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

The precise effects ethanol (ETOH), acetaldehyde (ACT) and acetate (AC) exert on microscopic resistance and capacitance vessels in skeletal muscle is unknown. In-situ studies on the skeletal (cremaster) microvasculature of the rat, using high-resolution television microscopy, were undertaken. Acute administration (topical, intra-arterial or iv) of ethanol (0.001-10%) to young rats produced a concentration-related vasoconstriction of arterioles (18-45 microns) and muscular venules (25-50 microns), ranging from a 7 to 80% reduction in microvessel lumen sizes. Acute administration of either ACT or AC, however, produced concentration-related vasodilatation of these same microvessels. No known amine or opiate pharmacologic antagonist or cyclooxygenase inhibitor could attenuate or prevent ETOH, ACT and AC from eliciting their unique microvascular responses. These new, direct in-situ microcirculatory findings clearly demonstrate: 1) ETOH exerts constrictor, and not dilator, effects on skeletal muscle microscopic resistance and capacitance vessels; 2) both ACT and AC exert dilator, and not constrictor, effects on these muscle microvessels; and 3) the effects of alcohol can not be due to metabolism to ACT or AC. A progressive increase in ischemia of the skeletal muscle microscopic resistance and capacitance vessels, over a period of time (weeks to years), could result in the well-known syndrome of alcoholic myopathy.
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PMID:Comparative effects of ethanol, acetaldehyde and acetate on arterioles and venules in skeletal muscle: direct in situ studies on the microcirculation and their possible relationship to alcoholic myopathy. 224 21

The influences of vitamin E deficiency on compression injury of the rat spinal cord associated with ischemia were investigated. Growing rats were divided into two groups and given a diet containing either 2 IU/100 g or less than 0.1 IU/100 g of alpha-tocopherol acetate, respectively, for 6-8 weeks before experiments. Motor disturbances induced by spinal cord injury were found to be enhanced by vitamin E deficiency. The spinal cord blood flow (SCBF) was reduced by compression and subsequently increased transiently and then decreased gradually in both groups, but the level was lower in the vitamin E-deficient group than in the control group. After injury, the vitamin E-deficient group showed lower recoveries than the control group in the amplitude and latency of spinal cord evoked potentials and greater pathological changes of the spinal cord, such as bleeding and edema. The increase in the level of TBA-reactive substances in the spinal cord after injury increased with decrease in the dietary level of vitamin E. These results suggest that vitamin E may have a protective effects against ischemic spinal cord injury by its antioxidant effect.
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PMID:Influence of dietary vitamin E deficiency on compression injury of rat spinal cord. 229 24

This study analyzes the importance of the source and rate of ATP production (glucose flux, glycogenolysis, and oxidative phosphorylation) in the prevention of ischemic contracture in isolated rat hearts. Ischemic contracture was initiated at about 10 minutes by buffer perfusion with nonglycolytic substrates whereas the addition of 11 mM glucose prevented contracture for 2 hours. Tissue values of ATP, phosphocreatine, and lactate could be dissociated from onset of ischemic contracture. In hearts perfused with acetate or free fatty acid, with 11 mM glucose, glycolytic ATP production was 2.3-2.8 mumol/g fresh wt/min; as initial rates of glycogenolysis fell, glycolysis was maintained by a steady increase of glucose flux to values in excess of 2 mumol ATP/g fresh wt/min. Decreasing the glucose flux by lowering the perfusate glucose or by the addition of 2-deoxyglucose precipitated ischemic contracture. When oxidative phosphorylation was further reduced by hypoxia, glucose still prevented ischemic contracture; however, when oxidative phosphorylation dropped to near zero (near-anoxic) rates, glycolysis was inhibited, and glucose could only delay ischemic contracture to about 45 minutes. Combined ATP production rates could be dissociated from contracture. The metabolic parameter that correlated best with prevention or delay of ischemic contracture was the rate of glycolytic flux from glucose, which in this model of global low-flow ischemia had to accelerate to provide a rate of ATP production from glucose in excess of 2 mumol/g fresh wt/min within 30 minutes of the start of ischemia to prevent ischemic contracture.
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PMID:Glucose flux rate regulates onset of ischemic contracture in globally underperfused rat hearts. 229 7

