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

The Langendorff perfused rat heart was used to investigate whether myocardial damage during ischemia and reperfusion could be protected by free radical scavengers, calcium antagonist and adenosine. Myocardial high energy phosphates were measured by phosphorus-31 NMR spectroscopy during normal perfusion, 20 min of ischemia and 20 min of reperfusion. In hearts, which were treated both with free radical scavengers (FRS) (Superoxide dismutase): 24 IU/ml and catalase 22 IU/ml) and verapamil (10(-7) M), beta-ATP was significantly higher than that of FRS at the end of ischemia. However, beta-ATP recovered only to 83% of baseline value at the end of reperfusion. In view of myocardial metabolism, verapamil treated hearts were good for recovery of creatine phosphate (PCr) but not ATP at the end of reperfusion. Hearts which were treated with only adenosine did not differ from control hearts. However, when hearts were treated with both verapamil and adenosine (10(-4) M), recovery of both ATP and PCr content was significantly greater than that of control hearts. These results suggested that pretreatment with both verapamil and adenosine before and after global ischemia could protect ischemic myocardium, but, further studies are necessary to clarify the precise mechanism of protection.
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PMID:Effects of calcium antagonists and free radical scavengers on myocardial ischemia and reperfusion injury: evaluation by 31P-NMR spectroscopy. 260 Oct 5

Forebrain ischemia was induced in Mongolian gerbils by bilateral occlusion of the common carotid arteries for 30 minutes. These animals do not have a complete circulus arteriosus Willisii. Mitochondria were prepared from the forebrain tissue at the end of the 30 minutes occlusion period as well as at different time points after the release of the occlusion. Tissue blood flow in the forebrain was also determined by measuring the brain tissue accumulation of 14C-iodoantipyrine. Tissue blood flow in the forebrain decreased from a control level of 1.43 +/- 0.03 ml/min/gr to 0.13 +/- 0.03 ml/min/gr by the 30th minute of ischemia, increased to 1.12 +/- 0.25 ml/min/gr after 5 minutes of reflow, but decreased again to 0.41 +/- 0.07 ml/min/gr after 1 1/2 hours of reflow. Oxygen consumption rate of mitochondria prepared from the forebrain (glutamate + malate as substrates in the presence of ADP) was 98 +/- 13 nmoles O2/min/mg protein in control animals, decreased to 61 +/- 9 nmoles O2/min/mg protein after 30 minutes of occlusion, recovered to 106 +/- 9 nmoles O2/min/mg protein during the first 30 minutes of reperfusion. During extended reperfusion, mitochondrial respiratory activity declined reaching 20 +/- 5 nmoles O2/min/mg protein after 5 1/2 hours of reperfusion. Respiratory control ratio of the mitochondria (relative increase of respiration upon addition of ADP) was 9.2 +/- 1.3 in control animals, 7.0 +/- 1.5 after 30 minutes of carotid occlusion, 9.0 +/- 1.2 after 30 minutes of reperfusion, and 5.8 +/- 0.8 after 5 1/2 hours of reperfusion. Superoxide dismutase activity of the forebrain mitochondria was 5.10 +/- 0.7 I.U./mg protein in control animals, decreased to 3.3 +/- 1.6 I.U./mg protein after 30 minutes of occlusion and remained at this level throughout the reperfusion period. These data confirm earlier reports that deterioration of mitochondrial function may contribute to the development of ischemic and post-ischemic brain tissue damage. It also appears possible that postischemic damage of mitochondrial function develops secondary to postischemic deterioration of tissue blood flow.
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PMID:Parallel changes in brain tissue blood flow and mitochondrial function during and after 30 minutes of bilateral forebrain ischemia in the gerbil. 264 Apr 8

Isolated rat hearts (n = 15 per group) were subjected to regional ischemia (10 min) and reperfusion. Superoxide dismutase (SOD; 8 X 10(3), 2 X 10(4), 4 X 10(4), 6 X 10(4), 8 X 10(4), 1.2 X 10(5), or 1.6 X 10(5) IU/l) given early (i.e., throughout the experiment) reduced the incidence of reperfusion-induced ventricular fibrillation (VF), the dose-response characteristics describing an asymmetric U-shaped curve. The optimal dose of SOD (8 X 10(4) IU/l) reduced VF incidence from its control value of 87 to 27% (P less than 0.05). Given late (i.e., 2 min before reperfusion), this dose of SOD exerted a reduced but nonetheless significant antifibrillatory effect. Early administration of catalase (1 X 10(3), 1 X 10(4), 2.5 X 10(4), 5 X 10(4), 1 X 10(5), 1.5 X 10(5), or 1 X 10(6) IU/l) reduced VF incidence in a linear dose-dependent manner, from its control value of 87 to 7% with 1 X 10(6) IU/l (P less than 0.05). Late administration of this dose reduced VF incidence from its control value of 87 to 27% (P less than 0.05). Allopurinol (0.07, 0.15, 0.37, 0.73, 1.10, or 1.47 mM added to the perfusate throughout the experiment) significantly reduced VF incidence over a wide range of doses, but low and high doses were ineffective. Pretreatment with allopurinol (0, 0.01, 0.02, 0.05, 0.10, 0.20, or 0.50 g.kg-1.day-1 per os 48, 24, and 1 h before study) reduced VF incidence from its control value of 93 to less than 50% at several doses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reperfusion arrhythmias: dose-related protection by anti-free radical interventions. 271 33

