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

Male Wistar rats were subjected to forebrain ischemia of 10 min duration by clamping both common carotid arteries and simultaneously lowering systemic blood pressure to 40 mm Hg by exsanguination. Recovery was achieved by removing the arterial clamps and reinfusing the blood. Cortical levels of high-energy phosphates and glycolytic substrates were determined enzymatically. Naftidrofuryl (10 or 20 mg/kg i.p.) or ketamine (5 mg/kg i.v.) were applied 30 min prior to the induction of ischemia. S(-)-Emopamil (4 mg/kg) or nimodipine (50 micrograms/kg) were administered by intravenous infusion over 30 min. Nimodipine and emopamil increased the blood glucose level and lowered preischemic blood pressure. Under control conditions, a tendency toward a higher cortical glucose level was observed in treated brains. Brain energy stores were exhausted after ischemia in control and treated animals to the same degree. Lactate levels, however, were higher in emopamil-treated animals. This effect was attributed to the elevated preischemic glucose levels. During the early recovery period, the restoration of high-energy phosphates was accelerated by both calcium entry blockers. Nimodipine and emopamil increased the levels of glucose and glucose-6-phosphate in the early postischemic period. Naftidrofuryl (10 mg/kg) increased the level of creatine-phosphate and ATP after 2 min of recovery. Naftidrofuryl (20 mg/kg) exerted no effect on cerebral energy metabolism, but considerably reduced postischemic blood pressure (possibly thereby masking its ameliorative action). Ketamine accelerated the postischemic restoration of high-energy phosphates. In the conscious rat, local cerebral blood flow (LCBF) was determined with the 14C-iodoantipyrine technique following emopamil (20 mg/kg s.c.) or naftidrofuryl (10 mg/kg i.v.) application.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of cerebroprotective agents on cerebral blood flow and on postischemic energy metabolism in the rat brain. 361 Dec 6

Clinical experience indicates that the risk of reparative cardiac operations is increased in the neonatal period relative to that in older infants and children. Age-related differences in the susceptibility to myocardial ischemic dysfunction were evaluated by comparison of left ventricular function and metabolism in neonatal (mean age = 7 days) and weanling (mean age = 96 days) piglets. Six animals in each group supported on cardiopulmonary bypass were subjected to (1) 120 minutes of hypothermic crystalloid cardioplegic arrest (CP-120) and (2) 15 minutes of normothermic ischemic arrest (NA-15) after a 60 minute interval of reperfusion. Left ventricular systolic and diastolic function was measured after each intervention via endocardially implanted ultrasonic dimension crystals in a septolateral minor-axis position. In both groups, systolic dysfunction was evidenced by an increase in the dimension-axis intercept (p = 0.001), but not the slope of the end-systolic pressure-dimension relation. Left ventricular end-diastolic stiffness, expressed as left ventricular end-diastolic pressure versus Lagrangian strain, increased to a similar degree in both groups (p = 0.001). Adenosine triphosphate levels declined significantly (p = 0.001) in both groups in response to the ischemic interventions with no evident intergroup differences. Lactate levels increased significantly during the course of the experiment (p = 0.04); however, the increases were greater (p = 0.009) at all intervals in the neonatal group. This study demonstrates age-related metabolic differences in response to ischemia consistent with a greater dependence on glycolysis in neonatal myocardia. However, the fact that discriminating age-related differences in left ventricular function were not evident suggests that factors other than young age per se account for the increased surgical mortality in the neonatal period.
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PMID:Age-related differences in the response to myocardial ischemic stress. 365 56

In nine pigs the arterial blood flow to one hind leg was reduced to 5% of resting values during 8 hours in order to study changes in muscle energy metabolism. Biopsy samples from the gastrocnemius muscle were analyzed for ATP, ADP, AMP, PC, Cr, lactate, pyruvate, glycogen and pH before ischemia, at the end of the ischemic period and during 2.5 hours of reperfusion. During ischemia ATP/TCr decreased to 25%, ECP to 80% and PC/TCr to 6% of preischemic values. Lactate increased eightfold and glycogen fell to 40%. In the reperfusion period, lactate decreased to 1/3 of the end-ischemic value, PC/TCr showed threefold rise and ATP/Cr doubled. TCr fell to 66% of preischemic value. Other changes were not significantly affected by reperfusion. The end-ischemic values indicated severe ischemia, but some improvement of metabolism occurred during early reperfusion. The pig model is suitable for further studies aiming to improve the energy state of the cells during ischemia.
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PMID:Muscle metabolic changes in induced subtotal ischemia of the leg in a pig model. 366 Oct 35