Hindlimb ischemia and reperfusion results in local limb and distant lung injury. This study tests whether the mechanism of injury is by ischemia mediated polymorphonuclear leukocyte (PMN) activation and diapedesis. Anesthetized rabbits were subjected to three hours of hindlimb ischemia (n = 8) or sham ischemia (n = 4). PMN derived solely from the reperfused ischemic limb and assayed flow cytometrically displayed an oxidative burst of 135 /- 8 fentamoles dichlorofluorescein (fmDCF)/cell compared to preischemc levels of 74 +/- 14 fmDCF/cell (p less than 0.05). Additional aliquots of isolated neutrophils were treated with phorbol myristate acetate (PMA) 10(-7) M. In contrast to a 162% increase in oxidative burst before ischemia, neutrophils at ten minutes of reperfusion had an enhanced response to PMA of 336% (p less than 0.05). Plasma collected from the ischemic hindlimb at ten minutes of reperfusion when introduced into an abraded skin chamber or intratracheally induced diapedesis in nonischemic animals. PMN accumulations in the skin chamber were 1636 +/- 258 PMN/mm3 after three hours (n = 8) compared to 63 +/- 18 PMN/mm3 induced by sham plasma (n = 4, p less than 0.05). Introduction of ischemic plasma intratracheally into a lobar bronchus (n = 4) induced PMN accumulations after three hours, measured by bronchoalveolar lavage fluid of 19 +/- 2 X 10(4) PMN/mm3 compared to 5 +/- 1 X 10(4) PMN/mm3 with sham plasma (n = 4, p less than 0.05). Diapedesis was completely prevented (0-3 PMN/mm3, p less than 0.05) by introducing ischemic plasma into skin chambers in animals whose hindlimbs had been made ischemic (n = 6) or into chambers located on skin regions that had been previously made ischemic (n = 6). Similarly after hindlimb ischemia, lavage of the lung with ischemic plasma yielded few PMN 0-3/mm3 (p less than 0.05). These data indicate that ischemia and reperfusion lead to generation of a circulating component in plasma that causes an oxidative burst in PMN and inhibits their diapedesis but promotes diapedesis when applied extravascularly to a naive animal.
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PMID:Ischemia activates neutrophils but inhibits their local and remote diapedesis. 230 97

Free radical-mediated reperfusion injury has been established as an important mechanism leading to post-ischemic reperfusion myocardial damage. The present study was undertaken to determine the protective role of vitamin E, a membrane-bound free-radical scavenger, on ischemia-reperfusion myocardial injury. After 4 months of feeding a semipurified diet containing 0, 30, and 3000 ppm of R,R,R,-alpha-tocopherol acetate, rat hearts were subjected to Langendorff perfusion. Myocardial damage was judged by the release of creatine phosphokinase (CPK) after 45 min of global ischemia followed by 20 min of reperfusion. Effluent CPK was significantly lowered in the two tocopherol-supplemented groups, although increasing dietary vitamin E by 100-fold above requirement did not confer further protection. However, effluent prostacyclin, detected as the stable metabolite 6-keto-PGF1 alpha by radioimmunoassay, was potentiated by dietary vitamin E in a dose-dependent manner. Analysis of lipids in cardiac subcellular fractions showed considerable enrichment of tocopherol in these membranes by diets, but the levels of polyunsaturated fatty acids, phospholipids, and cholesterol were essentially unchanged by dietary treatment or ischemia-reperfusion. These data demonstrated that requirement level of tocopherol (30 ppm) in the diet is sufficient to protect against reperfusion injury of the myocardium and suggests that tocopherol is important in maintaining cardiac prostacyclin synthesis under conditions of oxygen stress.
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PMID:Effects of vitamin E on prostacyclin release and lipid composition of the ischemic rat heart. 231 Feb

