Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A prototype laser-fiber optic based sensor for in situ monitoring of nicotinamide adenine dinucleotide (NADH) has been developed. This system is based on a compact neodymium-yttrium-aluminum-garnet (Nd:YAG) laser with associated harmonic generators. Light distribution to and from tissue is handled by a fiber optic network, including a long optical fiber to be inserted into the target tissue. Immobilizing the enzyme lactate dehydrogenase on the fiber tip converts the monitoring channel into a lactate sensor. A new dual beam reflection approach for blood volume artifact compensation is tested. Detection sensitivity of free NADH in the micromolar region is achieved. The method and system configuration appear feasible for continuous in situ monitoring of two important indices of ischemia and hypoxia in a clinical setting.
 ...
PMID:Tissue viability measurement by in situ fluorometry. 145 92

Oxygenated cardioplegic solutions can deliver sufficient oxygen to support aerobic metabolism of heart tissue during cardiac arrest, but little is known about oxygen use after cardioplegic solution infusion. Exhaustion of myocardial oxygen stores after infusion of oxygenated crystalloid cardioplegic solution or Krebs-Henseleit buffer was measured in rat hearts. Since nicotinamide adenine dinucleotide accumulates when mitochondria become anaerobic, the epicardium was monitored during perfusion and ischemia. As ischemia progressed, nicotinamide adenine dinucleotide fluorescence increased, indicating exhaustion of oxygen. After buffer perfusion, at 37 degrees C, 50% of peak fluorescence was seen at 13 +/- 1 seconds and 90% at 37 +/- 3 seconds. Oxygenated cardioplegic solution increased these intervals to 57 +/- 6 and 114 +/- 9 seconds, respectively. Oxygenated cardioplegic solution at 10 degrees C increased the time to 50% fluorescence to 238 +/- 12 seconds and to 90% to 320 +/- 14 seconds. Differences between buffer and cardioplegic solution were less at 10 degrees C. Aerobic metabolism was completely abolished 6 minutes after infusion of 10 degrees C oxygenated cardioplegic solution. Maintenance of continuous aerobic metabolism during surgical cardiac arrest would require frequent administration of oxygenated crystalloid cardioplegic solution.
 ...
PMID:Effects of oxygenated cardioplegic solutions on myocardial aerobic metabolism. 151 53

The metabolic basis for the enhanced tolerance of immature hearts to ischemia remains to be elucidated. Loss of high-energy phosphate nucleotides occurs during ischemia/reperfusion in mature (adult) hearts through the breakdown of adenosine triphosphate, diphosphate, and monophosphate (nondiffusible) to adenosine (freely diffusible). However, previous work has shown that after ischemia nondiffusible nucleotides are better retained by immature (neonatal) hearts than by mature hearts. The enzyme responsible for the conversion of adenosine monophosphate to adenosine is 5'-nucleotidase. We therefore hypothesized lower activity of this enzyme in neonatal than in adult myocardium. The purposes of this study were (1) to document 5'-nucleotidase activities in neonatal and adult rabbit myocardium and (2) to correlate differences of 5'-nucleotidase activity with functional recovery from ischemia. Neonatal (5- to 10-day-old) and adult (4- to 6-month-old) rabbit hearts were isolated and perfused (retrograde Langendorff). A left ventricular balloon measured functional parameters. Hearts were subjected to 20 minutes of global 37 degrees C ischemia and 10 minutes of reperfusion followed by freeze clamping. Tissue homogenates were assayed for 5'-nucleotidase by the linked formation of nicotinamide-adenine dinucleotide at 340 nm (Arkesteijn method). Postischemic recovery of developed pressure was 86% +/- 3% in neonates (n = 5) versus 38% +/- 3% in adults (n = 8) (mean +/- standard deviation) (p less than 0.01). 5'-Nucleotidase activity was 4400 +/- 1208 nmol/min/gm in neonates (n = 5) versus 13,938 +/- 830 nmol/min/gm in adults (n = 8) (mean +/- standard deviation) (p less than 0.01). We conclude that (1) 5'-nucleotidase activity is 68% lower in neonatal than in adult myocardium and (2) functional recovery after ischemia inversely relates to 5'-nucleotidase activity.
 ...
PMID:Cardiac 5'-nucleotidase activity increases with age and inversely relates to recovery from ischemia. 173 85

