Biomedical subjects

C Kern

Publications and source records attributed to C Kern.

At least 19 recordsLinked to original sources

PubMed2006

Primary mouse hepatocytes for systems biology approaches: a standardized in vitro system for modelling of signal transduction pathways.

Complex cellular networks regulate regeneration, detoxification and differentiation of hepatocytes. By combining experimental data with mathematical modelling, systems biology holds great promises to elucidate the key regulatory mechanisms involved and predict targets for efficient intervention. For the generation of high-quality quantitative data suitable for mathematical modelling a standardised in vitro system is essential. Therefore the authors developed standard operating procedures for the preparation and cultivation of primary mouse hepatocytes. To reliably monitor the dynamic induction of signalling pathways, the authors established starvation conditions and evaluated the extent of starvation-associated stress by quantifying several metabolic functions of cultured primary hepatocytes, namely activities of glutathione-S-transferase, glutamine synthetase, CYP3A as well as secretion of lactate and urea into the culture medium. Establishment of constant metabolic activities after an initial decrease compared with freshly isolated hepatocytes showed that the cultured hepatocytes achieve a new equilibrium state that was not affected by our starving conditions. To verify the highly reproducible dynamic activation of signalling pathways in the in vitro system, the authors examined the JAK-STAT, SMAD, PI3 kinase, MAP kinase, NF-kappaB and Wnt/beta-catenin signalling pathways. For the induction of gp130, JAK1 and STAT3 phosphorylation IL6 was used, whereas TGFbeta was applied to activate the phosphorylation of SMAD1, SMAD2 and SMAD3. Both Akt/PKB and ERK1/2 phosphorylation were stimulated by the addition of hepatocyte growth factor. The time-dependent induction of a pool of signalling competent beta-catenin was monitored in response to the inhibition of GSK3beta. To analyse whether phosphorylation is actually leading to transcriptional responses, luciferase reporter gene constructs driven by multiple copies of TGFbeta-responsive motives were applied, demonstrating a dose-dependent increase in luciferase activity. Moreover, the induction of apoptosis by the TNF-like cytokine Fas ligand was studied in the in vitro system. Thus, the mouse hepatocyte in vitro system provides an important basis for the generation of high-quality quantitative data under standardised cell culture conditions that is essential to elucidate critical hepatocellular functions by the systems biology approach.

Animals↗

PubMed2006

Ropivacaine versus bupivacaine 0.125% with fentanyl 1 microg/ml for epidural labour analgesia: is daily practice more important than pharmaceutical choice?

UNLABELLED: Ropivacaine might be superior to bupivcaine for epidural labour analgesia because it appears to induce less lower extremity motor blockade. The clinical relevance of this difference is not yet clear. METHODS: In a double-blind randomised trial bupivacaine and ropivacaine each at 0.125% with 1 microg/ml fentanyl were compared for epidural labour analgesia. This study was performed in two university hospitals. RESULTS: Sixty-three nulliparous women with singleton pregnancies at term were included. There were no differences between bupivacaine and ropivacaine as far as motor blockade, analgesic outcome, mode of delivery and neonatal outcome are concerned. However, the clinical management of epidural analgesia differed significantly between the two institutions involved. Parturients of one institution had their epidural catheter placed earlier, needed less top-up medication, and had more successful mobilisations, when compared to the other institution. CONCLUSIONS: Institutional clinical practice can be significantly different. Pharmacological differences between bupivacaine and ropivacaine at 0.125% with 1 microg/ml fentanyl seem to be less important than differences between institutions in terms of clinical practice.

Adjuvants, Anesthesia↗

PubMed2004

Sequential combined spinal-epidural anesthesia for cesarean section in a woman with a double-outlet right ventricle.

