RESUMO
OBJECTIVES: Quantify the relationship between perioperative anaerobic lactate production, microcirculatory blood flow, and mitochondrial respiration in patients after cardiovascular surgery with cardiopulmonary bypass. DESIGN: Serial measurements of lactate-pyruvate ratio (LPR), microcirculatory blood flow, plasma tricarboxylic acid cycle cycle intermediates, and mitochondrial respiration were compared between patients with a normal peak lactate (≤ 2 mmol/L) and a high peak lactate (≥ 4 mmol/L) in the first 6 hours after surgery. Regression analysis was performed to quantify the relationship between clinically relevant hemodynamic variables, lactate, LPR, and microcirculatory blood flow. SETTING: This was a single-center, prospective observational study conducted in an academic cardiovascular ICU. PATIENTS: One hundred thirty-two patients undergoing elective cardiovascular surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with a high postoperative lactate were found to have a higher LPR compared with patients with a normal postoperative lactate (14.4 ± 2.5 vs. 11.7 ± 3.4; p = 0.005). Linear regression analysis found a significant, negative relationship between LPR and microcirculatory flow index ( r = -0.225; ß = -0.037; p = 0.001 and proportion of perfused vessels: r = -0.17; ß = -0.468; p = 0.009). There was not a significant relationship between absolute plasma lactate and microcirculation variables. Last, mitochondrial complex I and complex II oxidative phosphorylation were reduced in patients with high postoperative lactate levels compared with patients with normal lactate (22.6 ± 6.2 vs. 14.5 ± 7.4 pmol O 2 /s/10 6 cells; p = 0.002). CONCLUSIONS: Increased anaerobic lactate production, estimated by LPR, has a negative relationship with microcirculatory blood flow after cardiovascular surgery. This relationship does not persist when measuring lactate alone. In addition, decreased mitochondrial respiration is associated with increased lactate after cardiovascular surgery. These findings suggest that high lactate levels after cardiovascular surgery, even in the setting of normal hemodynamics, are not simply a type B phenomenon as previously suggested.
Assuntos
Ponte Cardiopulmonar , Ácido Láctico , Microcirculação , Mitocôndrias , Humanos , Microcirculação/fisiologia , Masculino , Estudos Prospectivos , Feminino , Ponte Cardiopulmonar/efeitos adversos , Ácido Láctico/sangue , Pessoa de Meia-Idade , Idoso , Mitocôndrias/metabolismo , Anaerobiose/fisiologia , Ácido Pirúvico/metabolismo , Ácido Pirúvico/sangueRESUMO
The exposure to extremely low-frequency electromagnetic fields (EMFs) could adversely affect the endocrine system and cellular proliferative response. Nonetheless, the use of 60-Hz EMFs in the form of magneto-therapy exerts beneficial actions on human health but can also induce hyperglycaemia. Therefore, the present study was aimed to search for metabolic responses of fed or fasted male rats to a single EMF exposure. We performed a 15 min-single exposure to 60-Hz (3.8 mT, intensity) EMF, and determined serum levels of glucose, lipids, and indicators of cellular redox state and energy parameters. A single exposure to a 60-Hz EMF induced hyperglycaemia in both animal groups, and an attenuated second serum insulin peak. The 60-Hz EMF also decreased free fatty acids and lactate serum levels, oppositely increasing pyruvate and acetoacetate levels. Significant increases in blood glucose level and rat's glucose metabolism were related to a more oxidized cellular redox state and variations in insulin and glucagon secretion. The 60-Hz EMF's effects were not modified in animals previously subjected to chronic EMFs exposure (14 days). In conclusion, increased serum glucose levels and glucose metabolism induced by a single 60-Hz EMF exposure were closely related to the cellular redox state and the insulin/glucagon ratio.
