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)

The effects of hypothermic lung preservation were evaluated in 12 mongrel dogs receiving double lung allografts. Animals underwent transplant procedures after 12 hours of static preservation at 4 degrees C following pulmonary artery flush with 60 to 80 ml/kg cold modified Collins solution. Donors were pretreated with allopurinol and recipients with methylprednisolone and perireperfusion deferoxamine. Six donor animals received a PGE1 infusion (20 to 500 ng/kg/min) for 20 minutes before harvest at doses causing a significant reduction in pulmonary vascular resistance. After implantation, recipients were maintained at ventilator settings identical to those used in donors. A fixed FIO2 (0.4) was maintained, except for 15-minute periods of FIO2 1.0 that were used to measure left-to-right intrapulmonary shunt fraction (Qs/Qt) and alveolar-arterial oxygen gradients (PAO2-PaO2). Cardiopulmonary function was studied for 20 hours. Pretreatment with PGE1 resulted in reduced survival (p less than 0.05) and increased PAO2-PaO2 (p less than 0.05) and Qs/Qt (p less than 0.05) 30 minutes after reperfusion. After 60 minutes of reperfusion, mean arterial pO2 (FIO2 0.4) was 148 mm Hg in controls and 80.5 mm Hg in the PGE1 group (p less than 0.02). There was no significant difference in pulmonary vascular resistance, cardiac output, mixed venous oxygen saturation, airway resistance, compliance and physiologic dead space between groups at any time after implantation. After 20 hours of reperfusion, pO2 (FIO2 0.4) in the control group was well maintained at 140 (+/- 52) mm Hg. The method of lung preservation in control animals resulted in good survival and adequate gas exchange after 12 hours of ischemia and 20 hours of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of prostaglandin E1 in twelve-hour lung preservation. 203 30

The dose-response effects of 6-h intravenous infusion of PGI2 (0, 5, 10, 25 or 75 ng/kg/min) or PGE1 (0, 25, 50, 100 or 300 ng/kg/min) on skin hemodynamics and viability were studied in 4 x 10 cm random pattern skin flaps (n = 24) raised on both flanks of the pig. Infusion of PGI2 or PGE1 was started immediately after intravenous injection of a loading dose 30 min before skin flap surgery. PGI2 infusion significantly (P less than 0.05) increased the total skin flap capillary blood flow at the dose of 10 ng/kg/min, compared with the control. However, the distance of blood flow along the skin flap from the pedicle to the distal end, i.e. perfusion distance, was not increased. Consequently, the length and area of skin flap viability was also not significantly increased. The effect of PGI2 infusion on skin blood flow was biphasic. Specifically, higher doses (greater than or equal to 25 ng/kg/min) of intravenous PGI2 infusion produced no beneficial effect on the skin flap capillary blood flow. PGI2 infusion at the dose of 10 or 75 ng/kg/min did not significantly increase plasma renin activities or plasma levels of norepinephrine compared with the control, therefore the biphasic effect of PGI2 on skin flap blood flow was not related to circulating levels of norepinephrine or angiotensin. Intravenous infusion of PGE1 did not produce any therapeutic effect on the skin capillary blood flow in the random pattern skin flaps at all doses tested. At the dose of 300 ng/kg/min, the mean arterial blood pressure was 17% lower (P less than 0.05) than the control, but the skin capillary flow still remained similar to the control. It was concluded that intravenous infusion of PGI2 or PGE1 was not effective in augmentation of distal perfusion or length of skin viability in the porcine random pattern skin flaps. Drug treatment modalities for prevention or treatment of skin flap ischemia is discussed.
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PMID:Efficacy of intravenous infusion of prostacyclin (PGI2) or prostaglandin E1 (PGE1) in augmentation of skin flap blood flow and viability in the pig. 205 39

The authors observed the effect of prostaglandin E1 (Prostavasine) on the blood flow in the lower extremities in 25 patients with chronic ischemia caused by thrombo-angitis obliterans and arteriosclerosis obliterans (clinical stage III and IV). The blood flow in the lower extremities and the effects of prostaglandin E1 were assessed by means of rheo-angiographic and Doppler-testing investigations. The parameters A (amplitude), S (area) and WOT (index) of rheo-angiographic curves showed significant increased. No significant changes were found in the determined Doppler's indexes. The observed differences of values the parameters of rheo-angiographic curves suggests that prostaglandin E1 evident improvement the tissue blood flow in patients with critical ischemia of the lower extremities. The authors found that prostaglandin E1 was without any significant effect dilating the great vessels, but an evident improvement was observed in rheo-angiographic records which reflect rather the blood flow values in the small vessels.
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PMID:[Prostaglandin E1 in the treatment of chronic ischemia of the extremities]. 207 25

