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)

Thromboxane A2 (TxA2) may aggravate myocardial ischemia by inducing vasoconstriction and platelet aggregation in small coronary vessels, whereas prostacyclin (PGI2) counteracts these effects. Acetylsalicylic acid (ASA) inhibits the formation of TxA2 as well as PGI2, whereas dazoxiben, a thromboxane synthetase inhibitor, reduces TxA2 formation selectively. In 25 patients with coronary artery disease, 2 identical atrial pacing stress tests were performed: before and after the administration of dazoxiben (200 mg) in 15 patients and before and after ASA (250 mg) in 10. The ischemic response, quantified by coronary sinus and aortic lactate levels and by ST depression, was significantly reduced after administration of dazoxiben (p less than 0.02) but not after ASA. Heart rate at rest, myocardial extraction of free fatty acids and the arteriovenous oxygen difference was unaffected by medication. Both drugs reduced TxB2 levels to the same extent, whereas collagen-induced aggregation was more reduced after ASA than after dazoxiben. The effect of dazoxiben on ischemia was probably a result of inhibited TxA2 and preserved PGI2 production, which increased blood flow to ischemic regions.
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PMID:Effects of a selective thromboxane synthetase inhibitor, dazoxiben, and of acetylsalicylic acid on myocardial ischemia in patients with coronary artery disease. 653 40

We evaluated the recently proposed concern that ECG anterior ST segment depression in patients with acute inferior wall myocardial infarction represents an additional area of ischemia and therefore implies worsened prognosis. We studied patients enrolled in the Aspirin Myocardial Infarction Study (AMIS), ages 30 to 69 years, who sustained an inferior myocardial infarction within 6 months from the start of the study. Two hundred nineteen patients who met those criteria were followed for an average of 38.2 months. One hundred ten patients had significant anterior lead ST depression (greater than or equal to 0.1 mV) during their acute inferior infarction and their 3-year mortality rate was 9.1%. One hundred nine patients had no anterior ST abnormality and a mortality rate of 10.1% (p = ns). Only one patient with significant depression had a subsequent anterior wall myocardial infarction. Anterior ST depression correlated closely with the magnitude of inferior ST segment elevation. Since ST depression does not alter long-term mortality but relates to magnitude of ST elevation, it probably represents a reciprocal change.
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PMID:Anterior ST segment depression during acute inferior myocardial infarction: evidence for the reciprocal change theory. 688 Oct 25

Novel compounds that induce or inhibit platelet aggregation and constrict or dilate blood vessels were recently discovered. These compounds are all derivatives of arachidonic acid and include prostaglandin endoperoxides, thromboxane A2, prostaglandin E2, prostaglandin D2 and prostacyclin. Thromboxane A2 (TxA2) could be one of the precipitating factors in coronary or cerebrovascular ischemia because it is a potent vasoconstrictor that is produced by platelets during their aggregation. On the other hand, prostacyclin (PGI2) is a potent vasodilator and inhibitor of platelet aggregation produced by vessel walls whose enhanced production should be beneficial. Aspirin inhibits prostaglandin endoperoxide synthetase and therefore prevents the subsequent production of TxA2, PGI2 and other prostaglandins. It has been suggested but not yet established that low doses of aspirin preferentially inhibit TxA2 biosynthesis. The roles of classic prostaglandins PGD2, PGE2 and PGF2 alpha in ischemia have not been determined.
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PMID:Thromboxane A2, prostacyclin and aspirin: effects on vascular tone and platelet aggregation. 700 50