The number of women with complex cyanotic heart disease reaching childbearing age is continuously increasing. For anesthesiologists, management of this 'new' obstetric population is particularly challenging. We report the case of a parturient with a palliated double-outlet right ventricle, who underwent a cesarean section at 34 weeks with low-dose sequential combined spinal-epidural anesthesia with patient-controlled epidural postoperative analgesia. Anesthetic considerations and specific limitations of invasive monitoring are discussed, along with a review of recent literature on maternal and neonatal complications associated with pregnancies in women with cyanotic congenital heart disease.

Adult↗

PubMed2004

Pain on injection: a double-blind comparison of propofol with lidocaine pretreatment versus propofol formulated with long- and medium-chain triglycerides.

The incidence of pain on injection of propofol has been reported to be 70%. A new propofol formulation with a 10% emulsion of long- and medium-chain triglycerides (LCT/MCT) is associated with less pain on injection. Our goal was to compare the effect of propofol-LCT/MCT on the incidence of pain versus propofol with lidocaine 40 mg IV pretreatment injected as a Bier's block. Two hundred healthy women scheduled for ambulatory gynecological procedures were allocated to 1 of 2 groups in a randomized double-blind fashion. Group LIDO received lidocaine 2% 2 mL injected with a tourniquet 1 min before propofol 1% 2 mg/kg IV; group LCT/MCT received NaCl 0.9% 2 mL with tourniquet 1 min before propofol-LCT/MCT 1% 2 mg/kg IV. Spontaneous verbal expressions of pain, movement of hand, frowning, and moaning during the injection were recorded. The incidence and severity of pain were assessed 30 min and 6 h after surgery. Recall of pain was considered with a visual analog scale (VAS) score >1, and pain was graded as VAS 0-10. More women reported spontaneous verbal expression of pain with propofol-LCT/MCT (47% versus 24%; P = 0.0014; relative risk 1.61 [95% confidence interval, 1.22-2.13]). Among women with a painful injection, there was no difference after surgery regarding the intensity of pain or recall of pain. In contrast to previous reports, we found that propofol-LCT/MCT resulted in a more frequent incidence of pain than propofol 1% with IV lidocaine pretreatment. This may be due to the diversity of pain definitions used in studies or to the lack of premedication in our study.

Adolescent↗

PubMed2003

Cholinesterase reactivation in vivo with a novel bis-oxime optimized by computer-aided design.

Recently, several bis-pyridiniumaldoximes linked by a variable-length alkylene chain were rationally designed in our laboratories as cholinesterase reactivators. Extensive in vitro tests of these oximes with acetylcholinesterase inhibited by two different organophosphate agents, echothiophate and diisopropylfluorophosphate, revealed one compound with particularly good reactivation kinetics and affinity for phosphorylated acetylcholinesterase (AChE). This compound, designated "ortho-7", with a heptylene chain bridging two aldoximes ortho to a pyridinium ring nitrogen, was chosen for detailed comparison with the classic reactivator pyridine-2-aldoxime methochloride (2-PAM). In vitro, ortho-7 reactivated AChE selectively, without restoring activity of the related enzyme butyrylcholinesterase (BChE). For in vivo studies, rats were injected with ortho-7 or 2-PAM before or after organophosphate exposure, and the activities of AChE and BChE were determined at multiple intervals in blood and solid tissues. Ortho-7 behaved nearly as well in the animal as in vitro, reactivating AChE to the same extent as 2-PAM in all peripheral tissues studied (serum, red blood cell, and diaphragm), but at doses up to 100-fold smaller. Like other oxime reactivators, ortho-7 did not reactivate brain AChE after systemic administration. Nonetheless, this agent could be useful in combination therapy for organophosphate exposure, and it may provide a platform for development of additional, even more effective reactivators.

Acetylcholinesterase↗

PubMed2003

Clinical evaluation of a new intracranial pressure monitoring device.

