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 effect of a newly developed oral agent, prostaglandin E1 (PGE1) analogue TFC 612, on diabetic neuropathy was studied by giving it for 6 wk to streptozocin-induced diabetic rats that had been diabetic for 3 mo and was compared with the effects of aldose reductase inhibitor ONO 2235. Although both compounds improved decreased motor nerve conduction velocity, the effect of TFC 612 continued during the 6 wk of treatment, whereas that of ONO 2235 became weaker from wk 4. The abnormality in sciatic nerve sorbitol and myo-inositol levels was reversed with ONO 2235, whereas it was unchanged with TFC 612. With the laser Doppler flowmetry technique, a decrease in the sciatic nerve blood flow in diabetic rats was shown to improve with both compounds, but TFC 612 had a greater effect than ONO 2235, and the increased lactate level of the diabetic nerve was corrected with both compounds, suggesting that both may be associated with the amelioration of ischemia in the diabetic endoneurium. Both TFC 612 and ONO 2235 partially but significantly normalized decreased fiber size in diabetic rats. On the other hand, TFC 612 completely normalized the dilated lumen area in diabetic rats, whereas ONO 2235 did not. These results suggest that the PGE1 analogue TFC 612 has a significant effect on diabetic neuropathy, possibly via vasotropic action, and may be a potent compound for the treatment of diabetic neuropathy.
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PMID:Effect of prostaglandin E1 analogue TFC 612 on diabetic neuropathy in streptozocin-induced diabetic rats. Comparison with aldose reductase inhibitor ONO 2235. 252 92

Ischemia-induced renal injury is prevented by inhibition of thromboxane (Tx) synthesis. This protection was believed to be secondary to a high prostaglandin (PG)/TxA2 ratio. This study tests whether increasing the PG/Tx ratio by administration of vasodilating PGs protects the reperfused ischemic kidney. Anesthetized rats underwent right nephrectomy and 45 minutes of left renal pedicle clamping. Beginning 10 minutes before clamp release, animals were treated intravenously with the following: saline placebo (n = 10); the cyclooxygenase inhibitor ibuprofen (Ibu), 12.5 mg/Kg in a bolus (n = 8); a stable analogue of prostacyclin (PGI2), 500 ng/kg/minute for 2 hours (n = 9); PGE1, 400 ng/kg/minute for 2 hours (n = 8); the combination Ibu and PGI2 (n = 8) or PGE1 (n = 8). In saline treated ischemic controls, 5 minutes after reperfusion plasma, thromboxane (TxB2) and 6-keto-PGF1 levels were 2537 and 317 pg/ml, respectively--higher than the TxB2 and 6-keto-PGF1 levels of 750 and 80 pg/ml, respectively, in nephrectomized but nonischemic sham controls (n = 7) (p less than 0.05). In ischemic control animals at 24 hours, creatinine levels were 4.6 mg/dl, relative to 0.9 ml/dl in sham animals (p less than 0.05); the weight of the left (L) ischemic kidney relative to the right (R) normal kidney was 118%, compared with 99% in sham animals (p less than 0.05); and renal histology of ischemic control animals at 24 hours showed acute tubular necrosis (ATN) relative to normal findings in sham animals. Pretreatment with Ibu led to: TxB2 and 6-keto-PGF1 levels of 116 and 40 pg/ml, lower than those of sham animals (p less than 0.05); creatinine levels of 4.6 mg/dl, L/R renal weight of 119%; and ATN similar to that of ischemic controls. Treatment with a PGI2 analogue or PGE1 was not protective and led to increases in TxB2, 6-keto-PGF1, creatinine, L/R renal weight, and ATN similar to that of ischemic controls. The combination of Ibu and either PGI2 or PGE1 led to: reduced levels of TxB2 and 6-keto-PGF1 (p less than 0.05); attenuated increases in creatinine to 2.2 and 2.3 mg/dl, respectively (p less than 0.05); and limited ATN (p less than 0.05). These data indicate that the vasodilating PG protect the ischemic reperfused kidney only when Tx is inhibited.
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PMID:Vasodilating prostaglandins attenuate ischemic renal injury only if thromboxane is inhibited. 264 99

