Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT02288 (NADH)
 21,914 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in steady-state levels of reduced pyridine nucleotide (PN) recorded by continuous monitoring of surface fluorescence were correlated with changes in physiological function of perfused rat kidneys when subjected to anoxia, ischemia, hypothermia, variations in perfusion pressure, inhibition of Na-K ATPase, and uncoupling of oxidative phosphorylation. Biphasic responses of PN reduction and oxidation during ischemic cycles at varying temperatures and anoxic cycles at different perfusion pressures demonstrated the presence of two different cell populations in the kidney cortex, those with sufficient oxygen and those without. The magnitude of PN fluorescence change during ischemia increased with decreasing temperature demonstrating better tissue oxygenation during hypothermia. The measurement of mitochondrial NADH oxidation in the perfused kidney during transitions from CO anoxia to normoxia was made possible by flash photolytic activation of mitochondrial electron transport. The half time for NADH oxidation (125 ms) was independent of the rate of oxygen delivery while the initial rate and extent of reaction was faster and steeper, respectively, at higher perfusion pressure, due to a better tissue oxygenation and faster CO washout.
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PMID:Oxygen delivery in perfused rat kidney: NADH fluorescence and renal functional state. 18 9

The effects of different levels of arterial blood oxygen content (CaO2) on brain tissue adenosine triphosphate (ATP), phosphocreatine (PCr), lactate, and reduced nicotinamide adenine dinucleotide (NADH) were studied during cerebral hypoxia in normothermic and hypothermic male Wistar rats with unilateral carotid ligation. Animals were exposed to hypoxia (PaO2 19--26 torr) for 25 min, and brain tissue metabolite values measured microfluorometrically were compared with those of normothermic normoxic controls. CaO2 was 4.0 +/- 0.2 ml/dl (mean +/- SEM) at PaO2 26 torr in normothermic animals. CaO2 was increased to 8.2 +/- 0.3 ml/dl at PaO2 26 torr by means of bicarbonate infusion producing a leftward shift of the oxyhemoglobin-dissociation curve in one normothermic hypoxic group. In all normothermic hypoxic groups ATP and PCr decreased and lactate and NADH increased significantly compared with control values. There was no significant difference in brain tissue metabolite values among these groups despite an increase in CaO2 by twofold in one group. Hypothermia (32 C) resulted in CaO2 8.4 +/- 0.2 ml/dl at PaO2 26 torr. This was decreased to 4.0 +/- 0.2 ml/dl by decreasing PaO2 to 19 torr in another group at the same temperature. ATP and PCr were well preserved in both groups despite the difference in CaO2s. Although the lactate and NADH levels were increased in the hypothermic group with CaO2 4.0 +/- 0.2 ml/dl, they were significantly lower than those values in normothermic hypoxic groups. These results indicate that the increase in CaO2 produced by hypothermia is not a major determinant in hypothermic protection during cerebral hypoxia.
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PMID:Effect of high vs. low arterial blood oxygen content on cerebral energy metabolite levels during hypoxia with normothermia and hypothermia in the rat. 676 65

The effect of arterial hypotension on cerebral cortical tissue levels of adenosine triphosphate (ATP), phosphocreatine (PGr), lactate, and reduced nicotinamide adenine dinucleotide (NADH) was studied in male Wistar rats with unilateral carotid ligation exposed to arterial by hypoxia (PaO2 25 torr) for 20 min. while the body temperature was maintained at 32 degrees C and 27 degrees C. Brain metabolite levels were normal in normotensive hypothermic animals exposed to hypoxia, but reduction in arterial pressure to 75 torr caused a significant (p less than 0.05) decrease in ATP and PCr values and a significant increase in lactate and NADH levels. These changes were comparable to those of normothermic normotensive, hypoxic animals. Furthermore, there was no significant differences in the brain metabolite levels between the two hypotensive hypoxic groups. These results indicate that arterial hypotension severely alters the cerebral protective effect of hypothermia against injury caused by hypoxia, and that further reduction in body temperature (from 32 degrees C to 27 degrees C) will not prevent the harmful effect of hypoxia upon the brain in hypotensive rats.
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PMID:Reduction of the cerebral protective effect of hypothermia by oligemic hypotension during hypoxia in the rat. 680 24

