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

This review provides a summary and assessment of research involving renal prostaglandins. Arachidonic acid released from phospholipids is converted by prostaglandin cyclo-oxygenase in the kidney to PGF2, PGF2alpha, PGD2, and, possibly, to PGI2 and thromboxane A2. Production of PGE2 and PGF2alpha is predominately but not exclusively in the medulla, whereas degradative enzymes are present in both cortex and medulla. Prostaglandins enter the tubular lumen by facilitated transport and are partially reabsorbed from the urine in the distal nephron. Urine prostaglandins probably reflect renal synthesis. PGE2 and endoperoxides stimulate and PGF2alpha and indomethacin inhibit renal renin synthesis. In response to ischemia, vasoconstriction, or angiotensin II the kidney increases prostaglandin synthesis to modulate renal vascular resistance. In conscious animals or man no role has been established for prostaglandins in the maintenance of basal renal blood flow or renal sodium excretion. PGE influences renal water excretion by inhibiting the action vasopressin. Despite conflicting data there is evidence that renal prostaglandins are involved either primarily or secondarily in many types of hypertension. Inhibitors of prostaglandin cyclooxygenase have been used with success in Bartter's syndrome. Conflicting results in many areas of investigation may be resolved by the use of more accurate and reliable assays, careful handling of samples, and the use of urine to further investigate renal prostaglandin synthesis.
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PMID:Prostaglandins and the kidney. 33 46

Twenty-seven heparinized dogs were exposed to 35 min of cerebrospinal fluid compression ischemia followed by 30 min of recirculation. The degree and distribution of post-ischemic reperfusion was then assessed by means of a 14C-antipyrine autoradiographic blood flow study. The animals were assigned to 5 groups by the administration of drugs as follows: 1) no additional drugs; 2) indomethacin 1.5 or 4 mg/kg prior to ischemia; 3) indomethacin 4 mg/kg 5 min after ischemia; 4) prostaglandin I2 (PGI2) infusion 30--180 ng/kg/min beginning 5 min after ischemia; and 5) indomethacin 4 mg/kg 5 min after ischemia plus PGI2 infusion 30--130 ng/kg/min beginning 5 min after ischemia. Animals receiving no additional drugs had relatively low post-ischemic blood flows with focal zones of greatly impaired reperfusion. Animals receiving either indomethacin or PGI2 after ischemia did not differ significantly from the no additional drug group. A significant enhancement of post-ischemic reperfusion occurred in animals receiving indomethacin prior to ischemia and those receiving the combination of indomethacin and PGI2 after ischemia. These observations implicate an imbalance in prostaglandin pathways at the blood-endothelial interface in the genesis of post-ischemic reflow impairment and suggest novel drug therapy for enhancing nutrient flow after ischemia.
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PMID:Prostaglandin I2 and indomethacin prevent impairment of post-ischemic brain reperfusion in the dog. 39 21

The ability of prostacyclin (PGI2) to alter responses to acute myocardial ischemia was studied in open-chest, anesthetized cats. PGI2 was infused intravenously at 0.5 nmoles kg-1 min-1 in cats subjected to 5 h of myocardial ischemia by occlusion of the LAD coronary artery, and in sham-operated controls. GI2 infusion resulted in significantly decreased arterial blood pressure and inhibition of platelet aggregation. Coronary ligation resulted in significant S-T segment elevations lasting 5 h in vehicle-treated animals but only 1 h in cats with myocardial ischemia and receiving PGI2. At 5 h, cats with ischemia and given the vehicle showed S-T segment elevations significantly greater than the other two groups. Ischemic myocardium from vehicle-treated animals exhibited significantly less creatine phosphokinase (CPK) specific activity than normal tissue from the same hearts or myocardial tissue from the other two groups. This loss of CPK from ischemic myocardium of the cats given vehicle was reflected in plasma CPK specific activities which were significantly greater than those of sham-operated cats. The cats with ischemia and treated with PGI2 exhibited lower plasma CPK activities. These changes were moderated by PGI2 infusion during myocardial ischemia. PGI2 infusion may protect the ischemic myocardium by reducing oxygen demand, primarily through reductions in cardiac work, and by perhaps inhibiting platelet aggregation and preserving myocardial cell integrity.
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PMID:Studies on the protective effect of prostacyclin in acute myocardial ischemia. 46 18

