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1.
Front Physiol ; 9: 1473, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30405433

RESUMO

Cardiovascular complications are the major cause of mortality and morbidity in diabetic patients. The changes in myocardial structure and function associated with diabetes are collectively called diabetic cardiomyopathy. Numerous molecular mechanisms have been proposed that could contribute to the development of diabetic cardiomyopathy and have been studied in various animal models of type 1 or type 2 diabetes. The current review focuses on the role of sodium (Na+) in diabetic cardiomyopathy and provides unique data on the linkage between Na+ flux and energy metabolism, studied with non-invasive 23Na, and 31P-NMR spectroscopy, polarography, and mass spectroscopy. 23Na NMR studies allow determination of the intracellular and extracellular Na+ pools by splitting the total Na+ peak into two resonances after the addition of a shift reagent to the perfusate. Using this technology, we found that intracellular Na+ is approximately two times higher in diabetic cardiomyocytes than in control possibly due to combined changes in the activity of Na+-K+ pump, Na+/H+ exchanger 1 (NHE1) and Na+-glucose cotransporter. We hypothesized that the increase in Na+ activates the mitochondrial membrane Na+/Ca2+ exchanger, which leads to a loss of intramitochondrial Ca2+, with a subsequent alteration in mitochondrial bioenergetics and function. Using isolated mitochondria, we showed that the addition of Na+ (1-10 mM) led to a dose-dependent decrease in oxidative phosphorylation and that this effect was reversed by providing extramitochondrial Ca2+ or by inhibiting the mitochondrial Na+/Ca2+ exchanger with diltiazem. Similar experiments with 31P-NMR in isolated superfused mitochondria embedded in agarose beads showed that Na+ (3-30 mM) led to significantly decreased ATP levels and that this effect was stronger in diabetic rats. These data suggest that in diabetic cardiomyocytes, increased Na+ leads to abnormalities in oxidative phosphorylation and a subsequent decrease in ATP levels. In support of these data, using 31P-NMR, we showed that the baseline ß-ATP and phosphocreatine (PCr) were lower in diabetic cardiomyocytes than in control, suggesting that diabetic cardiomyocytes have depressed bioenergetic function. Thus, both altered intracellular Na+ levels and bioenergetics and their interactions may significantly contribute to the pathology of diabetic cardiomyopathy.

2.
J Clin Monit Comput ; 32(1): 147-163, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28214930

RESUMO

The American Society of Anesthesiologist recommends peripheral physiological monitoring during general anesthesia, which offers no information regarding the effects of anesthetics on the brain. Since no "gold standard" method exists for this evaluation, such a technique is needed to ensure patient comfort, procedure quality and safety. In this study we investigated functional near infrared spectroscopy (fNIRS) as possible monitor of anesthetic effects on the prefrontal cortex. Anesthetic drugs, such as sevoflurane, suppress the cerebral metabolism and alter the cerebral blood flow. We hypothesize that fNIRS derived features carry information on the effects of anesthetics on the prefrontal cortex (PFC) that can be used for the classification of the anesthetized state. In this study, patients were continuously monitored using fNIRS, BIS and standard monitoring during surgical procedures under sevoflurane general anesthesia. Maintenance and emergence states were identified and fNIRS features were identified and compared between states. Linear and non-linear machine learning algorithms were investigated as methods for the classification of maintenance/emergence. The results show that changes in oxygenated (HbO2) and deoxygenated hemoglobin (HHb) concentration and blood volume measured by fNIRS were associated with the transition between maintenance and emergence that occurs as a result of sevoflurane washout. We observed that during maintenance the signal is relatively more stable than during emergence. Maintenance and emergence states were classified with 94.7% accuracy with a non-linear model using the locally derived mean total hemoglobin, standard deviation of HbO2, minimum and range of HbO2 and HHb as features. These features were found to be correlated with the effects of sevoflurane and to carry information that allows real time and automatic classification of the anesthetized state with high accuracy.


