[Neuropathies: the effect of relaxography and neuromuscular function].
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Humans↗
Biomedical subjects
M Blobner
Publications and source records attributed to M Blobner.
[Pharmacologic aspects of endotracheal intubation].
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Anesthesia, Inhalation↗
[Rapacuronium: a new, non-depolarizing muscle relaxant for rapid intubation?].
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Anesthesia, General↗
Rapacuronium 2.0 or 2.5 mg kg-1 for rapid-sequence induction: comparison with succinylcholine 1.0 mg kg-1.
The purpose of this nine-centre study in 602 patients was to show that the frequency of acceptable intubating conditions after rapacuronium 2.0 or 2.5 mg kg-1 is not more than 10% lower than the frequency after succinylcholine 1.0 mg kg-1 during rapid-sequence induction of anaesthesia with fentanyl 1-2 micrograms kg-1 and thiopental 2-7 mg kg-1. Laryngoscopy and intubation were carried out 60 s after administration of muscle relaxant by an anaesthetist blinded to its identity. Intubating conditions were clinically acceptable (excellent or good) in 91.8% of patients given succinylcholine and in 84.1 and 87.6% of patients given rapacuronium 2.0 and 2.5 mg kg-1 respectively. With respect to the percentage of clinically acceptable intubating conditions, the estimated difference (and the upper limit of the one-sided 97.5% confidence interval) between succinylcholine and rapacuronium 2.0 mg kg-1 was 7.8 (14.4)% and between succinylcholine and rapacuronium 2.5 mg kg-1 it was 4.0 (10.2)%. For both comparisons, the upper limit of the one-sided confidence interval exceeded the predefined 10% difference. Hence, it could not be demonstrated that the intubating conditions with either of the two doses of rapacuronium were not inferior to those with succinylcholine 1.0 mg kg-1. The increase in heart rate was significantly greater during the first 5 min in the rapacuronium groups, but the arterial pressure increased significantly only in the succinylcholine group (P < 0.001). Respiratory side-effects were observed in 4.0, 13.5 and 18.5% of patients after succinylcholine and rapacuronium 2.0 and 2.5 mg kg-1 respectively (P < 0.05). As the non-inferiority of intubating conditions after rapacuronium 2.0 and 2.5 mg kg-1 could not be proven, succinylcholine should be considered the neuromuscular blocking agent that provides better intubating conditions for rapid-sequence induction.
Adolescent↗
Effects of xenon on cerebral blood flow and autoregulation: an experimental study in pigs.
We have investigated the effects of xenon on regional cerebral blood flow (rCBF) and autoregulation in pigs sedated with propofol 4 mg kg-1 h-1. Balloon-tipped catheters were placed into the descending aorta and inferior vena cava of 15 Göttingen Minipigs for manipulation of arterial pressure and blood sampling. rCBF was measured using the sagittal sinus outflow technique. Xenon was adjusted randomly to end-tidal fractions (FE'Xe) of 0, 0.30, 0.50 and 0.70. After baseline measurements of heart rate (HR), mean arterial pressure (MAP), rCBF, sagittal sinus pressure (SSP) and calculation of regional cerebrovascular resistance (rCVR) at each respective FE'Xe, autoregulation was tested in the MAP range 60-120 mm Hg. Increasing FE'Xe had no effect on HR, MAP, rCBF or SSP. rCVR increased with increases in MAP, regardless of FE'Xe. Autoregulation was not impaired. We conclude that xenon inhalation had no effect on rCBF and autoregulation in our model, which could suggest that xenon is an adequate adjunct for neurosurgical anaesthesia.
Anesthetics, Inhalation↗
Preanesthetic train-of-four fade predicts the atracurium requirement of myasthenia gravis patients.
