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)

After cardiac surgery, transient renal dysfunction often occurs. The main reasons for impairment of renal function are intraoperative hypotension, ischemia/reperfusion injury and inflammatory response to cardiopulmonary bypass (CPB). Pentoxifylline is known to have anti-inflammatory properties. Gamma-hydroxybutyrate (GHB), an endogenous regulator of energy metabolism, showed beneficial effects on experimental intestinal ischemia/reperfusion injury and liver graft function. Both drugs may be of practical interest in diminishing renal damage during and after cardiac surgery. After approval by the ethics committee and informed consent, 45 patients for elective coronary artery bypass grafting with no clinical and laboratory impairment of renal function were randomized into 3 groups (15 patients each): group 1 received saline as control, group 2 received pentoxifylline intraoperatively (1 mg/kg/h after a priming dose of 1 mg/kg) and group 3 received GHB intraoperatively (25 mg/kg/h after a priming dose of 25 mg/kg) in a double-blinded fashion. During 3 periods (before CPB, from the beginning of CPB until the end of surgery, 24 hours postoperatively), glomerular (creatinine clearance, CCr) and tubular markers of renal function (beta-NAG, alpha 1-microglobulin) were detected in addition to clinical routine standards (creatinine, urea, fractional excretion of sodium). Changes in glomerular and in tubular function were comparable in all groups without characteristic effects of either GHB or pentoxifylline. With CPB, CCr decreased significantly until the end of operation, but showed a rise to preoperative levels on the first day after operation. Tubular function markers (beta-NAG, alpha 1-microglobulin, related to simultaneous excretion of creatinine) showed a remarkable rise after the beginning of CPB up to the postoperative period. The results of the present pilot study suggest the detection of tubular proteins and enzymes a useful addition to present routine clinical standards for recognizing early intraoperative changes in renal function. In the patients studied, there were no clinical signs of renal dysfunction. Neither GHB nor pentoxifylline--in the doses applied--was able to show a therapeutic benefit despite the theoretical advantages.
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PMID:[Effect of gamma-hydroxybutyric acid and pentoxifylline on kidney function parameters in coronary surgery interventions]. 937 42

Polymorphonuclear neutrophils (PMN) and monocytes play a role in vascular diseases. Animal experimental models, using deleukocytation or injection of anti-CD11b-anti-CD18 monoclonal antibodies (inhibition of leukocytic adhesion and of interaction with the endothelial cell) have confirmed this role in the ischemia-reperfusion syndrome and in myocardial infarction. In man, increased production of oxygen radicals, PMN release of elastase, increased monocyte formation of tissue factor (TF) and integrins have been noted in coronary artery disease, in chronic arteriopathy of the lower limbs and in association with vascular risk factors such as diabetes. Pharmacological alteration of leukocyte hyperactivity therefore seems to be justified. Pentoxifylline, used with good effect in arteriopathy of the lower limbs, affects numerous leukocytic functions: diminution in adherence and in PMN production of free radicals, diminution in the formation of TF and cytokines (TNF). Gingkolides reduce leukocytic interactions and platelet activation through an anti-PAF (Platelet Activation Factor) action. Aspirin may interfere with free radicals and inhibit TF formation. alpha-tocopherol blocks the activation, by free radicals, of the transcription factor NF k B. By altering the TNF and IL-1 cytokines, leukocytic activation can be controlled. Other cytokines (IL-4, IL-10) have an immunosuppressive action and reduce the formation of TF. The pharmacological targets are therefore multiple. Their use in vascular diseases is only at a very preliminary stage.
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PMID:[Modulators of leukocytic functions]. 960 25

