UMLS:C0022116 - FACTA Search

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

The effects of increased acidity and of lactate at acid pH values on the ultrastruct of normal dog myocardium were investigated using a simple in vitro system. Thin tissue slices incubated in isotonic, phosphate-buffered sodium chloride at pH 6.5, 6.8, or 7.0 developed within 10 minutes electron-dense mitochondrial inclusions resembling those seen in dog heart muscle after 40 or more minutes of ischemia. Mitochondria of tissue incubated in a comparable medium incorporating 3000 mu g. of lactate per ml. showed similar electron-dense inclusions, together with marked swelling. These results indicate that lowered tissue pH alone is not responsible for the mitochondrial changes typical of ischemic heart muscle. Since an earlier study has shown that marked mitochondrial swelling without dense granule formation can be produced by incubation of tissue in lactate at physiologic pH, it seems likely that the swelling of mitochondria in ischemic myocardium is due to the accumulation of lactate anions, whereas the development of the mitochondrial inclusions is associated with decreased pH.
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PMID:Mitochondrial changes in dog myocardium induced by lowered pH in vitro. 23 54

The effects of the dimethyl quarternary analog of propranolol, UM-272, on myocardial infarct volume were studied in the canine heart. Myocardial infarction was produced by occlusion of the left circumflex coronary artery for 60 minutes followed by reperfusion and quantitation of infarct volume 24 hours later. Groups of dogs were either untreated or pretreated with UM-272 with an initial loading dose of 5.0 mg/kg (group A) or 2.5 mg/kg (group B) 30 minutes before occlusion of the left circumflex coronary artery. Both group A and group B animals received additional doses of 2.5 mg/kg of UM-272 every 90 minutes for a period of 6 hours so that the total respective doses were 15 and 12.5 mg/kg. Control animals received comparable volumes of 0.9% sodium chloride solution. All animals were followed throughout the 6-hour procedure with continuous electrocardiographic recordings which were used to assess the effects of acute myocardial ischemia upon disturbances in cardiac rhythm and the effects of drug treatment. Dogs which survived the procedure were given tetracycline i.v. the next day and sacrificed 1 hour later by an overdose of pentobarbital sodium. The hearts were removed and the left ventricle was sliced and examined first under ultraviolet light to localize the ischemic zone by noting the tetracycline fluorescence. The ventricular slices were next incubated in nitro blue tetrazolium which stains normal myocardial tissue, thus allowing one to quantitate the volume of infarcted myocardium by excising and weighing the nonstained and stained muscle separately. The untreated control group had an infarct volume of 23.8 +/- 3.2 g/100 g of left ventricle. The treated animals in groups A and B had respective infarct volumes of 2.3 +/- 0.8 g/100 g (P less than .001) and 7.0 +/- 3.3 g/100 g (P less than .025) of left ventricle. During the acute phase of ischemia and reperfusion, arrhythmias and alterations in the ST-segment, R-wave amplituted and development of pathologic Q-waves were more prominent in the untreated animals and almost totally absent in the treated animals. UM-272 produced a dose-dependent decrease in heart rate as well as a decrease in developed isometric tension. Pretreatment with UM-272 did not prevent the derangement of function in the ischemic zone nor did it permit a return of function upon reperfusion, even though it reduced the degree of cellular damage resulting from 60 minutes of regional ischemia. A possible mechanism for the protective effect of UM-272 may be through its ability to reduce myocardial contractility and heart rate, both of which would reduce myocardial oxygen consumption and thus produce a more favorable balance between myocardial oxygen supply and myocardial oxygen demand.
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PMID:Ischemic changes in the canine heart as affected by the dimethyl quaternary analog of propranolol, UM-272 (SC-27761). 97 88