Rat gastric mucosal blood flow, hydrochloric acid (HC1) secretion, and morphological changes of parietal cells were studied by light and electron microscopy using histochemical techniques. Mucosal blood flow of restrained rats was remarkably decreased compared with that of control rats, whereas the acetylcholinesterase activity, demonstrated by the method of Karnovsky and Roots, was significantly increased especially near the ulcer. In contrast, the differences in volume, acidity and acid output of gastric juice were not significant between control and restrained rats. Hypersecretion of HC1 induced by a parasympathetic stimulant, bethanechol, was inhibited by blood loss or infusion of cytochalasin B, an actin depolymerizing agent. 14C-aminopyrine accumulation in the primary cultured parietal cells was decreased by the treatment with hypoxia and cytochalasin B. These treatments also prevented the increase of 14C-aminopyrine accumulation induced by bethanechol. Actin filaments were evident in the cytoplasm of the parietal cells, particularly around the intracellular canaliculi and beneath the plasma membrane using the FITC-labeled phalloidin reaction and transmission electron microscopic observations of uranyl acetate block stained preparations following heavy meromyosin decorations. Ultrastructural studies of the parietal cells in restrained rats revealed that intracellular canaliculi were dilated with loss of microvilli. Actin filaments were noted to be disassembled, and granular with focal aggregation of actin filaments. Hypoxic vacuoles were also found in the cytoplasm. Treatments with blood loss and cytochalasin B infusion in the in vivo model, and hypoxia and cytochalasin B in the in vitro model, resulted in the similar changes. These observations indicate that actin filaments in the parietal cells of restrained rats may be depolymerized by ischemia. As the result, HC1 secretion would not be enhanced even if the parasympathetic nerves are excessively stimulated in the gastric mucosa. Thus, disturbances of the gastric mucosal microcirculation are considered to be important in the pathogenesis of the stress-induced gastric ulcer.
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PMID:[Studies on the mechanism of restraint-induced gastric ulcer--with special reference to mucosal ischemia and gastric secretion]. 232 29

13C and 31P nuclear magnetic resonance (NMR) spectra were used to assess substrate oxidation and high-energy phosphates in postischemic (PI) isolated rabbit hearts. Phosphocreatine (PCr) increased in nonischemic controls on switching from glucose perfusion to either 2.5 mM [3-13C]pyruvate (120%, n = 7) or [2-13C]acetate (114%, n = 8, P less than 0.05). ATP content, oxygen consumption (MVO2), and hemodynamics (dP/dt) were not affected by substrate availability in control or PI hearts. dP/dt was 40-60% lower in PI hearts during reperfusion after 10 min ischemia. Hearts reperfused with either pyruvate (n = 11) or acetate (n = 8) regained preischemic PCr levels within 45 s. Steady-state ATP levels were 55-70% of preischemia with pyruvate and 52-60% with acetate. Percent maximum [4-13C]glutamate signal showed reduced conversion of pyruvate to glutamate via the tricarboxylic acid (TCA) cycle at 4-min reperfusion (PI = 24 +/- 4%, means +/- SE; Control = 48 +/- 4%). The increase in 13C signal from the C-4 position of glutamate was similar to control hearts within 10.5 min. The increase in [4-13C]glutamate signal from acetate was not different between PI and control hearts. The ratio of [2-13C]Glu:[4-13C]Glu, reflecting TCA cycle activity, was reduced in PI hearts with acetate for at least 10 min (Control = 0.76 +/- 0.03; PI = 0.51 +/- 0.09) until steady state was reached. Despite rapid recovery of oxidative phosphorylation, contractility remained impaired and substrate oxidation was significantly slowed in postischemic hearts.
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PMID:Reduced substrate oxidation in postischemic myocardium: 13C and 31P NMR analyses. 233 71