Assuntos
Anestesia Geral , Encéfalo/fisiopatologia , Circulação Cerebrovascular/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adulto , Algoritmos , Anestesia/métodos , Feminino , Frequência Cardíaca , Hemodinâmica , Hemoglobinas , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Oxigênio/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Reprodutibilidade dos Testes , Sevoflurano/administração & dosagem , Sociedades Médicas , Fatores de Tempo , Adulto Jovem
3.
Biomed Res Int ; 2015: 939418, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26495317

RESUMO

The standard-of-care guidelines published by the American Society of Anesthesiologists (ASA) recommend monitoring of pulse oximetry, blood pressure, heart rate, and end tidal CO2 during the use of anesthesia and sedation. This information can help to identify adverse events that may occur during procedures. However, these parameters are not specific to the effects of anesthetics or sedatives, and therefore they offer little, to no, real time information regarding the effects of those agents and do not give the clinician the lead-time necessary to prevent patient "awareness." Since no "gold-standard" method is available to continuously, reliably, and effectively monitor the effects of sedatives and anesthetics, such a method is greatly needed. Investigation of the use of functional near-infrared spectroscopy (fNIRS) as a method for anesthesia or sedation monitoring and for the assessment of the effects of various anesthetic drugs on cerebral oxygenation has started to be conducted. The objective of this paper is to provide a thorough review of the currently available published scientific studies regarding the use of fNIRS in the fields of anesthesia and sedation monitoring, comment on their findings, and discuss the future work required for the translation of this technology to the clinical setting.


Assuntos
Anestésicos Gerais/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Monitores de Consciência , Oxigênio/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Animais , Mapeamento Encefálico/métodos , Circulação Cerebrovascular/efeitos dos fármacos , Humanos , Monitorização Neurofisiológica Intraoperatória/métodos , Consumo de Oxigênio/efeitos dos fármacos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
4.
Cell Biochem Funct ; 33(2): 67-72, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25663655

RESUMO

Adenylate kinase plays an important role in cellular energy homeostasis by catalysing the interconversion of adenine nucleotides. The goal of present study was to evaluate the contribution of the adenylate kinase reaction to oxidative ATP synthesis by direct measurements of ATP using (31) P NMR spectroscopy. Results show that AMP can stimulate ATP synthesis in the presence or absence of ADP. In particular, addition of 1 mM AMP to the 0.6 mM ADP superfusion system of isolated superfused mitochondria (contained and maintained in agarose beads) led to a 25% increase in ATP synthesis as measured by the increase in ßATP signal. More importantly, we show that AMP can support ATP synthesis in the absence of ADP, demonstrated as follows. Superfusion of mitochondria without ADP led to the disappearance of ATP γ, α and ß signals and the increase of Pi . Addition of AMP to the medium restored the production of ATP, as demonstrated by the reappearance of γ, α and ß ATP signals, in conjunction with a decrease in Pi , which is being used for ATP synthesis. Polarographic studies showed Mg(2+) dependence of this process, confirming the specificity of the adenylate kinase reaction. Furthermore, data obtained from this study demonstrate, for the first time, that different aspects of the adenylate kinase reaction can be evaluated with (31) P NMR spectroscopy. SIGNIFICANCE OF RESEARCH PARAGRAPH: The data generated in the present study indicate that (31) P NMR spectroscopy can effectively be used to study the adenylate kinase reaction under a variety of conditions. This is important because understanding of adenylate kinase function and/or malfunction is essential to understanding its role in health and disease. The data obtained with (31) P NMR were confirmed by polarographic studies, which further strengthens the robustness of the NMR findings. In summary, (31) P NMR spectroscopy provides a sensitive tool to study adenylate kinase activity in different physiological and pathophysiological conditions, including but not exclusive of, cancer, ischemic injury, hemolytic anemia and neurological problems such as sensorineural deafness.


Assuntos
Monofosfato de Adenosina/metabolismo , Trifosfato de Adenosina/biossíntese , Adenilato Quinase/metabolismo , Mitocôndrias/metabolismo , Miocárdio/metabolismo , Consumo de Oxigênio , Animais , Espectroscopia de Ressonância Magnética/métodos , Polarografia/métodos , Ratos
5.
Neuroimage ; 85 Pt 1: 626-36, 2014 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-23850462