The present study was designed to investigate the effect of the calcium-channel antagonist gallopamil on myocardial ischemia during percutaneous transluminal coronary angioplasty (PTCA). Twenty-four adult patients with coronary artery disease and significant proximal stenosis of the left anterior descending coronary artery (LAD) were randomly assigned to receive gallopamil or placebo under double-blind conditions. Patients with recent myocardial infarction, apparent collateralization of the LAD, myocardial failure, sinoatrial or atrioventricular block, severe hepatic disease, or renal failure were excluded from the study. PTCA was performed with use of at least two balloon inflations, each of 2 min in duration. Gallopamil (0.4 mg) or placebo (0.9% sodium chloride) was administered during the 10-min interval between the two inflations. For determination of myocardial lactate and hypoxanthine release, blood samples were taken simultaneously from the great cardiac vein and the femoral artery before and immediately after each inflation. Electrocardiogram changes were analyzed by measuring ST-segment deviations (80 ms after the J point) and maximal T-wave deviations of the leads I, II, III, and V2, V4, and V6. The most sensitive leads for identification of myocardial ischemia in the LAD area were V2 and V4. If compared to the first balloon inflation, the degree of ST-segment/T-wave changes induced by the second inflation was significantly reduced only in the presence of gallopamil. Furthermore, if compared to placebo, ischemia-induced lactate and hypoxanthine release was decreased in the presence of gallopamil. These results suggest that intracoronary application of gallopamil attenuates myocardial ischemia during PTCA.
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PMID:Intracoronary gallopamil during percutaneous transluminal coronary angioplasty. 128 55

Sodium transport in the early postischemic period was studied using Mongolian gerbils with right common carotid artery ligation. [22Na]sodium chloride ([22Na]NaCl) was infused immediately after, 10 minutes before, and 4 hours before carotid ligation, and the 22Na distribution was measured in symptomatic animals by autoradiography 1 hour after ischemia. Regional cerebral blood flow was determined by [14C]iodoantipyrine autoradiography. The specific gravity of the brain was measured in symptomatic gerbils 1 and 2 hours after carotid ligation by a gradient column. There was a low uptake of 22Na in the ischemic core and a high uptake in the ischemic periphery when the tracer was given 10 minutes before or immediately after ischemia. In contrast, tracer given 4 hours before ischemia showed an increased radioactivity in both the ischemic core and periphery. It is suggested that increased sodium in the ischemic core is due to a decreased sodium clearance rate and increased sodium in the ischemic periphery is due to some active transport process.
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PMID:Relationship between 22Na distribution and cerebral blood flow in ischemic gerbil brain. 171 59

Myocardial ATP, ADP, and AMP were measured from cardiac biopsy in 11 dogs after intracoronary injection of 6 mL of sodium-meglumine diatrizoate (SMD), iohexol (IOH), or 0.9% sodium chloride (NaCl), and in three of the dogs at baseline before any injection. The ATP at baseline and after SMD, IOH, and 0.9% NaCl were 5.39 +/- 0.41, 3.72 +/- 0.70, 5.52 +/- 0.82, and 5.44 +/- 1.40 mumol/g wet weight, respectively. There were significant differences between SMD and IOH (P less than .02), and between SMD and 0.9% NaCl (P less than .05). The energy charge of SMD was 0.82 +/- 0.08, which differed from 0.89 +/- 0.02 for NaCl or 0.9 +/- 0.05 for baseline (P less than .05), but not from 0.85 +/- 0.04 for IOH. In conclusion, diatrizoate caused significant depletions in ATP stores in comparison with iohexol, but there was no significant difference with respect to energy charge. Nonionic contrast media would be preferable for coronary arteriography in patients whose high-energy stores might be depleted from severe ischemia.
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PMID:Effects of intracoronary administration of contrast media on myocardial high-energy phosphate. A comparison of sodium meglumine diatrizoate and iohexol. 173 78

