, P < 0.005). Renal blood flow (RBF) was significantly increased (+2.1 +/- 0.5 ml/min, P < 0.05) after bosentan, whereas bosentan had no effect on MAP, GFR, and RBF in age-matched controls. These data show that the paracrine renal endothelin system is activated in PKD and participates in the regulation of MAP, GFR, RBF, and possibly contributes to renal cyst formation and fibrosis.

Analysis of Variance↗

PubMed1998

Optimal erythropoietin expression in human hepatoma cell lines requires activation of multiple signalling pathways.

Hypoxia is thought to be a common precursor of coronary artery disease and malignant tumors, both diseases representing the leading causes of death in industrial nations. So far, investigations of oxygen-regulated erythropoietin (EPO) gene expression in the human hepatoma cell lines Hep3B and HepG2 allowed many important insights into the mechanisms of oxygen-sensing, signalling and regulation of an increasing number of oxygen-responsive genes. To differentiate the various signalling pathways involved in EPO production by these two cell lines, we examined several factors that positively influenced EPO expression. The results demonstrate a keen differential effect of cell density and oxygen concentration on EPO induction in Hep3B compared to HepG2 cells. Using optimized cell culture conditions, EPO production rates as high as 1 U EPO per 10(6) Hep3B cells in 24 h could be achieved. We also found a moderate but reproducible positive effect of CoCl2 on hypoxia-induced EPO expression in Hep3B but a negative CoCl2 effect on hypoxic induction in HepG2 cells. CoCl2 inhibited cell growth in a concentration-dependent manner. Interleukin-6 was synergistic with hypoxia on EPO induction in Hep3B as well as HepG2 cells, and dexamethasone enhanced this effect in Hep3B but not in HepG2 cells. The moderate CoCl2-dependent increase of EPO production observed in hypoxic Hep3B cells might indicate that CoCl2 and hypoxia do not necessarily act via, identical signalling pathways.

Carcinoma, Hepatocellular↗

PubMed1998

[Transgenic mice in basic research].

What are transgenic mice and what do we learn from them? In this review, we focus on the generation of "classical" transgenic and "knock-out" mice. The establishment of transgenic and gene-targeted mice provides an unique tool to study the function(s) of a given gene in the context of a whole organism. Based on selected examples, we demonstrate the potential of this transgenic technology to understand the interactions between cells, organs and organ systems in genetically engineered mice.

Alzheimer Disease↗

PubMed1998

[Halicephalobus (Syn. Micronema) deletrix as a cause of granulomatous gingivitis and osteomyelitis in a horse].

Therapy resistant swellings of the maxillary region and unilateral nasal discharge in older horses are mainly thought to be consequences of neoplasias of the oral cavity, especially of the gingiva and the teeth, or to develop from tumours of the nasal cavity. We report an unilateral swelling of the left nasal and buccal region in a 13-year-old gelding, which was accompanied by an aggressive destruction of involved osseous tissue due to a severe proliferative granulomatous inflammation. The granuloma was caused by the nematode Halicephalobus (syn. Micronema) deletrix. This nematode infection is known for over 30 years, even though the here reported form is uncommon and rarely diagnosed. However, this report shows that even in cases of unilateral maxillary swellings in horses a granulomatous inflammation due to nematodiasis should be considered as an additional differential diagnosis.

Animals↗

PubMed1998

[Supraventricular arrhythmia after pneumonectomy. Apropos of 100 cases and review of the literature].

Supraventricular arrhythmias are frequently observed in pneumonectomy surgery. We retrospectively studied a series of 100 consecutive patients undergoing pneumonectomy for cancer between 1994 and 1996. We found 24% of significant supraventricular arrhythmias, corresponding to atrial fibrillation in 75% of cases, occurring in 80% of cases until the third postoperative day. The only risk factor significantly associated with these arrhythmias was the patient's age. These arrhythmias are easily reduced, spontaneously in 25% of cases, and usually by amiodarone, alone or associated with digitalis alkaloids. While the mortality of the overall group was 12%, 8% of patients with arrythmia died. These deaths concerned patients whose arrythmias occurred after the fourth postoperative day in a context of a pulmonary infection.

Aged↗

PubMed1998

Colocalization of single ribosomes with intermediate filaments in puromycin-treated and serum-starved mouse embryo fibroblasts.

