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1.
Hautarzt ; 73(3): 195-200, 2022 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-35119482

RESUMO

In the world of allergology, alpha-gal syndrome remains one of the most fascinating discoveries over the last 15 years as it is triggered by specific IgE directed against the immunogenic sugar galactose-α­1,3­galactose (alpha-gal), found foremost in mammalian meat, milk and products derived thereof, potentially resulting in anaphylaxis. Also, mammalian-derived drugs and medical products have been identified as possible culprits. Nonetheless, tick bites remain the major cause of specific alpha-gal-sIgE. Herein, we summarize the current clinical knowledge and pathophysiology of alpha-gal syndrome in order to better understand this disease.


Assuntos
Anafilaxia , Hipersensibilidade Alimentar , Picadas de Carrapatos , Alérgenos , Anafilaxia/diagnóstico , Anafilaxia/etiologia , Anafilaxia/terapia , Animais , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/terapia , Humanos , Imunoglobulina E , Picadas de Carrapatos/complicações
2.
Anesth Analg ; 127(5): 1118-1126, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29533264

RESUMO

BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89-6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival. CONCLUSIONS: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.


Assuntos
Anestésicos Inalatórios/efeitos adversos , Cardiopatias/epidemiologia , Óxido Nitroso/efeitos adversos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Administração por Inalação , Idoso , Anestésicos Inalatórios/administração & dosagem , Biomarcadores/sangue , Avaliação da Deficiência , Feminino , Nível de Saúde , Cardiopatias/diagnóstico , Cardiopatias/mortalidade , Cardiopatias/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nitroso/administração & dosagem , Medição de Risco , Fatores de Risco , Procedimentos Cirúrgicos Operatórios/mortalidade , Fatores de Tempo , Resultado do Tratamento , Troponina/sangue , Regulação para Cima
4.
Anaesthesia ; 72(7): 840-844, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28419420

RESUMO

Pressure waveform analysis provides a reliable confirmatory adjunct to the loss-of-resistance technique to identify the epidural space during thoracic epidural anaesthesia, but its role remains controversial in lumbar epidural analgesia during labour. We performed an observational study in 100 labouring women of the sensitivity and specificity of waveform analysis to determine the correct location of the epidural needle. After obtaining loss-of-resistance, the anaesthetist injected 5 ml saline through the epidural needle (accounting for the volume already used in the loss-of-resistance). Sterile extension tubing, connected to a pressure transducer, was attached to the needle. An investigator determined the presence or absence of a pulsatile waveform, synchronised with the heart rate, on a monitor screen that was not in the view of the anaesthetist or the parturient. A bolus of 4 ml lidocaine 2% with adrenaline 5 µg.ml-1 was administered, and the epidural block was assessed after 15 min. Three women displayed no sensory block at 15 min. The results showed: epidural block present, epidural waveform present 93; epidural block absent, epidural waveform absent 2; epidural block present, epidural waveform absent 4; epidural block absent, epidural waveform present 1. Compared with the use of a local anaesthetic bolus to ascertain the epidural space, the sensitivity, specificity, positive and negative predictive values of waveform analysis were 95.9%, 66.7%, 98.9% and 33.3%, respectively. Epidural waveform analysis provides a simple adjunct to loss-of-resistance for confirming needle placement during performance of obstetric epidurals, however, further studies are required before its routine implementation in clinical practice.


Assuntos
Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Adulto , Espaço Epidural , Feminino , Humanos , Agulhas , Gravidez , Reprodutibilidade dos Testes
5.
Acta Anaesthesiol Scand ; 60(3): 289-334, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26514824

RESUMO

BACKGROUND: The present interdisciplinary consensus review proposes clinical considerations and recommendations for anaesthetic practice in patients undergoing gastrointestinal surgery with an Enhanced Recovery after Surgery (ERAS) programme. METHODS: Studies were selected with particular attention being paid to meta-analyses, randomized controlled trials and large prospective cohort studies. For each item of the perioperative treatment pathway, available English-language literature was examined and reviewed. The group reached a consensus recommendation after critical appraisal of the literature. RESULTS: This consensus statement demonstrates that anaesthesiologists control several preoperative, intraoperative and postoperative ERAS elements. Further research is needed to verify the strength of these recommendations. CONCLUSIONS: Based on the evidence available for each element of perioperative care pathways, the Enhanced Recovery After Surgery (ERAS®) Society presents a comprehensive consensus review, clinical considerations and recommendations for anaesthesia care in patients undergoing gastrointestinal surgery within an ERAS programme. This unified protocol facilitates involvement of anaesthesiologists in the implementation of the ERAS programmes and allows for comparison between centres and it eventually might facilitate the design of multi-institutional prospective and adequately powered randomized trials.