Calcium ion can enter ischemic neurons through both receptor-operated and voltage-sensitive Ca2+ channels. To attenuate this Ca2+ entry and Ca2(+)-induced neuronal injury, we tried a combined treatment with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist, MK-801, and the dihydropyridine calcium antagonist, nimodipine, in a cat middle cerebral artery occlusion (1 hour) and reperfusion (3 hours) model. We measured changes in cytosolic free calcium, nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide redox state, and blood flow in the cat cortex using a newly developed fluorometric technique with indo-1, a fluorescent intracellular Ca2+ indicator. The combined treatment, starting 5 minutes into ischemia, was effective in reducing both Ca2+ entry and histologic damage and in enhancing recovery of the electroencephalogram following reperfusion. MK-801 alone was also effective, but to a lesser extent. These data suggest that the dual blockade of Ca2+ entry using MK-801 and nimodipine may be a useful tool for protection against ischemic brain damage.
 ...
PMID:Combined therapy with MK-801 and nimodipine for protection of ischemic brain damage. 204 61

To assess the effects of left ventricular chamber volume on the mechanism of changes in left ventricular developed pressure we performed phosphorous-31 nuclear magnetic resonance spectroscopy, hydrogen-1 nuclear magnetic resonance spectroscopy with a shift reagent, two-dimensional echocardiography, atomic absorption spectrophotometry, microsphere analysis, and surface fluorometry on isovolumic isolated perfused rat hearts with incremental intraventricular balloon volumes, while left ventricular pressure was concurrently monitored. A three-phasic response of developed pressure was noted: 0 to 100 microliters balloon volumes resulted in an increase in developed pressure, whereas developed pressure remained constant at 250 microliters and fell at 400 microliters. Oxygen consumption and [Ca2+]i transients followed the same pattern as developed pressure and coronary flow. Intraventricular volumes of 250 microliters or greater (a volume overload) caused endocardial ischemia, a greater decrease in extracellular versus intracellular water, thinning of the left ventricular free wall, and an increase in chamber size. Mechanical pressure on the tissue, induced by the volume overload, caused ischemia as further evidenced by (1) a negative effect on developed pressure, (2) a decrease in [Ca2+]i transients, (3) a [Ca2+]i overload, (4) a moderate decrease in the phosphorylation potential, and (5) an increase in the oxidation-reduction state (nicotinamide-adenine dinucleotide). The high intracellular calcium associated with volume overload may have been due to both compression and ischemia, which leads to an increased number of cross-bridges in rigor, a high end-diastolic pressure, and an increase in wall stress.
 ...
PMID:Mechanism for depressed cardiac function in left ventricular volume overload. 199 Jul 59

During operation, biopsies from the gastrocnemius muscle and, in some cases, from the sartorius muscle were taken from 32 patients with peripheral arterial occlusive disease and from 5 subjects with normal peripheral circulation. In patients with inadequate circulation only during exercise, when compared with the control group, increased activities of enzymes involved in oxidative metabolism (malate dehydrogenase, nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase, cytochrome C oxidase, creatine kinase), in amino acid metabolism (asparate aminotransferase, alanine aminotransferase), and in anaerobic glycoysis (lactate dehydrogenase) were found. In patients with circulatory disturbances that manifested themselves already at rest, enzyme activities were, with the exception of LDH, lower than those of patients with exclusively exercise-related insufficiency. By means of intraindividual comparisons with the corresponding enzyme activities in the sartorius muscle, the author was able to show that the changes found were not simply the result of differences in training conditions. The diminished concentrations of energy-rich phosphate are an expression of the anaerobic metabolic state in patients with inadequate circulation at rest. It is concluded that chronic ischemia of muscle leads to changes in the energy metabolism of the cell. In the presence of more nearly adequate circulation at rest, the portion of oxidative potential of the total energy metabolism increases. In contrast, if there is an inadequate circulation at rest, the mainly anaerobic glycolysis becomes quantitatively predominant.
 ...
PMID:Investigations on the biochemical characteristics of chronically underperfused muscle. 201 45

To further define the ontogeny of "excitotoxic" injury to brain, intrastriatal injection of an N-methyl-D-aspartate agonist (quinolinate) and a non-N-methyl-D-aspartate agonist (quisqualate) was performed in rats at postnatal days 7 and 14, and in adults. Excitotoxic injury was quantified volumetrically and with neuronal counts of nicotine adenine dinucleotide phosphate-containing neurons as this cell population is spared in neonatal hypoxia ischemia. Only postnatal day 7 pups injected with quinolinic acid showed selective sparing of neurons containing the enzyme nicotinamide adenine dinucleotide phosphate. At postnatal day 14 and later ages, nicotinamide adenine dinucleotide phosphate neurons were susceptible to the actions of both quinolinic and quisqualic acids. The unusual sparing of nicotinamide adenine dinucleotide phosphate-reactive neurons after N-methyl-D-aspartate receptor agonist exposure in the first week of life appears to be unique to the neonatal brain and may be related to the pathophysiology of neonatal hypoxia-ischemia.
 ...
PMID:Ontogeny of excitotoxic injury to nicotinamide adenine dinucleotide phosphate diaphorase reactive neurons in the neonatal rat striatum. 214 27

