UMLS:C0022116 - FACTA Search

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

Numerous studies have described a progressive deterioration in resting myocardial blood flow following relief of sustained ischemia in both necrotic and salvaged myocardium (termed "no reflow" and "low reflow", respectively). We sought to determine whether release of the potent vasoconstrictor peptide endothelin-1 may play a role in these phenomena. As part of a previous study in our laboratory, 14 anesthetized open-chest dogs underwent 1 h of coronary artery occlusion and 4 h of reperfusion, while 2 dogs served as time-matched sham-operated controls (artery isolated but not occluded). Regional myocardial blood flow was measured by injection of radiolabeled microspheres at 30 min and 4 h post reflow; endothelin-1 concentrations in the coronary sinus were determined by radioimmunoassay at baseline, during coronary occlusion and at 30 min and 4 h after reperfusion; and the extent of myocardial necrosis was delineated by post-mortem tetrazolium staining. As expected, in dogs subjected to ischemia/reperfusion, regional myocardial blood flow deteriorated between 30 min and 4 h post reflow in both the subendocardium (1.40 +/- 0.30 versus 0.48 +/- 0.06 ml/min/g; p = 0.003; reflecting a mixture of no reflow and low reflow) and subepicardium (0.84 +/- 0.08 versus 0.64 +/- 0.07 ml/min/g; p = 0.03; due to low reflow). However, endothelin levels showed only a modest and nonsignificant increase during the protocol (4.1 +/- 0.5, 4.7 +/- 0.2 and 4.9 +/- 0.6 pg/ml plasma at baseline, 30 min and 4 h post reflow; p = NS), and regression analysis revealed no correlation between release of endothelin and deterioration in blood flow in either myocardial layer. Moreover, the sham-operated controls showed a similar modest increase in endothelin levels, with no change in myocardial perfusion during the course of the protocol. We therefore conclude that deterioration in myocardial blood flow following relief of sustained ischemia in the anesthetized open-chest dog is not associated with release of endothelin-1 into the coronary sinus.
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PMID:Deterioration in myocardial blood flow following relief of sustained ischemia is not associated with release of endothelin into the coronary sinus. 794 62

Endothelin-mediated vasoconstriction may theoretically aggravate ischemic neuronal damage. Although investigators have demonstrated that endothelins are produced by cerebral microvessel endothelial cells, astrocytes and neurons in vitro, whether endothelins are produced during cerebral ischemia is still unclear. The purpose of this study, therefore, was to measure endothelin-1 in brain tissue and plasma following middle cerebral artery occlusion and to examine the relationship between brain tissue and plasma endothelin-1 levels. The middle cerebral artery of rabbits was occluded for 2, 4 or 24 h. The amount of endothelin-1 in both brain tissue and plasma was determined by RIA. The results demonstrate that the concentrations of endothelin-1 in the ischemic brain tissue and plasma are both significantly increased after focal cerebral ischemia (P < 0.01). The data confirm that an acute and marked increase of endothelin-1 in brain tissue and plasma is associated with focal ischemic events. The possibility that endothelin-1 has a role in neuronal cell damage following focal ischemia warrants further attention.
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PMID:Increased endothelin-1 in the rabbit model of middle cerebral artery occlusion. 797 Jan 53

We examined the effects of endothelium-dependent responses on coronary perfusion pressure (CPP) in isolated, blood-perfused neonatal pig hearts under conditions of controlled coronary flow. Baseline CPP was increased 8%-21% by the cyclooxygenase inhibitor indomethacin (10-100 microM), and 30%-92% by NG-monomethyl-L-arginine (L-NMMA, 10-100 microM), an inhibitor of nitric oxide (NO) synthase, suggesting that both prostaglandin and nitric oxide synthesis contribute to basal coronary tone. Both acetylcholine (ACh) and bradykinin (BK) decreased CPP. These effects were enhanced by preconstriction with endothelin-1. L-NMMA markedly attenuated BK-induced coronary vasodilation and converted the ACh response to constriction, indicating a significant role for NO release in these responses. After 1 h of total, global normothermic ischemia and 45 min of reperfusion, vasoconstrictor responses to endothelin-1 and ACh were enhanced, while BK-induced dilation was significantly reduced. L-Arginine supplementation during reperfusion did not restore vasodilatory responses to ACh or BK. The magnitude of L-NMMA-induced coronary vasoconstriction during reperfusion was similar to that observed without ischemia-reperfusion. Coronary vasodilation in response to sodium nitroprusside, a NO precursor that causes endothelium-independent vasodilation by directly activating smooth muscle guanylate cyclase, was unaffected by ischemia-reperfusion. We conclude that NO production in the neonatal coronary circulation contributes to both basal tone and the response to ACh and BK. After ischemia-reperfusion, basal NO production and smooth muscle relaxation mediated by guanylate cyclase are intact, whereas agonist-stimulated dilation is significantly impaired.
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PMID:Endothelium-dependent regulation of coronary tone in the neonatal pig. 797 31