BACKGROUND: The most sensitive diagnostic criterion of myasthenia gravis is a decrement in the muscular response to repetitive stimulation. The authors hypothesized that myasthenia gravis patients who show a train-of-four ratio (T4/T1) < 0.9 in the preanesthetic period will have increased sensitivity to nondepolarizing neuromuscular blocking agents compared with myasthenia gravis patients with preanesthetic T4/T1 > or = 0.9. METHODS: After institutional review board approval was obtained, 20 electrophysiologically documented myasthenia gravis patients were studied. Current pyridostigmine therapy was continued until the morning of surgery. Before induction of anesthesia, neuromuscular transmission was recorded from the hypothenar muscles using electromyography with train-of-four stimulation of the ulnar nerve. According to the T4/T1 ratio, patients were assigned to the "normal" group (T4/T1 > or = 0.9) or the "decrement" group (T4/T1 < 0.9). After induction of intravenous anesthesia, the effective dose to achieve a 95% neuromuscular blockade (ED95) for atracurium was assessed with a cumulative bolus technique. Postoperatively, pyridostigmine was titrated to obtain a T4/T1 > 0.75 and to treat residual myasthenic symptoms. RESULTS: In 14 patients, preanesthetic T4/T1 was > or = 0.9 (normal), whereas 6 patients presented with T4/T1 < 0.9 (decrement). Decrement patients had a lower ED95 of 0.07 +/- 0.03 mg/kg atracurium (mean +/- SD) compared with normal patients with an ED95 of 0.24 +/- 0.11 mg/kg atracurium (P = 0.002). All patients were extubated within 30 min after surgery. Postoperative pyridostigmine infusion did not differ significantly between groups. CONCLUSIONS: The requirement for atracurium is significantly reduced in myasthenia gravis patients with a T4/T1 ratio < 0.9 before anesthesia. This study indicates that routine neuromuscular monitoring in myasthenia gravis patients should be extended into the preinduction period to identify patients who require less atracurium.
Adult↗
Cerebral histopathology following portal venous infusion of bacteria in a chronic porcine model.
BACKGROUND: The aim of this study was to histologically investigate brain damage after prolonged periods of bacteremia in pigs. METHODS: Twenty-one pathogen-free Göttingen minipigs were anesthetized and instrumented with a femoral arterial, a pulmonary arterial, and through midline abdominal incision with a portal venous catheter. After craniotomy the superior sagittal sinus was cannulated. A lumbosacral spinal catheter was inserted for sampling of cerebrospinal fluid. Twelve hours after instrumentation, the animals were randomized in two groups: septic and control animals. The septic group received an infusion of 107 colony-forming units per kilogram of living Escherichia coli over 0.5 h through portal venous catheter each day. The control group received saline. Postoperative intensive care treatment included 4 days of controlled mechanical ventilation, sedation, and intravenous nutrition. The brains then were removed, fixed, and processed for histology. Each pathologic alteration found in the samples was assessed and given a severity code (0-3). RESULTS: Sham-operated animals showed no alterations caused by the instrumentation and the intensive care treatment. The septic group showed typical clinical signs of sepsis. Vasopressor support and mechanical ventilation prevented systemic hypotension and hypoxemia. High serum and cerebrospinal fluid levels of interleukin-6 and tumor necrosis factor-alpha were detected. The septic group showed severe histologic abnormalities of the brain including perivascular edema, spongiform degeneration, hyperemia, and purpura. Damage of neurons was seen including eosinophilic cytoplasm, shrunken nuclei, and disintegration of the nuclear membrane. CONCLUSIONS: Abdominal sepsis induced severe brain damage that was not related to systemic hypoxia or ischemia. High cerebrospinal fluid levels of tumor necrosis factor-alpha and interleukin-6 were related to an inflammatory process in the brain resulting in cerebral edema and death of neurons.
Animals↗
[Rapid sequence induction with succinylcholine: an option to reduce side effects].
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Anesthesia, Inhalation↗
[Visceral resorption of intra-abdominal insufflated carbon dioxide in swine].
