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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The vasodilation of pregnancy is thought by many to be due to increased endothelial production of prostacyclin, a vasodilatory prostanoid. Indomethacin, a potent inhibitor of prostaglandin synthesis, is known to increase the maternal blood pressure response to angiotensin II infusion. We sought to measure directly the hemodynamic effects of a short course of indomethacin. Twenty-three healthy pregnant women with uncomplicated pregnancies between 26-32 weeks' gestation completed the study. Using Doppler technology, we determined cardiac output, stroke volume, and total peripheral resistance before and after three 25-mg doses of indomethacin. Although blood pressure did not change, peripheral resistance rose and stroke volume fell following indomethacin administration. Our findings support the hypothesis that indomethacin interferes with tonic prostaglandin-induced vasodilation in pregnancy. However, the increase in vascular resistance was very slight, suggesting that other vasodilators are also at work in pregnancy. We recommend that indomethacin be used judiciously in hypertensive pregnant patients until more information concerning possible adverse hemodynamic effects becomes available.
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PMID:The maternal hemodynamic effect of indomethacin in normal pregnancy. 156 45

Tumor necrosis factor-alpha (TNF alpha) has been implicated as an endogenous mediator of the cardiovascular manifestations of sepsis and septic shock. We studied the acute effects of a single dose (50 or 200 micrograms/kg) of intravenous recombinant human TNF alpha (rhTNF alpha) on myocardial function in halothane-anesthetized dogs. Regional cardiac dimensions were measured by using sonomicrometry. Intracavitary left ventricular, ascending aortic, and pulmonary artery pressures were measured by use of micromanometers. Cardiac index was determined by means of thermodilution. Myocardial performance was analyzed by assessing changes in the slope of the left ventricular end-diastolic length-stroke work relationship obtained by performing transient vena caval occlusions. Animals were resuscitated by means of normal saline solutions to maintain baseline regional end-diastolic length. Over a 3-hour period of observation, rhTNF alpha decreased systemic vascular resistance index, but the cytokine did not compromise intrinsic myocardial performance. The circulatory response to rhTNF alpha was a hyperdynamic state characterized by tachycardia, augmented cardiac index, and increased intrinsic myocardial contractility (leftward shift of the left ventricular end-diastolic length-stroke work relationship). In addition, rhTNF alpha caused systemic acidosis and increased plasma levels of prostacyclin metabolite (6-keto-prostaglandin F1 alpha). After the dose of rhTNF alpha large volumes of fluid were required to maintain baseline end-diastolic length. We conclude that in the acute setting, rhTNF alpha elicits abnormalities in peripheral vascular tone that are not accompanied by depression of myocardial function.
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PMID:Load-insensitive assessment of myocardial performance after tumor necrosis factor-alpha in dogs. 159 65

Researchers have found that oral contraceptives (OCs) change carbohydrate and lipoprotein metabolism and these changes are like those linked with increased risk of cardiovascular (CV) disease, especially myocardial infarction and stroke. Since CV disease is the major cause of death in US women, it is important that OCs not induce changes in carbohydrate and lipoprotein metabolism. A new progestin, norgestimate, has an advantage over other progestins in that it tends not to induce male traits. This is beneficial because androgenicity is related to atherosclerosis which increases the risk of myocardial infarction. Further studies show that the new combined OC (250 mcg norgestimate/35 mcg ethinyl estradiol) does not influence serum glucose tolerance levels. It also does not affect the physiologic regulating system of prostacyclin, the inhibitor of platelet aggregation, by high density lipoprotein (HDL). In addition, it increases prostacyclin metabolites and HDL which may indeed decrease the risk of occlusive thrombotic vascular diseases. Moreover a study in Germany demonstrates that it causes no changes in fibrinopeptide A,m the anticoagulation factors antithrombin III and protein C, or coagulation promoting factors fibrinogen, factor VII, and the components of VIII. In women, it is absorbed well and metabolized extensively before the body eliminates it. Moreover this new combined OC has an overall Pearl index of 0.25. Studies to data indicate that norgestimate/ethinyl estradiol may be more advantageous than other OC formulations. Yet only long term epidemiologic studies can determine if it can indeed decrease the risk of CV diseases linked with older OCs.
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PMID:Norgestimate: a clinical overview of a new progestin. 160 87