BACKGROUND: Continuous monitoring of intracranial pressure (ICP) still plays a key role in the management of patients at risk from intracranial hypertension. Numerous ICP-measuring devices are available. The aim of the present study was to investigate the clinical characteristics and the magnetic resonance imaging (MRI) compatibility of the recently developed Neurovent-P(REHAU AG+CO, REHAU, Germany) ICP monitoring device. METHOD: In a prospective two-center study, a total of 98 patients with severe head injury, subarachnoid haemorrhage, intracerebral haemorrhage, and non-traumatic brain edema underwent intraparenchymal monitoring of ICP using the Neurovent-P. A control group comprising 50 patients underwent implantation of the Camino-OLM-110-4B ICP monitor. The zero drift of the probes was determined before and after the ICP recording period. Technical and medical complications were documented. The MRI compatibility of the Neurovent-P ICP probe was investigated by evaluating artifacts caused by the probe, probe function and temperature changes during MRI, and probe movement caused by the magnetic field. FINDINGS: The mean zero drift was 0.2+/-0.41 mmHg (maximum 3 mmHg) for the Neurovent-P ICP probes and 0.4+/-0.57 mmHg (maximum 12 mmHg) for the Camino-OLM-110-4B ICP probes. No significant correlation was identified between the extent of zero drift following the removal of the probes and the length of monitoring. Intraparenchymal haemorrhage spatially related to the probe occurred in 1 out of 50 (2%) patients with a Camino-OLM-110-4B probe and in 1 out of 98 (1%) with a Neurovent-P. Damage of the probe due to kinking or overextension of the cable or glass fiber occurred in 4 of the 50 (8%) Camino-OLM-110-4B ICP probes and in 5 of the 98 (5%) Neurovent-P probes. On T2-weighted MR images, the Neurovent-P ICP probe induced only small artifacts with very good discrimination of the surrounding tissue. On T1-weighted MR images, there was a good imaging quality but artifact-related local disturbances in signal occurred. There was no temperature change in the Neurovent-P probe and in the surrounding brain tissue during MR imaging. INTERPRETATION: The Neurovent-P ICP measuring system is a safe and reliable tool for ICP monitoring. Handling of the Neurovent-P system is safe when performed properly.

Adolescent↗

PubMed2003

Flavopiridol downregulates the expression of both the inducible NO synthase and p27(kip1) in malignant cells from B-cell chronic lymphocytic leukemia.

Flavopiridol, an inhibitor of cyclin-dependent kinases and other protein kinases, induces in vitro apoptosis of malignant cells from B-cell chronic lymphocytic leukemia (B-CLL). Previously, we reported that nitric oxide (NO), produced by an inducible NO synthase (iNOS), spontaneously expressed by the B-CLL cells, contributed to their deficiency in apoptosis. In the present work, we show that ex vivo treatment of leukemic cells from B-CLL patients with flavopiridol results in the inhibition of iNOS expression, as determined by immunofluorescence and Western blotting, and in a marked inhibition of NO production measured in situ with a specific fluorescent probe (DAF-2 DA). These effects are accompanied by membrane, mitochondrial and nuclear events of apoptosis. Flavopiridol exposure also results in the stimulation of caspase 3 activity and in caspase-dependent cleavage of p27(kip1), a negative regulator of the cell cycle, which is overexpressed in B-CLL. Thus, flavopiridol is capable of downregulating both iNOS and p27(kip1) expression in B-CLL cells. Furthermore, flavopiridol-promoted apoptosis is partly reverted by an NO donor, suggesting that inhibition of the NO pathway could participate in the apoptotic effects of flavopiridol on the leukemic cells.

Aged↗

PubMed2002

Oxygen embolism after hydrogen peroxide irrigation of a vulvar abscess.

We report a case of venous oxygen embolism in a 33-yr-old healthy woman after irrigation of a vulvar abscess with 25 ml of 3% hydrogen peroxide. Venous oxygen embolism was diagnosed by the development of sudden hypoxia associated with a decrease in end-tidal carbon dioxide concentration from 5.3 kPa to 3.2 kPa, and a 'mill-wheel' sound on cardiac auscultation soon after injection of the solution. The patient responded to corrective treatment including the Trendelenburg position and 100% oxygen. She made an uneventful recovery. We discuss the possible causative mechanism of this embolism, the different diagnostic methods, and the controversial aspects of available treatments. We emphasize that hydrogen peroxide is a dangerous and unsuitable agent for routine wound irrigation and debridement.