This study documents the value of continuous observation of nicotinamide adenine dinucleotide (NADH) fluorescence (NADH-F). NADH-F monitoring is used to identify ischemic regions for the recognition of minor technical failures associated with ischemia and reperfusion experiments in the isolated perfused heart system. The visualization of NADH-F is possible by simply irradiating the heart with ultraviolet light. Rat hearts, in the working-heart mode, were subjected to occlusion/reperfusion of the left coronary artery, and analyzed. The perfusate was filtered through a 5 micron pore membrane. Out of 281 hearts which were judged to be free of technical failures by conventional physiological indices (heart rate greater than 200/min, cardiac output greater than 34 ml/min, and coronary flow 9-14 ml/min), 43 (15%) disclosed an abnormal NADH-F area prior to the coronary intervention. During coronary intervention, 29 technical failures were detected as indicated by sparse NADH-F distribution with occlusion, delayed disappearance of NADH-F upon reperfusion, or the exhibition of an abnormal NADH-F region unassociated with the coronary artery supply area. These technical failures are not detectable without the use of NADH-F, although the actual number of failures detected may depend on the skill of the operator. We recommend NADH-F monitoring for any preparations which do not contain hemoglobin, since NADH-F is an intrinsic probe for ischemia and is easily applicable to a variety of experiments.
 ...
PMID:The detection of technical failures in perfused heart with ischemia and reperfusion by epicardial NADH fluorescence. 222 7

Hypoxia and ischemia are potent stimuli to vascular growth. The mechanisms by which vascular growth is induced are unknown. During ischemia, such as that which occurs in the heart, purine and pyridine nucleotides are degraded and their metabolites accumulate. At least two of these metabolites, adenosine and nicotinamide, have previously been demonstrated to induce vascular growth. The goal of this study was to determine whether other purine and pyridine metabolites have the potential to stimulate angiogenesis in vivo, to determine the relative angiogenic potency of these metabolites, and to determine if their angiogenic effects is mediated through a direct effect on endothelial cell proliferation. Purine metabolites (adenosine, inosine, hypoxanthine, xanthine, guanosine, uric acid), the pyridine metabolite nicotinamide, and chemical derivatives of nicotinamide, were tested at various concentrations for their ability to stimulate angiogenesis in the chick choriollantoic membrane assay. Although none of the purine metabolites were effective in promoting the angiogenic response, nicotinamide as well as several derivatives of nicotinamide induced an angiogenic response in a dose-dependent manner. Nicotinamide was then evaluated to determine if its angiogenic effect is a result of a direct effect on capillary endothelial cell proliferation. In concentrations of 100 microM to 1 mM nicotinamide was not demonstrated to be mitogenic for bovine capillary endothelial cells. These results demonstrate that pyridine nucleotides are indirect angiogenic agents that do not exert a primary effect on endothelial cell proliferation. The results of this study suggest that increases in vascular growth induced by ischemia and hypoxia might be mediated, at least in part, by pyridine metabolites released from ischemic tissues.
 ...
PMID:Angiogenic potency of nucleotide metabolites: potential role in ischemia-induced vascular growth. 252 26

The effects of some components of the coenzyme nicotinamide adenine dinucleotide (NAD) on tissue viability were investigated in acute island skin flaps which were constructed to exceed the blood supply provided by a unilateral pedicle of inferior epigastric vessels. Control flaps undergo significant necrosis. Treatment with nicotinamide or nicotinic acid, precursors of NAD, prior to flap elevation significantly improved the area of viability in the random portion of the flap from 44 +/- 9% (mean +/- SD) to 67 +/- 12 and 65 +/- 5%, respectively. Similarly, NAD improved viability to 68 +/- 10% (P less than 0.001). Treatment with other components, adenosine diphosphoribose or quinolinic acid, had no effect on flap survival. The results suggest that nicotinic acid and nicotinamide deserve therapeutic consideration with regard to the treatment of ischemia/reperfusion injury in skin.
 ...
PMID:Improved skin flap survival with nicotinic acid and nicotinamide in rats. 253 Apr 1


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>