Leukocytes have been shown to contribute to ischemia-reperfusion injury in skeletal muscle. Pentoxifylline (PTXF), a xanthine-derived phosphodiesterase inhibitor, has received recent attention because of its action on leukocytes. To clarify the effects of PTXF in reperfusion injury, we measured the resting transmembrane potential difference (Em) and evaluated postcapillary venule microcirculation using intravital microscopy in rat skeletal muscle during ischemia and reperfusion. The infrarenal aorta was clamped for 90 min and then reperfused for 60 min. Persistent depolarization of the resting Em was observed in an ischemia-reperfusion (IR) group and was significantly repolarized in a PTXF group during the reperfusion period. The tissue water content was significantly reduced in the PTXF group, although no difference was noted in the tissue lactate content. Flowing erythrocyte velocity and wall shear rate in the PTXF group were significantly higher than in the IR group during the reperfusion period but without significant differences in vessel diameter and hemoglobin oxygenation. Blood flow measured by laser-Doppler flowmeter was also significantly improved in the PTXF group. Furthermore, the adherent leukocyte count was significantly reduced in the PTXF group during this same period. These results indicate that PTXF attenuated reperfusion-associated membrane injury and tissue edema and that PTXF suppressed leukocyte adhesion and improved hindlimb blood flow during the reperfusion period.
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PMID:Pentoxifylline attenuates reperfusion injury in skeletal muscle after partial ischemia. 961 47

Inflammatory mediators are implicated in the pathogenesis of ischemic injury in immature brain. The phosphodiesterase inhibitor pentoxifylline inhibits production of tumor necrosis factor-alpha and platelet-activating factor. We hypothesized that pentoxifylline treatment would attenuate hypoxic-ischemic brain injury in immature rats. Seven-day-old rats (n = 79) underwent right carotid ligation, followed by hypoxia (FiO2 = 0.08). Rats received pentoxifylline immediately before and again after hypoxia (two doses, 25-150 mg/kg/dose, n = 34), or vehicle (n = 27). In separate experiments, rats received pentoxifylline treatment (40 mg/kg/dose, n = 8), or vehicle (n = 10) immediately and again 3 h after hypoxia-ischemia. Severity of injury was assessed 5 d later by visual evaluation of ipsilateral hemisphere infarction and by measurement of bilateral hemispheric cross-sectional areas. Pentoxifylline pretreatment reduced the incidence of liquefactive cerebral infarction, from 75% in controls to 10% with pentoxifylline, 40 mg/kg/dose (p<0.001, chi2 trend test). Quantification of hemispheric areas confirmed these findings. In contrast, posthypoxic-ischemic treatment with pentoxifylline resulted in only a modest reduction in cortical damage, without an overall reduction in incidence of infarction. Phosphodiesterase inhibition may be an effective strategy to use to decrease the severity of neonatal hypoxic-ischemic brain injury. Pretreatment regimens could be clinically relevant in settings in which an increased risk of cerebral ischemia can be anticipated, such as in infants undergoing surgery to correct congenital heart disease.
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PMID:Pentoxifylline attenuates hypoxic-ischemic brain injury in immature rats. 1062 85

There are a limited number of clinically effective pharmacotherapeutic agents for treatment of peripheral vascular disorders. Pentoxifylline and cilostazol are available for the symptomatic treatment of intermittent claudication. Analogs of carnitine and L-arginine are being evaluated for treatment of the symptoms of intermittent claudication, and prostaglandins and growth factors are being evaluated for critical limb ischemia. Calcium channel blockers remain the treatment of choice for Raynaud's phenomenon. Alternative vasodilators may be used selectively to treat individuals with Raynaud's phenomenon who are intolerant of calcium channel blockers or in whom such therapy has been unsuccessful. Prostaglandins have been evaluated in patients with refractory Raynaud's phenomenon who also have digital ulceration. The mainstay of short-term treatment (and prophylaxis) of deep vein thrombosis (DVT) has been unfractionated heparin, but now the use of low molecular weight heparin (LMWH) has emerged. Newer agents, such as heparinoids and direct thrombin inhibitors, hold promise for the prevention and treatment of DVT. Prolonged treatment with warfarin is still required to prevent recurrent thrombosis, although the duration of treatment has come under debate.
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PMID:Drug treatment of peripheral vascular disease. 1172 42