Assuntos
Campos Eletromagnéticos/efeitos adversos , Glucagon/sangue , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Insulina/sangue , Animais , Biomarcadores , Modelos Animais de Doenças , Suscetibilidade a Doenças , Metabolismo Energético , Jejum , Hiperglicemia/sangue , Ácido Láctico/sangue , Lipídeos/sangue , Metabolômica , Oxirredução , Ácido Pirúvico/sangue , RatosRESUMO
Modulation of the gut microbiota may help in treating obesity by improving host metabolic health. We aimed to evaluate the effects of probiotics or symbiotics on body weight and serum metabolite profile in women with obesity. A double-blind, parallel, randomized, controlled clinical trial was conducted with 32 adult women with body mass index ranging from 30 to 34.9 kg m-2. Volunteers followed a low-energy diet and were subjected to 8 weeks intervention: probiotic group (PG - Bifidobacterium lactis UBBLa-70, n = 10), symbiotic group (SG - Bifidobacterium lactis UBBLa-70 and fructooligosaccharide, n = 11), or control group (CG - placebo, n = 11). Analyses of anthropometric variables, gut microbiota and serum metabolites by 1H nuclear magnetic resonance (NMR) were performed at baseline and after the intervention. Multivariate statistics showed that all groups presented a decrease in glycerol and increase in arginine, glutamine and 2-oxoisovalerate. Therefore, a low-energy diet per se promoted changes in the metabolite profile related to decreased inflammation and positive effects on body weight. SG presented unique changes in metabolites (increase in pyruvate and alanine and decrease in citrate and BCAA). Negative correlations between arginine and glutamine with fat mass were observed in the SG. PG presented a decrease in 1H NMR lipid signals and negative correlation between Verrucomicrobia and Firmicutes with (CH2)n lipids. Both probiotics and symbiotics promoted changes in metabolites related to improved metabolic health. Specific metabolite changes following symbiotic intervention might suggest some advantage in providing Bifidobacterium lactis in combination with fructooligosaccharide in a low-energy diet, rather than probiotics or diet alone. Clinical trial: NCT02505854.
Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Obesidade , Oligossacarídeos , Probióticos , Simbióticos , Adulto , Aminoácidos/sangue , Bifidobacterium animalis , Ácido Cítrico/sangue , Método Duplo-Cego , Feminino , Humanos , Inflamação/metabolismo , Obesidade/dietoterapia , Obesidade/metabolismo , Oligossacarídeos/farmacologia , Oligossacarídeos/uso terapêutico , Probióticos/farmacologia , Probióticos/uso terapêutico , Ácido Pirúvico/sangueRESUMO
The aim of this study was to investigate the effect of lactatemia elevation and glycemia reduction on strenuous swimming performance in fasted rats. Three rats were placed in a swimming tank at the same time. The first rat was removed immediately (control group) and the remaining ones were submitted to a strenuous swimming session. After the second rat was exhausted (Exh group), the third one was immediately removed from the water (Exe group). According to the period of time required for exhaustion, the rats were divided into four groups: low performance (3-7 min), low-intermediary performance (8-12 min), high-intermediary performance (13-17 min), and high performance (18-22 min). All rats were removed from the swimming tanks and immediately killed by decapitation for blood collection or anesthetized for liver perfusion experiments. Blood glucose, lactate, and pyruvate concentrations, blood lactate/pyruvate ratio, and liver lactate uptake and its conversion to glucose were evaluated. Exhaustion in low and low-intermediary performance were better associated with higher lactate/pyruvate ratio. On the other hand, exhaustion in high-intermediary and high performance was better associated with hypoglycemia. Lactate uptake and glucose production from lactate in livers from the Exe and Exh groups were maintained. We concluded that there is a time sequence in the participation of lactate/pyruvate ratio and hypoglycemia in performance during an acute strenuous swimming section in fasted rats. The liver had an important participation in preventing hyperlactatemia and hypoglycemia during swimming through lactate uptake and its conversion to glucose.