Oxygen radical-induced myocardial lipid peroxidation may cause injury during regional ischemia and reperfusion. However, in vivo detection of lipid peroxidation is difficult. Since conjugated dienes are lipid peroxidation products of unsaturated fatty acids, we evaluated the potential value of detection of these double-bonded fatty acids as a marker of oxygen radical injury. In seven untreated and five superoxide dismutase-treated anesthetized dogs exposed to 90 min of coronary occlusion and subsequent reperfusion, coronary sinus plasma draining the ischemic and reperfused region was assayed for dienes. Lipids were extracted and diene optical density measured at 233 nm wavelength. Superoxide dismutase (5 mg/kg, total dose) was infused into the left atrium during ischemia and the first 30 min of reperfusion. Coronary sinus diene optical density increased in untreated animals at 5 and 10 min of reperfusion (reperfusion optical density (x +/- SEM): 5 min = 1.49 +/- 0.20 absorbance units, 10 min = 1.36 +/- 0.06; both p less than 0.05 vs preocclusion optical density = 1.10 +/- 0.05 and 25 min reperfusion = 1.20 +/- 0.07). No increase in diene optical density occurred in superoxide dismutase-treated dogs. Myocardial lipid peroxidation products, as conjugated dienes, increased in coronary sinus plasma during early reperfusion and this increase was prevented by superoxide dismutase infusion.
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PMID:Superoxide dismutase decreases early reperfusion release of conjugated dienes following regional canine ischemia. 273 May 25

The calcium-channel inhibiting agent, diltiazem, has been shown to enhance salvage of reperfused myocardium independent of effects on coronary blood flow or myocardial work. Because lipid peroxidation may be a mediator of reperfusion injury and modifiable by calcium-sensitive pathways, we evaluated the effects of diltiazem on the formation of malondialdehyde (MDA), a product of lipid peroxidation, in isolated rabbit hearts perfused with buffer under control conditions or after 60 minutes of ischemia with or without 3 minutes of reperfusion. Diltiazem (5 x 10(-7)M) reduced tissue MDA content in seven reperfused hearts compared with levels measured in 14 hearts reperfused without drug (1.54 +/- 1.09 [SD] compared with 3.57 +/- 1.88 nmol/g, p less than 0.05). Superoxide dismutase and catalase were ineffective in reducing tissue MDA content in reperfused hearts (n = 8; MDA concentration, 3.88 +/- 2.82 nmol/g) although they were effective in preventing lipid peroxidation in separate studies in which oxygen-centered free radicals were generated directly by an infusion of xanthine oxidase and hypoxanthine. These results suggest that the salutary effects of diltiazem in the setting of reperfusion may be mediated by reduction of lipid peroxidation at a locus not accessible to scavengers of oxygen-centered free radicals or by a mechanism not mediated by free radical pathways.
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PMID:Reduction of lipid peroxidation in reperfused isolated rabbit hearts by diltiazem. 276 94

Freshly isolated adult rat heart cells were used to study the effects of oxygen-free radicals on the myocardial oxidation of different substrates. The calcium-tolerant quiescent cells were incubated with xanthine plus xanthine oxidase as the source of free radicals. The oxidation of exogenous glucose, lactate and octanoate was severely inhibited (approx. 70%) by products of xanthine oxidase activity. Superoxide dismutase plus catalase effectively prevented the inhibition of oxidation. Cellular high energy phosphate levels were decreased in the presence of the oxygen free radical generating system although cell viability determined by Trypan blue exclusion and light microscopic assessment of normal morphology was not affected. These data suggest that oxygen free radicals decrease myocardial substrate oxidation which may contribute to the functional and ultrastructural changes in the myocardium under conditions such as reoxygenation after hypoxia and reperfusion after ischemia.
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PMID:Effects of oxygen radicals on substrate oxidation by cardiac myocytes. 282 38