OBJECTIVES: Total intraperitoneal carbon dioxide (CO2) resorption from CO2-pneumoperitoneum increases in relation to intraabdominal pressure (IAP) up to an upper limit of 10 to 15 mmHg. The purpose of this prospective study was to evaluate the visceral fraction of CO2 resorption in comparison to total intraperitoneal CO2 resorption in pigs to address possible reasons for this upper limit. METHODS: 16 pigs were chronically instrumented. Via midline laparotomy, a transit-time ultrasound flow probe was placed around the portal vein for continuous recording of the portal venous blood flow and a catheter was inserted into the portal vein via lienal vein. After complete recovery (7-10 days), animals were anesthetized with propofol and fentanyl and a pulmonary artery, a hepatic venous, an arterial, and an intraabdominal insufflation catheter were inserted. Mechanical ventilation (O2/air; FiO2 = 0.4) was adjusted to maintain endtidal CO2 at 34 to 36 mmHg using an Engstrøm Elvira ventilator. After an equilibration period of 3h, CO2, (n = 8) or air (n = 8) was insufflated. IAP was increased in steps of 4 mmHg and maintained constant at each respective IAP-level for 20 min. Blood gas analyses were assessed from portal venous, hepatic venous, central venous, and arterial probes at each IAP-level. Total intraperitoneal CO2 resorption was calculated from parameters derived from indirect calorimetry, the portal venous fraction from blood gas values and the portal venous blood flow following Fick's principle. Data were analyzed using Friedman's test. RESULTS: Total CO2 resorption increased continuously with rising IAP. Highest values were measured at IAP = 16 mmHg with 84 (74-93) ml/min. A further increase of IAP resulted in a significant decrease of total CO2 resorption. The visceral fraction of intraperitoneal CO2 resorption increased up to 28 (17-36) ml/min at IAP = 12 mmHg. Portal venous blood flow was also elevated or unchanged up to this IAP. At IAP = 20 mmHg or IAP = 24 mmHg portal venous blood flow decreased (79% of baseline) and in consequence portal venous calculated fraction of intraperitoneal carbon dioxide resorption decreased to 14 (8-20) ml/min. 20 min after desufflation, intraabdominal CO2 resorption was completed. With air insufflation, all parameters of CO2 balance were unchanged. DISCUSSION: The IAP dependent increase in CO2 resorption is limited due to an IAP related occlusion of the peritoneal capillaries and the limited expansion of peritoneal diffusion area. In this model, it was possible to show that visceral fraction is about one third of the total intraperitoneal carbon dioxide resorption and that this fraction depends on portal venous blood flow. Thus, a decrease in total CO2 resorption may indicate a reduction in portal venous blood flow.
Abdomen↗
[Septic encephalopathy].
Impaired mental function, from clouding of consciousness to deep coma is often seen in patients with systemic inflammation. Diagnosis of this syndrome which is called "septic encephalopathy" is dependent on exclusion of other causes. The underlying mechanisms have only been defined in parts. The appearance of cerebral symptoms during an infection increases mortality. Primary symptoms of septic encephalopathy appear early, before other septic organ manifestations become apparent. The most sensible parameter for diagnosis of septic encephalopathy in comatose patients or under sedation is the EEG. It shows general alterations which increase parallelly to the severity of septic encephalopathy. Septic encephalopathy has to be considered a multifactorial event. In an early stage of the development of septic encephalopathy, bacteremia induces overproduction of cytokines and other mediators. This causes metabolic dysregulation with effects on the cerebral protein-, glucose and neurotransmitter metabolism. In addition, cytokines damage the blood-brain-barrier and exert direct cytotoxic effects. This results in histologic detectable neuronal damage. Further effects of the cytokine expression are perivascular edema and hemorrhage. The loss of metabolic regulation of the brain perfusion and local cerebral ischemia additionally contribute to the etiology of septic encephalopathy. A specific therapy is not yet known.
Brain Diseases↗
[Neuromuscular recovery following mivacurium is predictable in patients with severe systemic disease prognoses].