Assuntos
Hipoglicemia/fisiopatologia , Ácido Láctico/sangue , Fígado/fisiopatologia , Ácido Pirúvico/sangue , Natação/fisiologia , Animais , Glicemia/análise , Jejum/fisiologia , Hipoglicemia/sangue , Hipoglicemia/metabolismo , Masculino , Perfusão , Condicionamento Físico Animal/fisiologia , Ratos , Ratos Wistar , Fatores de TempoRESUMO
The aim of this study was to investigate the effect of lactatemia elevation and glycemia reduction on strenuous swimming performance in fasted rats. Three rats were placed in a swimming tank at the same time. The first rat was removed immediately (control group) and the remaining ones were submitted to a strenuous swimming session. After the second rat was exhausted (Exh group), the third one was immediately removed from the water (Exe group). According to the period of time required for exhaustion, the rats were divided into four groups: low performance (3-7 min), low-intermediary performance (8-12 min), high-intermediary performance (13-17 min), and high performance (18-22 min). All rats were removed from the swimming tanks and immediately killed by decapitation for blood collection or anesthetized for liver perfusion experiments. Blood glucose, lactate, and pyruvate concentrations, blood lactate/pyruvate ratio, and liver lactate uptake and its conversion to glucose were evaluated. Exhaustion in low and low-intermediary performance were better associated with higher lactate/pyruvate ratio. On the other hand, exhaustion in high-intermediary and high performance was better associated with hypoglycemia. Lactate uptake and glucose production from lactate in livers from the Exe and Exh groups were maintained. We concluded that there is a time sequence in the participation of lactate/pyruvate ratio and hypoglycemia in performance during an acute strenuous swimming section in fasted rats. The liver had an important participation in preventing hyperlactatemia and hypoglycemia during swimming through lactate uptake and its conversion to glucose.
Assuntos
Animais , Masculino , Ratos , Hipoglicemia/fisiopatologia , Ácido Láctico/sangue , Fígado/fisiopatologia , Ácido Pirúvico/sangue , Natação/fisiologia , Glicemia/análise , Jejum/fisiologia , Hipoglicemia/sangue , Hipoglicemia/metabolismo , Perfusão , Condicionamento Físico Animal/fisiologia , Ratos Wistar , Fatores de TempoRESUMO
OBJECTIVES: To assess the accuracy of blood lactate and lactate: pyruvate molar ratio (L:P) as a screen for mitochondrial, respiratory chain, or fatty acid oxidation disorders in children with pediatric acute liver failure (PALF); to determine whether serum lactate ≥ 2.5 mmol/L or L:P ≥ 25 correlated with biochemical variables of clinical severity; and to determine whether lactate or L:P is associated with clinical outcome at 21 days. STUDY DESIGN: Retrospective review of demographic, clinical, laboratory, and outcome data for PALF study group participants who had lactate and pyruvate levels collected on the same day. RESULTS: Of 986 participants, 110 had lactate and pyruvate levels collected on the same day. Of the 110, the etiology of PALF was a mitochondrial disorder in 8 (7%), indeterminate in 65 (59%), and an alternative diagnosis in 37 (34%). Lactate, pyruvate, and L:P were similar among the 3 etiologic groups. There was no significant association between the initial lactate or L:P and biochemical variables of clinical severity or clinical outcome at 21 days. CONCLUSIONS: A serum lactate ≥ 2.5 mmol/L and/or elevated L:P was common in all causes of PALF, not limited to those with a mitochondrial etiology, and did not predict 21-day clinical outcome. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00986648.
Assuntos
Ácido Láctico/sangue , Falência Hepática Aguda/diagnóstico , Doenças Mitocondriais/diagnóstico , Ácido Pirúvico/sangue , Sistema de Registros , Adolescente , Fatores Etários , Biomarcadores/sangue , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/cirurgia , Transplante de Fígado , Modelos Logísticos , Masculino , Doenças Mitocondriais/sangue , Doenças Mitocondriais/mortalidade , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To examine levels of lactate (LA) and pyruvate (PA) in both blood and cerebrospinal fluid (CSF) in patients with Menkes disease (MNK). STUDY DESIGN: A nationwide survey involving a retrospective review of medical records or medical record summaries of 42 male patients with MNK born between 1993 and 2008 were performed, and the genetic analysis of their ATP7A gene was reviewed. RESULTS: In these patients, LA and PA levels and the lactate vs pyruvate ratio (L/P ratio) at diagnosis in both blood and CSF were abnormally high. There were no significant differences in LA levels, PA levels, and the L/P ratio between blood and CSF at diagnosis (P > .05). There was also no correlation between LA levels, PA levels, and the L/P ratio, and age at measurement (P > .05). There was no or slight metabolic acidosis, as analyzed by blood gas analysis, in 7 patients. During treatment with subcutaneous injections of copper-histidine, LA and PA levels and the L/P ratio in both the blood and CSF decreased. CONCLUSION: Our findings suggest that LA and PA levels, and in particular, the L/P ratio, and blood gas analysis can be used to guide the diagnosis and management of MNK.