The spin trapping agent 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was used to investigate oxy-radical production in post-ischemic rat hearts previously exposed to 20, 30, or 40 minutes of global ischemia. A hydroxyl spin adduct (DMPO-OH) was identified in coronary effluent during the initial seconds of reperfusion by Electron Spin Resonance (ESR) Spectroscopy. The intensity of the ESR signal in post-ischemic effluent increased as ischemic duration was prolonged; however, regardless of the duration of ischemia, maximal spin adduct detection occurred 3 minutes after initiation of reperfusion. Superoxide dismutase inhibited the formation of DMPO-OH, suggesting that superoxide anion was initially generated and is the principle source for the production on the hydroxyl adduct. Our investigations indicate that superoxide anion is produced during the early moments of reperfusion and that its production in the post-ischemic heart is related to the severity of ischemia.
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PMID:Spin-trapping evidence that graded myocardial ischemia alters post-ischemic superoxide production. 282 47

Cerebral superoxide anion generation during reperfusion after total cerebral ischemia was measured in newborn pigs. Superoxide dismutase (SOD)-inhibitable nitroblue tetrazolium (NBT) reduction was determined using two closed cranial windows inserted over the parietal cortices. Twenty minutes of total cerebral ischemia was produced by increasing intracranial pressure, and SOD-inhibitable NBT reduction was determined during 20 min of reperfusion. SOD-inhibitable NBT reduction (8.7 +/- 1.5 pmol.mm-2.20 min-1) was greater in piglets subjected to cerebral ischemia followed by reperfusion than in control piglets not exposed to ischemia (1.6 +/- 1.3 pmol.mm-2.20 min-1). Pretreatment with indomethacin (5 mg/kg iv) markedly reduced postischemia SOD-inhibitable NBT reduction (2.8 +/- 1.1 pmol.mm-2.20 min-1). We conclude that superoxide anion radical is produced by newborn pig brain during postischemic reperfusion. Furthermore, cyclooxygenase metabolism of arachidonic acid appears to be a major source of this activated oxygen during reperfusion of ischemic piglet brain.
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PMID:Postischemic generation of superoxide anion by newborn pig brain. 284 77

It has been proposed that oxygen free radical production is an important mediator of the myocardial dysfunction during the course of acute ischemia. We tested this hypothesis by characterizing the pathway of calcium efflux across sarcoplasmic reticulum (SR) membranes affected by oxygen free radicals. The effect of oxygen free radicals on the steady state calcium load, calcium permeability, and Ca,Mg-ATPase activity of isolated canine cardiac SR vesicles was investigated at pH 7.0. In vitro generation of oxygen free radicals by xanthine oxidase (0.09 units/ml), acting on xanthine in doses up to 50 microM as a substrate, increased the permeability of the SR vesicles to calcium, determined by measuring net efflux of calcium after stopping pump-mediated fluxes, and decreased total intravesicular calcium and free intravesicular calcium with no effect on Ca,Mg-ATPase activity. The effect of oxygen free radicals on calcium permeability was calcium gradient-dependent. Xanthine alone or xanthine plus denatured xanthine oxidase had no effect on this system. Superoxide dismutase (SOD, 56 units/ml), but not denatured SOD, significantly inhibited the effect of xanthine-xanthine oxidase reaction. The calcium permeability of the SR membrane decreased with decreasing calcium load. In addition, inasmuch as extravesicular calcium exerts only a slight effect on calcium permeability, the decrease in the permeability with calcium load is specifically related to the calcium load. Oxygen free radical-induced increase in calcium permeability was unaffected by Mg concentration between 2.1 and 21 mM. In summary, our data reveal that .O2- can produce a diminished level of accumulated calcium, which is reflected by the decreased calcium load and an increase in passive calcium permeability, and that the decreased calcium accumulation in the presence of the xanthine-xanthine oxidase system may not be mainly due to an inhibited calcium pump but due to an increased calcium permeability. Our results also suggest that increased SR membrane passive calcium permeability induced by oxygen free radicals is not carrier mediated. It is postulated that, with the oxygen free radical-mediated progressive increase in calcium permeability, free cytosolic calcium concentrations would increase in ischemic myocardium.
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PMID:The effect of oxygen free radicals on calcium permeability and calcium loading at steady state in cardiac sarcoplasmic reticulum. 284 52

The contribution of free radical-mediated reperfusion injury to the ischemic damage caused by total arterial occlusion has been investigated in a model of transient spinal cord ischemia in the rabbit. Spinal cord ischemia was produced in 20 anaesthetized rabbits by temporary luminal occlusion (20 min) of the abdominal aorta below the renal arteries. Superoxide dismutase (5 mg/kg) (10 animals) was infused before and during reperfusion below aortic occlusion using an infusion pump that infused the enzyme through the contralateral femoral artery. Control (10 animals) received sterile saline with the same procedure. In this later group, 4 animals developed paraplegia, 4 were paretic and only 2 were normal. However, in the treated group, 6 animals were normal while 3 were paretic and only one appeared paralyzed. We conclude that: a) oxygen free radicals generated during reperfusion are involved in producing the ischemic injury, and b) the ischemic spinal cord injury is prevented by superoxide dismutase.
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PMID:Administration of bovine superoxide dismutase prevents sequelae of spinal cord ischemia in the rabbit. 291 49


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