Assuntos
Anestesia , Consenso , Procedimentos Cirúrgicos do Sistema Digestório , Injúria Renal Aguda/etiologia , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Humanos , Complicações Intraoperatórias/prevenção & controle , Monitorização Fisiológica , Náusea e Vômito Pós-Operatórios/prevenção & controle , Recuperação de Função Fisiológica
6.
Acta Anaesthesiol Scand ; 59(10): 1212-31, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26346577

RESUMO

BACKGROUND: The present article has been written to convey concepts of anaesthetic care within the context of an Enhanced Recovery After Surgery (ERAS) programme, thus aligning the practice of anaesthesia with the care delivered by the surgical team before, during and after surgery. METHODS: The physiological principles supporting the implementation of the ERAS programmes in patients undergoing major abdominal procedures are reviewed using an updated literature search and discussed by a multidisciplinary group composed of anaesthesiologists and surgeons with the aim to improve perioperative care. RESULTS: The pathophysiology of some key perioperative elements disturbing the homoeostatic mechanisms such as insulin resistance, ileus and pain is here discussed. CONCLUSIONS: Evidence-based strategies aimed at controlling the disruption of homoeostasis need to be evaluated in the context of ERAS programmes. Anaesthesiologists could, therefore, play a crucial role in facilitating the recovery process.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Assistência Perioperatória , Cuidados Pós-Operatórios , Recuperação de Função Fisiológica , Anestesia Epidural , Anestesiologia , Transtornos Cognitivos/etiologia , Homeostase , Humanos , Resistência à Insulina , Dor Pós-Operatória/prevenção & controle , Papel do Médico , Estresse Fisiológico , Equilíbrio Hidroeletrolítico
7.
Acta Anaesthesiol Belg ; 65(2): 55-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25223164

RESUMO

The increasing utilisation of the videolaryngoscope for awake tracheal intubation requires development and assessment of methods to decrease the gag reflex. We hypothesised that chewing gauze soaked with lidocaine would decrease the gag reflex during awake videolaryngoscope tracheal intubation. Twenty four morbidly obese patients assessed as having a potential difficult tracheal intubation were randomised to chew gauze soaked with 20 ml of 2% lidocaine or saline for 3 minutes. All patients then received 20 ml of aerosolised 2% lidocaine and underwent awake videolaryngoscope assisted tracheal intubation. Gagging scores, heart rate and blood pressure were assessed when best laryngeal view was obtained, when the tracheal tube was positioned at the cords, and when the tube was advanced into the trachea. In addition, serum lidocaine levels were measured. The primary outcome was the gagging score at best laryngeal visualisation, which was compared between groups with a Student's t-test. Gagging scores and hemodynamic parameters did not differ between groups, but the saline group had lower plasma levels of lidocaine after the intubation procedure. When used for awake videolaryngoscope assisted tracheal intubation of the morbidly obese, chewing lidocaine soaked gauze does not decrease the amount of gagging as compared to lidocaine aerosolisation, but does increase the plasma levels of lidocaine.


Assuntos
Intubação Intratraqueal/métodos , Laringoscopia , Lidocaína/administração & dosagem , Obesidade Mórbida , Cirurgia Vídeoassistida/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigília
8.
Br J Surg ; 100(5): 610-8, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23339047