Prostaglandins and leukotrienes are ubiquitous mediators of a wide variety of physiologic and immunologic effects in liver function and disease. Although the biochemical, synthetic and catabolic pathways of these compounds from arachidonic acid are well known, their cellular mechanisms of action are less well understood. Numerous studies have demonstrated the role for leukotrienes in the pathogenesis and the protective action of PG in experimental animal models of liver injury. These have included models of liver cell damage due to ischemia, galactosamine, carbon tetrachloride, and lipopolysaccharide. More importantly, the results of these studies have led to the demonstration of protective properties of 16, 16 dimethyl PGE2 (dm PGE2) in a mouse model of viral hepatitis. These results have led to the use of IV PGE1 in the treatment of patients with fulminant viral hepatitis, where 71% overall survival was observed as well as in the setting of primary non function and recurrent hepatitis B following liver transplantation. While the mechanisms of prostaglandin hepatic protection are not well understood, it has been demonstrated that dm PGE2 abrogates the induction of tumour necrosis factor, leukotriene B4 (LTB4) and procoagulant activity by macrophages as well as attenuating the expression of major histocompatibility class antigens on the surface of hepatocytes, and may inhibit viral replication. Finally, prostaglandins are known to play a role in the renal dysfunction associated with cirrhosis and fulminant hepatic failure, and therefore further studies of these agents in the pathophysiology and treatment of liver diseases and their complications are warranted.
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PMID:Eicosanoids and the liver. 213 47

In the hamster cheek pouch, microvascular effects of iloprost at a nonhypotensive dose include vasodilatation at the level of arterioles and venules without changes in microvascular permeability, increased number of perfused capillaries/cm2, prevention of microvascular spasm and capillary ischemia as caused by LTD4, and inhibition of histamine- and 5-HT-induced venular leakage of FITC-dextrane. As regards the effects on basal vessel tone, capillary density, and prevention of LTD4 effects, PGE1 had similar effects as also shown by others in the human cutaneous microcirculation. However, PGE1 did not prevent the microvascular leakage caused by histamine. The Ca2+-antagonist nifedipine, apart from arteriolar vasodilatation, neither increased venular diameter and capillary perfusion nor prevented the effects of LTD4 and histamine. The microvascular actions of iloprost by improvement of tissue perfusion and prevention of mediator-induced tissue edema and vasospasm could contribute to the beneficial effects observed in ischemic diseases.
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PMID:Microvascular effects of iloprost in the hamster cheek pouch. 244 80

In order to further elucidate the mechanisms involved in therapeutic effects of prostacyclin and Iloprost in peripheral ischemic disease, the actions on microvascular tone, capillary density, and increases in venular permeability induced by inflammatory mediators and by ischemia were investigated in the cheek pouch of anaesthetized Syrian hamsters using intravital videomicroscopy and--for quantification of vascular permeability--venular leakage of fluorescein-labelled dextran (FITC-D; Mw 70,000). Iloprost at the nonhypotensive, platelet aggregation-inhibiting dose of 0.5 microgram/kg/min i.v. significantly increased the diameters of arterioles and venules and the density of perfused capillaries and antagonized vasoconstriction and decrease of perfused capillary density as induced by Leukotriene D4 (LTD4; 10(-7) M). Iloprost significantly antagonized venular leakage of FITC-D induced by histamine (10(-5) M), serotonin (10(-5) M), bradykinin (10(-6) M) and reperfusion after 30 min ischemia. Topical application of Iloprost (10(-8) M), intraarterial infusion of Prostaglandin E1 (PGE1; 2.0 micrograms/kg/min), and topical Forskolin (10(-5) M) also attenuated histamine-induced venular FITC-D leakage, while topical PGE1 (10(-7) M) and i.v. infusion of Nifedipine (30 micrograms/kg + 10 micrograms/kg/min) were not effective. It is concluded, that microvascular effects of Iloprost by improvement of tissue perfusion and functional antagonism of mediator-induced tissue edema and vasospasm could contribute to therapeutic effectiveness in ischemic diseases.
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PMID:Action of the stable prostacyclin analogue iloprost on microvascular tone and -permeability in the hamster cheek pouch. 244 31