Four drugs that inhibit platelet function have been evaluated for their antithrombotic effects in humans. These are aspirin, dipyridamole, hydroxychloroquine and sulphinpyrazone. Aspirin has been shown to reduce the number of transient ischemic attacks (TIA), stroke and death in patients with multiple TIA. The reduction in TIA was greatest in males who were normotensive and when there was an angiographically demonstrated lesion in the carotid artery that accounted for the symptoms. Aspirin reduced venous thrombosis and non-fatal and fatal pulmonary embolism in patients after surgery for fractured hip and after elective hip replacement. There is evidence that the prophylactic effect of aspirin may be greater in male patients. Aspirin reduced the frequency of arteriovenous shunt thrombosis. Aspirin abolished symptoms in patients with peripheral ischemia associated with thrombocytosis and spontaneous platelet aggregation. There is no conclusive evidence at the present time that aspirin is effective in patients with coronary artery artery disease. Dipyridamole in combination with oral anticoagulants is effective in reducing the frequency of systemic embolism in patients with prosthetic heart valve replacement but is ineffective in patients with transient cerebral ischemic attacks or for the prevention of venous thromboembolism. Hydroxychloroquine was effective in reducing postoperative venous thrombosis in patients undergoing general abdominothoracic surgery but the evidence that it was effective in patients undergoing orthopaedic surgery is inconclusive. Sulphinpyrazone may be effective in reducing the frequency of sudden cardiac deaths in patients in the first year after myocardial infarction when it is started within 25 to 35 days after the infarction. Sulphinpyrazone reduced the incidence of arteriovenous shunt thrombosis in patients undergoing chronic hemodialysis and in combination with anticoagulants, it reduced the frequency of recurrent venous thrombosis. There have been no large scale trials of platelet suppressant drugs in clinical cancer and successful treatment of thromboembolic disorders cannot be used to predict success in the treatment of malignant disease.
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PMID:Antithrombotic effects of drugs which suppress platelet function: their potential in prevention growth of tumour cells. 705 Oct 35

Although platelets have been associated with angina pectoris, myocardial infarction, and sudden death, the platelet's capacity for induction and propagation of cardiac ischemia remains incompletely defined. We therefore evaluated the effects of platelet activation occurring within the coronary circulation and tested the hypothesis that inhibition of platelet function would prevent platelet-induced cardiac ischemia. Human platelets were isolated from blood obtained from normal donors by Sepharose 2B column chromatography, resuspended in Hepes buffer, and added to the perfusate of a Langendorff rabbit heart (platelet counts greater than 10,000/microliters). Without, and with low dose (10 microM) prostaglandin E1 (PGE1), a reversible inhibitor of platelet function, immediate and irreversible global cardiac ischemia, as monitored by NADH fluorescent photography, ensued (N = 4) following platelet activation with thrombin (0.1 to 1 U/ml). Higher concentrations of PGE1 (0.1 to 1 mM, N = 2) or aspirin ingestion (1000 mg taken approximately 12, 4, and 1 hr prior to experiment, N = 2) completely prevented this platelet-induced myocardial ischemia. Aspirin, unlike PGE1, was effective despite its inability to block thrombin-induced platelet aggregation in our in vitro gel-filtered system. We conclude that activation of platelets within the coronary circulation is sufficient for induction of irreversible cardiac ischemia. The efficacy of aspirin, a cyclooxygenase inhibitor, further suggests that the products of arachidonate metabolism (e.g., thromboxanes) have a fundamental role in the genesis of platelet-mediated myocardial ischemia.
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PMID:Platelet-mediated cardiac ischemia. 713 26

The effectiveness of preventive and therapeutic measures depends upon their adequacy in the individual diagnostic situation. This is also true for stroke which is a superimposed concept for different mechanisms leading to acute localized brain ischemia. For the choice of treatment we have to consider in each case the actual clinical situation, i.e. the natural stage of disease, the localization of cerebral dysfunction and its etiology and pathogenesis. Thus transient ischemic attacks (TIA), completed stroke with prolonged complete, partial or no recovery and progressive stroke (stroke in evolution) demand different treatment. Concerning pathogenesis it is important to differentiate between intracerebral hemorrhage, ischemia due to extracranial carotid stenosis or occlusion, intracranial arterial thrombosis, predominantly hemodynamic pathogenesis and embolism of cardiac origin. Prevention of stroke may be of general kind like treatment of hypertension or other risk factors for apoplexy, and there are more specific measures like surgery of vascular obliteration and treatment with agents inhibiting platelet aggregation (Aspirin) or anticoagulants. The indications for the various surgical and medical procedures are discussed. Because of the risk of hemorrhagic complications the indication for anticoagulants is limited considerably. The treatment of completed stroke has to consider the normalization of basic functions (cardiocirculatory, respiration, water-electrolyte balance a.o.). Vasoactive and especially vasodilatatory drugs are not recommended in the acute stage of stroke, as their effectiveness is not secure and may even be disadvantageous. Ischemic brain edema is treated with mannitol or sorbit and with dexamethasone although its effectiveness has not yet been proven. Low molecular dextran solution is supposed to improve microcirculation in the ischemic tissue by means of hemodilution i.e. improvement of rheological properties.
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PMID:[Prevention and therapy of stroke]. 740 3

