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 effect of beta-blocker (propranolol) on the metabolism and contraction of doxorubicin-induced cardiomyopathy during pacing or ischemia was examined by the phosphorus 31-nuclear magnetic resonance (31 P-NMR) in Langendorff hearts of chronically treated rabbits after cumulative doses of 16 mg doxorubicin/kg. After 8 weeks of doxorubicin treatment, beta-blocker (propranolol) was given orally over a period of 2 weeks for a cumulative dose of 1.4 mg/kg. Isolated hearts were paced at higher heart rates, or hearts were perfused on low flow. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), pH, left ventricular systolic developed pressure (LVDev P), and coronary flow were measured. The hearts were divided into three experimental groups: Group I consisted of controls, Group II consisted of doxorubicin treatment, and Group III consisted of doxorubicin treatment with propranolol. Group II showed a significant decrease of ATP during pacing (48 +/- 2%) and during low flow (61 +/- 6%) compared with Group I (86 +/- 9% at pacing, 94 +/- 6% on low flow). But Group III showed a significantly marked improvement of ATP during pacing (95 +/- 10%) and during low flow (83 +/- 3%) compared with Group II. Furthermore, Group II showed a significant decrease of LVDev P during pacing (69 +/- 6 mm Hg) and during low flow (63 +/- 3 mm Hg) compared with Group I (101 +/- 5 mm Hg at pacing, 95 +/- 9 mm Hg on low flow). But Group III showed a significantly marked improvement of LVDev P during pacing (93 +/- 5 mm Hg) and during low flow (83 +/- 14 mm Hg) compared with Group II. In conclusion, propranolol had a significant beneficial effect on metabolism and contraction during high-energy demand and during low oxygen supply of doxorubicin cardiomyopathy.
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PMID:Effect of beta-blocker on metabolism and contraction of doxorubicin-induced cardiotoxicity in the isolated perfused rabbit heart. 1082 57

The effect of a novel cardioprotective agent, JTV-519 on myocardial metabolism and contraction during ischemia and reperfusion was investigated by means of phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts. Normothermic, 20-min, global ischemia was followed by 30-min of postischemic reperfusion and JTV-519 was administered from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), intracellular pH (pHi), left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Fourteen hearts were divided into 2 experimental groups of 7: Group I were controls and Group II were perfused with JTV-519 (10(-6) mol/L). During ischemia, Group II showed a significant (p<0.01) inhibition of the increase in Pi and LVEDP and the decrease in ATP and pHi, compared with Group I. After postischemic reperfusion, Group II also showed a significant (p<0.01) improvement in ATP and pHi as compared with Group I. There were no differences in LVDP or coronary flow during ischemia and reperfusion between the 2 groups. In conclusion, JTV-519 had a significant beneficial effect on myocardial energy metabolism and relaxation during both myocardial ischemia and reperfusion.
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PMID:Effect of a novel cardioprotective agent, JTV-519, on metabolism, contraction and relaxation in the ischemia-reperfused rabbit heart. 1105 18

The role of cardiac adenosine triphosphate-sensitive K+ (K(ATP)) channels induced by angiotensin II type 1 (AT1) receptor antagonist, CV-11974, on myocardial metabolism and contraction during ischemia, and reperfusion by the phosphorus 31-nuclear magnetic resonance in Langendorff-perfused rabbit hearts was investigated. After 20 min of continuous normothermic global ischemia, 30 min of postischemic reperfusion was carried out. CV-11974 with or without the K(ATP) channel blocker, glibenclamide, or the bradykinin B2 receptor antagonist, D-Arg-[Hyp3,D-Phe7]bradykinin, was administered 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate (PCr), inorganic phosphate (Pi), intracellular pH (pHi), left ventricular systolic developed pressure, left ventricular end-diastolic pressure (LVEDP), and coronary flow were measured. Twenty-eight hearts were divided into 4 experimental groups consisting of 7 hearts each. Group I consisted of controls, Group II perfused with CV-11974 (10(-6) mol/L), Group III perfused with CV-11974 (10(-6) mol/L) in combination with glibenclamide (10(-6) mol/L), and Group IV perfused with CV-11974 (10(-6) mol/L) in combination with D-Arg-[Hyp3,D-Phe7]bradykinin (10(-6) mol/L). Group II showed a significant inhibition of the decrease in ATP during ischemia and reperfusion compared with Group I (p<0.01), being 42+/-3% and 19+/-4% at ischemia, 69+/-3% and 47+/-4% at reperfusion in Group II and Group I, respectively. Group II also showed a significant inhibition of the increase in LVEDP during ischemia and reperfusion compared with Group I (p<0.01), being 13+/-4 mmHg and 52+/-8 mmHg at ischemia, 8+/-2 mmHg and 26+/-5 mmHg at reperfusion in Group II and Group I, respectively. However, Group II did not inhibit the decrease in ATP and the increase in LVEDP during ischemia and reperfusion. Group IV also showed no inhibition of the aforementioned parameters during the same period. These results suggest that CV-11974 has a significant beneficial effect for improving myocardial energy metabolism and relaxation during both myocardial ischemia and reperfusion, which is provided by K(ATP) channels and bradykinin B2 receptor. The cardioprotective quality of the AT1 receptor antagonist is caused by the K(ATP) channels that are mediated by the bradykinin B2 receptor.
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PMID:Role of cardiac ATP-sensitive K+ channels induced by angiotensin II type 1 receptor antagonist on metabolism, contraction and relaxation in ischemia-reperfused rabbit heart. 1134 52