Abscess↗

PubMed2001

Similar haemodynamic, respiratory and metabolic changes with the use of sevoflurane or halothane in children breathing spontaneously via a laryngeal mask airway.

BACKGROUND: In preschool children, short-lasting surgical procedures are often performed under combined inhalational and regional anaesthesia with the child breathing spontaneously via a laryngeal mask airway (LMA). Despite widespread use, only limited data are available on haemodynamic, respiratory and metabolic effects of sevoflurane and halothane during LMA anaesthesia. METHODS: In an open-label, randomised, controlled study, 49 children (aged 3-8 years) were allocated to receive either sevoflurane or halothane in 60% nitrous oxide. After insertion of the LMA, end-tidal concentrations of sevoflurane or halothane were maintained at 1 MAC with the child ventilating spontaneously throughout the entire procedure. Analgesia was provided by caudal block. Haemodynamic and respiratory parameters were recorded, and capillary blood-gas samples were obtained repeatedly. RESULTS: Changes in heart rate (HR) and systolic blood pressure were similar in both groups during all observed periods, apart from a significantly higher increase in HR during inhalational induction with sevoflurane (P<0.05). Regression slope analysis during anaesthesia revealed a decrease of the respiratory rate of 5 breaths h-1 (P<0.001) and an increase of end-tidal PCO2 and capillary PCO2 of about 0.25 kPa h-1 (P<0.001), with no significant difference between the two groups. Base excess, calculated in capillary blood gas samples, did not change over time (P>0.5) in either group. CONCLUSIONS: The use of approximately 1 MAC sevoflurane or halothane in 60% N2O in children breathing spontaneously via LMA resulted in comparable haemodynamic, respiratory and metabolic changes, and clinically relevant deteriorations did not occur during the 65-min study period.

Anesthesia, Inhalation↗

PubMed2000

Truncation of the amino-terminus of the recombinant aggrecan rAgg1mut leads to reduced cleavage at the aggrecanase site. Efficient aggrecanase catabolism may depend on multiple substrate interactions.

Aggrecanase cleavage at the Glu(373)-Ala(374) site in the interglobular domain of the cartilage proteoglycan aggrecan is a key event in arthritic diseases. The observation that substrates representing only the aggrecanase cleavage site are not catabolized efficiently by aggrecanase prompted us to investigate the requirement of aggrecanase for additional structural elements of its substrate other than the actual cleavage site. Based on the recombinant substrate rAgg1mut we constructed deletion mutants with successively truncated N- or C-termini of the interglobular domain. Catabolism by aggrecanase activities induced in rat chondrosarcoma cells, porcine chondrocytes, and by human recombinant ADAMTS4 showed a gradually decreasing catabolism of progressively shortened, N-terminal deletion mutants of the substrate rAgg1mut. A reduction to 32 amino acids N-terminal to the aggrecanase site resulted in a decrease of at least 42% of aggrecanase cleavage products as compared with the wild-type substrate. When only 16 amino acids preceded the Glu(373)-Ala(374) site, aggrecanase cleavage was completely inhibited. In contrast, C-terminal deletions did not negatively affect aggrecanase cleavage up to the reduction to 13 amino acids C-terminal to the cleavage site. Unlike aggrecanase(s), membrane type 1-matrix metalloprotease (MT1-MMP), able to cleave rAgg1mut both at the aggrecanase and the MMP site, was insensitive to N-terminal deletions regarding aggrecanase cleavage, indicating that the importance of the N-terminus is characteristic for aggrecanase(s). Taken together, the results demonstrate that the amino-terminus of rAgg1mut, containing the MMP site, plays an important role for efficient cleavage by aggrecanase(s), possibly by serving as a further site of interaction between the enzyme and its substrate.