The investigators conducted a clinical study on antithrombotic effectiveness in ischemic stroke at Siriraj Hospital Medical School, Mahidol University from May 1987 to May 1989. Twenty-nine patients, 16 males and 13 females were enrolled in the study. The ages of the patients ranged from 30-87 years with a mean age of 63 +/- 11 years. Ticlopidine (250 mg) could significantly inhibit platelet aggregation induced by ADP and collagen within 24 hours of drug administration. After 1 week to 6 months, only aggregation by ADP was still inhibited significantly without significant effects on fibrinolytic activity and prostacyclin. Hematocrit was significantly decreased at the 1st and 2nd month of treatment. Serious side effects were skin rash and severe headache while the other common ones were dizziness, and diarrhea but these effects disappeared without discontinuing the drug. Most patients who suffered from nausea, diarrhea and headache, had temporary elevated SGPT. It may be concluded that only half of the recommended dose of ticlopidine has inhibitory effects on both phases of ADP-induced aggregation without interfering with fibrinolytic activity and can maintain prostacyclin. However, it also possesses either serious or common side-effects. This drug, therefore, should be used with the awareness of the clinician.
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PMID:Clinical study on antithrombotic effects of ticlopidine in ischemic stroke. 174 38

We used a chronic instrumented ovine model to investigate right heart function following an endotoxin bolus. Primary aim of the experiments was to elucidate the influence of the right heart on the cardiopulmonary system. Furthermore, we tried a thromboxane synthetase inhibitor as a therapeutical approach. At least we investigated the IR-ANF release, as the endocrinal function of the right heart, in this model. Following the endotoxin administration we observed a massive increase of the pulmonary arterial pressure. As a result of the increased right ventricular afterload right ventricular ejection fraction decreased and end-systolic volume increased. Impaired right heart function could not be compensated sufficiently using Frank Starling mechanism. Consequently, decreased left ventricular preload, stroke volume and cardiac output followed. Pretreatment with OKY-046, a selective thromboxane synthase inhibitor, attenuated the increase in pulmonary arterial pressure and prevented the early right heart failure including the drop of cardiac output. Furthermore, OKY-046 changed the thromboxane-prostacyclin relationship. Therefore we consider the cardiopulmonary reactions following pretreatment with OKY-046 as a result of the attenuated right ventricular afterload as well as of the increased prostacyclin concentration. Endotoxin induced hypoxaemia could not be prevented by pretreatment with OKY-046 and might be caused by interstitial edema following endothelial leakage. IR-ANF release in our model, accompanied by polyuria and natriuresis, seemed to be independent of right heart dysfunction and increase of right atrial pressure. We suggest endotoxin or a endotoxin induced mediator as a trigger of IR-ANF release.
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PMID:[Right heart function and endotoxemia in animals]. 183 87

Platelet deposition upon endarterectomy sites is a likely cause for early postoperative thrombosis, embolism and restenosis. Platelets aggregate by the thromboxane-prostacycline mechanism. Thromboxane synthetase inhibitors which have been safely administered to humans should reduce platelet deposition after surgical therapy and therefore reduce peri-operative mortality and the prevalence of stroke. A randomized prospective controlled trial was designed to determine vessel patency and platelet deposition associated with the use of 3 mg/kg and 30 mg/kg of Furegrelate (Upjohn U63557A) daily in dogs, who were to have carotid endarterectomy. The 46 treated and 46 control dogs had total carotid patency of 96% and 76% respectively (P less than 0.01). Fourteen dogs treated with 30 mg/kg Furegrelate had no occlusions, compared with a 19% prevalence in 13 controls (P less than 0.02). Furegrelate 10 mg/kg significantly lowered platelet aggregation. Platelet deposition was not significantly changed, however. The reason for this disparity was a probable persistence of vessel wall factors which promoted platelet deposition. This approach might therefore lower rates of peri-operative thrombosis but it would be very unlikely to alter the incidence of restenosis or embolism. Further research could be directed towards modifying the stimuli for platelet deposition upon the endarterectomy site.
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PMID:Effects of Furegrelate (Upjohn 63557A) on patency and platelet deposition after canine carotid endarterectomy. 186 16

Platelet-activating factor, an endogenous phospholipid of proinflammatory, hemostatic, and vasoactive properties, is synthesized by neurons and in injured brain. Platelet-activating factor is released together with eicosanoids such as thromboxane A2, prostacyclin, and leukotrienes. Its effects in neurons are mediated through a specific receptor coupled to phospholipase C and phosphoinositol metabolism. The cerebrovascular effects of platelet-activating factor include disruption of the blood-brain barrier, edema formation, and vasospasm. It has also been described to possess direct toxicity to neuronal cells in culture. Discovery and development of several highly potent and selective antagonists to platelet-activating factor receptors facilitated experimental studies underscoring the role of this factor as an endogenous mediator in cerebral disorders, particularly cerebral ischemia and trauma. Significant biochemical, microvascular, functional, and behavioral recovery has been demonstrated using these antagonists in an array of experimental models of focal and global ischemia in the central nervous system (CNS). Clearly, studies of platelet-activating factor in experimental models of CNS ischemia and reperfusion injury open a new perspective on phospholipid metabolism in stroke and offer an exceptionally promising therapeutic prospect. Data supporting this factor as a mediator of specific pathological sequelae in stroke and neuroinjury are surveyed in this review. We discuss the mechanisms and significance of platelet-activating factor-mediated effects and propose directions for future studies.
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PMID:Platelet-activating factor in stroke and brain injury. 189 6