Adenosine triphosphate (ATP)-MgCl(2) attenuates ischemia-reperfusion (I-R)-induced lung injury in rats. A previous study indirectly suggests that Mg(2+)-dependent ecto-ATPases on the surface of leukocytes are responsible for the hydrolysis of ATP-MgCl(2) to adenosine, which then contributes to the protective effect of ATP-MgCl(2). This study investigated the role of leukocytes in I-R injury and the protective effect of ATP-MgCl(2) in our buffer-perfused isolated rat lung model. After isolating the lung blood flow of adult male Sprague-Dawley rats, the lungs were perfused through the pulmonary artery cannula with a physiologic salt solution containing human serum albumin. The protective effect of ATP-MgCl(2) pretreatment with or without leukocytes was investigated. Capillary permeability (K(fc)), lung weight gain (LWG), lung wet weight/body weight ratio (LW/BW), lung lavage protein concentration (LPC) and pulmonary artery pressure (PAP) were measured. I-R produced a significant increase in K(fc), LWG, LW/BW, LPC, and PAP. The increases in these indices were significantly attenuated by pretreatment with ATP-MgCl(2) (1 x 10(-6)M) together with leukocytes (2.9 x 10(6)/ml in the perfusate) but not with ATP-MgCl(2) alone. Our data suggest that I-R-induced acute lung injury is not dependent on circulating leukocytes. Pretreatment with ATP-MgCl(2) plus leukocytes but not ATP-MgCl(2) alone had protective effects against I-R lung injury. Whether these findings occur in vivo could not be determined in this study. In our isolated lung red blood cell-free perfusate system, the protective effect of ATP-MgCl(2) requires the presence of leukocytes.
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PMID:The protective effect of adenosine triphosphate-MgCl2 on ischemia-reperfusion lung injury is leukocyte dependent. 1463 Nov 11

Adenosine triphosphate-sensitive potassium channel (KATP) openers protect ischemic myocardium by direct protection of cardiac myocytes, which is thought to be a result of activation of mitochondrial KATP (mKATP). KATP is expressed in skeletal muscle, and the purpose of this study was to determine the effect of the mKATP opener BMS-191095 on infarct size in an isolated gracilis model of ischemia and reperfusion in dogs. The right and left gracilis muscles were isolated in anesthetized dogs except for the artery and vein supplying these muscles (pedicle). BMS-191095 (0.4 mg) or vehicle were infused directly into the artery supplying each gracilis muscle (each animal had one drug-treated and one vehicle-treated muscle). The pedicle was completely occluded for 5 hours followed by 48 hours of reperfusion, after which infarct size was determined. In the vehicle-treated gracilis muscles, significant necrosis was observed (82% +/- 3% of gracilis muscle). BMS-191095 significantly reduced the infarct size in the contralateral gracilis muscle (55% +/- 6%). Reflow into the gracilis muscle was significantly greater in BMS-191095-treated muscles. BMS-191095 appears to reduce damage in ischemic/reperfused skeletal muscle, suggesting that mKATP activation is an important protective mechanism in this tissue.
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PMID:Protective effect of mitochondrial KATP activation in an isolated gracilis model of ischemia and reperfusion in dogs. 1463 2