Previous experiments have revealed a relatively weak electrostatic binding capacity of in vitro reconstituted intermediate filaments (IFs) as well as of natural IFs of whole cell mount preparations for purified ribosomal particles of mammalian origin. In order to demonstrate that such associations also occur in vivo, intact cells were subjected to double immunofluorescence microscopy using antibodies directed against vimentin and ribosomal protein S17. Since in proliferating cells the majority of the ribosomal particles are assembled into polyribosomes and these are to a great extent associated with microfilaments, in vitro cultured mouse embryo skin fibroblasts (MSF cells) were treated with puromycin to allow the formation of single ribosomes. Employing confocal laser scanning microscopy, the ribosomes were detected in colocalization with vimentin IFs. Disassembly of polyribosomes was also achieved by serum starvation of cultured cells. In this case, MSF cells of a low passage attained an extended and flattened appearance with the vimentin IFs being directly associated with the cell nuclei, radiating into the peripheral areas of the cells or showing a stress fiber-like distribution. In both cases, considerable quantities of ribosomal material were seen in close neighborhood to vimentin IFs. Frequently, these ribosome-IF associations were coaligned with microtubules and they also surrounded myosin I-decorated stress fibers. Double labeling with the vital, RNA-specific fluorochrome SYTO 14 produced a fluorescence pattern largely superimposable on that of ribosomal protein S17. Treatment of the starved cells with either demecolcine or cytochalasin D had an only moderately disturbing effect on vimentin IF distribution and the ribosomes stayed in contact with the vimentin IFs. On the basis of these results, it is conceivable that IFs play a role in the storage of ribonucleoprotein particles in general and non-translating ribosomes in particular in the cytoplasm of animal cells. In addition, the often seen coalignment of IFs with microtubules and microfilaments might serve facilitated and directional transport of ribonucleoprotein particles from the nucleus to peripheral areas of the cell.

Actin Cytoskeleton↗

PubMed1997

Bridged cobalt amine complexes induce DNA conformational changes effectively.

Cobalt(III) hexaamine ion [Co(NH3)6]3+ is known to facilitate the transition of B- to Z-DNA or B- to A-DNA depending on the DNA sequences. Specific interactions are found between the amines of [Co(NH3)6]3+ and DNA atoms of A-DNA or Z-DNA. Bridged Co(III)pentaamine complexes, with multiple amine groups arranged in a rigid framework, may enhance the effectiveness of the conformational transition by occupying simultaneously two of the Co(III) hexaamine binding sites. Therefore, the imidazole-bridged Co(III)pentaamine complexes have been synthesized and their interactions with DNA oligonucleotides investigated by circular dichroism (CD) and NMR spectroscopy. CD studies of the titrations of d(A2C15G15T2) with [(NH3)5Co(Im)Co(NH3)5]Br5 and [(NH3)5Co(Im)2Co(NH3)4]Br7 showed that the former metal compound indeed is more effective than [Co(NH3)6]3+ in inducing the transition from B- to A-DNA. The conversion of B- to A-DNA was also supported by one- and two-dimensional NMR studies. Similarly for the titrations of poly(dC-dG). poly(dC-dG) and d(m5C-G)15 with these two bridged Co(III) complexes, efficient induction of Z-DNA was observed. Our studies suggest that bridged Co(III)pentaamine complexes may be useful agents for studying nucleic acid structures.

Amines↗

PubMed1997

1H NMR analysis of novel sialylated and fucosylated lactose-based oligosaccharides having linear GlcNAc(beta 1-6) Gal and Neu5Ac(alpha 2-6) GlcNAc sequences.

Three novel oligosaccharides of human infant faeces have been fully characterised by methylation analysis and 500/600 MHz 1H NMR spectroscopy including DQF-COSY, TQF-COSY, TOCSY and ROESY experiments. The oligosaccharides were shown to be lactose-based structures two of which were substituted at C-6 of Gal with either the Le(x) trisaccharide, Gal(beta 1-4)[Fuc(alpha 1-3)]GlcNAc(beta 1-, or Neu5Ac(alpha 2-6)Gal(beta 1-4)GlcNAc(beta 1-. They differ from other free oligosaccharides previously isolated from the human by having the (1-->6) linkage to Gal in the absence of a (1-->3) branch. The third oligosaccharide has Neu5Ac(alpha 2-6) linked to GlcNAc of the trisaccharide GlcNAc(beta 1-3)Gal(beta 1-4)Glc. This is a linear fragment of the disialylated tetrasaccharide sequence Neu5Ac(alpha 2-3)Gal(beta 1-3)[Neu5Ac(alpha 2-6)]GlcNAc(beta 1-found in the milk oligosaccharide disialyl LNT (the GlcNAc residue of the tetrasaccharide linked to lactose) and also of N-linked chains (GlcNAc linked to Man).

Breast Feeding↗

PubMed1997

Field evaluation of a fenbendazole slow release bolus in the control of nematode infections in first-season cattle.