The effects of aspirin and L-arginine (biological precursor of nitric oxide) on the production of hydroxyl radicals, cyclic guanosine monophosphate levels, vascular tone, and the recovery of the ischemic myocardium were investigated in isolated rat hearts subjected to ischemia and reperfusion. After 30 minutes of perfusion, hearts were arrested with St. Thomas' Hospital cardioplegic solution, global ischemia was induced at 37 degrees C for 45 minutes, and the hearts were then reperfused at 37 degrees C for 30 minutes. The percent change in recovery of pulse pressure and maximal change of this pressure with time were better in the group perfused with Krebs-Henseleit solution containing aspirin plus L-arginine (17% +/- 23%, p = 0.001, and 10% +/- 25%, p = 0.002, respectively) compared with these values in the control group perfused with Krebs-Henseleit solution alone (-7% +/- 14% and -11% +/- 16%, respectively). Coronary vascular resistance before and after ischemia were lower in the aspirin plus L-arginine group (0.19 +/- 0.03 dynes.sec/cm5, p = 0.001, and 0.23 +/- 0.04 dynes.sec/cm5, p = 0.01, respectively) compared with those of the control group (0.24 +/- 0.02 and 0.28 +/- 0.07 dynes.sec/cm5, respectively). Cyclic guanosine monophosphate levels increased from 22.5 +/- 6 pmol/100 mg of tissue in the control group to 37.1 +/- 8.9 pmol/100 mg (p = 0.002) in the aspirin plus L-arginine group. Adding N omega-nitro-L-arginine methyl ester to the perfusion medium caused a deterioration in pulse pressure and maximal change of this pressure with time, a decrease in cyclic guanosine monophosphate, and a rise in coronary vascular resistance. The addition of L-arginine to the solution in the Krebs-Henseleit solution plus aspirin group increased the production of hydroxyl radicals from 0.32 +/- 0.18 nmol/gm per 3 minutes to 0.75 +/- 0.33 nmol/gm per 3 minutes (p = 0.03). Despite the association of nitric oxide with increased hydroxyl radical production, it appears that nitric oxide has an overall beneficial effect on the recovery of the ischemic myocardium. The synergism between aspirin and arginine may be caused in part by the scavenging of hydroxyl radicals. Alternatively, by inhibiting the prostaglandin pathway, aspirin may reduce the generation of superoxide anion, a free radical that inactivates nitric oxide. The prolonged half-life of nitric oxide may explain the increased levels of cyclic guanosine monophosphate seen in the group perfused with Krebs-Henseleit solution plus aspirin plus L-arginine. Aspirin and L-arginine, both readily available, may be useful adjuncts to clinical cardioplegia strategy.
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PMID:Simultaneous manipulation of the nitric oxide and prostanoid pathways reduces myocardial reperfusion injury. 747 34