RESUMO

BACKGROUND: Postoperative liver dysfunction is the major source of morbidity and mortality in patients undergoing partial hepatectomy. This study tested the benefits of a metabolic support protocol based on insulin infusion, for reducing liver dysfunction following hepatic resection. METHODS: Consecutive consenting patients scheduled for liver resection were randomized to receive preoperative dextrose infusion followed by insulin therapy using the hyperinsulinaemic normoglycaemic clamp protocol (n = 29) or standard therapy (control group, n = 27). Patients in the insulin therapy group followed a strict dietary regimen for 24 h before surgery. Intravenous dextrose was started at 2 mg per kg per min the night before and continued until surgery. Hyperinsulinaemic therapy for a total of 24 h was initiated at 2 munits per kg per min at induction of anaesthesia, and continued at 1 munit per kg per min after surgery. Normoglycaemia was maintained (3.5-6.0 mmol/l). Control subjects received no additional dietary supplement and a conventional insulin sliding scale during fasting. All patients were tested serially to evaluate liver function using the Schindl score. Liver tissue samples were collected at two time points during surgery to measure glycogen levels. RESULTS: Demographics were similar in the two groups. More liver dysfunction occurred in the control cohort (liver dysfunction score range 0-8 versus 0-4 with insulin therapy; P = 0.031). Median (interquartile range) liver glycogen content was 278 (153-312) and 431 (334-459) µmol/g respectively (P = 0.011). The number of complications rose with increasing severity of postoperative liver dysfunction (P = 0.032) CONCLUSION: The glucose-insulin protocol reduced postoperative liver dysfunction and improved liver glycogen content. REGISTRATION NUMBER: NCT00774098 (http://www.clinicaltrials.gov).


Assuntos
Glucose/administração & dosagem , Hepatectomia/métodos , Hipoglicemiantes/administração & dosagem , Insulina Regular Humana/administração & dosagem , Hepatopatias/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Administração Cutânea , Adulto , Idoso , Glicemia , Hepatectomia/efeitos adversos , Humanos , Infusões Intravenosas , Hepatopatias/metabolismo , Glicogênio Hepático/metabolismo , Pessoa de Meia-Idade , Assistência Perioperatória/métodos , Cuidados Pré-Operatórios/métodos , Adulto Jovem
10.
Anaesthesia ; 67(3): 232-5, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22321077

RESUMO

Awake videolaryngoscopy may be useful for the tracheal intubation of the morbidly obese. This prospective, observational study enrolled 50 patients undergoing bariatric surgery. After sedation and topical anaesthesia of the airway, awake tracheal intubation was attempted, assisted by videolaryngoscopy, and terminated if there was severe gagging, coughing, or inadequate laryngeal view. After three attempts the procedure was considered a failure. Twenty-seven intubations were successful on the first attempt, fifteen on the second, six on the third and two were not successful, giving a success rate of 96% (95% CI 86-100%). In one failure, inserting the tracheal tube caused severe gagging in spite of an adequate view of the larynx, and the trachea was intubated with the videolaryngoscope after induction of anaesthesia. The second failure was due to gagging, with subsequent tracheal intubation successful using fibreoptic bronchoscopy. When managing the morbidly obese airway, awake tracheal intubation using videolaryngoscopy may be considered.


Assuntos
Intubação Intratraqueal/métodos , Laringoscopia/métodos , Obesidade Mórbida/fisiopatologia , Adulto , Broncoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravação em Vídeo , Vigília
12.
Anaesthesia ; 65(1): 12-7, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19895618

RESUMO

Airway anaesthesia using atomised lidocaine for awake oral fibreoptic intubation in morbidly obese patients was evaluated using two doses of local anaesthetic. In this randomised, blinded prospective study, 40 ml of atomised 1% (n = 11) or 2% (n = 10) lidocaine was administered with high oxygen flow as carrier. Outcomes included time for intubation, patient tolerance to airway manipulation, haemodynamic parameters, the bronchoscopist's overall satisfaction, and serial serum lidocaine concentrations. Patients receiving lidocaine 1% had a longer mean (SD) time from the start of topicalisation to tracheal tube cuff inflation than those receiving lidocaine 2% (8.6 (0.9) min vs 6.9 (0.5) min, respectively; p < 0.05). Patients in the 1% cohort demonstrated increased responses to airway manipulation (p < 0.0001), reflecting lower bronchoscopist's satisfaction scores (p < 0.03). Haemodynamic responses to topicalisation and airway manipulation were similar in both groups. Peak plasma concentration was lower in the 1% group (mean (SD) 1.4 (0.3) and 3.8 (0.5) microg.ml(-1), respectively; p < 0.001). Airway anaesthesia using atomised lidocaine for awake oral fibreoptic intubation in the morbidly obese is efficacious, rapid and safe. Compared with lidocaine 1%, the 2% dose provides superior intubating conditions.


