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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The brain is a highly differentiated organ, exhibiting a variety of local metabolic and hemodynamic responses to ischemia. Several analytical strategies are useful in characterizing these abnormalities: these include the direct assay of tissue metabolites; topographic methods for depicting regional patterns of NADH, ATP, glucose, lactate, and pH; in vivo spectroscopic methods for analyzing mitochondrial redox state over time; autoradiographic approaches to quantitation of local glucose utilization, blood flow, protein synthesis, and pH; and the noninvasive methods of positron emission tomography and NMR spectroscopy, which are applicable as well to human studies. In focal ischemia, "core" regions of severe blood-flow reductions progress to irreversible injury, while the adjacent "penumbral" zone appears to represent an unstable region threatened with possible injury yet potentially amenable to therapeutic intervention. Glucose utilization in focal ischemia is remarkable for its local heterogeneity and, in the postischemic state, tends to be predictive of local tissue injury. The selective vulnerability of particular brain regions to injury following global ischemia has now been extensively correlated with alterations of local metabolism and hemodynamics. Hyperglycemia is generally deleterious to neuronal survival in ischemia--an effect mediated via tissue lactacidosis. Small differences in brain temperature also profoundly influence ischemic outcome. Areas remote from an ischemic focus may also show metabolic and functional abnormalities--so-called "diaschisis," which may be transneuronally and/or humorally mediated. Multiple neurotransmitters are released during ischemia and interact to influence tissue injury. Regional postischemic hypoperfusion may also influence outcome.
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PMID:Local metabolic responses to cerebral ischemia. 220 95

We studied neurologic morbidity and its evolution during hyperglycemia induced immediately after permanent unilateral common carotid artery ligation in Mongolian gerbils. A total of 60 animals were divided into five groups: one experiencing severe hyperglycemia for 1 hour after the onset of ischemia (brief hyperglycemia group, n = 13), a normoglycemic control group for the brief hyperglycemia group (n = 12), a group with severe hyperglycemia for 4 hours after the onset of ischemia (prolonged hyperglycemia group, n = 11), a normoglycemic control group for the prolonged hyperglycemia group (n = 13), and a hyperosmolar normoglycemic control group for the prolonged hyperglycemia group (n = 11). Neurologic morbidity and mortality were higher in the two hyperglycemic groups than in the three normoglycemic control groups. The neurologic deficit progressed according to the duration of severe hyperglycemia. In the three normoglycemic control groups neurologic status stabilized 120 minutes after the onset of ischemia, in the brief hyperglycemia group stabilization occurred at 210 minutes, and in the prolonged hyperglycemia group neurologic deficit progressed for approximately 360 minutes, coinciding with the death of all but one gerbil, in which the neurologic deficit remained stable until death 23 hours after ischemia. We suggest that hyperglycemia is another cause of progressing cerebral infarction.
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PMID:Progressing cerebral infarction in relation to plasma glucose in gerbils. 223 57

Controversy still exists in the published literature about the need for administration of intravenous glucose during liver transplantation. The ability of the grafted liver to metabolize insulin and glucagon and the appropriateness of secretion of these hormones are addressed in the present study. Two groups of pigs received unstored liver autografts, one with free infusion of 10% glucose and the other with limited infusion of 2.5% glucose solution, while attempting to maintain plasma glucose levels less than 200 mg/100 ml. In these animals, irrespective of moderate or major hyperglycemia, serum insulin levels were appropriate for blood glucose concentrations. However, in both groups, plasma glucagon levels rose three- to fourfold more than preoperative values and were inappropriate. Although facilities for measurement of blood flow were not available, application of the technique of transhepatic sampling has revealed that hepatic handling of insulin seems to be unimpaired after autograft with limited ischemia. Pancreatic secretion of glucagon, however, appeared to increase during the period immediately after revascularization. It is suggested that transhepatic sampling methods may be used in experimental transplantation to elucidate the effects of storage for prolonged periods.
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PMID:Transhepatic sampling during experimental porcine liver autotransplantation--its application to measurements of insulin, glucagon, and glucose. 226 87

Perfusion of ischemic tissue with glucose has been shown to be deleterious to heart, spinal cord, and kidney. Observations that glucagon improves survival after acute mesenteric ischemia, however, suggest that hyperglycemia may not be deleterious during bowel ischemia. This experiment examined the effect of glucose infusion on survival in an established rat model of acute mesenteric ischemia. The superior (cranial) mesenteric artery (SMA) was occluded for 85 min in 36 anesthetized Sprague-Dawley rats. Animals were randomized to receive 5% glucose in normal saline (n = 15; 16.5 mL/kg.min iv), normal saline alone (n = 13; 16.4 mL/kg.min iv), or no intravenous fluid (n = 8). Ninety-minute intravenous infusions were initiated 10 min after SMA occlusion. Survival to 48 h was 47% in glucose-saline-treated rats, 31% in saline-only-treated rats, and 12.5% in control rats. These results demonstrate no deleterious effect of glucose infusion on mortality after acute mesenteric ischemia in this model.
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PMID:The effect of glucose infusion on survival after acute mesenteric ischemia/reperfusion. 228 46