We determined the effect of thromboxane A2 (TXA2) prostaglandin endoperoxide (TP) receptor antagonism, using BMS-180291 or aspirin, on the severity of pacing-induced ischemia in anesthetized dogs. Thromboxane receptor antagonists may not only have antithrombotic activity, but may also have direct cardioprotective effects, unlike aspirin. Left anterior descending coronary artery (LAD) stenosis was adjusted so that a significant (10-12 mV) ST segment elevation was observed only when superimposed on atrial pacing. Each heart was subjected to 5-min episodes of pacing-induced ischemia 10, 40, and 70 min after initiation of BMS-180291 (1 mg/kg + 1 mg/kg/h) or vehicle. In the vehicle group, ST segment elevation was reproducible at all pacing-induced ischemia episodes, whereas BMS-180291 significantly reduced it by 30% at the later ischemia episodes. This reduction in ST segment increase was not accompanied by alterations in regional myocardial blood flow (RMBF) nor in hemodynamic status. Aspirin in the same model [10 mg/kg intravenously (i.v.) given 10 min before pacing-induced ischemia] did not significantly reduce ST segment elevation, indicating a lack of protective effect in this model. Thromboxane receptor blockade appears to protect myocardium subjected to pacing-induced ischemia, an effect not produced by aspirin.
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PMID:Thromboxane receptor antagonist BMS-180291, but not aspirin, reduces the severity of pacing-induced ischemia in dogs. 752 6

Forty-five ASA physical status I volunteers, divided in three groups of 15 each, received intravenous regional anesthesia (IVRA) of the upper limb with 40 mL meperidine 0.25%, lidocaine 0.5%, or 0.9% sodium chloride (isolated ischemia) by random allocation. Using a double-blind method, the onset and recovery of sensory block was tested at six sites of the forearm and hand. The onset of complete motor block was also assessed. The symptoms after deflation of the tourniquet were recorded. The onset of block, as determined by pin-prick touch, and cold was significantly faster in the meperidine group (P < 0.001) than in the saline group, but also slower (P < 0.001) than in the lidocaine group. After the tourniquet was deflated, recovery occurred in reverse order. A complete motor block was noted in all volunteers from the meperidine and lidocaine groups, but in only 11 cases from the 0.9% sodium chloride group (P < 0.01). In the meperidine group, motor block developed concomitantly or prior to sensory block. There was a significant increase in the incidence of dizziness, nausea, and pain at the injection site in the meperidine group in comparison with the lidocaine group. We conclude that meperidine has local anesthetic action on the peripheral nerve in vivo, but that its single use for IVRA should be a second choice for patients allergic to local anesthetics.
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PMID:Intravenous regional anesthesia with meperidine. 953 32

The thromboxane receptor antagonist ifetroban ([1S-(1 alpha,2 alpha,3 alpha, 4 alpha)]-2-[[3-[4-[(pentylamino)carbonyl]-2-oxazolyl]- 7-oxabicyclo[2.2.1]hept-2-yl]methyl]benzenepropanoic acid) and aspirin were evaluated for direct and combined effects on myocardial infarct size in anesthetized ferrets subjected to coronary artery occlusion (90 min) and reperfusion (5 h). Aspirin (10 mg/kg) or vehicle was administered as an i.v. bolus dose at the 45th min of occlusion in an initial assessment of its cardioprotective potential in this species. In interaction studies, aspirin was injected i.v. 10 min prior to occlusion (10 mg/kg) and at the 45th min of ischemia (5 mg/kg) both with and without subsequent administration of ifetroban (0.3 mg/kg + 0.3 mg/kg per h) beginning at the 75th min of occlusion. Aspirin administration alone caused non-significant (P > 0.05) 5-7% reductions in tissue damage (19.8-21.8% of left ventricle) from that observed in vehicle-controls (20.4-22.9% of left ventricle). Ifetroban alone significantly (P < 0.05) reduced infarct size compared to vehicle treatment (13 +/- 1% vs. 23 +/- 2% of left ventricle), and this was not prevented by combination with aspirin (12 +/- 2% vs. 22 +/- 3% of left ventricle). In the absence and presence of aspirin, ifetroban reduced infarct size by 42% and 43%, respectively. Concurrently, thromboxane A2-generating capacity in blood (measured as thromboxane B2 in clotted serum) was decreased ca. 99% by aspirin treatment. Thus, virtually complete platelet cyclooxygenase inhibition by aspirin afforded no cardioprotective action in the ferret and, more importantly, this inhibition did not interfere with the myocardial salvage efficacy of ifetroban.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Failure of aspirin to interfere with the cardioprotective effects of ifetroban. 770 47


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