A method of examining arteriolar function in situ using the in vitro-perfused hydronephrotic rat kidney is described. This approach facilitates direct visualization of arteriolar contractile responses in a well-controlled experimental environment while avoiding the consequences of traumatic microdissection and the accompanying exposure to ischemia, hypothermia, or hypoxia. The preparation has a remarkably well-preserved myogenic reactivity, exhibiting precisely graded vasoconstriction over the range in perfusion pressure subtending normal renal autoregulatory responses (i.e., 80-180 mm Hg). Using this preparation, the inhibitory effects of hypoxia on arteriolar myogenic reactivity have been demonstrated. The range over which reduced pO2 affected arteriolar reactivity in this model corresponded closely to that reported to alter vascular tone in vivo. A technique of adapting the model to incorporate simultaneous monitoring of arteriolar fluorescence measurements and contractile responses is also described. This approach has been used to examine the relationship between arteriolar contractility and NADH autofluorescence during the hypoxia-induced activation of ATP-sensitive K channels. Future applications may include the use of intravital fluorescent dyes to examine, for example, microvascular endothelial calcium signaling in an intact, functioning arteriole.
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PMID:In situ studies of renal arteriolar function using the in vitro-perfused hydronephrotic rat kidney. 886 Sep 40

Hypothermia, as well as anesthesia, are known to protect the brain against ischemia, hypoxia and other pathological damages. One of the mechanisms of this improvement could be by lowering brain function, and thereby lowering oxygen demand. We examined the effect of hypothermia on brain function and blood supply in awake and anesthetized rats and studied the interaction between partial ischemia and the responses to hypothermia. The brain function multiprobe (BFM) used enabled simultaneous measurements of cerebral blood flow (CBF), mitochondrial NADH redox state, extracellular K(+) concentration, DC potential and ECoG from the cerebral cortex in rats whose brain temperature was lowered by 5 degrees C. Hypothermia was induced in awake, anesthetized and brain ischemic-anesthetized rats. In anesthetized and ischemic-anesthetized rats, the time required for lowering the brain temperature by 5 degrees C was five times less than in the normal awake animals. No significant changes in CBF and NADH levels were found in response to hypothermia in the awake animals. In contrast, a significant decrease in extracellular K(+) concentration was recorded under hypothermia, probably due to the lower rate of depolarization. Hypothermia in anesthetized and in ischemic-anesthetized rats did not significantly affect the levels of mitochondrial NADH, CBF and extracellular K(+). Hypothermia under ischemia was expected to be more effective.
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PMID:Effect of hypothermia on brain multi-parametric activities in normoxic and partially ischemic rats. 1206 15

Presently available possibilities of macro- and microscopic diagnosis of death from hypothermia are very limited as the changes observed are either weakly specific (ecchymoses in the mucous membrane of the stomach, histological features of haemorrhagic pancreatic necrosis, cardiomyocyte necrosis or decreased content of glycogen in hepatocytes) or represent only local action of low temperatures (frostbites, violet patches in the region of knees and elbows, red livores) and they may not be present in cases of death from cooling at environmental temperature close to zero or higher. The study evaluated the usefulness of acetoacetic acid (Ac-Ac), beta-hydroxybutyric acid (beta-HBA) and acetone determinations in blood, urine and vitreous humour for diagnosis of death from hypothermia. These three substances called ketone bodies, are easily assimilated energetic substrates that get oxidized preferentially before glucose and fatty acids. In hypoglycaemia (also hypothermia-induced one), the tissues dependent on glucose (e.g. the brain) cover most of their energetic needs from oxidation of these compounds. The analysis of 16 cases of death in circumstances suggesting hypothermia (mainly of the alcohol abusers) showed that the degree of ketosis was inversely proportional to the blood ethanol concentration. This relation may result from stimulation of insulin release and a decrease in the release of its antagonists by ethanol, as well as from inhibition of free fatty acid (FFA) beta-oxidation due to increase in the NADH/NAD ratio. So, the antiketonaemic effects of ethanol (together with its influence on the dilatation of the peripheral vessels and inhibition of shivering thermogenesis by muscle relaxation), explain increased sensitivity of intoxicated persons to low temperatures.
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PMID:The influence of ethanol on the level of ketone bodies in hypothermia. 1209 31