ADAM Proteins↗

PubMed2000

Advantages of intrathecal nalbuphine, compared with intrathecal morphine, after cesarean delivery: an evaluation of postoperative analgesia and adverse effects.

UNLABELLED: We performed a prospective, randomized, double-blinded, multicenter study to compare the analgesic efficacy and adverse effects of intrathecal nalbuphine, at three different doses, and intrathecal morphine for postoperative pain relief after cesarean deliveries. Ninety healthy patients at full term who were scheduled for elective cesarean delivery with spinal anesthesia were enrolled in the study. They received 10 mg of hyperbaric bupivacaine 0.5% with either morphine 0.2 mg (Group 1), nalbuphine 0.2 mg (Group 2), nalbuphine 0. 8 mg (Group 3), or nalbuphine 1.6 mg (Group 4). Only patients in Groups 1 and 2 reported pain during surgery. Postoperative analgesia lasted significantly longer in the morphine group, compared with the nalbuphine groups (P: < 0.0001). In the nalbuphine groups, postoperative analgesia lasted longest with the 0.8-mg dose. The additional increase to 1.6 mg did not increase efficacy. The incidence of pruritus was significantly higher in Group 1 (11 of 22), compared with Group 2 (0 of 22, P: < 0.0002), Group 3 (0 of 23, P: < 0.0001), and Group 4 (3 of 20, P: < 0.02). Postoperative nausea and vomiting were more frequent in Group 1 (5 of 22), compared with Group 2 (0 of 22, P: < 0.05), Group 3 (0 of 23, P: < 0.05), and Group 4 (3 of 23, not significant). There was no maternal or newborn respiratory depression. Neonatal conditions (Apgar scores and umbilical vein and artery blood gas values) were similar for all groups. This study suggests that intrathecal nalbuphine 0.8 mg provides good intraoperative and early postoperative analgesia without side effects. However, only morphine provides long-lasting analgesia. IMPLICATIONS: Small doses of intrathecal nalbuphine produce fewer adverse effects, such as pruritus and postoperative nausea and vomiting, compared with intrathecal morphine. This may allow earlier discharge of patients from the recovery room.

Adult↗

PubMed1998

Patient evaluation and comparison of the recovery profile between propofol and thiopentone as induction agents in day surgery.

The patient's subjective perception of the quality of his/her recovery after day case anaesthesia with propofol or thiopentone as induction agents is still controversial. The authors investigated the perception and quality of awakening after anaesthesia during the recovery period and at 24 hours and 72 hours, in outpatients undergoing anaesthesia induced either with propofol or thiopentone and maintained with a volatile anaesthetic. In a double-blind study in adults undergoing knee arthroscopy in a day surgery unit, propofol and thiopentone were compared as induction agents in 60 randomized outpatients. A Critical Flicker Fusion Threshold test (CFFT), verbal test for anxiety, visual analog scale for anxiety and pain, and questionnaires were used to assess objectively and subjectively the quality of anaesthesia and awakening during the postoperative period. Demographic data and mean duration of anaesthesia were similar. In the propofol group, patients awoke more rapidly (9.2 +/- 5.8 vs 12.3 +/- 5.8 min) (P < 0.05); however, the CFFT measurements did not show any significant difference between the groups, except at time = 0 min, when 17 patients in the propofol group were able to perform the test versus only 10 patients in the thiopentone group (P < 0.05). At 4, 24, and 72 hours postoperatively, the authors were unable to detect any difference between the two groups. Except for early recovery, there were no differences between the intermediate and late recovery profiles, when propofol or thiopentone was used as the anaesthetic induction agent in day surgery.

Adolescent↗

PubMed1997

Chronic cocaine administration does not modify haemodynamic responses to isoflurane anaesthesia in sheep.