Assuntos
Anestésicos Locais/administração & dosagem , Intubação Intratraqueal/métodos , Lidocaína/administração & dosagem , Obesidade Mórbida/cirurgia , Adulto , Anestesia Local/métodos , Anestésicos Locais/sangue , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Tecnologia de Fibra Óptica/métodos , Derivação Gástrica , Frequência Cardíaca/efeitos dos fármacos , Humanos , Lidocaína/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
13.
Exp Clin Endocrinol Diabetes ; 124(5): 318-23, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27050068

RESUMO

BACKGROUND: Brain death is a major stress that is associated with a massive inflammatory response and systemic hyperglycemia. Severe inflammation leads to increased graft immunogenicity and risk of graft dysfunction; while acute hyperglycemia aggravates the inflammatory response and increases the risk of morbidity and mortality. Insulin therapy not only controls hyperglycemia but also suppresses inflammation. The present study is to investigate the anti-inflammatory properties and the normoglycemia maintenance of high dose insulin on brain dead organ donors. DESIGN: 15 brain dead organ donors were divided into 2 groups, insulin treated (n=6) and controls (n=9). Insulin was provided for a minimum of 6 h using the hyperinsulinemic normoglycemic clamp technique. The changes of serum cytokines, including IL-6, IL-10, IL-1ß, IL-8, TNFα, TGFα and MCP-1, were measured by suspension bead array immunoassay and glucose by a glucose monitor. RESULTS: Compared to controls, insulin treated donors had a significant lower blood glucose 4.8 (4-6.9) vs. 9 (5.6-11.7) mmol/L, p<0.01); the net decreases of pro-inflammatory cytokines, such as IL-6 and MCP-1, and the net increase of anti-inflammatory cytokine, such as IL-10, reached significant level in insulin treated donors compared with those in controls. CONCLUSION: High dose insulin therapy decreases the concentrations of inflammatory cytokines in brain dead donors and preserves normoglycemia. High dose of insulin may have anti-inflammatory effects in brain dead organ donors and therefore, improve the quality of donor organs and potentially improve outcomes.


Assuntos
Morte Encefálica/sangue , Citocinas/sangue , Inflamação/sangue , Insulina/farmacologia , Transplante de Órgãos/métodos , Adulto , Idoso , Citocinas/efeitos dos fármacos , Feminino , Humanos , Inflamação/tratamento farmacológico , Insulina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos
14.
Br J Pharmacol ; 118(3): 790-6, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8762109

RESUMO

1. This study was designed to investigate the role of rat phosphodiesterase 3 (RPDE3) in regulation of liver metabolism in sepsis. We studied the effects of the phosphodiesterase 3 inhibitor (PDI), enoximone, alone and in combination with regulating factors of hepatic carbohydrate metabolism and bile secretion in the perfused liver of rats treated 4 h earlier with endotoxin. In addition, cyclic AMP and cyclic GMP levels were determined in the effluate and bile by radio immunoassay methods. 2. After endotoxin treatment, infusion of enoximone at three concentrations (1 microM, 10 microM) resulted in an increased glucose output from -1.4 +/- 0.9 to 7.8 +/- 2.5 mumol l-1 20 min-1. Bile acid-independent bile flow increased also, in a dose-dependent manner. 3. In untreated livers, cyclic AMP release increased in the effluate from 1000 +/- 73 fmol g-1 min-1 to 1710 +/- 143 fmol g-1 min-1 when enoximone (10 microM) was administered. In bile from untreated livers, the level of cyclic AMP was also significantly increased by enoximone. After endotoxin treatment, the enoximone (10 microM) effect on cyclic AMP levels in effluate and bile was greatly reduced. Levels of cyclic GMP in the effluate and bile appeared unchanged in the presence of enoximone. 4. During co-infusion of glucagon (1 nM) and enoximone (10 microM), cyclic nucleotide levels in the effluate and bile of livers after endotoxin treatment were determined. In the effluate, cyclic AMP release increased from 827 +/- 144 fmol g-1 min-1 to 17802 +/- 2821 fmol g-1 min-1 when glucagon was administered. The presence of enoximone enhanced cyclic AMP further to 41696 +/- 920 fmol g-1 min-1. The same changes in cyclic AMP release were found in bile. Levels of cyclic GMP in the effluate and bile were not significantly affected by the administration of glucagon and the PDI. 5. Glucose release was determined during glucagon, sympathetic nerves stimulation and phenylephrine administration in the presence and absence of enoximone. The addition of enoximone to glucagon increased glucose release by 8.2 +/- 2.8 mumol g-1 20 min-1, without alteration of lactate balance. The PDI enhanced the glycogenolytic effects of nerve stimulation and of phenylephrine, accompanied by a reduction in lactate production. 6. Enoximone significantly enhanced the bile acid independent bile flow after glucagon, nerves stimulation and after administration of phenylephrine. Bile acid secretion was unaffected by the PDI. The vasoconstrictor effect of nerve stimulation was reduced by the PDI. 7. We conclude that endotoxin treatment reduces the ability of the PDI, enoximone, to increase cyclic AMP release in the perfused liver. The significant increase in cyclic AMP release after stimulation with glucagon and enoximone favours the view that RPDE3 is involved in the degradation of cyclic AMP in the liver after exposure to endotoxin. Additionally, the inhibition of the RPDE3 results in glucose release, vasodilatation and choleresis in endotoxin pretreated livers.