RESUMO

Endoscopic procedures performed in the United States routinely involve the use of conscious sedation as standard of care. The use of sedation reduces patient discomfort and anxiety while improving the technical quality of the procedure, and as a result, over 98% of clinicians have adopted the practice. The tremendous benefits of sedation are offset by heightened costs, increased patient discharge time, and cardiopulmonary complication risks. The inherent liabilities of putting patients under sedation have necessitated a large number of physiological monitoring systems in order to ensure patient comfort and safety. Currently American Society of Anesthesiologist (ASA) guidelines recommend monitoring of pulse oximetry, blood pressure, heart rate, and end-tidal CO2; although important safeguards, these physiological measurements do not allow for the reliable assessment of patient sedation. Proper monitoring of patient state ensures procedure quality and patient safety; however no "gold-standard" is available to determine the depth of sedation which is comparable to the anesthesiologist's professional judgment. Developments in functional near-infrared spectroscopy (fNIRS) over the past two decades have introduced cost-effective, portable, and non-invasive neuroimaging tools which measure cortical hemodynamic activity as a correlate of neural functions. Anesthetic drugs, such as propofol, operate by suppressing cerebral metabolism. fNIRS imaging methods have the ability to detect these drug related effects as well as neuronal activity through the measurement of local cerebral hemodynamic changes. In the present study, 41 patients were continuously monitored using fNIRS while undergoing outpatient elective colonoscopy with propofol sedation. The preliminary results indicated that oxygenated hemoglobin changes in the dorsolateral prefrontal cortex, as assessed by fNIRS were correlated with changes in response to bolus infusions of propofol, whereas other standard physiological measures were not significantly associated.


Assuntos
Colonoscopia/métodos , Sedação Consciente , Neuroimagem Funcional/métodos , Hipnóticos e Sedativos/farmacologia , Propofol/farmacologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Dióxido de Carbono/sangue , Interpretação Estatística de Dados , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica , Pacientes Ambulatoriais , Adulto Jovem
6.
Biochim Biophys Acta ; 1642(1-2): 53-8, 2003 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-12972293

RESUMO

To test the hypothesis that decreased hepatocyte ATP is transduced into a hepatic neuronal signal via a change in sodium pump activity, we examined the effect of 2,5-anhydro-D-mannitol (2,5-AM), which stimulates feeding behavior in rats, on intracellular sodium levels using 23Na nuclear magnetic resonance (NMR) spectroscopy. Isolated hepatocytes suspended in agarose beads were superfused with either 2.5 mM 2,5-AM or fructose in the presence of the paramagnetic shift reagent, thulium(III)(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylenephosphonate)). Superfusion with 2,5-AM decreased hepatocyte ATP and increased intracellular sodium levels compared with superfusion with either fructose or shift reagent alone starting within 15 min of exposure, reaching a maximum level of 120% of baseline by 30 min and declining gradually thereafter over the next 90 min. Superfusion with fructose, which also decreased hepatocyte ATP but by less than half the amount seen with 2,5-AM, had no significant effect on cellular sodium levels. The results support the hypothesis that changes in sodium pump activity could participate in transducing a hunger stimulus associated with hepatocyte energy status into a signal for hunger.


Assuntos
Hepatócitos/enzimologia , Fome/fisiologia , Fígado/fisiologia , Manitol/análogos & derivados , Manitol/farmacologia , Sódio/metabolismo , Trifosfato de Adenosina/deficiência , Animais , Regulação do Apetite/efeitos dos fármacos , Regulação do Apetite/fisiologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/enzimologia , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Frutose/metabolismo , Frutose/farmacologia , Hepatócitos/efeitos dos fármacos , Fome/efeitos dos fármacos , Fígado/citologia , Espectroscopia de Ressonância Magnética , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia
7.
Exp Biol Med (Maywood) ; 227(7): 520-8, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12094017

RESUMO

The possible relationships between intracellular Na(+) (Na(i)(+)), bioenergetic status and intracellular pH (pH(i)) in the mechanism for ischemic preconditioning were studied using (23)Na and (31)P magnetic resonance spectroscopy in isolated Langendorff perfused rat heart. The ischemic preconditioning (three 5-min ischemic episodes followed by two 5-min and one 10-min period of reperfusion) prior to prolonged ischemia (20 min stop-flow) resulted in a decrease in ischemic acidosis and faster and complete recovery of cardiac function (ventricular developed pressure and heart rate) after 30 min of reperfusion. The response of Na(i) during ischemia in the preconditioned hearts was characterized by an increase in Na(i)(+) at the end of preconditioning and an accelerated decrease during the first few minutes of reperfusion. During post-ischemic reperfusion, bioenergetic parameters (PCr/P(i) and betaATP/P(i) ratios) were partly recovered without any significant difference between control and preconditioned hearts. The reduced acidosis during prolonged ischemia and the accelerated decrease in Na(i)(+) during reperfusion in the preconditioned hearts suggest activation of Na(+)/H(+) exchanger and other ion transport systems during preconditioning, which may protect the heart from intracellular acidosis during prolonged ischemia, and result in better recovery of mechanical function (LVDP and heart rate) during post-ischemic reperfusion.