The efficacy of a fenbendazole slow release bolus in controlling nematode infections of first-season cattle was evaluated in a field study in northern Germany. Two groups, each of 11 male calves, were set-stocked on separate pastures from May until October 1989 (157 days). The animals of one group were given the bolus at turnout and the animals of the control group were treated with fenbendazole (7.5 mg/kg bodyweight) eight weeks after turnout. Clinical inspections and measurements of faecal egg and larval counts, herbage trichostrongyle larval counts, plasma pepsinogen concentrations and bodyweight were made throughout the study. All the animals were slaughtered for worm counts and the evaluation of carcase quality two weeks after housing. The pasture grazed by the control group showed a marked increase in trichostrongyle larvae from late August onwards and, as a result, the control calves had increasing faecal egg counts and increased plasma pepsinogen concentrations in the latter part of the grazing season, although no clinical signs of parasitic gastroenteritis were apparent. The fenbendazole slow release bolus suppressed the trichostrongyle infections during the grazing season, and larval counts on the pasture grazed by the bolus-treated group remained low throughout the study. Postmortem examination showed that the bolus-treated calves harboured significantly (P < 0.01) fewer trichostrongyle worms, including inhibited stages, than the controls. Because of an inadequate lungworm challenge during the grazing season it was not possible to evaluate the efficacy of the fenbendazole slow release bolus in preventing parasitic bronchitis. At slaughter, the bolus-treated animals weighed more than the controls and tended to have a better carcase quality.

Animals↗

PubMed1997

Endothelin-1 transgenic mice develop glomerulosclerosis, interstitial fibrosis, and renal cysts but not hypertension.

The human endothelin-1 (ET-1) gene under the control of its natural promoter was transferred into the germline of mice. The transgene was expressed predominantly in the brain, lung, and kidney. Transgene expression was associated with a pathological phenotype manifested by signs such as age-dependent development of renal cysts, interstitial fibrosis of the kidneys, and glomerulosclerosis leading to a progressive decrease in glomerular filtration rate. This pathology developed in spite of only slightly elevated plasma and tissue ET-1 concentrations. Blood pressure was not affected even after the development of an impaired glomerular filtration rate. Therefore, these transgenic lines provide a new blood pressure-independent animal model of ET-1-induced renal pathology leading to renal fibrosis and fatal kidney disease.

Animals↗

PubMed1997

Intensified regimen for advanced head and neck squamous cell carcinomas.

OBJECTIVE: To devise an intensified treatment regimen for patients with advanced, resectable head and neck squamous cell carcinomas. DESIGN: Phase I/II clinical trial consisting of perioperative cisplatin chemoradiotherapy, surgical resection, intraoperative radiotherapy, and postoperative cisplatin chemoradiotherapy. SETTING: The Ohio State University Comprehensive Cancer Center, Columbus. PATIENTS: Thirty-seven patients (median age, 63 years) with advanced oral cavity, oropharyngeal, or hypopharyngeal carcinomas. RESULTS: The range of time at risk was 1 to 30 months (median, 21 months). Thirty of the 37 registered patients were analyzable; 11 have died (5 with distant metastases; 1 of lung carcinoma; and 5 were cancer-free); 2 experienced second primary tumors in the oral cavity (out of or adjacent to the previous radiotherapy portals). Treatment compliance was excellent (92%), morbidity was low, and excellent locoregional control was achieved. CONCLUSIONS: The initial results are encouraging; the future strategy will intensify the systemic component of therapy based on results from concurrent laboratory studies.

Antineoplastic Agents↗

PubMed1997

[Deferoxamine-conjugated hydroxyethyl starch reduces reperfusion injury to the liver following hemorrhagic shock].

UNLABELLED: Deferoxamine is known to reduce the iron-dependent generation of toxic oxygen-derived radicals during reperfusion of ischaemic tissue. The present study investigates the antioxidative properties of a deferoxamine-conjugated hydroxyethyl starch solution and its effects on the hepatic microcirculation in a haemorrhagic-shock rat model. METHODS: Anaesthetized Sprague-Dawley rats were tracheotomized, prepared for invasive haemodynamic monitoring, and subject to haemorrhagic shock (MAP = 40 mmHg during 60 min). The animals were resuscitated blood-free with lactated Ringer's (RILA, n = 10), gelatin (GELA, n = 10), hydroxyethyl starch (HES, n = 10), or deferoxamine-conjugated HES (DFO, n = 8) solution (MAP > or = 70 mmHg). After 1 h of resuscitation the hepatic microcirculation was investigated by intravital microscopy, the glutathione concentration was measured in liver homogenate, and the thiobarbituric acid reactive substances (TBARS) were determined as markers of lipid peroxidation. RESULTS: Resuscitation resulted in restoration of MAP to > or = 70 mmHg within a short time. The volume required to stabilise the arterial pressure during 1 h of resuscitation was significantly less in the DFO group compared with HES, GELA, and RILA. Significantly higher glutathione levels in liver homogenate as well as decreased TBARS levels were observed in the DFO group. The shock-induced increase of leukocyte adhesion in liver sinusoids was significantly attenuated by DFO. CONCLUSION: DFO significantly attenuates shock-induced oxidative stress, thereby reducing the early inflammatory reaction and improving the hepatic microcirculation.