Assuntos
Endotoxinas/farmacologia , Fígado/efeitos dos fármacos , Diester Fosfórico Hidrolases/farmacologia , Sepse/metabolismo , Animais , AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Enoximona/farmacologia , Fígado/metabolismo , Masculino , Ratos , Ratos Wistar , Fatores de Tempo
15.
J Appl Physiol (1985) ; 91(6): 2523-30, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11717214

RESUMO

The aim of this study was to assess dynamic changes in protein and glucose metabolism during surgery. Twelve patients undergoing colorectal surgery received either intravenous propofol anesthesia (n = 6) or inhalational anesthesia with desflurane (n = 6). Pre- and intraoperative protein and glucose kinetics were analyzed by an isotope dilution technique using L-[1-(13)C]leucine and [6,6-(2)H(2)]glucose. Plasma concentrations of glucose, lactate, free fatty acids, insulin, glucagon, and cortisol were measured before and after 2 h of surgery. The rates of appearance of leucine and glucose, leucine oxidation, protein synthesis, and glucose clearance decreased during surgery, independent of the type of anesthesia (P < 0.05). A correlation between the rate of appearance of leucine and glucose was observed (r = 0.755, P < 0.001). Intraoperative plasma cortisol and glucose concentrations increased (P < 0.05), whereas plasma concentrations of lactate, free fatty acids, insulin, and glucagon did not change. Surgery causes a depression of whole body protein and glucose metabolism, independent of the anesthetic technique. There is a correlation between perioperative glucose production and protein breakdown.


Assuntos
Anestesia , Anestésicos Inalatórios , Anestésicos Intravenosos , Colo/cirurgia , Glucose/metabolismo , Isoflurano , Propofol , Proteínas/metabolismo , Reto/cirurgia , Adulto , Idoso , Sangue/metabolismo , Glicemia/análise , Desflurano , Feminino , Humanos , Hidrocortisona/sangue , Período Intraoperatório , Isoflurano/análogos & derivados , Masculino , Pessoa de Meia-Idade
16.
Clin Nutr ; 14(4): 237-41, 1995 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16843937

RESUMO

The clearance rate of glycerol has been found to be impaired in alcoholic liver disease. However it remains unclear, if this can be ascribed to a defect of hepatic gluconeogenesis. Thus, the purpose of this work was to investigate glycerol clearance and hepatic glucose production in patients with liver cirrhosis. 13 patients with alcohol-induced Child B cirrhosis and 8 healthy volunteers were studied. Rates of appearance (R(a)) of glycerol, glucose and alanine were determined using stable isotope techniques. In addition indocyanine green clearance (ICGC) and plasma substrate concentrations were measured. Clearance rates were calculated as R(a) divided by the corresponding substrate concentration. R(a) of glycerol in patients was not different from controls, but glycerol clearance was significantly reduced (29 +/- 3 vs. 41 +/- 4 ml/kg/min). No differences in R(a) of glucose and alanine and corresponding plasma concentrations were observed. ICGC in patients was about 35% lower than reference values. Diminished glycerol clearance in patients with liver cirrhosis was not due to impaired hepatic gluconeogenesis. Since glycerol is almost completely extracted by the liver decreased glycerol clearance possibly simply reflected compromised liver perfusion as seen by reduced ICGC.