Thromboxane is known to alter the endothelial cytoskeleton, thereby causing increased endothelial permeability and polymorphonuclear leukocyte (PMN) sequestration in the lungs. We investigated whether iloprost (a stable prostacyclin analog) can decrease thromboxane activity and consequently PMN sequestration because of its anti-platelet aggregation effect. This premise was investigated in a canine isolated gracilis muscle model using 18 animals. Six animals (group I) had the gracilis muscle subjected to 6 hours of complete ischemia followed by 48 hours of reperfusion. Group II (n = 6) received intravenous infusion of iloprost (0.45 micrograms/kg/hr) throughout the experiment (1 hour preischemia, 6 hours of ischemia and 1 hour of reperfusion) and boluses of 0.45 micrograms/kg 10 minutes before ischemia and reperfusion. Group III (n = 6) underwent a similar ischemic interval, but were given iloprost bolus of 0.45 micrograms/kg followed by intravenous infusion of 0.45 micrograms/kg/hr during 48 hours of reperfusion. Gracilis venous samples were obtained at preischemia (PI) and 1 hour of reperfusion (all 3 groups) and at 48 hours of reperfusion (groups I and III) to measure thromboxane (TXB2) levels. Muscle biopsies were taken at the same time to measure myeloperoxidase (MPO) activity, a marker of PMN infiltration. In group I, TXB2 level increased from a pre-ischemic value of 2983 +/- 1083 pg/ml to 9483 +/- 2218 pg/ml at 1 hour of reperfusion (p < 0.05) and then decreased to 2386 +/- 1533 pg/ml at 48 hours of reperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does iloprost mediate thromboxane activity and polymorphonuclear leukocyte sequestration in ischemic skeletal muscle? 128 Feb 71

By means of the radioimmunologic method changes of concentration of 6-keto-prostaglandin F1 alpha (PGF1 alpha)--the stable metabolite of prostacyclin in the rat brain have been evaluated during 5-min clinical death and up to 2 hrs after resuscitation. Ischemia did not produce significant changes of 6-keto-PGF1 alpha concentration in the brain. In the early postresuscitation period the concentration of 6-keto-PGF1 in the and 7-fold control values. Later the concentration of 6-keto-PGF1 alpha in the brain decreased reaching in 30 min a 3-fold the control level, and in 60 and 120 min after resuscitation control values. The reasons of unsuccessful therapy of ischemic stroke with prostacyclin are discussed.
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PMID:Changes in endogenous prostacyclin in the rat brain during clinical death and after resuscitation. 129 27

Eicosanoids (prostaglandins, leukotrienes, thromboxane A2 and other metabolites of C-20 polyunsaturated fatty acids) have numerous effects in the cardiovascular system. Direct inotropic actions have been repeatedly described, but appear in only very few cases to be due to direct modification of the inotropic state of the heart. Specific eicosanoid receptors have been identified on the surface of the sarcolemmal membrane. Signal transduction pathways in the cardiac myocyte involve the adenylate cyclase/cAMP system or stimulation of the phospholipase C/IP3 pathway. In general, concentrations of eicosanoids which affect myocardial contractility are higher as the response is less predictable than the effects on platelet function or vessel tone. Therefore, eicosanoid-induced extracardiac effects may be superimposed to more direct changes in the contractile state of the intact heart in vitro or in vivo. In contrast to non-failing hearts, there is a significant improvement of the contractile function in contractile failure ("stunning", ischemia, congestive heart failure) by vasodilating prostaglandins (e.g., PGI2). The mechanism of this action is still unknown.
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PMID:Inotropic actions of eicosanoids. 131 58