The lack of adequate myocardial preservation because of maldistribution of cardioplegic solution in coronary artery disease remains a perplexing problem. We compared two methods of cardioplegic delivery in dogs: antegrade aortic root perfusion (Group I) and retrograde coronary sinus perfusion (Group II). Metabolic changes and regional function in the coronary occlusion model, in which the left anterior descending artery was occluded at its prediagonal portion, were studied. In the distribution of the occluded coronary artery, adenosine triphosphate and total adenine nucleotides at the end of 120 minutes of ischemia were preserved better in Group II (16.80 and 22.94 mumol/gm dry weight) than in Group I (11.06 and 16.19 mumol/gm dry weight, p less than 0.05). Lactate accumulation tended to be higher in Group I than in Group II (114.0 and 87.2 mumol/gm dry weight, respectively; not significant). Percent recovery of segmental shortening was also better in Group II than in Group I (100% and 22.3% at the same left atrial pressure, 4 mm Hg; p less than 0.01). In the region supplied by the intact coronary artery, there were no significant differences between the two groups with regard to metabolic changes and regional function. These observations suggest that retrograde cardioplegic perfusion via the coronary sinus is preferable for surgically treatment of severe coronary artery disease.
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PMID:Myocardial protection in coronary occlusion by retrograde cardioplegic perfusion via the coronary sinus in dogs. Preservation of high-energy phosphates and regional function. 373 83

The left anterior descending coronary artery (LAD) of five dogs was ligated, and blood was withdrawn from the great cardiac vein, left marginal cardiac vein, femoral vein, and aorta. After ligation, immunoreactive 6-ketoprostaglandin (PG) F1 alpha rose from less than 0.1 to a mean value of 1.2 pmol/ml plasma in the great cardiac vein (GCV) and 0.88 pmol/ml in the left marginal vein, with no change in peripheral circulation. Immunoreactive thromboxane (TX) B2 remained below 0.075 pmol/ml throughout the experiments. LAD of 11 dogs was stenosed 60-80% with consequent cyclical reductions in blood flow. 6-Keto-PGF1 alpha in GCV rose in seven dogs (range 0.5-2.2 pmol/ml) and remained unchanged in four. No change was observed in peripheral plasma levels of 6-keto-PGF1 alpha. In these experimental conditions TXB2 remained below 0.075 pmol/ml. Lactate concentrations rose in both experimental conditions in GCV but not in peripheral circulation or in the left marginal vein. This study confirms a link between cardiac ischemia and increased coronary prostacyclin release, but we were unable to detect a similar correlation with TXB2 in plasma.
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PMID:Coronary and systemic 6-ketoprostaglandin F1 alpha and thromboxane B2 during myocardial ischemia in dog. 383 23

Brain tissue lactate, pyruvate, and adenosine triphosphate (ATP) were measured 60 min after bilateral carotid ligation in spontaneously hypertensive rats, of which hematocrit (HCT) was varied by exchanging with isovolemic homologous red cells, plasma or whole blood. Supratentorial lactate of the ischemic brain was increased more in high HCT (greater than or equal to 50%) and less in low HCT (30-39%) compared with normal HCT (40-49%). In very low HCT (less than 30%), however, lactate was increased to further extent compared with any other group of HCT (ANOVA p less than 0.0001). Lactate/pyruvate (L/P) ratio of the ischemic brain showed similar changes, namely U-shaped correlation to HCT. In contrast, supratentorial ATP was decreased more markedly in very low HCT, followed by high and normal HCT, and minimally decreased in low HCT, demonstrating an inverse U-shaped relationship to HCT. Mean arterial pressure and arterial acid-base parameters in ischemic animals did not differ among HCT groups. There were no HCT-related changes of brain metabolites in non-ischemic control rats. These findings indicate that cerebral ischemia following carotid ligation is more severe in high HCT but less in low HCT, probably due to hemodynamic effects of HCT changes. When HCT is reduced to below 30%, however, insufficient oxygen supply to the brain or anemic hypoxia may superimpose on ischemia, resulting in more markedly impairment of brain metabolism. The role of HCT as a cause of cerebral ischemia and its severity is discussed.
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PMID:Effects of hematocrit on brain metabolism in experimentally induced cerebral ischemia in spontaneously hypertensive rats (SHR). 393 3

We compared the levels of hormones and metabolites in the plasma of 37 survivors of Reye's syndrome with the levels in 8 fatal cases, at four time periods within 72 hours of admission. The most prominent differences were found for norepinephrine (NE), which was significantly elevated in fatal cases compared with survivors at all periods. Lactate and dopamine were elevated in the earlier periods. Epinephrine and alpha-amino acid nitrogen were also elevated in fatal cases, but the differences usually were not significant. NE elevation may reflect an increased sympathoadrenal medullary output associated with brain edema, compounded by impaired hepatic clearance of monoamines. Skeletal muscle ischemia from NE-induced vasoconstriction may explain the association between lactic acidemia and the severity of encephalopathy.
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PMID:The metabolic course of Reye's syndrome: distinction between survivors and nonsurvivors. 395 18