17.
Life Sci ; 56(20): 1721-6, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7723601

RESUMO

The use of phosphodiesterase-III-inhibitors (PDI) as inotropic substances in the treatment of cardiac failure can be associated with hyperglycaemia. This phenomenon could be caused by hepatic events induced by PDI. The purpose of our study was to investigate the effects of the PDI enoximone on hepatic carbohydrate metabolism and bile flow. In the rat liver perfusion model, hepatic glucose and lactate production, portal flow and bile flow were determined. Administration of enoximone (1, 10, 100 microM) increased hepatic glucose output and bile acid-independent bile flow in a dose-dependent manner. The PDI enhanced the glycogenolytic effects of glucagon (from 15.7 to 38.6 mumol glucose/g/20 min), of epinephrine (from 7.1 to 38.7 mumol glucose/g/20 min), of norepinephrine (from 9.8 to 32 mumol/g/20 min) and of phenylephrine (from 25.5 to 40.8 mumol glucose/g/20 min). Furthermore, lactate production was significantly reduced by enoximone. The effect of epinephrine and phenylephrine on portal flow was blocked or diminished by enoximone administration. In summary, it was shown that the PDI enoximone is able to enhance hepatic glucose production. Bile acid-independent bile flow was increased by the inhibition of phosphodiesterase-III. The effects of enoximone and glycogenolytic hormones on glucose release were synergistic. The vasoconstrictive action of catecholamines was reduced or completely prevented by enoximone. In conclusion, enoximone has glycogenolytic, vasodilatory and choleretic properties in the liver.


Assuntos
Bile/efeitos dos fármacos , Bile/fisiologia , Enoximona/farmacologia , Glucose/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Animais , Cálcio/fisiologia , Metabolismo dos Carboidratos , AMP Cíclico/biossíntese , Relação Dose-Resposta a Droga , Epinefrina/farmacologia , Glucagon/farmacologia , Lactatos/metabolismo , Ácido Láctico , Masculino , Norepinefrina/farmacologia , Perfusão , Fenilefrina/farmacologia , Proteína Quinase C/fisiologia , Ratos , Ratos Wistar , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Sistemas do Segundo Mensageiro/fisiologia , Taxa Secretória/efeitos dos fármacos , Estimulação Química
18.
Nutrition ; 10(4): 342-5, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8000156

RESUMO

The stable isotope-labeled [1,1,2,3,3-2H5]glycerol analyzed by negative-ion chemical ionization (NCI) mass spectrometry has been proven a valid tracer for studying glycerol kinetics in humans. Because of its high technical complexity, NCI mass spectrometry is available to only a few laboratories. Thus, the aim of our study was to create an alternative method for measuring [1,1,2,3,3-2H5]glycerol enrichment in plasma with a new derivative and positive-ion chemical ionization (PCI) mass spectrometry. It could be demonstrated that the trisacetyl[1,1,2,3,3-2H5]glycerol derivative was able to produce a fragment at m/z = 164 with sufficient intensity. Application of [1,1,2,3,3-2H5]glycerol in seven healthy volunteers resulted in reproducible measurements of basal glycerol turnover rates. The mean glycerol flux rate of 3.02 +/- 0.37 mumol.kg-1 body wt.min-1 after an overnight fast was similar to values reported from studies with comparable protocols. Physiological changes of lipolysis rates after 48 h of fasting followed by infusion of 4 mg.kg-1 body wt.min-1 glucose could also be adequately studied in one subject. Fast-induced elevated glycerol turnover at 7.56 mumol.kg-1 body wt.min-1, was substantially suppressed to 1.13 mumol.kg-1 body wt.min-1, when glucose was administered. The easily performed trisacetyl[1,1,2,3,3-2H5]glycerol derivative analyzed by PCI mass spectrometry is suitable for studying glycerol kinetics in humans.


