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

Phosphocreatine (PCr) is a critical intracellular energy reservoir used in the regeneration of ATP. The aim of this study was to determine the efficacy of exogenously added PCr on preservation of renal function in an in vitro model. The renal artery and ureter of a rat were cannulated and the kidney was subjected to 45 min of normothermic in vivo ischemia. The kidneys were then perfused ex vivo with either a Krebs-bicarbonate solution (Krebs) or a Krebs solution containing 3 mM PCr or an osmotically balanced solution containing 3 mM PCr. Our results indicate that the perfusion of kidneys subjected to 45 min of warm ischemia with solutions containing PCr resulted in significant improvements in GFR, RPF, and V, FRNa and FRH2O compared to KREBS alone. This suggests that the important factor in preservation of kidney function after an initial ischemic insult may be the addition of PCr rather that the electrolyte solution used.
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PMID:Amelioration of renal ischemic injury by phosphocreatine. 192 64

We used phosphorus-31 nuclear magnetic resonance spectroscopy in a rat model of 10 minutes' severe incomplete forebrain ischemia (two-vessel occlusion with hypotension) to study the effects of preischemic and postischemic treatment with 3 mg/kg i.v. U74006F on the recovery of high-energy phosphates and intracellular pH during early reperfusion. The mean +/- SD time to 85% recovery of phosphocreatine was 14.1 +/- 8.4 minutes in the control group (n = 10) compared with 6.6 +/- 3.5 minutes (p less than 0.05) in the preischemic (n = 8) and 4.2 +/- 1.0 minutes (p less than 0.001) in the postischemic (n = 11) treatment groups. The mean +/- SD time to 80% recovery of adenosine triphosphate was 15.4 +/- 8.5 minutes in the control group compared with 6.3 +/- 1.8 (p less than 0.005) and 5.4 +/- 2.8 (p less than 0.001) minutes in the preischemic and postischemic treatment groups, respectively. There were no differences in intracellular pH between the control and either of the treatment groups. We conclude that U74006F led to quicker recovery of high-energy phosphates during early reperfusion, and this beneficial effect was also seen with postischemic treatment.
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PMID:Quicker metabolic recovery after forebrain ischemia in rats treated with the antioxidant U74006F. 192 63

The effect of lidocaine on the ischemic nor-mothermic rat heart was studied in a Langendorff preparation. Ventricular fibrillation, total retrograde coronary flow and effluent lactate concentration were monitored in preischemia (control), ischemia (20 min) and reperfusion (20 min). Myocardial metabolites were determined in specimens excised at termination of reperfusion. Six hearts were infused with lidocaine in Ringer solution at onset of ischemia (group A) and six with only Ringer solution (group B). Sinus rhythm proceeded directly to diastolic arrest after 17 sec in group A, while all group B hearts showed ventricular fibrillation before arrest at 174 sec. Effluent lactate concentration was reduced in group A during the first 10 min of ischemia, but not subsequently. After 10 min of reperfusion, coronary flow was reduced by 12% in group A and 20% in group B. ATP was higher and ADP, AMP and IMP were lower in group A than in group B after 20 min of reperfusion. Creatine phosphate showed no intergroup difference, but creatine was higher in group B. Cardiac arrest with lidocaine thus reduced lactate formation during ischemia and lessened high-energy phosphate depletion after reperfusion.
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PMID:The effect of lidocaine on myocardial ischemia with asanguinous reperfusion. An in vitro study. 194 8

We studied the effects of rapid atrial pacing during the final 10 minutes of a 70-minute, 31% reduction in coronary blood flow in anesthetized swine to understand the significance of apparent metabolic improvements during the initial 60 minutes of segmental ischemia. Within 5-10 minutes of ischemia, subendocardial phosphocreatine (PCr) and ATP were depleted to 47% and 63% of control, respectively; lactate accumulated within the subendocardium to 300% of control; and net arteriovenous lactate production occurred. Despite continued ischemia and no significant changes in the external determinants of myocardial oxygen consumption, by 60 minutes subendocardial PCr and lactate contents returned to near control levels and there was net arteriovenous lactate consumption. Ischemic left ventricular wall thickening and ATP levels remained depressed throughout the experiment. Atrial pacing during the final 10 minutes of ischemia again resulted in depletion of PCr and lactate production. Since the myocardium was capable of hydrolyzing PCr in response to atrial pacing at 60 minutes of ischemia, we conclude it was capable of hydrolyzing PCr during the period of constant ischemia when instead it was accumulating PCr. We propose the ischemic myocardium downregulates regional energy requirements below blood flow-limited rates of energy production during ischemia. This appears to be an active adaptation to ischemia and not a result of passive damage or cellular injury.
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PMID:Active downregulation of myocardial energy requirements during prolonged moderate ischemia in swine. 195 70