Oxygen free radicals have been suggested to cause the myocardial damage resulting in the prolonged contractile depression following brief periods of regional ischemia. In pigs, we infused the natural antioxidant alpha-tocopherol as its water-soluble acetate [0.3 g/kg intravenously (i.v.), n = 6] three times during 1 week, prior to thoracotomy, 8-min distal left anterior coronary artery (LAD) occlusion and 90-min reperfusion. Plasma levels of alpha-tocopherol [high-performance liquid chromatography (HPLC)] on the experimental day were 148.91 +/- 21.47 micrograms/ml as compared to preinfusion control of 0.51 +/- 0.14 micrograms/ml. Myocardial levels of alpha-tocopherol were elevated to 93.15 +/- 14.78 micrograms/g as compared to 4.08 +/- 0.60 microgram/g in the control group (n = 6). Malondialdehyde levels in ischemic-reperfused myocardium of the treatment group were insignificantly lower (441.96 +/- 59.55 nmol/g) as compared to the control group (500.9 +/- 72.72 nmol/g). Heart rate was significantly higher in the treatment group by the end of the experiments (135 +/- 10 vs. 105 +/- 4 beats/min, p less than 0.01). Regional segment shortening (SS, sonomicrometry) became normal within 1 min of reperfusion in both the treatment and the control group. During the following 10 min, SS decreased to 52 +/- 6% of preischemic control in the alpha-tocopherol group and to 54 +/- 7% in the control group (NS). SS remained at these depressed values throughout the reperfusion period. Pretreatment with the antioxidant alpha-tocopherol resulted in a tendency to lower lipid peroxidation products but did not prevent development of contractile depression in reversibly ischemic reperfused myocardium.
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PMID:Effect of alpha-tocopherol (vitamin E) in a porcine model of stunned myocardium. 247 14

Indirect evidence exists that the reperfusion of ischemic tissue activates white blood cells. Thus local and systemic reperfusion injuries are prevented by making animals leukopenic or by inhibiting white blood cell lung entrapment by blocking thromboxane A2 generation. This study tests directly whether ischemia and reperfusion activates neutrophils, as measured by their oxidative burst, and whether thromboxane mediates this event. Anesthetized rats underwent 4 hours of bilateral hind limb tourniquet ischemia followed by 60 minutes of reperfusion. Plasma thromboxane B2 levels increased to 2750 pg/ml at 5 minutes of reperfusion, higher than the sham control (n = 36) value of 370 pg/ml (p less than 0.01). In untreated ischemic animals (n = 30) the intracellular H2O2 production of circulating neutrophils, as assayed flow cytometrically by dichlorofluorescein oxidation, increased from a preischemic value of 133 to a peak of 251 femtomoles dichlorofluorescein/neutrophil at 5 minutes of reperfusion (p less than 0.01). Treatment of neutrophils with phorbol myristate acetate (PMA) 10(-7) mol/L led to a 91% increase in neutrophil H2O2 production before ischemia, and 5 minutes after reperfusion there was an enhanced response to PMA of 222% (p less than 0.01). Pretreatment of animals with the thromboxane-synthetase inhibitor OKY 046 (n = 36) prevented ischemia-induced thromboxane generation, neutrophil H2O2 production (p less than 0.05), as well as the enhanced response to PMA stimulation (p less than 0.05). Treatment with the thromboxane-receptor antagonist SQ 29,548 (n = 36) did not affect the increase in plasma thromboxane levels after ischemia but was as effective as OKY 046 in preventing the ischemia-induced increase in neutrophil H2O2 production and the enhanced response to PMA stimulation. These data indicate that lower-torso ischemia leads to neutrophil activation, manifest by H2O2 production, an event mediated by thromboxane.
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PMID:Thromboxane mediates the ischemia-induced neutrophil oxidative burst. 252 18

The effect of low flow ischemia and subsequent reperfusion with 5.5 mM glucose or 5 mM acetate on energy metabolism and catabolism of myocardial glutamate and aspartate was studied in isolated perfused guinea pig hearts. Reperfusion with acetate was followed by low recovery of the cardiac contractile function associated with a great rise in isovolumic end-diastolic pressure. It was combined with more profound losses of tissue adenine nucleotides and the total Cr compared to reperfusion with glucose. The total glutamate and aspartate pool decreased more than two-fold compared to the initial one regardless of substrate. However, glutamate content was reduced by 58 and 38% with acetate and glucose, respectively. The expenditure of both amino acids was caused by alanine formation stimulated by glycolysis/glycogenolysis. The remaining glutamate and aspartate pool in the reperfused hearts positively correlated with adenine nucleotides (r = 0.62), the total creatine (r = 0.65), and the recovery of contractile function (r = 0.64). The results suggest that the glutamate and aspartate pool may be of critical importance for postischemic functional and metabolic recovery of the heart.
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PMID:Association of myocardial glutamate and aspartate pool and functional recovery of postischemic heart. 257 52


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