We studied the effect of pentoxifylline on retinal lipid peroxidation and histopathologic changes due to ischemia/reperfusion (I/R). A total of 15 pigmented male guinea pigs were divided into 3 equal groups as control, sham and treatment groups. After application of high intraocular pressure for 90 min for the induction of retinal ischemia, 24-hour reperfusion was established in the sham and treatment groups. In the treatment and sham groups, either 45 mg/kg of pentoxifylline or saline was given 3 times at 8-hour intervals. Biochemical assay and histopathologic evaluation were performed on one randomly selected eye of each animal which was enucleated at the end of the reperfusion period, and retinal malondialdehyde (MDA) levels and thickness of the retinal tissue were determined for each group. The mean MDA level of the sham group was significantly higher versus the control and treatment groups (p < 0.001). When compared with the control group, the mean MDA level of the treatment group was slightly higher, but the difference was not statistically significant (p > 0.05). In comparison with the control group there was a significant increase in the thickness of the retina in the sham group (p < 0.0001), and no significant difference was found in the retinal thickness of the treatment group (p > 0.05). Pentoxifylline might have a preventive effect on the I/R injury of the retina.
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PMID:Protective effects of pentoxifylline in retinal ischemia/reperfusion injury. 1291 23

Pentoxifylline (PTX) and vitamin E inhibit the release of superoxide and hydroxyl radicals, and PTX improves capillary flow and tissue oxygenation. This experimental study was designed to determine the effects of PTX and vitamin E in the ovary after unilateral ovarian ischemia reperfusion (I-R) in albino Wistar rats. A vascular clamp was placed on the left ovary for 4 hours in all groups except for the control group. Following this, in the ischemia (I) group bilateral ovariectomy was performed. Saline, PTX, vitamin E, and PTX plus vitamin E were infused 30 min before reperfusion in the reperfusion (R), pentoxifylline (P), vitamin E (E), and pentoxifylline plus vitamin E (PE) groups, respectively. After 4 hours of reperfusion, the ovaries were removed for biochemical and histologic examination. MDA levels of bilateral ovaries in the PE group were significantly lower than in the E group (p < 0.0033). NO levels of bilateral ovaries in the PE group were significantly lower than in the P and E groups (p < 0.0033). Massive hemorrhage was determined in the ipsilateral ovaries of the R group. Hemorrhage was minimal or moderate in the ipsilateral ovaries of other groups. The contralateral ovaries showed congestion in different degrees. The contralateral ovaries of the group PE and the bilateral ovaries of the control group showed no pathological changes. PTX and vitamin E given together seems to be more effective in reducing I-R injury in ovarian tissue compared to administration of PTX, or vitamin E alone. However, further studies are required to evaluate the effective dose and duration of PTX and vitamin E on bilateral ovaries.
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PMID:Effects of pentoxifylline and vitamin E on the bilateral ovary after experimental ovarian ischemia. 1587 59

Peritoneum has an intrinsic fibrinolytic activity that breaks the peritoneal adhesions. Peritoneal injuries with ischemia interfere this fibrinolytic activity and cause adhesions. Pentoxifylline, a methyl xanthine derivative, improves blood flow by decreasing its viscosity and also increases fibrinolytic activity in plasma. We hypothesized that pentoxifylline would increase peritoneal fibrinolysis and ameliorate adhesions. A rat model of peritoneal adhesion (cecal abrasion with gauze, n = 15 for each group) was used to test this hypothesis and cardinal parameters of peritoneal fibrinolysis were measured in peritoneal samples. No medication was given in control animals, while pentoxifylline was administered intraperitonealy (IP) (25 mg/kg, before abdominal closure to whole abdomen) or intravenously (IV) (25 mg/kg, for 9 days after operation) in the experimental groups. At postoperative day 10, peritoneal biopsies were obtained and adhesions were graded qualitatively. Activities and concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), tPA/PAI-1 complex and hydroxyproline contents were determined. Total adhesion scores were decreased in both treated groups. Mean levels of tPA concentration and tPA activity were increased in the treated groups compared to controls (p < 0.001 and p = 0.001, respectively). The tPA/PAI-1 complex levels were similar among the three groups. PAI-1 levels were lower in animals receiving IP pentoxifylline compared to control animals and those treated with IV pentoxifylline (p = 0.048, p = 0.015, respectively). Peritoneal hydroxyproline levels were similar among the three groups. Our results suggest that pentoxifylline administration either through IV or IP may reduce peritoneal adhesion formation probably by altering peritoneal fibrinolytic activity.
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PMID:Pentoxifylline, a methyl xanthine derivative, reduces peritoneal adhesions and increases peritoneal fibrinolysis in rats. 1677 72

