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)

The presence of hyperglycemia before brain ischemia increases stroke-related morbidity and mortality in experimental animals and humans. However, little is known of the effect of hyperglycemia on regional cerebral blood flow (rCBF). Acute hyperglycemia was induced in awake but restrained rats by intraperitoneal injection of 50% D-glucose. Regional flow was determined using [14C]iodoantipyrine and quantitative autoradiography. Elevation of plasma glucose from 11 to 39 mM was associated with a 24% reduction in rCBF when compared with controls that received normal saline. Intraperitoneal D-mannitol produced an elevation of plasma osmolality equivalent to that observed with glucose. However, rCBF was only reduced by 10%. Hyperglycemia appears to produce a global decrease in rCBF in awake rats that cannot be completely explained by the attendant increase in plasma osmolality. If a similar influence is present during brain ischemia, hyperglycemia could extend areas of critical flow limitation.
 ...
PMID:Regional cerebral blood flow decreases during hyperglycemia. 392 83

Brain tissue acidosis is a result of either an increase in tissue PCO2 or an accumulation of acids produced by metabolism. Severe hypercapnia (arterial PCO2 around 300 mm Hg) may cause a fall in tissue pH to around 6.6 without any deterioration of the cerebral energy state or morphologic evidence of irreversible cell damage. In severe ischemia and tissue hypoxia, anaerobic glycolysis leads to lactic acid accumulation. This is aggravated by hyperglycemia and by a (trickling) residual blood flow. Under such circumstances lactate concentration in the tissue may increase to levels above 20 to 25 mumol/g (tissue wet weight), causing a decrease in pH to around 6.0. If lactic acidosis during ischemia or hypoxia reaches these excessive levels, metabolic and functional restitution is severely hampered upon subsequent recirculation and reoxygenation. In these circumstances cell morphology shows signs of irreversible damage. Conversely there is less damage if severe tissue lactic acidosis can be hindered. The deleterious effect of excessive lactic acidosis may be related to an influence on the following: synthesis and degradation of cellular constituents; mitochondrial function; cell volume control; postischemic blood flow; and stimulation of pathologic free radical reactions. Possibilities for therapeutic interventions include the avoidance of hyperglycemia, inhibition of glycolysis, and measures for increasing the buffer capacity of the brain.
 ...
PMID:Brain acidosis. 392 94

The present study was designed to clarify the effect of blood glucose level on cerebral blood flow and metabolism during and after acute cerebral ischemia induced by bilateral carotid ligation (BCL) in spontaneously hypertensive rats (SHR). Blood glucose levels were varied by intraperitoneal infusion of 50% of glucose (hyperglycemia), insulin with hypertonic saline (hypoglycemia) or hypertonic saline (normoglycemia). Cerebral blood flow (CBF) in the parietal cortex and thalamus was measured by hydrogen clearance technique, and the supratentorial metabolites of the brain frozen in situ were determined by the enzymatic method. In non-ischemic animals, blood glucose levels had no influence on the supratentorial lactate, pyruvate or adenosine triphosphate (ATP) concentrations. In ischemic animals, however, cortical CBF was reduced to less than 1% of the resting value at 3 hours after BCL. However, there were no substantial differences of CBF during and after ischemia among 3 glycemic groups. Cerebral lactate in the ischemic brain greatly increased in hyperglycemia (34.97 +/- 1.29 mmol/kg), moderately in normoglycemia (23.43 +/- 3.13 mmol/kg) and less in hypoglycemia (7.20 +/- 1.54 mmol/kg). In contrast, cerebral ATP decreased in hyperglycemia (0.93 +/- 0.19 mmol/kg) as much as it did in normoglycemia (1.04 +/- 0.25 mmol/kg), while ATP reduction was much greater in hypoglycemia (0.45 +/- 0.05 mmol/kg). At 1-hour recirculation after 3-hour ischemia, ATP tended to increase in all groups of animals, indicating the recovery of energy metabolism. Such metabolic recovery after recirculation was good in hypo- and normoglycemia, and was also evident in hyperglycemia. Our results suggest that hyperglycemia is not necessarily an unfavorable condition in acute incomplete cerebral ischemia.
 ...
PMID:Cerebral blood flow and tissue metabolism in experimental cerebral ischemia of spontaneously hypertensive rats with hyper-, normo-, and hypoglycemia. 396 37