PURPOSE: Cocaine use is epidemic in the developed world, resulting in numerous patients presenting for surgery and anaesthesia with a history of chronic cocaine exposure. The purpose of this study was to determine the effect of chronic cocaine exposure on the cardiovascular response to isoflurane general anaesthesia. METHODS: The changes in mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP) and systemic vascular resistance (SVR) with increasing concentration of isoflurane (1%, 1.7%, and 2.4% end tidal) were determined at baseline in six sheep. The animals then received a continuous cocaine infusion (0.2 mg.kg-1.hr-1) and twice daily cocaine boluses (4 mg.kg-1) for 17 days followed on day 18 by a cocaine binge consisting of eight cocaine boluses (4 mg.kg-1) administered at one hour intervals. The haemodynamic studies conducted at baseline prior to cocaine exposure were then repeated on days 15 and 18. RESULTS: Increasing concentrations of isoflurane produced the expected dose-dependent cardiovascular depression, but this was not altered by cocaine exposure. CONCLUSION: Although chronic cocaine exposure has been shown to increase isoflurane minimum alveolar concentration by 25% in sheep; chronic cocaine exposure does not result in tolerance of the cardiovascular depression produced by isoflurane.

Anesthetics, Inhalation↗

PubMed1997

Chinese hamster ovary cells are non-permissive towards infection with coxsackievirus B3 despite functional virus-receptor interactions.

Viral infection is a complex process which includes binding and interaction of the virus with specific cell surface receptors, uptake and uncoating of the virus, and finally replication. Chinese hamster ovary (CHO) cells are non-permissive towards infection with coxsackieviruses of group B (CVB), although they do express a putative CVB-specific receptor protein. In order to localize the block of infection in CHO cells, these cells were tested for binding of radiolabelled CVB3, receptor-mediated transformation of virions into A-particles, and replication of the viral genome. Binding of CVB3 to CHO cells was found to be comparable to the binding of this virus to permissive cell lines. Detergent-solubilized membrane proteins of CHO cells were tested in virus overlay protein-binding assays (VOPBAs) and shown to express a 100 kDa CVB-binding membrane protein similar to the CVB receptor protein which we recently described for permissive HeLa cells. Incubation of CVB3 with intact CHO cells resulted in transformation of cell-bound virions into non-infectious A-particles (deprived of capsid protein VP4), demonstrating the functional activity of the CVB receptor protein on CHO hamster cells. Transfection of recombinant CVB3 cDNA or viral RNA into CHO cells resulted in the production of infectious CVB3 virions, implying that the failure of CVB to infect CHO cells is not caused by a defect in virus replication but results from a block in the uptake of virus particles into the cell after the initial steps of virus-receptor interactions.

Animals↗

PubMed1997

Haemodynamic responses to sevoflurane compared with halothane during inhalational induction in children.

We studied the haemodynamic changes during induction of anaesthesia in 50 ASA I and II children (1-12 yrs) undergoing minor elective surgery. The patients were randomly divided into two groups to receive either halothane (n = 25) or sevoflurane (n = 25) in a mixture of O2 and N2O (40:60) for mask induction of anaesthesia. Induction of anaesthesia was performed with an overpressure technique by administering rapid increases of gas concentrations, in increments of 1% up to 7% for sevoflurane and of 0.5% up to 3% for halothane. Induction was smooth and rapid in both groups but characterized by increases in heart rate and systolic blood pressure up to 20% especially in the sevoflurane group (P < 0.05); these increases in the latter group were significant compared with baseline and the halothane group (P < 0.05). No serious complications were observed. The authors conclude that more children experienced heart rate and blood pressure increases during the early stage of inhalational induction with sevoflurane compared with halothane.

Analysis of Variance↗

PubMed1997

Muscle biopsy for malignant hyperthermia screening in children.