Intermittent digital ischemia is frequently resistant to therapy despite various treatment modalities. Recent studies have reported the successful treatment of intermittent digital ischemia with prostaglandin infusion therapy. We present a severe case of intermittent digital ischemia associated with mixed connective tissue disease, responsive to prostaglandin E1 infusion therapy.
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PMID:Prostaglandin infusion therapy for intermittent digital ischemia in a patient with mixed connective tissue disease. Case report and review of the literature. 265 23

A prostaglandin oligomeric derivative was synthesized by alkaline treatment of prostaglandin E1. This compound protected the perfused rat heart from global ischemia. This compound was found to inhibit several lipolytic and proteolytic enzymes in vitro. When phospholipase A2 from Naja naja venom was used as an enzyme and phosphatidylcholine was used as a substrate, 50 per cent inhibition was achieved at 50 microM of the prostaglandin derivative. When trypsin and casein were used as enzyme and substrate, 50 per cent inhibition was obtained at 80 microM. A possible mechanism of beneficial effect of this compound in protecting membranes during ischemia is discussed.
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PMID:A prostaglandin oligomeric derivative inhibits activities of phospholipase and protease: a possible mechanism of membrane protection during ischemia. 275 36

We studied the efficacy of an oligomeric derivative of prostaglandin E1 in protecting the rat brain against focal ischemia. The degree of ischemic damage was evaluated from three parameters, namely, the degree of edema formation, reduction of motor performance, and memory disturbance as measured by a passive avoidance test. The pre-ischemic administration of the drug (6 mg/kg i.p.) had some effects, but the differences were not significant. The post-ischemic administration (6 mg/kg i.p.) produced significant improvement in all three parameters. The increase of water content of the ischemic hemisphere was reduced (p less than 0.05); the total motor score was improved (p less than 0.01); and the memory disturbance as estimated by the passive avoidance test was reduced (p less than 0.01). A possible mechanism of protection is discussed.
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PMID:Inhibition of ischemic brain edema formation by post-ischemic administration of a prostaglandin oligomer. 278 Jul 65

This study investigates the action of intravenous PGE1 on myocardial reperfusion injury and the possible involvement of antineutrophil activities. Cats were subjected to 3 h of temporary ligation of the left anterior descending coronary artery, followed by 2 h of reperfusion. Animals were treated with PGE1 (5 micrograms/kg x min) or vehicle (saline solution), starting 0.5 h after coronary artery occlusion. Vehicle-treated cats exhibited a significant loss of cardiac creatine phosphokinase specific activity at 5 h, accompanied by a significant ischemia-induced rise in the ST segment of the ECG and development of a Q wave after starting reperfusion. All of these alterations were largely prevented by PGE1 treatment. PGE1 exerted some blood-pressure-lowering activity at 5 h (P greater than 0.05) but did not reduce myocardial contractile force and oxygen consumption. PGE1 modestly antagonized ischemia-induced formation of platelet aggregates. However, PGE1 prevented the rise in peripheral white blood cell count during ischemia and reperfusion and inhibited the generation of reactive oxygen species (myeloperoxidase assay) from zymosan-stimulated whole blood ex vivo. The ratio of generation of reactive oxygen species/white blood count remained unchanged. It is concluded that PGE1 protects the ischemic myocardium from acute reperfusion injury and that this effect involves an action of the compound on neutrophils, probably by improved myocardial tissue preservation, resulting in reduced formation of chemotactic products and, consequently, less local neutrophil accumulation and release of noxious metabolites.
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PMID:Protection of the ischemic myocardium from reperfusion injury by prostaglandin E1 inhibition of ischemia-induced neutrophil activation. 284 5

The protective effects of PGE1 on ischemia-related liver damage were evaluated in dogs. Ninety minutes warm hepatic ischemia was induced by the total clamping of hepatic inflow vasculatures with portal bypassing. The survival rate improved up to 62.5% when PGE1 was administered intravenously prior to ischemia, while no dog survived for longer than 1 week in the nontreated group. Hepatic ATP content was restored up to 80% of preischemic level 2 h after reflow in the PGE1 pretreated group, compared to 55% recovery in the nontreated group. Complete normalization of hepatic energy charge and rapid decrease of lactate were also seen in the PGE1 group. The clearance rate of intravascular lipid emulsion remained fairly normal in the PGE1 group, thereby suggesting well-preserved hepatic reticuloendothelial functions. The serum activities of beta-glucuronidase, GOT and GPT were suppressed in the PGE1-pretreated group, thereby implying a well-protected hepatic integrity. The histology revealed well-preserved hepatic architecture. The remarkable cytoprotective effect of PGE1 on hepatic ischemia shown in this study indicates that PGE1 warrants further study for protection of ischemically compromised hepatic allografts.
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PMID:Protective effect of prostaglandin E1 (PGE1) on energy metabolism and reticuloendothelial function in the ischemically damaged canine liver. 292 40