Assuntos
Deutério , Glicerol/sangue , Espectrometria de Massas , Anidridos Acéticos , Adulto , Esterificação , Ácidos Graxos não Esterificados/sangue , Humanos , Cinética , Lipólise , Masculino
19.
Nutrition ; 17(2): 85-90, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11240333

RESUMO

The purpose of this study was to investigate the effect of glucose infusion on lipid metabolism after abdominal surgery. Patients (n = 6) with non-metastasized colorectal carcinoma were investigated on the second day after surgery and healthy volunteers were studied after an overnight fast. The rates of glycerol appearance (R(a) glycerol), i.e., lipolysis rates, were assessed by primed continuous infusion of [1,1,2,3,3,-5H2]glycerol before and after 3 h of glucose infusion (4 mg x kg(-1) x min(-1)). Plasma concentrations of glycerol, free fatty acids, glucose, lactate, insulin, and glucagon were determined. Fasting R(a) glycerol was higher in patients than in volunteers (7.7 +/- 1.8 versus 1.9 +/- 0.3 micromol x kg(-1) x min(-1), P < 0.05). Glucose infusion suppressed the R(a) glycerol in volunteers to 1.0 +/- 0.2 micromol x kg(-1) x min(-1) (P < 0.05), whereas lipolysis was not affected in patients. Plasma concentrations of glycerol and free fatty acids similarly decreased during glucose administration by 50% in both groups (P < 0.05). In contrast to the patients, a significant correlation (r = 0.78, P < 0.05) between the R(a) glycerol and plasma glycerol concentration was observed in normal subjects. The hyperglycemic response to glucose infusion was significantly more pronounced (P < 0.05) in patients (10.7 +/- 0.7 mmol/L) than in volunteers (7.1 +/- 0.4 mmol/L), whereas the plasma insulin increased to the same extent in the two groups (P < 0.001). In conclusion, lipolysis rates are increased after abdominal surgery and glucose administration, most likely due to insulin resistance, and fail to inhibit stimulated whole-body lipolysis.


Assuntos
Glucose/administração & dosagem , Glicerol/sangue , Metabolismo dos Lipídeos , Lipólise/efeitos dos fármacos , Abdome/cirurgia , Adulto , Estudos de Casos e Controles , Neoplasias Colorretais/cirurgia , Deutério , Ácidos Graxos/sangue , Feminino , Glucose/farmacologia , Glicerol/farmacocinética , Humanos , Infusões Intravenosas , Resistência à Insulina , Marcação por Isótopo , Cinética , Masculino , Pessoa de Meia-Idade
20.
Nutrition ; 13(3): 191-5, 1997 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9131677

RESUMO

The aim of this study was to investigate metabolic changes during and after abdominal hysterectomy with specific regard to glycerol metabolism. Seven otherwise healthy patients with benign uterine myoma were enrolled in this study. Glycerol turnover and hepatic glucose production were measured before and after the operation by using stable-isotope technique ([1,1,2,3,3-2H5]-glycerol, [6,6-2H2]-glucose). Metabolic substrates (glycerol, nonesterified fatty acids, beta-hydroxybutyrate, glucose, lactate) and hormones (insulin, glucagon, cortisol, catecholamines) were determined pre-, intra- and postoperatively. Hysterectomy was associated with an increase of postoperative glycerol turnover from 3.56 +/- 1.28 to 6.46 +/- 2.44 mumol.kg-1.min-1 (P < 0.05). This increment was inversely related to the age of the patients (r = 0.872, P < 0.05). Glycerol concentration tended to increase perioperatively. These changes, however, were not of statistical significance. Hepatic glucose production and glucose plasma levels increased postoperatively from 9.75 +/- 1.61 to 12.79 +/- 1.45 mumol.kg-1.min-1 (P < 0.05) and 4.6 +/- 0.9 to 6.2 +/- 0.9 mmol/L (P < 0.05), respectively. Cortisol and catecholamine levels rose during and after surgery, while insulin and glucagon remained unchanged. The enhanced rate of lipolysis after hysterectomy was not detectable from plasma glycerol levels alone. The results of this study showed that using stable isotope technique allowed a more differentiated look at metabolic pathways than static plasma substrate concentrations, especially under perioperative conditions.


Assuntos
Catecolaminas/metabolismo , Glucose/metabolismo , Glicerol/metabolismo , Hormônios/metabolismo , Histerectomia , Adulto , Fatores Etários , Catecolaminas/sangue , Feminino , Glucose/análise , Glicerol/análise , Hemodinâmica , Hormônios/sangue , Humanos , Período Intraoperatório , Leiomioma/cirurgia , Fígado/metabolismo , Pessoa de Meia-Idade , Período Pós-Operatório , Trítio , Neoplasias Uterinas/cirurgia
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