The effect of intracoronary (IC) pretreatment with different calcium antagonists (diltiazem, nifedipine, verapamil) on the development of infarcts was investigated in two experimental series including 35 open-chest pigs. The left anterior descending coronary artery (LAD) was distally ligated for 75 minutes (series A) or for 45 minutes (series B) and was reperfused for 24 hours. Infarct size was determined as the ratio of infarcted myocardium (tetrazolium stain) to the risk region (dye technique). In series A, 20 pigs were pretreated immediately before occlusion with either IC diltiazem (n = 5, 4 mg/2 min), IC nifedipine (n = 5, 0.4 mg/2 min), IC verapamil (n = 5, 1 mg/2 min), or isotonic sodium chloride solution (n = 5). In series B, IC diltiazem (n = 5, 4 mg/2 min), IC verapamil (n = 5, 1 mg/2 min), or isotonic saline solution (n = 5) were administered 8 minutes prior to ischemia. The IC infusion of all calcium antagonists (series A) depressed left ventricular peak pressure, diastolic blood pressure, and dp/dt max and increased heart rate and coronary venous oxygen saturation. The development of infarcts was significantly delayed by IC diltiazem and IC verapamil. Mean infarct sizes (series A) amounted to 62% in the diltiazem group, 88% in the nifedipine group, 40% in the verapamil group, and 94% in the control group. In series B, where a time period of 8 minutes elapsed between pretreatment and induction of ischemia, mean infarct sizes after 45 minutes of ischemia and 24 hours of reperfusion amounted to 47% in the diltiazem group, 4% in the verapamil group, and 76% in control experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative study on the enhancement of ischemic tolerance by intracoronary pretreatment with three calcium antagonists in pig hearts. 248 97

Stroke is a major cause of morbidity and mortality in the United States with 250,000 cases per year. Cerebral ischemia is the largest category of stroke with cardiac arrest, profound hypotension, and vascular occlusion the principal causes. Traditional approaches to the treatment of ischemic stroke focus on maintaining cardiac output, blood pressure, cerebral blood flow, and on preventing thrombosis. Recently, attention has been focused on developing new therapies that are directed toward abnormal biochemical events at excitatory synapses. Ischemia causes impairment of brain energy metabolism and the release of excessive amounts of glutamate into the extracellular space. This process secondarily excites neurons and further depletes energy stores. The excitotoxic hypothesis of brain injury proposes that glutamate is a principal cause of damage in ischemia. Three components of this hypothesis have been tested and largely proved in experimental studies in tissue culture and in animal models of stroke. First, elevated concentrations of glutamate cause excessive excitation at a subset of glutamate receptors, the N-methyl-D-aspartate (NMDA) receptor. Second, excitation at this receptor leads to excessive influx of sodium chloride and water which causes acute neuronal damage, and calcium which causes delayed and more permanent damage. Third, pharmacologic blockade at the NMDA receptor-ion channel complex prevents ischemic neuronal damage. Studies using specific pharmacologic compounds that block glutamate's action hold particular promise for treating stroke in humans, including competitive antagonists at the NMDA glutamate binding site (for example, 2-amino-5-phosphonovalerate, AP5), noncompetitive antagonists at the calcium channel (for example, MK-801, dextromethorphan, ketamine), and agents that might be directed at the glycine, zinc, and magnesium sites.
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PMID:Selective vulnerability of the brain: new insights into the pathophysiology of stroke. 254 55