To assess the relation of ventricular arrhythmias to myocardial K(+) movement during ischemia, we placed an electrode catheter in the left anterior descending coronary artery for thrombus production in intact anesthetized dogs. (85)Kr injections distal to the thrombus permitted serial coronary blood flow measurements. Animals of Group I with a moderate flow reduction exhibited no arrhythmia or myocardial egress of K(+). In Group II, marked flow reduction was accompanied by an injury potential and loss of K(+) from the ischemic site, before and during ventricular tachycardia. Therapeutic interventions were performed in animals having the same degree of ischemia as Group II. Systemic procaine amide in Group III interrupted the tachycardia and egress of K(+), despite persistent ischemia. Group IV did not respond to intracoronary insulin with K(+) uptake, as did normal dogs, and progressed to fibrillation. During the production of hyperglycemia in Group V, myocardial loss of K(+) ceased with maintenance of sinus rhythm. Hemodynamic factors did not appear to have a major role in the genesis of the arrhythmia.Since intracoronary infusion of K(+) in normal dogs similarly altered repolarization and produced fibrillation, it would appear that during ischemia egress of K(+) before development of the arrhythmia indicates a major role of the ion in pathogenesis. This view is supported by the myocardial loss of K(+) and arrhythmia induced in normal dogs by strophanthidin and by the fact that pharmacologic regulation of K(+) loss is associated with correction of the arrhythmia, despite persistence of low blood flow.
 ...
PMID:Ventricular arrhythmias and K+ transfer during myocardial ischemia and intervention with procaine amide, insulin, or glucose solution. 606 41

There is evidence for a physiological role of the adrenal cortex in the early responses to limb ischemia in the rat. Trilostane, which inhibits steroid production and prevents the usual rise in corticosterone concentration, impairs compensatory fluid movement during the 3 h after removal of bilateral hindlimb tourniquets and truncates the accompanying hyperglycemia. We have now studied whether altering the corticosterone concentration has similar effects over a 3-h period after a 35% hemorrhage in the conscious rat. After hemorrhage there was only a small rise in plasma glucose concentration, which was unaffected by inhibition of the adrenocortical response with trilostane or its prolongation with adrenocorticotrophic hormone. However, if hindlimb tourniquets were applied 4 h beforehand, the hyperglycemia after hemorrhage was as large as after tourniquet removal and was similarly curtailed by trilostane. Compensatory fluid movement, in contrast, was unaffected by any of the alterations in corticosterone concentration, with or without tourniquets. Thus the method of producing fluid loss is critical in determining whether glucocorticoids play a role in compensation but not in maintaining hyperglycemia after injury.
 ...
PMID:Early responses to hemorrhage in the conscious rat: effects of corticosterone. 628 70

The efficacy of hyperglycemia and insulin therapy for reducing ischemic myocardial injury is controversial and unproven. Accordingly, factors that might influence the effects of hyperglycemia and insulin were studied in isolated perfused rabbit hearts at two degrees of global ischemia, either "severe" or "moderate." During the ischemic period, different groups (n = 15-28/group) received either 100 mg/100 ml glucose-no insulin (control group), 500 mg/100 ml glucose + 100 mU/ml insulin (G + I), or 100 mg/100 ml glucose + 400 mg/100 ml mannitol (osmotic control). During moderate ischemia, effective washout of myocardial lactate was maintained, and hyperglycemia and insulin doubled the glycolytic flux, completely prevented contracture during ischemia, decreased contracture during reperfusion, increased recovery of postischemic contractile function, decreased ultrastructural damage, and increased high energy phosphate levels. Hyperglycemia and insulin increased glycolytic flux only after 30 minutes of ischemia had elapsed, suggesting that endogenous glycogen provided adequate glycolytic substrate prior to this time. The mannitol-glucose substrate had no beneficial effects, indicating that the hyperglycemia and insulin substrate had a metabolic rather than an osmotic mechanism of action. In contrast, during severe ischemia, tissue lactate washout was ineffective; the hyperglycemia and insulin substrate increased glycolytic flux by only 15% and produced no persistent beneficial effects. These results suggest that hyperglycemia and insulin therapy is beneficial to the ischemic myocardium when two conditions are met. First, the degree of myocardial perfusion, although in the ischemic range, must be adequate to prevent the accumulation of high tissue levels of lactate which inhibit glycolysis and prevent any glycolytic stimulation by hyperglycemia and insulin. Second, the ischemic myocardium must be "glucose dependent" for glycolytic substrate; in our studies this occurred after 30-45 minutes of sustained ischemia, probably because myocardial glycogen stores became depleted.
 ...
PMID:Determinants of a protective effect of glucose and insulin on the ischemic myocardium. Effects on contractile function, diastolic compliance, metabolism, and ultrastructure during ischemia and reperfusion. 634 32