Isolated perfused guinea pig hearts were arrested by a high K+ cardioplegic solution containing (PG group) or lacking (control group) 10 mM phosphocreatine + 15 mM glutamate. Total normothermic ischemia lasted 45 min followed by 30 min reperfusion. Mitochondrial respiration in the absence and presence of different concentrations of ADP and creatine was studied in biopsy samples (6-8 mg) after saponin treatment. The samples were taken before and after ischemia, as well as after the reperfusion period. A slightly better relative recovery of developed pressure (RRDP) in PG group was associated with higher mitochondrial acceptor control ratio after reperfusion (5.74 +/- 0.32 vs. 4.54 +/- 0.21 in PG and control groups, resp., p less than 0.01). When the results obtained in both groups were treated together, tight correlations between the pre- or postischemic mitochondrial state and RRDP were revealed. Higher values of RRDP were found for the hearts with lower preischemic values of (low ADP + creatine)-stimulation of mitochondrial respiration (r = -0.57, p less than 0.01). Relative changes in this mitochondrial parameter during ischemic period were in a good correlation with the RRDP (r = 0.82, p less than 0.001). The data suggest that the study of the mitochondrial function in myocardial biopsy samples before ischemia and reperfusion could provide a useful information for the prognosis of cardiac function recovery.
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PMID:Mitochondrial respiration in myocardial biopsy samples as a criterion of postischemic recovery of the cardiac contractility. 197 19

Ischemia and subsequent reperfusion with 5.5 mM glucose or sodium acetate were studied for impact on energy metabolism of the guinea pig isolated heart and glutamate, aspartate, and alanine levels in it and myocardial outflow. Acetate reperfusion resulted in a more significant reduction in the pool of adenine nucleotides and total creatine (phosphocreatine + creatine) by 48 and 60% of the baselines, respectively than did glucose reperfusion (as much as 65 and 76% reduction, respectively). The total glutamate and aspartate pool was twice as less as the baseline after reperfusion with any of the substrates, with acetate, tissue glutamate concentration was decreased by 42% of the baseline, whereas with glucose, it was reduced by as much as 62%. The consumption of amino acids was largely associated with their implication in alanine synthesis, which was stimulated by glycolysis/glucogenolysis at the early stage of reperfusion. The residue glutamate and aspartate contents in the reperfused hearts positively correlated with the pool of adenine nucleotides, total creatine, and the recovery of myocardial contractility. The findings suggest that the myocardial levels of these amino acids are closely associated with its energy state following ischemia and thus may affect the recovery of cardiac contractility.
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PMID:[Relations of glutamate and aspartate contents of the heart and its energy state after ischemia]. 197 60

After ligation of the left coronary artery, porcine cardiac mitochondria were isolated by homogenizing the tissue and treating the myofibrillar pellet with nagarse. When compared with unligated controls, the ischemic myocardium showed decreases in phosphocreatine (to 41%), ATP (to 56%) and in the mitochondrial respiratory control index (to 69% and 78% as measured with glutamate and succinate respectively). No changes were found in the corresponding P/O ratios. Similar results were obtained upon separation of the mitochondria into two main fractions by a density gradient technique, though only one of these fractions showed a fall in succinate-supported respiration. The results suggest that ischemia decreases the NADH-dehydrogenase activity of cardiac mitochondria.
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PMID:Changes in myocardial mitochondrial respiration after ligation of the coronary artery in pigs. 198 32

