Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the efficacy of defibrotide, a prostacyclin-stimulating agent, in preventing ischemia reperfusion injury in Wistar rat heart by using three experimental models: (1) hearts from donors were perfused with the drug (32 mg/kg/hr) during 15, 30, 45, and 60 min of cold ischemia following 5, 10, and 15 min of warm ischemia; (2) hearts from donors treated with the drug were cold-stored for 12 or 24 hr; and (3) procured hearts perfused with the drug were isografted, after 30 or 60 min of warm ischemia, in recipient rats treated daily with defibrotide. Hearts perfused with saline and/or vehicle of the drug were used as controls. At the end of established ischemia times, and after 30 min, and 2, 4, 7 and 14 days from transplantation, hearts were rapidly cooled in liquid nitrogen. ATP, ADP, AMP, cAMP contents, and NAD+/NADH ratios were evaluated in prepared tissue extracts. Cardiac ATP and ADP levels and NAD+/NADH ratios were significantly higher in defibrotide-treated organs than in controls. Isografted defibrotide-treated hearts were also significantly preserved, with respect to controls, from the loss of ATP levels until rejection occurred. Our results demonstrate the protective activity of the drug against the myocardial metabolic damage due to ischemia-reperfusion.
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PMID:Protection of rat heart from damage due to ischemia-reperfusion during procurement and grafting by defibrotide. 192 39

The role of oxygen (O2) in blood cardioplegia (BCP) remains controversial. On the one hand, O2 reduces ischemic injury between BCP infusions by maintaining energy production through oxidative pathways. On the other hand, O2 carried by blood may not be released to the tissue at 4 degrees C or potentially provides substrate for deleterious O2 radical species. This study tests the hypothesis that O2 is a critical component in myocardial protection afforded by BCP. In 17 anesthetized dogs, left ventricular performance was measured by left ventricular end-systolic pressure-volume relations using the position of the end-systolic pressure-volume relation quantitated by the left ventricular midrange volume intercept at 100 mm Hg (V100) to describe performance. After 30 minutes of global normothermic ischemia, hearts were protected with multidose 4 degrees C BCP for 1 hour of arrest. Oxygen content in BCP was adjusted to 1.1 +/- 0.2 vol% (n = 7; desaturated BCP group), 4.3 +/- 0.5 vol% (n = 5; intermediate oxygenated BCP group), or 10.2 +/- 0.6 vol% (n = 5; saturated BCP group) using a membrane oxygenator interposed in the BCP circuit and aerated with an appropriate mixture of O2, nitrogen, and carbon dioxide. After 1 hour of 37 degrees C reperfusion, 3 of the 7 dogs in the desaturated BCP group failed to generate sufficient cardiac output to discontinue bypass. In the remaining 4 dogs, severe left ventricular depression caused a rightward shift in V100 from 17 +/- 4 to 47 +/- 9 mL (p = 0.02). With intermediate BCP, all hearts were weaned from bypass with marginal left ventricular depression (V100, 20 +/- 5 versus 46 +/- 16 mL; p = 0.10). In contrast, hearts protected with saturated BCP showed no significant increase in V100 (13 +/- 4 versus 24 +/- 13 mL; p = 0.23). We conclude that O2 in BCP is critical to its myocardial protective properties.
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PMID:Efficacy of myocardial protection with hypothermic blood cardioplegia depends on oxygen. 192 59

A trace element selenium (Se) is an integral component of glutathione peroxidase (GSHPx) which is one of the important free radical scavenger. We previously reported that serum Se level and serum and myocardial GSHPx activities were significantly lower in infant rats than adult ones. Exactly the same conditions were made by feeding Se-deficient diet for 8 weeks in Wistar rats. Vulnerability to ischemic injury was tested using these Se-deficient rats. Wistar rats fed a commercial laboratory ration were used as a control. Isolated hearts were perfused aerobically with Krebs-Henseleit solution in the Langendorff mode for 15 minutes followed by coronary perfusion with St. Thomas Hospital cardioplegic solution. The hearts were subjected to 60 minutes global ischemia at 4 degrees C. The hearts were reperfused for 30 minutes in working mode, and aortic pressure, LV pressure, LV max dp/dt, coronary flow and aortic flow were measured. In Se-deficient rats aortic pressure (58.5 +/- 1.9 versus 77.3 +/- 8.5 mmHg, p less than 0.01), LV max dp/dt (2023 +/- 153 versus 2722 +/- 513 mmHg/sec, p less than 0.05), aortic flow (8.7 +/- 2.7 versus 17.0 +/- 2.5 ml/g wet wt., p less than 0.01), cardiac output (17.0 +/- 4.6 versus 24.6 +/- 2.0 ml/g wet wt., p less than 0.05) and stroke volume (67.5 +/- 11.6 versus 95.6 +/- 9.8 microliters/g wet wt., p less than 0.01) were significantly inferior to control rats. Then the hearts were iced instantly by fluid nitrogen and myocardial thiobarbituric acid reactive substance (TBARS) level was measured.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Significance of selenium deficiency on myocardial protection of the mature and immature rat hearts]. 196 Apr 31