The regional concentrations of intravenously injected 45Ca and total calcium were measured in rat brain during recovery from transient occlusion of the four major arteries to the brain. 45Ca was injected at intervals after ischemia, and the regional distribution of 45Ca was estimated by autoradiography. The 45Ca appeared to enter the brain via the choroid plexus, labeling the paraventricular tissue at 1 h after the injection. Control brains had more 45Ca in the gray matter compared to fiber-rich areas at 5 and 24 h, but within these regions the optical density was nearly uniform. The accumulation and retention of 45Ca in postischemic brain were selective and time-dependent. The regional pattern of 45Ca uptake correlated with the temporal progression of ischemic cell change. Infarction and preischemic hyperglycemia increased morphological damage, and increased the extent and distribution of 45Ca accumulation. The rise in total calcium concentration appeared to be biphasic in irreversibly damaged tissue.
 ...
PMID:Regional accumulation of calcium in postischemic rat brain. 647 Jul 13

Brain protection is the prevention or amelioration of neuronal damage occurring after a hypoxic or ischemic event. Controversies in this field focus on whether incomplete global ischemia may produce a worse insult than does complete global ischemia; whether barbiturates provide protection following complete global ischemia; and whether the calcium entry blockers have a role in brain protection. Current knowledge dictates that incomplete ischemia coupled with hyperglycemia will cause a severe cerebral lactic acidosis and produce a worse insult than does complete ischemia. In the absence of hyperglycemia complete cerebral ischemia produces more neuronal damage. The barbiturates have been shown to provide protection in focal ischemia and incomplete global ischemia in which neuronal function is still present, but have not been shown to provide protection following complete global ischemia. Those calcium entry blockers with cerebral vascular selectivity may well provide some brain protection following complete cerebral ischemia by ameliorating the postischemic hypoperfusion state.
 ...
PMID:Cerebral resuscitation: advances and controversies. 647 55

Glucose treatment prior to cerebral ischemia is followed by similar metabolic and hemodynamic recovery (Siemkowicz & Gjedde 1980), and normalisation of brain extracellular ions (Siemkowicz & Hansen 1981). In view of this, the present study investigated whether post-ischemic hyperglycemia influenced recovery from cerebral ischemia. In rats which received 50% glucose during a 10 min period of cerebral ischemia, and which had a plasma glucose level of 28.5 mM after 10 min of recirculation, recovery was inferior to that of rats receiving either 8% NaCl or 0.9% NaCl (and hence the rats were normoglycemic). Furthermore, rats which had been rendered hyperglycemic (39 mM) prior to ischemia, and which had plasma glucose lowered to 15 mM by insulin treatment during ischemia, did not recover and died within 4 days. Conversely, rats with somewhat lower preischemic hyperglycemia (28 mM), and which had plasma glucose lowered to 12 mM by insulin treatment during ischemia, recovered as well as the normoglycemic rats. In conclusion, preischemic and postischemic hyperglycemia is detrimental to recovery from cerebral ischemia.
 ...
PMID:Hyperglycemia in the reperfusion period hampers recovery from cerebral ischemia. 679 27

Glucose, lactate, pyruvate and adenosine triphosphate (ATP) concentrations in the supratentorial brain tissue frozen in situ were measured one hour after bilateral carotid occlusion in spontaneously hypertensive rats, of which blood glucose levels were varied by intraperitoneally injected insulin (hypoglycemia), saline (normoglycemia) and 50% glucose (hyperglycemia). Cerebral glucose concentrations as well as blood glucose levels were significantly increased in hyperglycemic animals, and decreased in hypoglycemic ones. Cerebral lactate, and lactate/pyruvate ratio at one-hour ischemia tended to increase in hyperglycemic animals comparing with those in normoglycemic ones, although cerebral ATP levels were slightly higher in the former. In hypoglycemic animals with one-hour ischemia, cerebral lactate was less increased but ATP was significantly reduced. It has been reported that hyperglycemia has vulnerable effects on brain metabolism of complete cerebral ischemia, presumably due to hyperglycemia-induced lactic acidosis of the brain. In incomplete cerebral ischemia as demonstrated in the present study, however, ATP concentrations remained at slightly higher level, despite tendency to more increase in lactate in hyperglycemic animals, indicating that high blood glucose level might be beneficial, rather than vulnerable, to incomplete cerebral ischemia. On the other hand, hypoglycemia causes more severe impairment of the brain energy metabolism because of an insufficient supply of substrates to the brain.
 ...
PMID:[Effects of hypo- or hyperglycemia on brain metabolism in experimental cerebral ischemia]. 684 11


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