The protective effects of the PGI2 analogue, OP-2507 against hypoxic tissue injury were investigated in a 60-70 min acute hemorrhagic shock model in 29 rats. To assess the metabolic recovery of mitochondria after tissue injury induced by hemorrhagic hypotension with a mean arterial pressure of 30 mmHg, we have non-invasively monitored changes in the brain tissue parameters of cyt. aa3 redox state, blood oxygenation and relative blood volume by spectrophotometry through the closed skull and intact skin. Pretreatment with 0.1 mg/Kg s.c. of OP-2507 at 30-40 min before induction of shock was performed on 14 rats (OP-treated group). The remaining 15 rats were used as a control (control group). There was a consistent prolongation of survival time and a significant improvement in survival rate after reinfusion of the shed blood in the OP-treated group. In this group there was a rapid and complete reoxidation of cyt. aa3 with a mean overshoot of 9 +/- 5.5% above the baseline value after reinfusion. On the other hand, in the control group the extent of reoxidation was significantly lower, with a minimal 11 +/- 3.2% below the base line. In order to evaluate the mechanisms involved 10 mg of NaCN i.v. was administered to the living rats at 60-70 min after reinfusion of the blood in both groups. In the OP-treated group, brain Hb saturation increased up to 20% above the pre-cyanide infusion level. However in the control group there was a non-significant increase in the Hb oxygenation level. These observation indicate that in the OP-treated group oxygen consumption by mitochondria is significantly higher than that in the control group. Thus, enhanced oxygen utilization could lead to the active restoration of injured tissue by promoting oxidative phosphorylation. Under these experimental conditions the oxidative response of cyt. aa3 is concluded to correlate closely with the prognosis of shock animals in both groups. These results indicate the potential usefulness of OP-2507 in protecting the brain and other organs from oxygen insufficiency as a result of tissue ischemia and anoxia.
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PMID:Protective effects of a PGI2 analogue OP-2507 on hemorrhagic shock in rats--with an evaluation of the metabolic recovery using near-infrared optical monitoring. 131 77

The role of NO-formation induced by accumulated endogenous bradykinin (BK) via local ACE-inhibition with ramiprilat (RT) or by adding BK exogenously was evaluated in cultured bovine aortic endothelial cells (BAEC) and in isolated rat hearts with post-ischaemic reperfusion injuries. Furthermore we used the n-octyl-ester of ramipril (RA-octil) which was shown to have no ACE-inhibitory action. In BAEC, ACE-inhibition by RT (1 x 10(-8)-1 x 10(-6) mol/l) or addition of BK (1 x 10(-8)-1 x 10(-6) mol/l) stimulated the formation of NO and prostacyclin (PGI2) as assessed by endothelial cyclic GMP- and 6-keto-PGF1a formation. Cyclic GMP and PGI2 synthesis was completely suppressed by the NO synthase inhibitor NG-nitro-L-arginine (L-NNA, 1 x 10(-5) mol/l) and by the B2 kinin receptor antagonist HOE 140 (1 x 10(-7) mol/l). RA-octil (1 x 10(-8)-1 x 10(-4) mol/l) did not affect endothelial cyclic GMP production in BAEC. In isolated working rat hearts subjected to local ischemia with reperfusion both RT (1 x 10(-8) mol/l) and BK (1 x 10(-9) mol/l) reduced the incidence and duration of ventricular fibrillation. In parallel myocardial function (left ventricular pressure, coronary flow) and metabolism (high energy rich phosphates) were improved showing a comparable fingerprint for RT and BK. Addition of L-NNA (1 x 10(-6) mol/l) or HOE 140 (1 x 10(-9) mol/l) abolished these protective effects of RT and BK. As in the BAEC studies RA-octil was without beneficial effects on the isolated ischaemic rat heart. The findings on BAEC show that inhibition of ACE localized on the luminal side of the vascular endothelium results in increased synthesis of NO and prostacyclin by local accumulation of endothelium-derived BK. Similar mechanisms may occur in the ischaemic rat heart leading to cardioprotection.
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PMID:ACE-inhibition induces NO-formation in cultured bovine endothelial cells and protects isolated ischemic rat hearts. 133 74