The molecular mechanisms of hepatic ischemia/reperfusion (I/R) damage are incompletely understood. We investigated the role of ceramide in a murine model of warm hepatic I/R injury. This sphingolipid induces cell death and participates in tumor necrosis factor (TNF) signaling. Hepatic ceramide levels transiently increased after the reperfusion phase of the ischemic liver in mice, because of an early activation of acidic sphingomyelinase (ASMase) followed by acid ceramidase stimulation. In vivo administration of an ASMase inhibitor, imipramine, or ASMase knockdown by siRNA decreased ceramide generation during I/R, and attenuated serum ALT levels, hepatocellular necrosis, cytochrome c release, and caspase-3 activation. ASMase-induced ceramide generation activated JNK resulting in BimL phosphorylation and translocation to mitochondria, as the inhibition of ASMase by imipramine prevented these events. In contrast, blockade of ceramide catabolism by N-oleyolethanolamine (NOE), a ceramidase inhibitor, enhanced ceramide levels and potentiated I/R injury compared with vehicle-treated mice. Pentoxifylline treatment prevented TNF upregulation and ASMase activation. Furthermore, 9 of 11 mice treated with imipramine survived 7 days after total liver ischemia, compared with 4 of 12 vehicle-treated mice, whereas 8 of 8 NOE-treated mice died within 2 days of total liver ischemia. In conclusion, ceramide generated from ASMase plays a key role in I/R-induced liver damage, and its modulation may be of therapeutic relevance.
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PMID:Critical role of acidic sphingomyelinase in murine hepatic ischemia-reperfusion injury. 1694 86

Pentoxifylline (PTX) has been shown to protect the liver against normothermic ischemia-reperfusion (I-R) injury. The aims of this study were to investigate the action of PTX on tumor necrosis factor alpha (TNFalpha) gene transcription following normothermic liver I-R as well as to evaluate the resulting effects on liver function and survival. A segmental normothermic liver ischemia was induced for 90 minutes. Rats were divided into three groups: group 1, control, Ringer lactate administration; group 2, PTX treatment; group 3, sham-operated control rats. PTX (50 mg/kg) was injected intravenously 30 minutes before induction of ischemia and 30 minutes before reperfusion. The nonischemic liver lobes were resected at the end of ischemia. Survival rates were compared and serum activities of TNFalpha, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were measured. Liver histology was assessed 6 hours after reperfusion. Liver TNFalpha mRNA was assessed by polymerase chain reaction amplification at different times after reperfusion. PTX treatment significantly decreased serum activities of TNFalpha and inhibited liver expression of TNFalpha mRNA. The extent of liver necrosis and serum levels of liver enzymes were significantly decreased by PTX treatment, resulting in a significant increase in 7-day survival compared with nontreated control rats. In conclusion, PTX inhibits liver TNFalpha gene transcription, decreases serum TNFalpha levels, and reduces liver injury following normothermic I-R.
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PMID:Inhibition of tumor necrosis factor alpha gene transcription by pentoxifylline reduces normothermic liver ischemia-reperfusion injury in rats. 1769 5


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