Assuntos
Ácido Láctico/sangue , Ácido Láctico/líquido cefalorraquidiano , Síndrome dos Cabelos Torcidos/sangue , Síndrome dos Cabelos Torcidos/líquido cefalorraquidiano , Ácido Pirúvico/sangue , Ácido Pirúvico/líquido cefalorraquidiano , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
PURPOSE: To investigate the effects of preventive enteral administration of ornithine alpha-ketoglutarate (OKG) in an ischemia-reperfusion rat model. METHODS: Sixty rats were randomized into five groups (G1-G5, n = 12). Each group was divided into two subgroups (n = 6) and treated with calcium carbonate (CaCa) or OKG by gavage. Thirty minutes later, the animals were anesthetized with xylazine 15mg + ketamine 1mg ip and subjected to laparotomy. G1-G3 rats served as controls. Rats in groups G4 and G5 were subjected to ischemia for 30 minutes. Ischemia was achieved by clamping the small intestine and its mesentery, delimiting a segment of bowel 5 cm long and 5 cm apart from the ileocecal valve. In addition, G5 rats underwent reperfusion for 30 minutes. Blood samples were collected at the end of the laparotomy (G1), after 30 minutes (G2, G4) and 60 minutes (G3, G5) to determine concentrations of metabolites (pyruvate, lactate), creatine phosphokinase (CPK), thiobarbituric acid reactive substances (TBARS) and glutathione (GSH). RESULTS: There was a significant decrease in tissue pyruvate and lactate and plasma CPK levels in OKG-treated rats at the end of reperfusion period. GSH levels did not change significantly in ischemia and reperfusion groups. However, TBARS levels increased significantly (p<0.05) in tissue samples in OKG-treated rats subjected to ischemia for 30 minutes. CONCLUSION: Short-term pretreatment with OKG before induction of I/R decreases tissue damage, increases pyruvate utilization for energy production in the Krebs cycle and does not attenuate the oxidative stress in this animal model.
Assuntos
Enteropatias/prevenção & controle , Intestino Delgado/irrigação sanguínea , Isquemia/complicações , Ornitina/análogos & derivados , Traumatismo por Reperfusão/prevenção & controle , Animais , Carbonato de Cálcio/sangue , Carbonato de Cálcio/uso terapêutico , Modelos Animais de Doenças , Intestino Delgado/efeitos dos fármacos , Isquemia/sangue , Ácido Láctico/sangue , Ligadura , Ornitina/sangue , Ornitina/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Ácido Pirúvico/sangue , Distribuição Aleatória , Ratos , Traumatismo por Reperfusão/sangue , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the metabolic and oxidative effects of sevoflurane and propofol in children undergoing surgery for correction of congenital heart disease. METHODS: Twenty children with acyanotic congenital heart disease, scheduled for elective cardiac surgery with cardiopulmonary bypass, age range 1 day to 14 years were randomly assigned to 2 groups: Group GP, programmed to receive total intravenous anesthesia with propofol and group GS scheduled to use balanced anesthesia with sevoflurane. Exclusion criteria were cyanotic heart disease or complex, association with other malformations, severe systemic diseases, infection or children undergoing treatment and palliative or emergency surgery. Blood samples were collected at three different time-points: T0, after radial artery cannulation, T1, 30 minutes after cardiopulmonary bypass (CPB) launch and T2, at the end of procedure. Parameters analyzed included thiobarbituric acid-reactive substance (TBARS), glutathione (GLN), lactate and pyruvate plasmatic concentrations. RESULTS: TBARS, GSH, lactate and pyruvate concentrations did not change significantly by Friedman´s test. Lactate/pyruvate ratio (L/P) was >10 in both groups. There was a moderate Pearson correlation for TBARS, in T1 (r=0.50; p=0.13) e T2 (r=0.51;p=0.12). Pearson correlation was high between groups during CPB (T1) for lactate (r=0.68; p=0.02), pyruvate (r=0.75; p=0.01) and L/P ratio (r=0.83; p=0.003). CONCLUSION: Anesthetic techniques investigated in this study showed a similar pattern, with no increase in metabolic substrates and oxidative stress during surgical correction of congenital heart defects in non-cyanotic children.