This study was designed to test the usefulness of nitrogen-13 (N-13) glutamate imaging with positron emission tomography in defining myocardial ischemia in humans. Seventeen patients who had undergone coronary arteriography were studied with N-13 glutamate at peak supine exercise using a bicycle ergometer, as well as with the flow tracer N-13 ammonia at peak exercise during a second similar exercise test. Six of the patients also underwent imaging with N-13 glutamate at rest before exercise testing; in the remaining 11 patients imaging with fluorine-18 (F-18) fluorodeoxyglucose was performed to assess glucose metabolism after the second exercise test. Seven patients had classic metabolism-flow mismatches consistent with ischemia (that is, decreased N-13 ammonia uptake in a region with relatively increased F-18 fluorodeoxyglucose uptake). There was no evidence of increased N-13 glutamate uptake in the ischemic mismatched regions in any of these patients. In all 17 patients, the uptake of N-13 glutamate during exercise paralleled the uptake of N-13 ammonia during exercise, suggesting that N-13 glutamate behaves as a flow tracer rather than as a metabolic marker of ischemia in humans.
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PMID:Dynamic positron tomographic imaging with nitrogen-13 glutamate in patients with coronary artery disease: comparison with nitrogen-13 ammonia and fluorine-18 fluorodeoxyglucose imaging. 197 78

Positron emission tomography has been employed in vivo to assess flow using N-13 (nitrogen-13) ammonia and glucose metabolism, with the glucose analog F-18 (fluorine-18) fluorodeoxyglucose. Flow metabolism mismatches in which glucose metabolism is increased with respect to flow have been used to define ischemic, but viable myocardium. The feasibility of detecting exercise-induced ischemia using this technique was explored. Eleven normal volunteers and 16 patients who had undergone coronary arteriography were studied with N-13 ammonia at rest and with bicycle exercise, and with F-18 fluorodeoxyglucose in the postexercise period. Each image was divided into 16 sectors. Comparison of absolute net extractions of N-13 ammonia at rest and with exercise was not sensitive in detecting functionally significant coronary artery lesions. Myocardial uptakes of F-18 fluorodeoxyglucose and exercise N-13 ammonia were normalized to the sector with the highest N-13 ammonia uptake (corresponding to the highest flow rate). The differences and ratios of these normalized uptakes were successfully used to objectively define flow metabolism mismatches and to identify functionally significant coronary artery disease. Our data suggest that exercise flow and metabolic imaging are superior to rest and exercise flow imaging, particularly in patients with prior myocardial infarctions.
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PMID:Noninvasive detection of functionally significant coronary artery stenoses with exercise and positron emission tomography. 206 38

Apart from pharmacological interventions, four methods can be used to induce myocardial damage in the isolated, perfused heart. These are (i) total global ischemia, where perfusion is stopped completely; (ii) partial ischemia where perfusion is restricted; (iii) regional ischemia, produced by occlusion of the coronary circulation, and (v) hypoxia where the oxygenated buffer is replaced with a buffer bubbled with nitrogen. Using rat hearts, coronary artery occlusion was found to have potential as a screening device for antiischemic compounds. In these studies 45Ca uptake and enzyme release were found to increase with ligation time. The inclusion of the Ca2+ antagonist verapamil (0.01 to 1 microM) resulted in a concentration-dependent inhibition of 45Ca uptake (IC50 = 68 nM); however the proportion of tissue damaged remained unchanged. Similar findings were obtained in the presence of the dihydropyridine Ca2+ antagonist nicardipine (0.1 or 1 microM). Measurement of enzyme release during the reperfusion period confirmed significant correlations between levels of either lactate dehydrogenase (LDH) or creatine kinase (CK) and 45Ca uptake. Studies involving LDH show that cation uptake precedes enzyme release (r = 0.93; p = less than 0.001).
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PMID:Determination of the extent of ischemic damage and the effect of the calcium antagonist, verapamil following coronary artery ligation in the rat. 208 46

Calcium is believed to be responsible for initiating a deleterious cascade of events that leads to irreversible cell injury during prolonged ischemia. Theoretically, the calcium-dependent cascade of events can be interrupted at three distinct points: a) by reducing calcium inflow into the cytosol using a calcium channel blocker such as verapamil, b) by increasing the mitochondrial capacity to sequester calcium using ethane-1-hydroxy-1:1-diphosphonic acid (EHDP), and c) by inhibiting the activation of the calcium-calmodulin complex using trifluoperazine (TFP). To evaluate the protective role of these agents in prolonged ischemia, 190 unilaterally nephrectomized rats underwent total occlusion of the renal artery for 90 min. One hour before surgery, all the rats received an i.p. injection of either saline or one of the drugs. Of the 190 rats, 130 were used to determine survival and optimal drug doses; the remaining 60 rats were used to determine blood urea nitrogen and serum creatinine at 40 h and 5 days after surgery. Only 33% of the rats in the control group survived for 10 days. However, 87.5% (P less than 0.005), 90% (P less than 0.005), and 60% (P less than 0.01) of the rats pretreated with verapamil, TFP and EHDP respectively survived for 10 days. No differences, however, were seen in renal function tests among the control, TFP or EHDP groups. This suggests that calcium antagonists are successful in protecting the kidney from prolonged ischemic injury despite impaired renal function tests. It may also indicate that these agents delay or prevent the ischemic cells from undergoing irreversible damage.
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PMID:Blocking the calcium cascade in experimental acute renal failure. 211 82