Malignant Hyperthermia (MH) remains a life-threatening event in anaesthetic practice. In paediatric patients, triggering agents such as volatile anaesthetics and other succinylcholine are widely used. For children with a positive family history or previous clinical signs of MH, muscle biopsy for the halothane and caffeine in vitro muscle contracture tests is the only reliable procedure for diagnosis of MH susceptibility. Here we investigated outcome and compliance of patients and parents involved in the test. Twenty-four children between 6 and 14 yrs of age were admitted to hospital for biopsy. Muscle withdrawal was performed at the upper leg from lateral vastus muscle using regional or trigger-free general anaesthesia. Outcome and compliance were controlled by a telephone interview or direct physical re-evaluation. Seventeen patients out of 24 were diagnosed as clinically MH-susceptible according to the protocol of the European MH Group. Seven children were excluded as MH-negative by the test. Twenty-one children were evaluated postoperatively. Minor side effects of wound healing occurred, but none of the patients showed any abnormalities of muscle contracture or movement performance. Considering the high risk of fatal complications in the presence of MH-susceptibility, muscle biopsy of the upper leg for in-vitro diagnosis is a justified procedure that is acceptable to children and their parents.

Adolescent↗

PubMed1997

Ascorbic acid inhibits spinal meningeal catechol-o-methyl transferase in vitro, markedly increasing epinephrine bioavailability.

BACKGROUND: The spinal menings have previously been shown to contain catechol-o-methyl transferase (COMT), the enzyme that metabolizes epinephrine to the inactive metabolite metanephrine. The authors of this study aimed to quantitate the metabolism of epinephrine traversing the spinal meninges and to determine if that metabolism could be inhibited. In addition, they tried to determine the meningeal permeability of epinephrine. METHODS: Macca nemestrina spinal meninges were mounted in a diffusion cell and epinephrine was added to the donor reservoir at time 0. Three hundred minutes later, all buffer in the recipient reservoir was collected and analyzed for epinephrine metabolites. The experiments were conducted with either ascorbic acid (1 mM) or sodium metabisulfite (5.3 mM) added as antioxidants. RESULTS: In the presence of sodium metabisulfite, 60 +/- 6% of the epinephrine traversing the meningeal specimens was metabolized by COMT. In contrast, in the presence of ascorbic acid, less than 3% of the epinephrine traversing the spinal meninges was metabolized by COMT (P = 0.0001). The meningeal permeability coefficient for epinephrine was 0.38 +/- 0.08 cm/min x 10(-3). CONCLUSIONS: Epinephrine permeability through the spinal meninges is low, and meningeal COMT markedly reduces the bioavailability of what little epinephrine can traverse the meninges. However, a clinically relevant concentration of ascorbic acid, a competitive inhibitor of COMT, almost completely blocks epinephrine metabolism and increases the bioavailability of epinephrine.

Animals↗

PubMed1997

Effect of chronic cocaine administration on the hemodynamic response to acute hemorrhage in awake and anesthetized sheep.

BACKGROUND: Although Cocaine use is common in trauma victims, little is known about how cocaine affects the cardiovascular response to trauma and associated blood loss. This study determined the effect of chronic cocaine use on the cardiovascular response to hemorrhage in awake and anesthetized sheep. METHODS: The hemodynamic and acid-base responses to graded hemorrhage were determined in awake and anesthetized sheep at baseline and after 15 and 18 days of chronic cocaine exposure. RESULTS: Chronic cocaine exposure resulted in a moderate paradoxical bradycardic response to hemorrhage in awake sheep, but did not otherwise alter the hemodynamic response to hemorrhage. In anesthetized animals, cocaine exposure impaired the ability to maintain mean arterial pressure and cardiac output during hemorrhage, and resulted in a marked paradoxical bradycardic response to hemorrhage. CONCLUSIONS: Chronic cocaine exposure did not have an important effect on the cardiovascular response to hemorrhage in awake sheep. However, in anesthetized sheep, chronic cocaine exposure diminished the compensatory cardiovascular response to graded hemorrhage.

Anesthesia, General↗