Cardiac tissue from different parts of hearts from guinea pigs and rabbits have the capacity to rapidly synthesize prostacyclin (PGI2). Auricles show a higher PGI2-formation than ventricles. Addition of the endoperoxide PGH2 markedly enhanced the myocardial PGI2-biosynthesis. Furthermore many cardiotonic drugs induced a significant rise, but eicosanoids or cyclooxygenase inhibitors a marked reduction of the cardiac PGI2-formation. Acute pressure overload by graduated aortic stenosis, ischemia by coronary ligation or pacing with high frequency reduced the cardiac contractility. After aortic stenosis the myocardial PGI2-biosynthesis is lowered, but increased after coronary ligation or pacing. Under these conditions indomethacin, PGE1, iloprost, verapamil and trapidil markedly reduced the PGI2-biosynthesis and exert a protective effect in regard to cardiac damage. The results indicate that pathophysiological changes significantly influence the PGI2-biosynthesis of the heart. The drug induced inhibition of the myocardial PGI2-formation parallels a cardioprotective effect of these substances.
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PMID:Myocardial biosynthesis of prostacyclin and the influence of cardiac loading and drugs. 307 64

For no organ is the need more acute than for the lung or heart-lung block. The new improved "freezing" technique with simultaneous use of intravenous prostaglandin E1 will result in reliable and adequate heart-lung block preservation. The lungs are flushed with high-volume (60 ml/kg), low-pressure (less than 20 mmHg), low-flow (15 ml/kg/min), using modified Euro-Collins solution (added 12 Meq/L of MgSO4 and 65 ml/L of 50% Dextrose). Additional topical cooling has been achieved by cold Physiosol and the excised graft is then placed in a plastic bag filled with Physiosol. This static hypothermia has been successfully used with extended ischemia times of more than six hours in primates and almost four hours in man. Forty heart-lung transplantations have been done from March 1981 to September 1986 and nine of them have been performed using this "freezing" technique with prostaglandin E1. Distant graft procurement has been used twice for heart-lung transplantation. All nine most recent patients who have received the graft harvested with this new "freezing" technique are doing well.
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PMID:Intravenous prostaglandin E1, cold crystalloid flush and topical hypothermia for cardiopulmonary graft preservation. 329 33

The effects of prostaglandin E1 (PGE1) were assessed in 24 patients with coronary artery disease. Quantitative coronary angiography was performed in 15 patients. PGE1 was found to produce dilation of coronary stenoses (6 +/- 12% to intravenous PGE1, difference not significant, 19 +/- 22% to intracoronary PGE1, p less than 0.05), but usually no change in the diameter of angiographically normal segments. In these patients intracoronary nitroglycerin consistently dilated the normal segments not altered with PGE1 and often led to further dilation of the stenoses. In 9 other patients who were undergoing coronary angioplasty, hemodynamics and the time to ischemia induced by coronary occlusion were measured. In both patient groups PGE1 led to decreases in aortic, pulmonary artery and pulmonary arterial wedge pressures and an increase in heart rate (all p less than 0.05). Before coronary occlusion PGE1 produced coronary vasodilation manifested by preservation in coronary sinus flow (130 +/- 41 to 126 +/- 42 ml/min, difference not significant); as aortic pressure declined coronary resistance decreased (0.9 +/- 0.3 to 0.8 +/- 0.3 mm Hg/ml/min, p less than 0.05). During coronary occlusion residual flow to the affected region was usually similar to control occlusions (37 +/- 20 to 36 +/- 25 ml/min, difference not significant) and collateral resistance was decreased (3.2 +/- 2.9 to 2.9 +/- 2.6 mm Hg/ml/min, p less than 0.05). However, time to ischemia usually remained unchanged. PGE1 shows an interesting angiographic and hemodynamic profile in patients with coronary artery disease. Although no obvious clinical benefit was seen, PGE1 was safely administered both intravenously and directly into narrowed coronary arteries.
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PMID:Hemodynamic and angiographic effects of prostaglandin E1 in coronary artery disease. 342 Nov 67


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