Hypothermic perfusion of the heart decreases oxidative phosphorylation and increases NADH. Because O(2) and substrates remain available and respiration (electron transport system, ETS) may become impaired, we examined whether reactive oxygen species (ROS) exist in excess during hypothermic perfusion. A fiberoptic probe was placed on the left ventricular free wall of isolated guinea pig hearts to record intracellular ROS, principally superoxide (O(2)(-).), and an extracellular reactive nitrogen reactant, principally peroxynitrite (ONOO(-)), a product of nitric oxide (NO.) + O(2)(-). Hearts were loaded with dihydroethidium (DHE), which is oxidized by O(2)(-). to ethidium, or were perfused with l-tyrosine, which is oxidized by ONOO(-) to dityrosine (diTyr). Shifts in fluorescence were measured online; diTyr fluorescence was also measured in the coronary effluent. To validate our methods and to examine the source and identity of ROS during cold perfusion, we examined the effects of a superoxide dismutase mimetic Mn(III) tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), the nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME), and several agents that impair electron flux through the ETS: menadione, sodium azide (NaN(3)), and 2,3-butanedione monoxime (BDM). Drugs were given before or during cold perfusion. ROS measured by DHE was inversely proportional to the temperature between 37 degrees C and 3 degrees C. We found that perfusion at 17 degrees C increased DHE threefold versus perfusion at 37 degrees C; this was reversed by MnTBAP, but not by l-NAME or BDM, and was markedly augmented by menadione and NaN(3). Perfusion at 17 degrees C also increased myocardial and effluent diTyr (ONOO(-)) by twofold. l-NAME, MnTBAP, or BDM perfused at 37 degrees C before cooling or during 17 degrees C perfusion abrogated, whereas menadione and NaN(3) again enhanced the cold-induced increase in ROS. Our results suggest that hypothermia moderately enhances O(2)(-). generation by mitochondria, whereas O(2)(-). dismutation is markedly slowed. Also, the increase in O(2)(-). during hypothermia reacts with available NO. to produce ONOO(-), and drug-induced O(2)(-). dismutation eliminates the hypothermia-induced increase in O(2)(-).
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PMID:Hypothermia augments reactive oxygen species detected in the guinea pig isolated perfused heart. 1464 63

Ischemic preconditioning (IPC) induces distinctive changes in mitochondrial bioenergetics during warm (37 degrees C) ischemia and improves function and tissue viability on reperfusion. We examined whether IPC before 2 h of hypothermic (27 degrees C) ischemia affords additive cardioprotection and improves mitochondrial redox balance assessed by mitochondrial NADH and flavin adenine dinucleotide (FAD) autofluorescence in intact hearts. A mediating role of ATP-sensitive K(+) (K(ATP)) channel opening was investigated. NADH and FAD fluorescence was measured in the left ventricular wall of guinea pig isolated hearts assigned to five groups of eight animals each: hypothermia alone, hypothermia with ischemia, IPC with cold ischemia, 5-hydroxydecanoic acid (5-HD) alone, and 5-HD with IPC and cold ischemia. IPC consisted of two 5-min periods of warm global ischemia spaced 5 min apart and 15 min of reperfusion before 2 h of ischemia at 27 degrees C and 2 h of warm reperfusion. The K(ATP) channel inhibitor 5-HD was perfused from 5 min before until 5 min after IPC. IPC before 2 h of ischemia at 27 degrees C led to better recovery of function and less tissue damage on reperfusion than did 27 degrees C ischemia alone. These improvements were preceded by attenuated increases in NADH and decreases in FAD during cold ischemia and the reverse changes during warm reperfusion. 5-HD blocked each of these changes induced by IPC. This study indicates that IPC induces additive cardioprotection with mild hypothermic ischemia by improving mitochondrial bioenergetics during and after ischemia. Because effects of IPC on subsequent changes in NADH and FAD were inhibited by 5-HD, this suggests that mitochondrial K(ATP) channel opening plays a substantial role in improving mitochondrial bioenergetics throughout mild hypothermic ischemia and reperfusion.
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PMID:Warm ischemic preconditioning improves mitochondrial redox balance during and after mild hypothermic ischemia in guinea pig isolated hearts. 1565 57