Assuntos
Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Cardiopatias Congênitas/cirurgia , Éteres Metílicos/farmacologia , Propofol/farmacologia , Adolescente , Criança , Pré-Escolar , Feminino , Glutationa/sangue , Humanos , Lactente , Recém-Nascido , Ácido Láctico/sangue , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estudos Prospectivos , Ácido Pirúvico/sangue , Sevoflurano , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de TempoRESUMO
PURPOSE: To investigate the effects of preventive enteral administration of ornithine alpha-ketoglutarate (OKG) in an ischemia-reperfusion rat model. METHODS: Sixty rats were randomized into five groups (G1-G5, n = 12). Each group was divided into two subgroups (n = 6) and treated with calcium carbonate (CaCa) or OKG by gavage. Thirty minutes later, the animals were anesthetized with xylazine 15mg + ketamine 1mg ip and subjected to laparotomy. G1-G3 rats served as controls. Rats in groups G4 and G5 were subjected to ischemia for 30 minutes. Ischemia was achieved by clamping the small intestine and its mesentery, delimiting a segment of bowel 5 cm long and 5 cm apart from the ileocecal valve. In addition, G5 rats underwent reperfusion for 30 minutes. Blood samples were collected at the end of the laparotomy (G1), after 30 minutes (G2, G4) and 60 minutes (G3, G5) to determine concentrations of metabolites (pyruvate, lactate), creatine phosphokinase (CPK), thiobarbituric acid reactive substances (TBARS) and glutathione (GSH). RESULTS: There was a significant decrease in tissue pyruvate and lactate and plasma CPK levels in OKG-treated rats at the end of reperfusion period. GSH levels did not change significantly in ischemia and reperfusion groups. However, TBARS levels increased significantly (p<0.05) in tissue samples in OKG-treated rats subjected to ischemia for 30 minutes. CONCLUSION: Short-term pretreatment with OKG before induction of I/R decreases tissue damage, increases pyruvate utilization for energy production in the Krebs cycle and does not attenuate the oxidative stress in this animal model.
OBJETIVO: Investigar os efeitos da administração enteral preventiva de ornitina alfa-cetoglutarato (OKG) em modelo de isquemia-reperfusão no rato. MÉTODOS: Sessenta ratos foram randomizados em cinco grupos (G1-G5, n=12). Cada grupo foi redistribuído em dois subgrupos (n=6) e tratado com carbonato de cálcio (CaCa) ou OKG por gavagem. Trinta minutos mais tarde, os animais foram anestesiados com xilazina 1mg+cetamina 15mg i.p. e submetidos à laparotomia. Os ratos dos grupos G4-G5 foram submetidos à isquemia por 30 minutos. A isquemia foi obtida por pinçamento do intestino delgado, delimitando um segmento com 5 cm de comprimento e distando 5 cm da válvula ileocecal. O grupo G5 foi submetido à reperfusão por 30 minutos. Amostras de sangue foram coletadas no final da laparotomia (G1), após 30 minutos (G2, G4) e 60 minutos (G3, G5) para determinação das concentrações de metabolitos (piruvato, lactato), creatinofosfoquinase (CPK), substâncias reativas ao ácido tiobarbitúrico (TBARS) e glutationa (GSH). RESULTADOS: Observou-se redução significante (p<0,05) das concentrações de piruvato e lactato, teciduais e CPK plasmático em ratos tratados com OKG, no final do período de reperfusão. Não houve alteração significante nos níveis plasmáticos e teciduais de GSH. Entretanto os níveis de TBARS aumentaram significativamente (p<0,05) em amostras de tecido de ratos tratados com OKG submetido à isquemia por 30 minutos. CONCLUSÃO: o pré-tratamento em curto prazo com OKG antes da indução da I/R diminui a lesão tecidual, aumenta a utilização de piruvato para produção de energia no ciclo de Krebs, mas não atenua o estresse oxidativo neste modelo animal.