OBJECTIVES: Fast recovery from mivacurium-induced neuromuscular blockade is impaired in patients with decreased plasma cholinesterase activity which is often associated with dysfunction of different organs. Nevertheless, predictability of neuromuscular recovery may be given. Thus, this study evaluates parameters to predict individual neuromuscular recovery in patients with uncommon diseases. METHODS: 84 male or female patients (18-70 years of age) were allocated to one of two groups according to their ASA risk profile (without severe systemic diseases: ASA 1 and 2; with severe systemic diseases: ASA 3 and 4). Plasma cholinesterase activity (PChE) had been determined preoperatively. Anaesthesia was performed with propofol and fentanyl. Neuromuscular transmission was monitored by electromyography. The ulnar nerve was stimulated by train-of four stimuli and neuromuscular transmission was measured at the hypothenar. After mivacurium 0.1 mu mg/kg, an infusion of mivacurium was adjusted to maintain T1/T0 at approximately 5% for at least 60 min. Duration from application of the initial bolus until recovery to T1/T0 = 5% (dur 5), the mean mivacurium infusion rate (IR), infusion time, the early recovery time from cessation of infusion to T1/T0 = 25% (rec 25) and the final recovery time from T1/T0 = 25% to T4/T1 = 75% (final rec) was measured. Statistical analysis of data was performed using t-tests. (alpha = 0.05). Predictability of the recovery times (rec 25 and final rec) was tested by multiple linear least-squares regressions. Dependent variables were PChE, dur 5, IR, infusion time, and rec 25, respectively. To test for predictability of neuromuscular blockade by mivacurium with respect to severe systemic diseases, the ASA risk score was defined to be the second independent variable at each regression, the respective interaction was defined to be the third independent variable (variable 1 x group). Variables entered multiple regression analysis in a forward stepwise manner (F > 4.0). RESULTS: PChE was significantly lower in patients with severe systemic diseases (3.7 +/- 1.2 kU/l vs. 4.5 +/- 0.9 kU/l), dur 5 significantly prolonged (17.3 +/- 7.3 min vs. 11.0 +/- 3.0 min), IR significantly lower (4.6 +/- 2.6 micrograms/kg/min vs. 6.5 +/- 2.8 micrograms/kg/min), and rec 25 (8.7 +/- 4.0 min vs. 6.0 +/- 1.7 min) as well as final rec (23.0 +/- 16.3 min vs. 13.0 +/- 3.7 min) significantly prolonged compared to patients without severe systemic diseases. Both recovery intervals correlated significantly with PChE, dur 5, or IR, but not with the ASA risk score. Multiple regression analysis revealed a close correlation between rec 25 and final rec very closely (R2 = 0.875). Prolonged mivacurium infusion time and additionally high ASA risk score were correlated with a prolonged neuromuscular recovery (R2 = 0.130). DISCUSSION: Prolonged neuromuscular recovery could be predicted from a reduced PChE, a prolonged duration of action of the initial mivacurium bolus and a decreased mivacurium-infusion rate required to maintain a 95% neuromuscular blockade. Measurement of plasma cholinesterase and monitoring of mivacurium induced neuromuscular blockade can avoid resting neuromuscular blockade postoperatively despite of prolonged neuromuscular recovery.
Adolescent↗
Comparison of intubating conditions after rapacuronium (Org 9487) and succinylcholine following rapid sequence induction in adult patients.
We have assessed intubating conditions provided by rapacuronium (Org 9487) and succinylcholine after rapid sequence induction of anaesthesia in adult patients undergoing elective surgery. We studied 335 patients, ASA I and II, in five centres. Two hundred and thirty-four subjects with normal body weight and 101 obese subjects were allocated randomly to one of four treatment groups differing in the neuromuscular blocking drug administered (rapacuronium 1.5 mg kg-1 or succinylcholine 1 mg kg-1) and in the technique used for induction of anaesthesia (fentanyl 2-3 micrograms kg-1 with thiopental 3-6 mg kg-1 or alfentanil 20 micrograms kg-1 with propofol 1.5-2 mg kg-1). Intubation was started at 50 s by an anaesthetist blinded to the drugs used. Intubating conditions were clinically acceptable (excellent or good) in 89.4% of patients after rapacuronium and in 97.4% after succinylcholine (P = 0.004), the estimated difference being 8.1% (95% confidence interval (CI) 2.0-14.1%). Neither anaesthetic technique nor subject group had an influence on intubating conditions. After intubation, the maximum increase in heart rate averaged 23.1 (SD 25.4%) and 9.4 (26.1%) after rapacuronium and succinylcholine, respectively (P < 0.001). Pulmonary side effects (bronchospasm and increased airway pressure) were observed in 10.7% (95% CI 5.8-17%) and 4.1% (95% CI 1.3-8.8%) of patients given rapacuronium and succinylcholine, respectively (P = 0.021). We conclude that after rapid sequence induction of anaesthesia in adults, clinically acceptable intubating conditions were achieved less frequently after rapacuronium 1.5 mg kg-1 than after succinylcholine.
Adolescent↗
Pharmacokinetics and pharmacodynamics of vecuronium in rats with systemic inflammatory response syndrome: treatment with NG-monomethyl-L-arginine.