We studied resistance to ischemic nerve conduction failure (RINCF) following rapid alterations of blood glucose in normal and diabetic rats. We measured RINCF hourly for 4 hours in normal and diabetic rats. We then made normal rats hyperglycemic and diabetics euglycemic. In normal rats, we measured RINCF sequentially for 4 hours immediately after glucose injection and once after 1, 2, 3, or 4 hours of hyperglycemia. In diabetics, we measured RINCF sequentially for 4 hours after insulin injection. In normal rats, in sequential measurements, RINCF progressively fell but glucose injection prevented this fall. Hyperglycemia without preceding ischemia increased RINCF. In diabetic rats, sequential measurements also produced a decline in RINCF, accentuated with insulin injection. The results suggest that both glucose and insulin are important in determining the response of peripheral nerve to ischemia. They also underscore the importance of knowing the blood glucose and time of most recent insulin injection when measuring RINCF.
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PMID:Acute changes in blood glucose affect resistance to ischemic nerve conduction failure. 229 56

The authors retrospectively reviewed the charts of 36 pediatric patients who had undergone cardiac surgery with hypothermic cardiopulmonary bypass (CPB) (n = 24) or profound hypothermia with circulatory arrest (PHCA) (n = 12), none of whom had received dextrose in the clear CPB pump prime, maintenance iv fluids, or cardioplegia solution. The authors studied whether the doses of fentanyl or methylprednisolone, or rates of dextrose infusion from blood products during CPB or from vasoactive infusions in 5% dextrose in water, were correlated with the blood glucose concentrations at the termination of CPB. Because other investigations have indicated that even moderate hyperglycemia during cerebral hypoxia or ischemia may predispose patients to an increased risk of neurologic deficit, the authors wished to determine whether any of these factors might contribute significantly to the elevation in blood glucose commonly seen in these patients. Multiple regression analysis and ANOVA were performed on these data, and a P value of 0.0125 was considered significant. The dose of methylprednisolone, and rates of infusions of dextrose from blood products in the CPB pump prime or from 5% dextrose in water at the termination of CPB did not correlated significantly with the blood glucose level. The dose of fentanyl administered to patients prior to the end of CPB was significantly correlated with the glucose concentration (r2 = 0.416; P = 0.0001). No patient who received greater than or equal to 50 micrograms/kg of fentanyl had a blood glucose concentration of greater than 200 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fentanyl dosage is associated with reduced blood glucose in pediatric patients after hypothermic cardiopulmonary bypass. 233 96

Transient cerebral ischemia in normoglycemic animals is followed by a decrease in glucose utilization, reflecting a postischemic cerebral metabolic depression and a reduction in the activity of the pyruvate dehydrogenase complex (PDHC). Preischemic hyperglycemia, which aggravates ischemic brain damage and invariably causes seizure, is known to further reduce cerebral metabolic rate. To investigate whether these effects are accompanied by changes in PDHC activity, the postischemic cerebral cortical activity of this enzyme was investigated in rats with preischemic hyperglycemia (plasma glucose 20-25 mM). The results were compared with those obtained in normoglycemic animals (plasma glucose 5-10 mM). The activated portion of PDHC and total PDHC activity were measured in neocortical samples as the rate of decarboxylation of [14C]pyruvate in crude brain mitochondrial homogenates after 5 min, 15 min, 1 h, 6 h, and 18 h of recirculation following 15 min of incomplete cerebral ischemia. In normoglycemic animals the fraction of activated PDHC, which rises abruptly during ischemia, was reduced to 19-25% during recirculation compared with 30% in sham-operated controls. In hyperglycemic rats the fraction of activated PDHC was higher during the first 15 min of recirculation. However, after 1 and 6 h of recirculation, the fraction was reduced to values similar to those measured in normoglycemic animals. Fifteen of 26 rats experienced early (1-4 h post ischemia) seizures in the recovery period. The PDHC activity appeared unchanged prior to these early postischemic seizures. We conclude that the accentuated depression of postischemic metabolic rate observed in hyperglycemic animals is not coupled to a corresponding postischemic depression of PDHC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preischemic hyperglycemia and postischemic alteration of rat brain pyruvate dehydrogenase activity. 234 83