Simultaneous lactate production and extraction have been previously demonstrated in the myocardium in patients with coronary artery disease. To quantitate this lactate production and determine its source, dual carbon-labeled isotope experiments were performed. L-[1,2,3-13C3] lactate and D-[6-14C] glucose were infused in 10 patients with significant coronary artery disease. Metabolic samples were obtained at rest and during atrial pacing. Despite net chemical myocardial lactate extraction in the 10 patients at rest and no evidence of clinical ischemia, the L-[1,2,3-13C3] lactate analysis demonstrated that lactate was being released by the myocardium. During atrial pacing, seven patients did not develop clinical symptoms of ischemia, and the chemical lactate analysis showed net lactate extraction. However, tracer analysis demonstrated that there was a significant increase in the lactate released during atrial pacing (from 6.9 +/- 2.3 to 16.2 +/- 10.1 mumol/min) (p less than 0.05). In these seven patients, circulating glucose was the source of 23 +/- 15% of the lactate released at rest, and there was no significant change during pacing. The remaining three patients had mild chest pain and net chemical lactate production during pacing. Lactate release detected by the tracer increased from 5.7 +/- 3.0 mumol/min at rest to 50.9 +/- 16.8 mumol/min during pacing (p less than 0.01). In these patients, the contribution of glucose to lactate production increased significantly during pacing-induced clinical ischemia from 25 +/- 22 to 67 +/- 14% (p less than 0.005). Thus, dual carbon-labeled isotopic experiments are powerful tools for investigating myocardial metabolic pathways.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dual carbon-labeled isotope experiments using D-[6-14C] glucose and L-[1,2,3-13C3] lactate: a new approach for investigating human myocardial metabolism during ischemia. 398 25

The advantages of buffering cardioplegic solutions to improve adenosine triphosphate preservation and postarrest hemodynamic function have been previously promoted. We evaluated the benefit of histidine buffering (195 mmol/L) in a low sodium (27 mEq/L) cardioplegic solution (Roe's) in a canine model of multidose cardioplegic arrest. Four solutions, two unbuffered (K+ = 10 mEq/L and K+ = 30 mEq/L) and two buffered (K+ = 10 mEq/L and K+ = 30 mEq/L), were tested in four groups of dogs for a 4 1/2 hour arrest period followed by 1 hour of reperfusion. Use of the unbuffered solution resulted in a drop in myocardial adenosine triphosphate from 29 +/- 1 mmol/kg (mean +/- standard error of the mean) (K+ = 30 mEq/L) and 28 +/- 2 mmol/kg (K+ = 10 mEq/L) to 8 +/- 2 mmol/kg and 7 +/- 2 mmol/kg, respectively, during the arrest period. In both buffered groups, adenosine triphosphate remained at preischemic levels during the entire arrest period. Myocardial glycogen followed the same pattern as adenosine triphosphate in the buffered groups. Lactate production was markedly elevated in all groups during ischemia. Postarrest hemodynamic function, as assessed by intraventricular isovolumic developed pressure measurements, was better (p less than 0.05) in the buffered low-potassium group than in the other three groups. The extent of myocardial necrosis, measured by triphenyl tetrazolium staining and confirmed by electron microscopy, was minimal (2% +/- 1% of biventricular mass) in the buffered low-potassium group, significantly greater (7% +/- 2% and 10% +/- 2%) in the unbuffered high-potassium and low-potassium groups, respectively, and highest (35% +/- 9%) in the buffered high-potassium group. These findings indicate that significant buffering capacity (similar to that of blood) in a crystalloid cardioplegic solution can be effective in preserving myocardial adenosine triphosphate stores, improving postarrest contractile function, and minimizing myocardial necrosis, provided the combination of high extracellular potassium and high pH levels is avoided.
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PMID:The role of cardioplegic solution buffering in myocardial protection. A biochemical and histopathological assessment. 399 Mar 19

We used a validated radioimmunoassay to examine plasma thromboxane B2 (TxB2) levels in 6 consecutive vasotonic angina (VA) patients, 14 patients with fixed, occlusive coronary artery (VO) disease and 9 healthy volunteers. In the latter groups, basal TxB2 release was absent. However, all 6 VA patients showed basal release. In one, sustained levels of up to 12 pmol/ml over 2 months of clinical instability were found. Daily aspirin rendered TxB2 undetectable with clinical improvement. In a second patient, angina coincided with up to 14 pmol/ml of TxB2 in peripheral blood, and myocardial infarction produced still further increases. The 14 VO patients were then studied by rapid atrial pacing to detect TxB2 release coinciding with pacing-induced angina and myocardial lactate production. All demonstrated significant occlusive disease (2.5 critical lesions per patient). Blood was taken simultaneously from coronary sinus (CS) and brachial artery (BA) catheters for lactate and TxB2 analysis before, immediately after and 10 min after pacing-induced ischemia. Lactate extraction fell from 29.3 +/- 3.7 per cent to -21.1 +/- 12.8 per cent to -74.3 +/- 20.3 per cent during pacing (all p less than 0.01) but was normal in 10 min (25.1 +/- 3.55). CS TxB2 rose from 18 per cent to 204 per cent of control during pacing but was absent after 10 min. BA TxB2 rose from 40 per cent to 132 per cent of control during and after pacing, but was absent after 10 min (p less than 0.05). In VA, TxB2 is uniquely, continuously present in peripheral blood and levels rise further during symptomatic intervals and myocardial infarction. In VO, even CS TxB2 is absent at rest, and rises less rapidly than in VA, even during pacing-induced ischemia. Although antiplatelet agent will block all TxB2 release even in VO, their clinical potential seems greatest in VA.
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PMID:Role of thromboxanes in vasotonic versus vaso-occlusive angina. 640 35


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