BACKGROUND: Insufficient detoxification caused by nitric oxide-related inhibition of cytochrome P450 may be important for metabolism of numerous drugs, including vecuronium. The present study investigated the pharmacodynamics and pharmacokinetics of vecuronium in rats with inflammatory liver dysfunction. METHODS: Male Sprague-Dawley rats (n = 56) were randomly allocated into two groups: In the sepsis group, liver inflammation was established by injection of 56 mg/kg heat-killed Corynebacterium parvum; control rats received the solvent. At day 4, groups were subdivided according to treatment with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (250 mg/kg) or placebo. The aminopyrine breath test was performed to assess cytochrome P450 activity. Rats were anesthetized with propofol and mechanically ventilated. Duration of action of vecuronium (1.2 mg/kg) was measured by evoked mechanomyography (stimulation of the sciatic nerve, contraction of the gastrocnemius muscle). In seven rats of each subgroup a 50% neuromuscular blockade was established by a continuous vecuronium infusion. Vecuronium plasma levels were measured and plasma clearance of vecuronium was calculated. Nitric oxide synthesis was assessed by measuring nitrite/nitrate serum levels. RESULTS: In sepsis/placebo rats, vecuronium-induced neuromuscular blockade was prolonged (144% of contro/placebo), vecuronium plasma levels at 50% neuromuscular blockade were increased (122% of control/placebo), and plasma clearance was decreased (68% of control/placebo). N(G)-monomethyl-L-arginine therapy in rats with sepsis improved cytochrome P450 activity and plasma clearance of vecuronium, shortened duration of action of vecuronium, but did not alter the elevated vecuronium plasma levels. CONCLUSIONS: A systemic inflammatory response syndrome with liver dysfunction results in decreased sensitivity to and a decreased elimination of vecuronium. Modulation of nitric oxide synthesis may be a strategy that can be used in the future to improve xenobiotic metabolism in sepsis.
Alanine Transaminase↗
Phase-related changes in right ventricular cardiac output under volume-controlled mechanical ventilation with positive end-expiratory pressure.
OBJECTIVE: To examine determinants of right ventricular function throughout the ventilatory cycle under volume-controlled mechanical ventilation with various positive end-expiratory pressure (PEEP) stages. DESIGN: Prospective observational animal pilot study. SETTING: Animal research laboratory at a university hospital. SUBJECTS: Eight healthy swine under volume- controlled mechanical ventilation. INTERVENTIONS: Flow probes were implanted in eight swine in order to continuously measure blood flow in the pulmonary artery and inferior vena cava. After a recovery phase of 14 days, the swine were subjected to various PEEP stages (0, 5, 10 cm H2O) during volume-controlled positive pressure ventilation. MEASUREMENTS AND MAIN RESULTS: Continuous flow measurement took place in the pulmonary artery and inferior vena cava. Data on standard hemodynamic parameters were additionally acquired. Respiration-phase-specific analysis of right ventricular cardiac output and of additional hemodynamic function parameters followed, after calculation of mean values throughout five respiration cycles. PEEP at 5 cm H2O led to significant decreases in inferior vena cava flow (4.1%), and in right ventricular cardiac output (5.2%); the respective decreases at PEEP 10 cm H2O were 13.9% and 18.3%. In the inspiration phase at PEEP 10 cm H2O, results revealed an overproportionally pronounced decrease in comparison with the expiration phase in inferior vena cava flow (-24.6% vs. -10%) and right ventricular cardiac output (-35% vs. -13.5%). This phenomenon is presumably caused by a PEEP-related increase in mean airway pressure by the amount of 10.7 cm H2O in inspiration. CONCLUSIONS: Increases in PEEP during volume-controlled mechanical ventilation leads to respiration-phase-specific reduction of right ventricular cardiac output, with a significantly pronounced decrease during the inspiration phase. This decrease in cardiac output should be taken into particular consideration for patients with already critically reduced cardiac output.
Airway Resistance↗
The NO synthase inhibitors L-Name and L-NMMA, but not L-arginine, block the mammalian nicotinic acetylcholine receptor channel.
(1) Nitric oxide (NO) synthase inhibitors (NOS-I) such as L-Name (N(G)-nitro L-arginine methyl ester) and L-NMMA (N(G)-monomethyl L-arginine) may enhance anesthesia indirectly by inhibiting the NO pathway. Moreover, NOS-I interact directly with receptor proteins. In an animal study, L-NMMA potentiated muscle relaxants. (2) The present experiments investigate the effects of L-NMMA, L-Name, and L-arginine on the nicotinic acetylcholine receptor channel (nAChR) using patch clamp techniques and a piezo-driven application system. Both NOS-I appear to directly interact with the nAChR in the open as well as in the closed conformation. L-Arginine has no effect.
Animals↗
Effects of intraabdominally insufflated carbon dioxide and elevated intraabdominal pressure on splanchnic circulation: an experimental study in pigs.