The influence of iloprost, PGE1 and of the combined application of iloprost and PGE1 on high energy phosphate contents was investigated in isolated rat hearts perfused aerob at 37 degrees C in Langendorff mode. Changes in creatine phosphate, ATP and inorganic phosphate were registered during 20 minutes of global ischemia and 56 minutes of reperfusion with 31P-NMR-spectroscopic methods starting drug application prior to ischemia simultaneously with onset of heart perfusion. Most effective in preservation of high energy phosphates was the combined application of PGE1 and iloprost resulting in a creatine phosphate/inorganic phosphate ratio of 103.2 +/- 30.9% of pre-ischemia values compared to 52.5 +/- 6.1% in control group without drug application 0-5 minutes after onset of reperfusion, 148.8 +/- 24.8% vs 78.8 +/- 15.2% at 6-11 minutes of reperfusion and 116.6 +/- 16% vs 68.9 +/- 12.7% at 12-17 minutes of reperfusion. The same trend was observed employing ATP/inorganic phosphate ratio. The improved energy state in reperfused hearts following application of PGE1 and iloprost in combination is presumed to be supported by a reduction of the loss of high energy phosphates (HEP) during global ischemia and by a cytoprotective effect of iloprost immediately after starting reperfusion.
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PMID:Action of iloprost and PGE1 on global ischemic and reperfused myocardium: a 31P-NMR-study. 247 Mar 51

Recent investigations in several organs indicate cytoprotective effects of prostanoids. For further elucidation of this efficacy the investigations dealt with the cardioprotection of prostanoids (iloprost, PGE1) and the cyclooxygenase inhibitor indomethacin under in vivo- and in vitro-conditions. The experiments were carried out in isolated perfused guinea pig hearts and anaesthetized rabbits. Cardiac damage was induced by chemical substances or loading by aortic constriction or ischemia. In isolated perfused hearts iloprost and indomethacin suppressed the toxic effects of carbon tetrachloride, chloroform, benzene, sodium dithionate and phenylethylbarbituric acid, but not the efficacy of quinine sulfate and 2,4-dinitro-phenol. Cardiac loading by aortic stenosis or ischemia induced a decrease of contractility and blood pressure and changes in the myocardial PGI2-biosynthesis. On the other side application of indomethacin, iloprost or PGE1 diminished the cardiac damage and inhibit the myocardial PGI2-formation. The results show that indomethacin and prostanoids have a protective effect in pathophysiological changes or toxic damage of the heart, possibly caused by a stabilization of the cellular membrane.
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PMID:Significance of the cardioprotective effect of prostanoids and indomethacin. 247 Mar 59

The influence of PGE1, iloprost and a combination of both on high energy phosphate levels in isolated rat hearts reperfused 1 h following 20 min of global ischemia was investigated employing 31P-NMR-spectroscopy. Whereas PGE1 induced a slight reduction in the decline of the creatine phosphate/inorganic phosphate. ATP/inorganic phosphate ratio and NMR-energetic index during ischemia, iloprost application was followed predominantly by a temporary but marked improvement of the creatine phosphate/inorganic phosphate ratio during the early period of reperfusion. The best results in preservation of high energy phosphates were achieved after simultaneous application of PGE1 and iloprost. It is presumed that the accelerated normalization of the heart function observed immediately after ischemia in the eicosanoid treated hearts is related to the more rapid recovery of intracardial high energy phosphate level.
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PMID:PGE1 and iloprost affect the high energy phosphates in the global ischemic and reperfused rat heart: a 31P-NMR study. 247 19

Thrombolytic therapy has gained widespread acceptance as a means of treating coronary artery thrombosis in patients with acute myocardial infarction. Although experimental data have demonstrated that timely reperfusion limits the extent of infarction caused by regional ischemia, there is growing evidence that reperfusion is associated with an inflammatory response to ischemia that exacerbates the tissue injury. Ischemic myocardium releases archidonate and complement-derived chemotactic factors, e.g., leukotriene B4 and C5a, which attract and activate neutrophils. Reperfusion of ischemic myocardium accelerates the influx of neutrophils, which release reactive oxygen products, such as superoxide anion and hydrogen peroxide, resulting in the formation of a hydroxyl radical and hypochlorous acid. The latter two species may damage viable endothelial cells and myocytes via the peroxidation of lipids and oxidation of protein sulfhydryl groups, leading to perturbations of membrane permeability and enzyme function. Neutrophil depletion by antiserum and inhibition of neutrophil function by drugs, e.g., ibuprofen, prostaglandins (prostacyclin and PGE1), or a monoclonal antibody, to the adherence-promoting glycoprotein Mo-1 receptor, have been shown to limit the extent of canine myocardial injury due to coronary artery occlusion/reperfusion. Recent studies have challenged the hypothesis that xanthine-oxidase-derived oxygen radicals are a cause of reperfusion injury. Treatment with allopurinol or oxypurinol may exert beneficial effects on ischemic myocardium that are unrelated to the inhibition of xanthine oxidase. Furthermore, the human heart may lack xanthine oxidase activity. Further basic research is needed, therefore, to clarify the importance of xanthine oxidase in the pathophysiology of reperfusion injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial ischemia and reperfusion: the role of oxygen radicals in tissue injury. 248 90


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