Free radicals and lipid peroxidation of membrane fatty acids are thought to play a role in the pathogenesis of arterial vasospasm and the physiopathologic patterns of neuronal damage after subarachnoid hemorrhage. We have evaluated the effects of treatment with either high-dose methylprednisolone every 8 hours or a single dose of U74006F on the temporal profile of ex vivo synthesis of four selected eicosanoids in brain slices after experimental induction of subarachnoid hemorrhage in rats. Prostaglandins D2 and E2, prostacyclin and leukotriene C4 levels were determined by radioimmunoassay after 1-hour incubation of the brain slices. The synthesis of prostaglandin D2 and 6-ketoprostaglandin F1 alpha at 48 hours after subarachnoid hemorrhage was significantly higher when compared to sham-operated animals (p = 0.01); prostaglandin E2 release was significantly enhanced at 6 hours after subarachnoid hemorrhage (p = 0.01). The release of the lipoxygenase metabolite was significantly enhanced at 1, 6, and 48 hours after subarachnoid hemorrhage induction. Both treatment regimens significantly reduced the ex vivo synthesis of prostaglandin D2, prostaglandin E2, and leukotriene C4 at 1, 6, and 48 hours after subarachnoid hemorrhage, whereas the effects on 6-ketoprostaglandin F1 alpha synthesis differed in the two treatment groups. U74006F enhanced the synthesis of prostacyclin metabolite in the early phase after subarachnoid hemorrhage, and high-dose methylprednisolone reduced the increasing synthesis at 48 hours. A strict comparison between the two treatments was not possible because of the different modalities of administration. However, these data suggest that the antioxidant effect of single-dose treatment with U74006F influenced the early and delayed effects on enzymatic lipid peroxidation, whereas the effects of methylprednisolone administration every 8 hours were more significant in the delayed phase.
Stroke 1991 Feb
PMID:Effect of high-dose methylprednisolone and U74006F on eicosanoid synthesis after subarachnoid hemorrhage in rats. 190 Jun 45

Cigarette smoking is associated with an increased risk and extent of advanced atherosclerotic vascular disease in peripheral as well as coronary arteries. The likelihood of claudication, amputation, stroke, abdominal aortic aneurysm, and failure of vascular reconstruction is higher in smokers than nonsmokers. Smoking exerts its deleterious effects through many interactive mechanisms. Nicotine and carbon monoxide produce acute cardiovascular consequences, including altered myocardial performance, tachycardia, hypertension, and vasoconstriction. Smoking injures blood vessel walls by damaging endothelial cells, thus increasing permeability to lipids and other blood components. Among metabolic and biochemical changes induced by smoking are elevated plasma, free fatty acids, elevated vasopressin, and a thrombogenic balance of prostacyclin and thromboxane A2. Chronic smoking is associated with a tendency for increased serum cholesterol, reduced high density lipoprotein, and other lipid effects that contribute to atherosclerosis. In addition to rheologic and hematologic changes from increased erythrocytes, leukocytes, and fibrinogen, smokers have alterations in platelet aggregation and survival that produce thrombosis. Considering the ubiquitous repercussions of this menace, vascular surgeons should play an active role in motivating their patients to quit smoking.
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PMID:The peripheral vascular consequences of smoking. 206 25

Defibrotide, a deoxypolyribonuclide, has been found to modulate endothelial cell function causing increase in t-PA and decrease in PAI levels and also increase in PGI2 production. In addition, it increases platelet c-AMP levels and decreases MDA and TXB2 formation in human. Defibrotide inhibits platelet aggregate formation in vitro experiments as well as end-to-end anostomosis in rats. So, defibrotide inhibits the activation of platelets. Besides an increase of protein C and S levels a synergic action of heparin was observed in animal experiments. A strong antithrombotic effect has been observed in animal models. The drug has a beneficial effect in the cases of DVT, POVD, stroke and thromboembolism. Through its action we may say that the drug acts in a novel fashion in contrast to the other drugs used in this area. Defibrotide is a single-stranded polydeoxyribonucleotide obtained from deoxyribonucleic acid of mammalian lungs by controlled depolimerization. Since 1981 in our laboratory and in the clinical department we have been investigating a newly developed agent defibrotide in vitro experiments, animal experiments, and also its clinical pharmacology and clinical application. Some of our findings are already published and compared with literature (40, 43, 46). Because of the limited space we are not going to review the literature in detail but we are going to summarize our observations on this compound in the following order. I--in vitro experiments, II--Animal experiments, III--clinical pharmacology in human.
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PMID:The pharmacology and clinical pharmacology of defibrotide: a new profibrinolytic, antithrombotic and anti-platelet substance. 210 24


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