Phospholipase A2 (PLA2) activity results in the formation of lysophospholipids and free fatty acids which may contribute to ischemic myocardial dysfunction. We evaluated the cardioprotective activity of two putative PLA2 inhibitors, quinacrine and 7,7-dimethyleicosadienoic acid (DEDA), in isolated globally ischemic rat hearts. Pretreatment with 1, 5 and 50 microM quinacrine before ischemia did not alter coronary flow but did cause significant cardiodepression. Twenty five minutes of global ischemia and 30 min of reperfusion caused severe myocardial dysfunction and lactate dehydrogenase release. Quinacrine significantly improved reperfusion contractile function and reduced lactate dehydrogenase release, indicative of cardioprotection. In contrast, 30 to 100 microM DEDA produced neither preischemic cardiodepression nor cardioprotective activity. PLA2 inhibition was inferred from measurements of the prostacyclin metabolite, 6-keto-prostaglandin F1 alpha in the coronary effluent and myocardial palmitoyl-lysophosphatidylcholine. Quinacrine and DEDA reduced both 6-keto-prostaglandin F1 alpha and palmitoyl-lysophosphatidylcholine by similar degrees. These results suggest that the cardioprotective activity of quinacrine is independent of PLA2 inhibition. A possible role of calcium inhibition was investigated in rat aortic smooth muscle strips. Norepinephrine-, KCl- and BAY K8644-induced contractions were antagonized in the presence of 5 and 50 microM quinacrine, but were unaffected by 30 to 60 microM DEDA. The ability of quinacrine to inhibit calcium was investigated further in cardiac ventricular myocytes. Measurement of mean whole cell calcium currents showed that quinacrine (5 microM) could inhibit this current up to 70%. Thus, these results suggest that quinacrine-induced cardioprotection may not be due to PLA2 inhibition, but may be related to calcium entry blocking activity.
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PMID:Effect of the phospholipase A2 inhibitors quinacrine and 7,7-dimethyleicosadienoic acid in isolated globally ischemic rat hearts. 138 29

Metabolic disturbances in the canine liver during warm ischemia by Pringle's method for 60 minutes and the role of Coenzyme Q10 (CoQ10), Prostaglandin E1 (PGE1) and ONO-3708, TXA2 receptor antagonist, were studied. Mongrel dogs were divided into five groups; control group, group of liver ischemia without drugs, groups of liver ischemia with CoQ10, PGE1 and ONO-3708 pretreatment. Metabolic rates of PGI2, TXA2, insulin, glucagon and glucose and production of lipid peroxides in the five groups were measured at the points before Pringle's procedure, 5 minutes, 60 minutes and 120 minutes after declamping. In the group of ischemia without drug administration, the hepatic metabolism of PGI2, TXA2, insulin and glucose were decreased after declamping. The metabolism of glucagon, however, was not disturbed by warm ischemia. The production of lipid peroxides increased at 5 minutes after declamping. In the groups of CoQ10, PGE1 and ONO-3708 pretreatment, changes of PGI2, TXA2 and insulin metabolism in the liver were improved, and an increased production of lipid peroxides by warm ischemia was normalized. This study suggests that CoQ10, PGE1 and ONO-3708 protect liver damage by warm ischemia as results of improvement of metabolic disturbances of PGI2, TXA2, insulin and suppression of lipid peroxides production.
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PMID:[Assessment for protective effects of CoQ10, PGE1 and TXA2 receptor antagonist (ONO-3708) on warm ischemic liver]. 138 60


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