Assuntos
Precondicionamento Isquêmico Miocárdico , Isquemia Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Acidose/metabolismo , Animais , Metabolismo Energético , Concentração de Íons de Hidrogênio , Membranas Intracelulares/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Oxazóis/farmacologia , Perfusão , Fosfatos/metabolismo , Fosfocreatina/metabolismo , Pirimidinonas/farmacologia , Ratos , Ratos Sprague-Dawley , Sódio/metabolismo , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores
9.
J Surg Res ; 103(2): 243-51, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11922741

RESUMO

BACKGROUND: Ca(2+) overload leads to mitochondrial uncoupling, decreased ATP synthesis, and myocardial dysfunction. Pharmacologically opening of mitochondrial K(ATP) channels decreases mitochondrial Ca(2+) uptake, improving mitochondrial function during Ca(2+) overload. Ischemic preconditioning (IPC), by activating mitochondrial K(ATP) channels, may attenuate mitochondrial Ca(2+) overload and improve mitochondrial function during reperfusion. The purpose of these experiments was to study the effect of IPC (1) on mitochondrial function and (2) on mitochondrial tolerance to experimental Ca(2+) overload. METHODS: Rat hearts (n = 6/group) were subjected to (a) 30 min of equilibration, 25 min of ischemia, and 30 min of reperfusion (Control) or (b) two 5-min episodes of ischemic preconditioning, 25 min of ischemia, and 30 min of reperfusion (IPC). Developed pressure (DP) was measured. Heart mitochondria were isolated at end-Equilibration (end-EQ) and at end-Reperfusion (end-RP). Mitochondrial respiratory function (state 2, oxygen consumption with substrate only; state 3, oxygen consumption stimulated by ADP; state 4, oxygen consumption after cessation of ADP phosphorylation; respiratory control index (RCI, state 3/state 4); rate of oxidative phosphorylation (ADP/Deltat), and ADP:O ratio) was measured with polarography using alpha-ketoglutarate as a substrate in the presence of different Ca(2+) concentrations (0 to 5 x 10(-7) M) to simulate Ca(2+) overload. RESULTS: IPC improved DP at end-RP. IPC did not improve preischemic mitochondrial respiratory function or preischemic mitochondrial response to Ca(2+) loading. IPC improved state 3, ADP/Deltat, and RCI during RP. Low Ca(2+) levels (0.5 and 1 x 10(-7) M) stimulated mitochondrial function in both groups predominantly in IPC. The Control group showed evidence of mitochondrial uncoupling at lower Ca(2+) concentrations (1 x 10(-7) M). IPC preserved state 3 at high Ca(2+) concentrations. CONCLUSIONS: The cardioprotective effect of IPC results, in part, from preserving mitochondrial function during reperfusion and increasing mitochondrial tolerance to Ca(2+) loading at end-RP. Activation of mitochondrial K(ATP) channels by IPC and their improvement in Ca(2+) homeostasis during RP may be the mechanism underlying this protection.


Assuntos
Cálcio/administração & dosagem , Precondicionamento Isquêmico , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/fisiologia , Difosfato de Adenosina/metabolismo , Difosfato de Adenosina/farmacologia , Animais , Ácidos Cetoglutáricos/metabolismo , Masculino , Isquemia Miocárdica/metabolismo , Reperfusão Miocárdica , Consumo de Oxigênio , Fosforilação , Ratos , Ratos Sprague-Dawley
10.
J Surg Res ; 102(2): 221-8, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11796022