Hyperglycemia has been shown to exacerbate neurological deficit associated with central nervous system ischemia. Iodoacetate or dichloroacetate was administered intraperitoneally to rats in a study to examine the role of glycolysis in hyperglycemic exacerbation of neurological deficit. Sprague-Dawley rats were injected with saline, iodoacetate, or dichloroacetate and then made paraplegic by temporary occlusion for 10, 12, 13, or 15 minutes of the right and left subclavian arteries and the aorta distal to the left subclavian artery. Glycolytic blockage by iodoacetate was lethal in doses of 15 mg/kg or more, whereas rats receiving 10 mg/kg survived but showed no significant neurological improvement compared to the saline-treated control group. Dichloroacetate, 500 mg/kg, protected neurological function, which suggests a possible detrimental role for lactate accumulation and the benefit of maintaining tricarboxylic acid cycle activity by stimulating pyruvate dehydrogenase. The protection seen with dichloroacetate depended on the severity of ischemic injury. Dichloroacetate administration had a minimal effect on neurological outcome with occlusion periods of 13 and 15 minutes, mild improvement with 12 minutes of occlusion, and a significant protective effect with a 10-minute occlusion period. The dose-response nature of ischemic injury and neurological outcome in this rat model of paraplegia therefore appears to play an important role in determining the effect observed with a specific intervention.
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PMID:Neurological protection by dichloroacetate depending on the severity of injury in the paraplegic rat. 235 11

Normothermic ischemia tolerance is an important aspect of organ procurement and transplantation. The function of pancreas and kidney autografts was investigated in totally pancreatectomized or nephrectomized canine recipients. In 30 dogs the left limb (tail) of the pancreas was removed but left in the abdominal cavity after cessation of blood flow to produce warm ischemia for 30, 60, and 120 min (10 dogs at each time point), and then was flushed with cold Ringers' lactate and transplanted to the iliac vessels. Twenty dogs with fresh pancreatic transplants were controls. The success rate of pancreas transplants with warm ischemia of 1/2 and 1 hr was the same as that of controls (80%); however, after 1 hr normothermia 5/10 dogs had episodes of hyperglycemia for 1 week before glucose levels came back to normal. All but one graft with 2 hr warm ischemia failed. Intravenous glucose tolerance test (IVGTT) mean (+/- SEM) K values were not different in the successful groups, i.e., no warm ischemia: -1.55 +/- 0.15%; 1/2 hr warm ischemia: -1.81 +/- 0.18%; 1 hr warm ischemia: -1.64 +/- 0.09%. Amylase levels increased after transplant with maximum values at Day 2, then returned to normal, but the levels remained elevated in recipients of grafts subjected to longer normothermia with evidence of pancreatitis after 1 hr warm ischemia. Fifteen kidney grafts were treated similarly with warm ischemia exposure of 1/2 hr (n = 9) and 1 hr (n = 6) before being flushed and autotransplanted, and were compared to 16 fresh kidney transplants. After 1/2 hr warm ischemia none of the kidney grafts failed but 78% of the recipients had elevated serum creatinine and urea nitrogen levels which returned slowly to normal after 3 to 4 weeks. There was only one long-term survivor after 1 hr warm ischemia. Thus the pancreas seems to be more resistant to warm ischemia damage than is the kidney. This difference should be taken into consideration in regard to organ procurement for clinical transplantation.
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PMID:Definition of normothermic ischemia limits for kidney and pancreas grafts. 242 97

The characterization of tissue acid-base status related to the penumbral zone of increased glucose consumption surrounding a focal cerebral ischemic lesion may suggest therapeutic techniques to maximize tissue survivability from stoke. We measured local cerebral metabolic rate for glucose (1 CMRglc) and an index of brain tissue pH (pHt) concurrently and characterized their interaction in a model of focal cerebral ischemia in rats in a double-label autoradiographic study, using [14C]2-deoxyglucose and [14C]dimethyloxazolidinedione. Computer-assisted digitization and analysis permitted the simultaneous quantification of the two variables on a pixel-by-pixel basis in the same brain slices. Hemispheres ipsilateral to intravascular tamponade-induced middle cerebral artery occlusion showed areas of normal, depressed, and elevated glucose metabolic rate (as defined by an interhemispheric asymmetry index) after 2 hr of ischemia. Regions of increased 1 CMRglc showed moderate acidosis (6.87 +/- 0.05), while regions of normal glucose metabolic rate showed normal pHt (pH +/- SD = 6.98 +/- 0.05) and regions of decreased 1 CMRglc showed severe acidosis (6.69 +/- 0.11). A repeated-measures analysis of variance found these values to differ from each other at the P less than 0.0005 significance level. The finding of moderate acidosis coupled with increased 1 CRMglc in the metabolic penumbra suggests that the excess protons may result from the anaerobic dissociation of ATP synthesis and hydrolysis.
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PMID:Glucose metabolism and acidosis in the metabolic penumbra of rat brain. 260 42


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