The brain ischemia of spontaneously hypertensive rat was produced gradually by bilateral ligation of the common carotid arteries. The cortical blood flow was measured with a laser doppler flowmeter before and after ligation of the arteries. At the specified intervals, the brain was frozen in situ with liquid nitrogen. The concentration of blood glucose and glycolytic intermediate in frozen brain were measured and the relationship between glycolytic activity and the concentrations of effectors to PFK-1, such as fructose 2,6-bisphosphate, fructose 1,6-bisphosphate, AMP, ATP, Pi and citrate, was investigated. The changes in glycolytic intermediates, pyridine and adenine nucleotides concentration showed that ischemic change occurred in the brain tissue after 30 min of bilateral ligation of the common carotid arteries, in correlation with the decrease in cortical blood flow. The rate of lactate formation increased during the 30-60 min interval and finally decreased during 60-120 min period of ischemia. This indicates that anaerobic glycolysis was accelerated during the early stages of ischemia. The most potent activator of PFK-1, fructose 2, 6-bisphoshate, increased from 5.3 or 6.7 nmol g during the initial stage of ischemia, and this change preceded the activation of glycolysis and the increase in fructose 1,6-bisphosphate concentration, a result indicated that fructose 2,6-bisphosphate does participate in the activation of glycolysis during brain ischemia in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Glycolytic activity and fructose 2, 6-bisphosphate changes in rat brain during ischemia]. 214 15

This experiment was designed to determine if nitrous oxide alters neurologic and pathologic outcome from temporary focal cerebral ischemia in spontaneously hypertensive rats deeply anesthetized with a barbiturate. Two groups of rats were given intravenous methohexital such that a stable EEG pattern of burst suppression was achieved. In one group of rats (n = 11), the lungs were mechanically ventilated with 70% N2O/30% O2, and in the other group (n = 10), ventilation was done with 70% nitrogen/30% O2. The middle cerebral artery was then occluded for 2 h, during which time mean arterial pressure, blood gases, hematocrit, plasma glucose, and head temperature were held constant between groups. The total doses of methohexital administered were similar in both groups as were the plasma methohexital concentrations immediately prior to onset of ischemia. After reperfusion of the middle cerebral artery, the animals were allowed to awaken. Neurologic evaluations were performed prior to ischemia and at 24 and 96 h postischemia. Cerebral infarct volume was measured at 96 h postischemia using triphenyl tetrazolium chloride staining and computer imaging techniques. There were no neurologic differences between the N2O and nitrogen groups at any experimental interval although both groups exhibited deficits at both 24 and 96 h postischemia relative to preischemic values. The two groups also had nearly identical cerebral infarct volumes (N2O = 231 +/- 97 mm3; nitrogen = 226 +/- 75 mm3; mean +/- SD).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitrous oxide does not alter infarct volume in rats undergoing reversible middle cerebral artery occlusion. 222 37

Xanthine oxidase (XO) has been implicated as a source of free radicals mediating ischemia-reperfusion injury. Conversion of the non-free radical generating xanthine dehydrogenase (XD) to the free radical producing XO during ischemia has been demonstrated in several tissues. We examined the irreversible conversion of XD to XO in the dog brain after ischemia and after ischemia and reperfusion. Under pentobarbital sodium anesthesia and by use of a cerebrospinal fluid compression model of global cerebral ischemia, dogs were subjected to 30 min of ischemia (n = 8) or 30 min of ischemia and 60 min of reperfusion (n = 8). A cerebral perfusion pressure of 60 mmHg was maintained during reperfusion. Eight control dogs were not subjected to ischemia. After the dogs were killed their brains were rapidly removed and frozen in liquid nitrogen. XO and XD + XO activities were measured with a radioassay utilizing 8-[14C]hypoxanthine and separating substrate and products by thin-layer chromatography. Total XD + XO activity was significantly (P less than 0.05) decreased after ischemia and reperfusion (35.6 +/- 8.0 vs. 60.8 +/- 20.8 nmol.min-1.g protein-1 in controls, means +/- SD) but not after ischemia alone (48.2 +/- 20.4). XO/(XD + XO) was approximately 20% in all three groups. Irreversible XD to XO conversion is not an important mechanism leading to early tissue injury in global cerebral ischemia.
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PMID:No conversion of xanthine dehydrogenase to oxidase in canine cerebral ischemia. 226 Jun 92


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