RESUMO

BACKGROUND: Coenzyme Q10 (CoQ10) protects myocardium from ischemia-reperfusion (IR) injury as evidenced by improved recovery of mechanical function, ATP, and phosphocreatine during reperfusion. This protection may result from CoQ10's bioenergetic effects on the mitochondria, from its antioxidant properties, or both. The purpose of this study was to elucidate the effects of CoQ10 supplementation on mitochondrial function during myocardial ischemia-reperfusion using an isolated mitochondrial preparation. METHODS: Isolated hearts (n = 6/group) from rats pretreated with liposomal CoQ10 (10 mg/kg iv, CoQ10), vehicle (liposomal only, Vehicle), or saline (Saline) 30 min before the experiments were subjected to 15 min of equilibration (EQ), 25 min of ischemia (I), and 40 min of reperfusion (RP). Left ventricular-developed pressure (DP) was measured. Mitochondria were isolated at end-equilibration (end-EQ), at end-ischemia (end-I), and at end-reperfusion (end-RP). Mitochondrial respiratory function (State 2, 3, and 4, respiratory control index (RCI, ratio of State 3 to 4), and ADP:O ratio) was measured by polarography using NADH (alpha-ketoglutarate, alpha-KG)- or FADH (succinate, SA)-dependent substrates. RESULTS: CoQ10 improved recovery of DP at end-RP (67 +/- 11% in CoQ10 vs 47 +/- 5% in Vehicle and 50 +/- 11% in Saline, P < 0.05 vs Vehicle and Saline). CoQ10 did not change preischemic mitochondrial function. IR decreased State 3 and RCI in all groups using either substrate. CoQ10 had no effect in the mitochondrial oxidation of alpha-KG at end-I. CoQ10 improved State 3 at end-I when SA was used (167 +/- 21 in CoQ10 vs 120 +/- 10 in Saline and 111 +/- 10 ng-atoms O/min/mg protein in Vehicle, P < 0.05). Using alpha-KG as a substrate, CoQ10 improved RCI at end-RP (4.2 +/- 0.2 in CoQ10 vs 3.2 +/- 0.2 in Saline and 3.0 +/- 0.3 in Vehicle, P < 0.05). Using SA, CoQ10 improved State 3 (181 +/- 10 in CoQ10 vs 142 +/- 9 in Saline and 140 +/- 12 ng-atoms O/min/mg protein in Vehicle, P < 0.05) and RCI (2.21 +/- 0.06 in CoQ10 vs 1.85 +/- 0.11 in Saline and 1.72 +/- 0.08 in Vehicle, P < 0.05) at end-RP. CONCLUSIONS: The cardioprotective effects of CoQ10 can be attributed to the preservation of mitochondrial function during reperfusion as evidenced by improved FADH-dependent oxidation.


Assuntos
Antioxidantes/farmacologia , Mitocôndrias/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Animais , Cardiotônicos/farmacologia , Respiração Celular , Coenzimas , Técnicas In Vitro , Masculino , Mitocôndrias/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Consumo de Oxigênio , Ratos , Ratos Sprague-Dawley
11.
Am J Physiol Regul Integr Comp Physiol ; 282(3): R710-4, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11832390

RESUMO

Administration of the fructose analog 2,5-anhydro-D-mannitol (2,5-AM) stimulates eating in rats fed a low-fat diet but not in those fed a high-fat diet that enhances fatty acid oxidation. The eating response to 2,5-AM treatment is apparently triggered by a decrease in liver ATP content. To assess whether feeding a high-fat diet prevents the eating response to 2,5-AM by attenuating the decrease in liver ATP, we examined the effects of the analog on food intake, liver ATP content, and hepatic phosphate metabolism [using in vivo 31P-NMR spectroscopy (NMRS)]. Injection (intraperitoneal) of 300 mg/kg 2,5-AM increased food intake in rats fed a high-carbohydrate/low-fat diet, but not in those fed high-fat/low-carbohydrate (HF/LC) food. Liver ATP content decreased in all rats given 2,5-AM compared with saline, but it decreased about half as much in rats fed the HF/LC diet. NMRS on livers of anesthetized rats indicated that feeding the HF/LC diet attenuates the effects of 2,5-AM on liver ATP by reducing phosphate trapping. These results suggest that rats consuming a high-fat diet do not increase food intake after injection of 2,5-AM, because the analog is not sufficiently phosphorylated and therefore fails to decrease liver energy status below a level that generates a signal to eat.