Available data demonstrate that oxygen free radicals and derived reactive species of oxygen are produced during myocardial ischemia as well as upon reperfusion of the ischemic tissue. The present study was designed to determine if polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), with its extended plasma half-life in excess of 30 hours in contrast to the native form of the enzyme (Native-SOD), could provide protection to the ischemic myocardium subjected to a 6-hour regional ischemia followed by reperfusion for 24 hours. We hypothesized that myocardial injury due to an ischemic interval is a dynamic process involving the sustained production of cytotoxic oxygen radicals that may continue beyond the ischemic interval. The ability to demonstrate a protective effect of the free radical scavenger enzyme superoxide dismutase would require the continued presence of the antioxidant during the ischemic interval and especially during reperfusion. To test this hypothesis, 22 anesthetized, open-chest dogs underwent 6 hours of circumflex coronary artery occlusion followed by reperfusion for 24 hours. Rapid administration of either Native-SOD (1,000 U/kg), PEG-SOD (1,000 U/kg), PEG-albumin (PEG-ALB), or 0.9% sodium chloride solution for injection (saline) was administered via the left atrium 15 minutes before occlusion of the vessel. A continuous infusion of an additional 1,000 U/kg of the respective enzyme interventions or an equivalent volume of PEG-ALB or saline was given during the 6-hour coronary artery occlusion and terminated 15 minutes after reperfusion. The animals were euthanized 24 hours after reperfusion, and the myocardial region at risk and the infarct region were quantitated by the tetrazolium method. The area of myocardium at risk of infarction, expressed as a percent of the left ventricle, did not differ among the groups: Native-SOD (n = 8), 46.2 +/- 1.8%; PEG-SOD (n = 6), 45.7 +/- 2.1%; PEG-ALB, 38.4 +/- 2.3% (n = 4); and saline 46.0 +/- 2.1% (n = 4). Hemodynamic parameters, the calculated rate-pressure-product, as well as regional myocardial blood flow (radiolabeled microsphere method) in the endocardial, midmyocardial, and epicardial segments of the risk and the nonrisk regions were comparable for all groups. Mean infarct size, determined 24 hours after reperfusion, in the group treated with PEG-SOD was 47.1 +/- 2.9% of the area at risk (n = 6), significantly smaller than that observed in each of the other treatment groups: Native-SOD, 63.5 +/- 2.2% (n = 8); PEG-ALB, 64.6 +/- 2.4% (n = 4); saline, 70.8 +/- 2.2% (n = 4).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of superoxide dismutase on myocardial infarct size in the canine heart after 6 hours of regional ischemia and reperfusion: a demonstration of myocardial salvage. 270 30

Animal studies suggest that hyperglycemia (glucose concentrations greater than 225 mg/dl) occurring prior to periods of brain ischemia exacerbates neurologic damage. Neurosurgical patients, a group at risk for intraoperative brain ischemia, often receive glucose. Therefore, the effects of intraoperative glucose administration (IGA) on these patients were studied. Sixteen patients undergoing supratentorial craniotomy were randomly assigned to receive either 5% glucose in 0.9% sodium chloride solution (G) or 0.9% sodium chloride solution (S) infusion (both at a rate of 3-4 ml X kg-1 X h-1) during the first 4 h of surgery. All patients received glucose infusions postoperatively. Plasma glucose, insulin, free fatty acids, alanine, ketones, base excess, pH, triglycerides, and lactate were measured during the infusion period and 24 h postoperatively. Urinary nitrogen was measured, commencing with the infusion and continuing for 24 h. Neurologic testing included preoperative and postoperative neurologic and psychomotor exams, time to extubation (min), and degree of alertness at the completion of anesthesia. The G group had significantly greater intraoperative plasma glucose concentrations at all time periods studied during the infusion (P less than 0.05). Glucose levels ranged from 200-242 mg/dl compared with 120-160 mg/dl in G and S groups, respectively. G group hyperglycemia was within the range associated with exacerbation of ischemic brain damage in animal studies. Free fatty acids and ketones were significantly greater (P less than 0.05) intraoperatively in the S group. Lactate and insulin were significantly greater in the G group at 4 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of intraoperative glucose on protein catabolism and plasma glucose levels in patients with supratentorial tumors. 351 17

The antioxidant lodoxamide tromethamine was assessed for effects on experimental spinal cord ischemia in the rabbit. Lodoxamide (20 mg/kg/hr) or 0.9% sodium chloride was infused beginning 15 minutes before infrarenal aortic occlusion and continuing for 105 minutes. With an occlusion time of 20 minutes, eight of eight lodoxamide-treated animals and five of eight saline-treated animals regained function after reperfusion. However, by 48 hours after occlusion, seven of eight saline-treated animals were completely paralyzed, whereas only two of eight lodoxamide-treated animals were paralyzed. An ischemia time of 30 minutes exceeded the protective capacity of this treatment. These results suggest lodoxamide may be useful in alleviating ischemic damage to the spinal cord.
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PMID:Effects of lodoxamide tromethamine on paraplegia that occurs after infrarenal aortic occlusion in the rabbit. 369 55

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