In patients undergoing coronary surgery, the uptake of amino acids, which has been shown to correlate with oxygen consumption, is a mechanism of cardiac adaptation to the iatrogenic ischemia-reperfusion injury associated with cardioplegic arrest. Based on these premises, we sought to determine whether oral supplementation with mixed amino acids may protect the rat heart exposed to ischemia-reperfusion and to address whether this hypothesized cardioprotection is achieved, at least in part, through preservation of the energy-producing properties of mitochondria. Sprague-Dawley rats were fed (by enteral route) a liquid diet, with or without mixed essential amino acids (daily dose of 1 g/kg) for 30 days. Hearts from anesthetized rats were perfused by the Langendorff method and randomized to 3 groups. The control group was perfused with buffer for 60 minutes; the ischemia-reperfusion control and the amino acid-treated groups were exposed to 35 minutes of ischemia, followed by 60 or 120 minutes of reperfusion. Amino acid supplements minimized infarct size (22 +/- 1.8% vs 33 +/- 2.5%; p <0.05) and occurrence of cardiomyocyte apoptosis, as assessed by co-localization of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and caspase-3-positive staining (p <0.01). Long-term treatment with amino acids also reduced the proportion of cardiomyocytes exhibiting immunostaining for cleaved caspase-9 (p <0.01) but was ineffective on processing of caspase-8. Similar results were obtained in the whole heart by caspase activity assays (p <0.01). The lessened activation of caspase-9 detected in amino acid-treated hearts paralleled a strong reduction in mitochondrial release of cytochrome c. Adenosine triphosphate (ATP) content and rate of ATP production in isolated mitochondria were reduced by >75% in control hearts after 2 hours of reperfusion (p <0.05 vs control hearts); these values returned toward those of the control group in hearts supplemented with amino acids (p <0.01). Finally, the oxygen consumption rate in myocardial skinned bundles was markedly reduced in ischemia-reperfusion control hearts and almost normalized in amino acid-treated hearts (approximately 20% and 93% of the value for normoxic hearts; p <0.01). These results suggest that oral amino acid supplementation attenuates the extent of ischemia-reperfusion injury in the rat heart, through preservation of the mitochondria-generated production of high-energy phosphates.
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PMID:Nutritional supplementation with mixed essential amino acids enhances myocyte survival, preserving mitochondrial functional capacity during ischemia-reperfusion injury. 1509 4

Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels, incorporating Kir6.x and sulfonylurea receptor subunits, are weak inward rectifiers that are thought to play a role in neuronal protection from ischemic insults. However, the involvement of Kir6.2-containing KATP channel in hippocampus and neocortex has not been tested directly. To delineate the physiological roles of Kir6.2 channels in the CNS, we used knockout (KO) mice that do not express Kir6.2. Immunocytochemical staining demonstrated that Kir6.2 protein was expressed robustly in hippocampal neurons of the wild-type (WT) mice and absent in the KO. To examine neuronal sensitivity to metabolic stress in vitro, and to ischemia in vivo, we 1) exposed hippocampal slices to transient oxygen and glucose deprivation (OGD) and 2) produced focal cerebral ischemia by middle cerebral artery occlusion (MCAO). Both slice and whole animal studies showed that neurons from the KO mice were severely damaged after anoxia or ischemia, whereas few injured neurons were observed in the WT, suggesting that Kir6.2 channels are necessary to protect neurons from ischemic insults. Membrane potential recordings from the WT CA1 pyramidal neurons showed a biphasic response to OGD; a brief hyperpolarization was followed by a small depolarization during OGD, with complete recovery within 30 min after returning to normoxic conditions. By contrast, CA1 pyramidal neurons from the KO mice were irreversibly depolarized by OGD exposure, without any preceding hyperpolarization. These data suggest that expression of Kir6.2 channels prevents prolonged depolarization of neurons resulting from acute hypoxic or ischemic insults, and thus protects these central neurons from the injury.
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PMID:Enhanced neuronal damage after ischemic insults in mice lacking Kir6.2-containing ATP-sensitive K+ channels. 1635 31