Animals↗

PubMed1997

[Organ specific expression pattern of a carbon monoxide generating stress protein (hemoxygenase-1/heatshock protein 32) following hemorrhagic shock].

OBJECTIVE: Recent evidence suggests a possible role for Haeme oxygenase (HO)-derived carbon monoxide (CO) in the regulation of vascular tone through elevation of cyclic 3'-5' guanosine monophosphate (cGMP). Previous work from our laboratory has shown that blockade of the HO pathway by tin-protoporphyrin-IX (SnPP) after resuscitation from hemorrhage leads to a specific and profound increase in portal resistance while neither systemic nor hepatic arterial resistance are affected. We therefore investigated the organ-specific expression pattern of the stress-inducible protein haeme oxygenase-1/heat shock protein 32 after haemorrhage and resuscitation. MATERIALS AND METHODS: After approval of the protocol by the local review board, male Sprague-Dawley rats (n = 6/group) were anaesthetised with pentobarbitone, instrumented for assessment of central haemodynamics and subjected to haemorrhagic hypotension (40 mm Hg for 1 h) followed by resuscitation with 60% shed blood and Ringer's solution or a time-matched sham protocol. Samples of liver, spleen, kidney intestine, aorta, and lungs were harvested 5 h after the onset of resuscitation and subjected to Western-blot analysis using a specific anti-rat HO-1/hsp 32 antibody (StressGen, Sidney, Canada). RESULTS: Resuscitation with shed blood/Ringer's solution restored central haemodynamics and acid-base status while significant haemodilution was observed. Haemorrhage and resuscitation led to strong induction of HO-1 in the liver and slight induction in aortic tissue, while no increase in steady-state protein levels was observed in the other organs studied. CONCLUSION: These results suggest a specific contribution of the HO/CO pathway to maintenance of low hepatic portal resistance in vivo in a clinically relevant model of haemorrhagic shock and adequate resuscitation.

Animals↗

PubMed1997

Role of nitric oxide in the regulation of the hepatic microcirculation in vivo.

BACKGROUND/AIMS: Nitric oxide (NO) is an important mediator in the regulation of vascular tone. However, no data exist on the physiological role of NO in the regulation of the hepatic microcirculation. This study was designed to evaluate the role of NO in the hepatic microcirculation in vivo under physiological conditions. METHODS: The hepatic microcirculation was investigated in anesthetized rats by intravital fluorescence microscopy after injection of fluorescein-isothiocyanate-labeled erythrocytes. Following assessment of baseline sinusoidal perfusion, animals were randomly treated with L-NMMA (n=6), L-arginine (n=6), nitroprusside sodium (NPS, n=5) or a comparable volume of NaCl (n=4). Drugs were given through a portal vein catheter at three doses (Dx), each followed by intravital microscopy. L-NMMA was given: 5 mg/kg (D1), 25 mg/kg (D2), 50 mg/kg (D3); L-arginine 30 mg/kg (D1), 150 mg/kg (D2), 300 mg/kg (D3); and NPS continuously 80 microg x kg(-1) x h(-1). RESULTS: L-NMMA induced a significant increase of mean arterial blood pressure (MAP) (114 vs. 129 mm Hg; p<0.05). In contrast, MAP of NPS-treated animals decreased (107 vs. 91 mm Hg; p<0.01) whereas MAP of animals receiving L-arginine did not significantly differ. Sinusoidal blood flow revealed dose-dependent changes: L-NMMA significantly decreased perfusion of sinusoids (D1: 65%, D2: 57%, D3: 50% of baseline, p<0.05). Injection of L-arginine increased the sinusoidal flow even with the lowest dose (D1: 137%, D2: 133%, D3: 123%, p<0.05). Continuous infusion of NPS had little effect on sinusoidal blood flow at the first and second times of microscopy but sinusoidal blood flow was significantly increased at the third time (D1: 103%, D2: 106%, D3: 122%). CONCLUSIONS: Inhibition of NOS results in a dose-dependent disturbance of the hepatic microcirculation despite significantly increased MAP, whereas L-arginine increases the sinusoidal blood flow. The results indicate an important role for NO in the regulatory mechanisms of hepatic sinusoidal perfusion under physiological conditions.

Animals↗