Assuntos
Gorduras na Dieta/administração & dosagem , Ingestão de Alimentos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Manitol/análogos & derivados , Manitol/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Gorduras na Dieta/farmacologia , Espectroscopia de Ressonância Magnética , Masculino , Fósforo , Ratos , Ratos Sprague-Dawley
12.
Am J Physiol Regul Integr Comp Physiol ; 282(3): R715-20, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11832391

RESUMO

The fructose analog 2,5-anhydro-D-mannitol (2,5-AM) stimulates feeding in rats by reducing ATP content in the liver. These behavioral and metabolic effects occur with rats fed a high-carbohydrate/low-fat (HC/LF) diet, but they are prevented or attenuated when the animals eat high-fat/low-carbohydrate (HF/LC) food. To examine the metabolic bases for this effect of diet, we assessed the actions of 2,5-AM on ATP content, oxygen consumption, and substrate oxidation in isolated hepatocytes from rats fed one of the two diets. Compared with cells from rats fed the HC/LF diet ("HC/LF" cells), cells from rats fed the HF/LC diet ("HF/LC" cells) had similar ATP contents but lower oxygen consumption, decreased fructose, and increased palmitate oxidation. 2,5-AM did not decrease ATP content or oxygen consumption in HF/LC cells as much as it did in HC/LF hepatocytes, and it only affected fructose and palmitate oxidation in HC/LF cells. 31P-NMR spectroscopy indicated that differences in phosphate trapping accounted for differences in depletion of ATP by 2,5-AM. These results suggest that intake of the HF/LC diet prevents the eating response and attenuates the decline in liver ATP by shifting hepatocyte metabolism to favor fat over carbohydrate as an energy-yielding substrate.


Assuntos
Gorduras na Dieta/farmacologia , Metabolismo Energético/efeitos dos fármacos , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Manitol/análogos & derivados , Manitol/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Separação Celular , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/farmacologia , Frutose/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Oxirredução , Consumo de Oxigênio/efeitos dos fármacos , Palmitatos/metabolismo , Fósforo , Ratos , Ratos Sprague-Dawley
13.
Surgery ; 131(2): 172-8, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11854695

RESUMO

Background. Ischemic preconditioning (IPC) protects the myocardium from ischemia reperfusion injury. The effect of IPC on the mitochondria is not well known. However, one of the mechanisms postulated in IPC (the opening of the mitochondrial K(ATP) channels) is likely to result in changes in mitochondrial function. Therefore, the purpose of this study was to determine the effect of IPC on mitochondrial function during ischemia reperfusion. Methods. Isolated rat hearts (n = 6/group) were subjected to (1) 30 minutes of equilibration, 25 minutes of ischemia, and 30 minutes of reperfusion (RP) (control group) or (2) 10 minutes of equilibration, two-5 minute episodes of IPC (each followed by 5 minutes of re-equilibration), 25 minutes of ischemia, and 30 minutes of RP (IPC group). Left ventricular rate pressure product (RPP) was measured. At end-equilibration (end-EQ) and at end-reperfusion (end-RP) mitochondria were isolated. Mitochondrial respiratory function (state 2, 3, and 4), respiratory control index (RCI), rate of oxidative phosphorylation (ADP/Delta t), and ADP:O ratio were measured by polarography with the use of NADH- or FADH-dependent substrates. Results. IPC improved recovery of RPP at end-RP (72% +/- 5% in IPC vs 30% +/- 4% in control, P <.05). Ischemia reperfusion (IR) decreased state 3, ADP/Delta t, and RCI in both groups compared with end-EQ. IPC improved state 3 (47 +/- 3 in IPC vs 37 +/- 2 ng-atoms O/min/mg protein in control), ADP/Delta t (17 +/- 1 in IPC vs 13 +/- 1 nmol/s/mg protein in control), and RCI (3.7 +/- 0.1 in IPC vs 2.1 +/- 0.2 in control) at end-RP compared with control with the use of NADH-dependent substrate (P <.05 vs control). IPC also improved state 3 (85 +/- 6 in IPC vs 71 +/- 4 ng-atoms O/min/mg protein in control), ADP/Delta t (18 +/- 2 in IPC vs 12 +/- 1 nmol/s/mg protein in control), RCI (2 +/- 0.1 in IPC vs 1.5 +/- 0.1 in control), and ADP:O ratios (1.4 +/- 0.04 in IPC vs 1.7 +/- 0.09 in control) at end-RP compared with control with the use of FADH-dependent substrate (P <.05 vs control). Conclusions. The cardioprotective effects of IPC can be attributed at least in part to the preservation of mitochondrial function during reperfusion.


Assuntos
Precondicionamento Isquêmico Miocárdico , Mitocôndrias Cardíacas/fisiologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Trifosfato de Adenosina/metabolismo , Animais , Cálcio/metabolismo , Masculino , Consumo de Oxigênio , Ratos , Ratos Sprague-Dawley
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