Cold ischemia time is a risk factor for the development of acute renal failure in the immediate post-transplant period. In this study, we aimed to determine if intravenous fructose-1,6-diphosphate (FDP), given before nephrectomy, attenuates renal cell injury in a cold ischemia model. Male adult Wistar rats were subjected to infusion of either FDP 350 mg/kg (group F, n=6), an equal volume of 0.9% NaCl (group S, n=6), an equal volume/osmolality of mannitol (group M, n=6) or no infusion (group C, n=7). Kidneys were then perfused in situ with Collins solution and nephrectomy was performed. Other kidney slices were stored in Collins solution at 4 degrees C. Adenosine triphosphate (ATP) levels and lactate dehydrogenase (LDH) release were examined at 0, 24, 48 and 72 h. Other slices, obtained after 50 min immersion in Collins solution at 37 degrees C, were frozen for characterization of cytoskeletal preservation using phalloidin-FITC staining. Apical fluorescence intensity of proximal tubule cells, indicative of the F-actin concentration, was measured in a fluorescence microscope interfaced with computer image analysis system. Adenosine triphosphate levels, after up to 72 h of tissue incubation, were higher (P<0.05) in the FDP group when compared to other groups. In addition, LDH release was smaller (P<0.0001) in the FDP group. The F-actin concentration of proximal tubule cells cells was greater in the FDP group (P<0.0001). Results indicate that FDP is a useful tool to increase tissue viability in a rat kidney subjected to cold ischemia, by maintaining ATP cell content, decreasing LDH release and preventing microfilament disruption of proximal tubule cells.
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PMID:Fructose-1,6 diphosphate as a protective agent for experimental ischemic acute renal failure. 1637 25

Glutathione (GSH) is an important endogenous scavenger against reactive oxygen species. Elective abdominal surgery without ischemia and reperfusion leads to decreased muscle GSH concentrations 4-72 hr postoperatively without altering GSH redox status. In the present study, we investigated to what extent muscle GSH status was affected during and following elective abdominal aortic aneurysm repair. From patients (n = 10) undergoing abdominal aortic repair, thigh muscle specimens were taken preoperatively, at maximal ischemia, and at 10 min and 4, 24, and 48 hr of reperfusion. Specimens were analyzed for GSH, amino acids, and energy-rich compounds. At maximal ischemia, phosphocreatine decreased by 37% (p < 0.05) and lactate and creatine increased by 274% and 57% (p < 0.001 and 0.05), respectively, indicating ischemia during the clamping of aorta. Adenosine triphosphate, on the other hand, remained unaltered during the entire study period. Total GSH (tGSH) decreased by 46% at 24 hr and by 43% at 48 hr of reperfusion (p < 0.001), while reduced GSH decreased by 48% at 24 hr and by 44% at 48 hr (p < 0.001). The redox status (GSH/tGSH) of GSH and oxidized GSH remained unaltered. Among the constituent amino acids of GSH, glycine and cysteine remained unaltered while glutamine and glutamate decreased by 55% and 55%, respectively (p < 0.001). Abdominal aortic aneurysm repair induces metabolic alterations characteristic for ischemia. The antioxidative capacity in terms of muscle levels of GSH was decreased. However, the oxidative stress during reperfusion did not change GSH status more than what has been reported following abdominal surgery without ischemia and reperfusion. The results indicate that the oxidative stress elicited by elective abdominal aortic aneurysm repair is outbalanced by a compensated GSH metabolism not giving rise to an increased amount of oxidized GSH or an altered GSH redox status.
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PMID:Effects on skeletal muscle glutathione status of ischemia and reperfusion following abdominal aortic aneurysm surgery. 1637 52

Adenosine triphosphate-sensitive potassium (K(ATP)) channels are thought to mediate the stress response by sensing intracellular ATP concentration. Cardiomyocyte K(ATP) channels are composed of the pore-forming Kir6.2 subunit and the regulatory sulfonylurea receptor 2 (SUR2). We studied the response to acute isoproterenol in SUR2 null mice as a model of acute adrenergic stress and found that the episodic coronary vasospasm observed at baseline in SUR2 null mice was alleviated. Similar results were observed following administration of a nitric oxide donor consistent with a vasodilatory role. Langendorff-perfused hearts were subjected to global ischemia, and hearts from SUR2 null mice exhibited significantly reduced infarct size (54+/-4 versus 30+/-3%) and improved cardiac function compared to control mice. SUR2 null mice have hypertension and develop cardiac hypertrophy. However, despite longstanding hypertension, fibrosis was absent in SUR2 null mice. SUR2 null mice were administered nifedipine to block baseline coronary vasospasm, and hearts from nifedipine-treated SUR2 null mice exhibited increased infarct size compared to untreated SUR2 null mice (42+/-3% versus 54+/-3%). We conclude that conventional sarcolemmal cardiomyocyte K(ATP) channels containing full-length SUR2 are not required for mediating the response to acute cardiovascular stress.
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PMID:Mice lacking sulfonylurea receptor 2 (SUR2) ATP-sensitive potassium channels are resistant to acute cardiovascular stress. 1776 61

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