We examined if sevoflurane given before cold ischemia of intact hearts (anesthetic preconditioning, APC) affords additional protection by further improving mitochondrial energy balance and if this is abolished by a mitochondrial KATP blocker. NADH and FAD fluorescence was measured within the left ventricular wall of 5 groups of isolated guinea pig hearts: (1) hypothermia alone; (2) hypothermia+ischemia; (3) APC (4.1% sevoflurane)+cold ischemia; (4) 5-HD+cold ischemia, and (5) APC+5-HD+cold ischemia. Hearts were exposed to sevoflurane for 15 minutes followed by 15 minutes of washout at 37 degrees C before cooling, 2 hours of 27 degrees C ischemia, and 2 hours of 37 degrees C reperfusion. The KATP channel inhibitor 5-HD was perfused before and after sevoflurane. Ischemia caused a rapid increase in NADH and a decrease in FAD that waned over 2 hours. Warm reperfusion led to a decrease in NADH and an increase in FAD. APC attenuated the changes in NADH and FAD and further improved postischemic function and reduced infarct size. 5-HD blocked the cardioprotective effects of APC but not APC-induced alterations of NADH and FAD. Thus, APC improves redox balance and has additive cardioprotective effects with mild hypothermic ischemia. 5-HD blocks APC-induced cardioprotective effects but not improvements in mitochondrial bioenergetics. This suggests that mediation of protection by KATP channel opening during cold ischemia and reperfusion is downstream from the APC-induced improvement in redox state or that these changes in redox state are not attenuated by KATP channel antagonism.
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PMID:Improved mitochondrial bioenergetics by anesthetic preconditioning during and after 2 hours of 27 degrees C ischemia in isolated hearts. 1611 32

Suppression of peri-infarct depolarizations (PIDs) is one of the major mechanisms of hypothermic protection against transient focal cerebral ischemia. Previous studies have shown the lack of hypothermic protection against permanent focal ischemia. We hypothesized the lack of hypothermic protection was due to the poor efficacy in suppression of PIDs. To examine the hypothesis, we elucidated the effects of hypothermia on the manner of propagation of PIDs with temporal and spatial resolutions using NADH (reduced nicotinamide adenine dinucleotide) fluorescence images by illuminating the parietal-temporal cortex with ultraviolet light. Spontaneously hypertensive rats (n=14) were subjected to permanent focal ischemia by occlusion of the middle cerebral and left common carotid arteries. 2-h hypothermia (30 degrees C) was initiated before ischemia. Although hypothermia delayed the appearance of PIDs, it did not suppress their appearance. Furthermore, 54% of the PIDs enlarged the high-intensity area of NADH fluorescence in the hypothermia group, similar to the normothermia group (53%). The high-intensity area of NADH fluorescence widened by each PID was larger in the hypothermia group than in the normothermia group. These findings suggest that PIDs even in hypothermia are one of the major factors causing growth of infarction, emphasizing the importance of therapy that targets suppression of PIDs even during hypothermia.
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PMID:Dynamic changes in cortical NADH fluorescence in rat focal ischemia: evaluation of the effects of hypothermia on propagation of peri-infarct depolarization by temporal and spatial analysis. 1897 97


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