BACKGROUND: Intraabdominally insufflated carbon dioxide (CO2) during laparoscopy may have a specific effect on splanchnic circulation that may be unrelated to the effects of increased intraabdominal pressure alone. Therefore, the influences of insufflation with CO2 versus air on splanchnic circulation were compared. METHODS: Pigs were chronically instrumented for continuous recording of mesenteric artery, portal venous, inferior vena cava, and pulmonary arterial blood flow and portal venous pressure. After induction of anesthesia, CO2 or air was insufflated in 14 and 10 pigs, respectively. With the pigs in the supine position, intraabdominal pressure was increased in steps of 4 mmHg up to 24 mmHg by graded gas insufflation. RESULTS: During air insufflation, mesenteric artery vascular resistance was unchanged, whereas mesenteric arterial blood flow decreased with increasing intraabdominal pressure. Shortly after CO2 insufflation to an intraabdominal pressure of 4 mmHg, mean arterial pressure, mesenteric arterial blood flow, and mesenteric arterial vascular resistance were increased by 21%, 12% and 9%, respectively. Subsequently, with the onset of CO2 resorption in the third minute, mean arterial pressure declined to baseline values and mesenteric arterial vascular resistance declined to 85% of baseline values, whereas mesenteric arterial blood flow continued to increase to a maximum of 24% higher than baseline values. At steady-state conditions during CO2 insufflation, mesenteric arterial blood flow was increased up to an intraabdominal pressure 16 mmHg but decreased at higher intraabdominal pressures. CONCLUSIONS: In contrast to air insufflation, intraabdominal insufflation of CO2 resulted in a moderate splanchnic hyperemia at an intraabdominal pressure < or = 12 mmHg. At higher intraabdominal pressure values, pressure-induced changes became more important than the type of gas used.
Abdomen↗
Quantification of the neuromuscular blocking agent rocuronium and its putative metabolite 17-desacetylrocuronium in heparinized plasma by capillary gas chromatography using a nitrogen sensitive detector.
We have developed a sensitive and specific capillary GC (cGC) assay for the quantification of the quarternary aminosteroidal compound rocuronium (roc), a neuromuscular blocking agent, and its putative metabolite 17-desacetylrocuronium (17OH-roc), using 3-desacetylvecuronium (3OH-vec) as an internal standard (I.S.). This novel method has been applied to a pharmacokinetic study with roc, monitoring sixty patients who were classified according to four different body mass index (BMI) groups. The isolation of these drugs from plasma was carried out using a dichloromethane liquid-liquid extraction after ion-pairing of the positively charged ammonium compounds with iodide. To achieve thermal stability, tert.-butyldimethylsilyl-ethers were formed at the 3OH- and 17OH-steroidal positions by reaction with N-methyl-N-(tert.-butyldimethylsilyl)-trifluoroacetamide at 70 degrees C overnight. An automated cGC system fitted with a nitrogen sensitive detector with a specially prepared glass phase bead and a computer controlled data handling system was used to analyze and quantify the compounds, which were separated on a DB1 capillary column with helium as the carrier gas and a temperature program ranging from 120 to 300 degrees C. The method is linear for 50-6400 ng/ml for roc and 80-6400 ng/ml for 17OH-roc. The detection limits were 10 ng/ml for roc and 50 ng/ml for 17OH-roc. The lower limit of quantification was 50 ng/ml for roc and 80 ng/ml for 17OH-roc. Intra-assay coefficients of variation (C.V.s) were 10% and 15% and the inter-assay C.V.s 8-18% and 16-21% for roc and 17OH-roc, respectively.
Androstanols↗
Inhibition of nitric oxide synthesis improves detoxication in inflammatory liver dysfunction in vivo.
Inflammatory stimulation of the liver induces nitric oxide (NO) biosynthesis and suppression of detoxication. In this study the effect of NO biosynthesis on cytochrome P-450 (CYP) enzyme activity was investigated by comparing in vivo and in vitro assays. To establish liver inflammation, CD rats were injected with Corynebacterium parvum (C. parvum) suspension. After 5 days NO biosynthesis was highly induced as indicated by increased NO2- plus NO3- serum concentrations. At the same time the aminopyrine breath test (ABT), measuring CYP activity in vivo, was reduced to 42% and the in vitro assay of aminopyrine turnover was suppressed to 12% of NaCl- injected controls. When C. parvum-injected animals were treated with the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA), CYP activities significantly improved with an ABT of 76% and an in vitro aminopyrine turnover of 47% of controls. Neither C. parvum injections nor L-NMMA treatment resulted in a significant change of CYP protein concentrations. These data indicate that suppression of xenobiotic metabolism can be attenuated by inhibition of NO biosynthesis during an ongoing process of inflammation.
Animals↗