The metabolic brain acidosis after trauma has been thought to be harmful and to contribute to neurological deterioration. Amelioration of the brain acidosis either by systemic buffering agents or by hyperventilation has been proposed as a method of treatment. The objective of this study was to explore with magnetic resonance (MR) spectroscopy the metabolic changes in brain that occur with the use of hyperventilation, THAM (tromethamine; tris[hydroxymethyl]aminomethane), and a combination (THAM and hyperventilation) therapy in experimental fluid-percussion injury. Brain lactate, brain pH, inorganic phosphate (Pi), and adenosine triphosphate levels were measured by 1H and 31P MR spectroscopy. Arterial and cerebrovenous lactate and water content in brain tissue was determined in 29 cats using the specific gravimetric technique. Following injury, the phosphocreatine (PCr)/Pi ratio, which is an index of cerebral energy depletion, decreased to 76% in four untreated animals, to 79% in 11 THAM-treated animals, to 68% in seven animals receiving hyperventilation, and to 66% in seven animals with combination THAM and hyperventilation therapy. The PCr/Pi ratio returned to a normal level in 8 hours in animals treated with THAM and THAM in combination with hyperventilation. The brain lactate index increased to 157% in the hyperventilation group after trauma. In cats receiving THAM plus hyperventilation, the brain lactate index was reduced to 142%, while the minimum rise of 126% was associated with treatment of THAM alone. In the THAM-treatment and combination-treatment groups, the water content of the white and gray matter was significantly decreased compared with that in untreated cat brains. Prolonged hyperventilation provided relative ischemia in brain tissue and promoted more production of brain lactate, no recovery of the PCr/Pi ratio, and no decrease in brain edema. On the other hand, administration of THAM decreased production of brain lactate and brain edema and promoted the recovery of cerebral energy dysfunction. It was found that THAM ameliorates the deleterious effects of hyperventilation by minimizing energy disturbance and that it also decreases brain edema. The authors conclude that THAM may be effective in reducing brain tissue acidosis and helpful as a metabolic stabilizing agent following severe head injury.
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PMID:Effects of tromethamine and hyperventilation on brain injury in the cat. 198 13

The basis of early ischemic contractile failure was investigated in perfused ferret hearts at 27 degrees C. Isovolumic left ventricular developed pressure fell by more than 50% within 30 seconds of the onset of total global ischemia and reached zero by 5 minutes. Monophasic action potential recordings revealed no decrease in excitability during this period. Phosphorus nuclear magnetic resonance spectra obtained at 30-second resolution showed no significant changes in inorganic phosphate or phosphocreatine during the first 30 seconds of ischemia. Intracellular pH (pHi) and ATP changed even more slowly; therefore, none of these metabolites could account for the rapid fall in force. To gauge the contribution of intravascular pressure, we compared ordinary aortic flow occlusion with tissue-level ischemia induced by massive coronary microembolization at the level of the precapillary arterioles. Functional depression developed significantly more slowly in the microembolized hearts, despite accumulation of inorganic phosphate and protons comparable with that in ordinary ischemia. After microembolization, the time course of functional depression reflected much more closely the concomitant inorganic phosphate and pHi changes. Thus, our results provide novel evidence supporting the importance of vascular collapse in the mechanism of early ischemic contractile failure.
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PMID:Mechanism of early ischemic contractile failure. Inexcitability, metabolite accumulation, or vascular collapse? 198 66

The effect of adenosine receptor antagonism on function and metabolism was examined in isolated hearts during low flow ischemia and reperfusion. Isovolumic rat hearts perfused at constant flow were subjected to 30 min of ischemia followed by 30 min of reperfusion. Infusion of vehicle or 10 microM 8-phenyltheophylline (8-PT) was initiated 10 min before ischemia and maintained throughout reperfusion. 8-PT infusion had no significant effects on hemodynamic parameters or metabolism preischemia. During ischemia, left ventricular developed pressure declined to approximately 15% of preischemic values in control and 8-PT hearts, and ATP and PCr decreased to approximately 73 and 60% of preischemic values. Inorganic phosphate (Pi) increased to 353 = 41 and 424 +/- 53% of preischemic values in control and 8-PT hearts, respectively. After reperfusion, function recovered to greater than 95% of preischemic levels in control and 8-PT hearts. Unlike control hearts, recovery of metabolites was significantly different during reperfusion in 8-PT hearts (P less than 0.05); ATP, phosphocreatine, and Pi recovered to 82 +/- 8, 71 +/- 8, and 281 +/- 27% of preischemic values, respectively. Venous purine washout was significantly greater (P less than 0.05) during reperfusion in 8-PT hearts (327 +/- 113 nmol) than in control hearts (127 +/- 28 nmol). Blockade of adenosine receptors appears to adversely affect metabolic but not functional recovery in the ischemic-reperfused myocardium.
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PMID:Adenosine antagonism decreases metabolic but not functional recovery from ischemia. 199 97


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