Hepatic microcirculatory perturbation is observed after ischemia/reperfusion. Endothelin-1, a potent vasoconstrictive peptide, is known to modulate local circulation. This study was designed to examine whether endothelin-1 participates in the mechanism of microcirculatory disturbance and damage of the liver after ischemia/reperfusion. Ischemia in the median and left lateral lobes of the liver was induced for 60 min; it was followed by reperfusion for 24 hr. In some rats, endothelin-1 antiserum or control serum without endothelin-1-blocking activity was administered intravenously just before reperfusion. Rats were divided into three groups: an ischemia/reperfusion group that was injected with control serum, an endothelin-1 antiserum-treated group and a sham-operated group. Endothelin-1 concentrations in blood collected from the suprahepatic vena cava were measured before and after ischemia/reperfusion by use of a sandwich enzyme immunoassay. Index of blood volume in regional hepatic tissue and index of blood oxygenation in regional hepatic tissue were assessed with an organ reflectance spectrophotometry system before and at 5 min and 1, 2, and 24 hr after reperfusion. The endothelin-1 concentration in the ischemia/reperfusion group started to rise immediately at onset of reperfusion from basal values around 1 pg/ml and reached a value of 5 to 6 pg/ml 5 min after reperfusion; it was maintained at significantly high levels during the reperfusion period compared with the sham-operated group. Hepatic microcirculatory disturbance indicated by lowered index of blood volume in regional hepatic tissue and index of blood oxygenation in regional hepatic tissue levels was observed in the early phase of reperfusion in the ischemia/reperfusion group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endothelin-1 is involved in the pathogenesis of ischemia/reperfusion liver injury by hepatic microcirculatory disturbances. 811 92

In acute cerebral ischemia there are severe damages of endothelium which have been recognized as the stimuli to secrete endothelin-1, an endothelium-derived peptide and the most potent vasoconstrictor ever known. This study was to measure plasma endothelin-1 level in patients with cerebral infarction and explore the relationship between endothelin-1 and ischemic stroke. The possible involvement of endothelin-1 in local regulation of cerebral arterioles was also investigated. Plasma levels of endothelin-1 were measured by radioimmunoassay in 21 patients. Using a micro-video system, the endothelin-1 actions were also observed on rat pial arterioles in vivo, and with incomplete cerebral ischemia model (rat), effect of ischemia affects the endothelin-1 action. There was a marked increase in plasma endothelin-1 level in the patients and the elevation persisted during the acute and subacute period of stroke. There was a positive correlation between the peptide concentration and infarct size (r = 0.655, P < 0.01). In rats, endothelin-1 (dose range: 10(-10) mole/L-10(-7) mole/L) induced a dose-dependent arteriole contraction after subdural administration. Arteriole calibers were decreased by 27.7% +/- 3.8% (10(-9) mole/L), 46.8% +/- 4.9% (10(-8) mole/L) and 78.5% +/- 4.7% (10(-7) mole/L), respectively. Cerebral ischemia significantly enhanced the action of endothelin-1 (96.4% +/- 7.2% vs 58.2% +/- 6.8%). Endothelin-1 plays an important role in regulating local circulation of ischemic brain. The notable and lasting increase in plasma level of endothelin-1 are associated with cerebral ischemia and infarction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased plasma endothelin-1 concentration in patients with acute cerebral infarction and actions of endothelin-1 on pial arterioles of rat. 814 9

The effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) in brain hypoxia have been studied in mice using the following experimental models: hypobaric hypoxia induced by low atmospheric pressure, histotoxic hypoxia induced by 12.5 mg/kg KCN i.p., and complete ischemia induced by decapitation. ET-1 and ET-3 were injected intracerebroventricularly (i.c.v.) 15 min before the tests. Forebrain tissue concentrations of 6-keto-PGF1 alpha and thromboxane B2 (TxB2) were measured 15 min following i.c.v. administration of ET-1 (5 pmol/mouse) and ET-3 (10 pmol/mouse). ET-1 (1-5 pmol/mouse) and ET-3 (5-25 pmol/mouse) showed a dose-dependent increase in the survival/gasping time in all models of hypoxia. The effect reached its maximum between 15 and 30 min after ET administration and lasted for about 120 min. ET-1 and ET-3 did not significantly change the brain levels of 6-keto-PGF1 alpha and TxB2. The protective effect of ET-1 and ET-3 was unexpected, because endothelins (ETs) are the most potent vasoconstrictors known, and in doses close to those used in this study they cause vasoconstriction and decrease in cerebral blood flow. The protection was not likely to be due either to stimulation of the endogenous release of prostacyclin (PGI2) or to a decrease in the deleterious prostanoid thromboxane A2 (TxA2). Additional experiments are necessary to explain the cerebroprotective effects of ET-1 and ET-3.
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PMID:Studies on the effects of endothelin-1 (ET-1) and endothelin-3 (ET-3) in brain hypoxia and on the participation of brain prostanoids in their actions. 823 56

We studied the effects of bolus injections and infusion of endothelin-1 (ET-1) in female rabbits by measuring serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactic dehydrogenase (LDH), antithrombin III (AT-III), thrombin antithrombin (TAT) complexes, platelet counts and indirect bilirubin. Two successive bolus doses of 0.125 and 0.25 nmol/kg of ET-1 with an interval of 30 min were given to conscious non-pregnant female rabbits (n = 8). GOT, GPT and LDH were found to be significantly increased after injections of ET-1 (p < 0.02, p < 0.04 and p < 0.05, respectively). The percent AT-III activity decreased significantly (p < 0.005). Vasospasm of the hepatic artery was demonstrated by angiography with the same bolus doses in rabbits. There was also an increase in GOT (p < 0.003), GTP (p < 0.05), LDH (p < 0.007), indirect bilirubin (p > 0.07) and TAT complexes (p < 0.02) and a decrease in AT-III (p < 0.03) and platelet counts (p < 0.02) in rabbits (n = 10) after 24 h of continuous infusion of ET-1 (0.6 nmol/kg/h). Histological examination of rabbit liver tissues showed varying degrees of ischemic necrosis of hepatocytes. Thus this study suggests that exogenously administered ET-1 causes vasospasm and liver ischemia resulting in HELLP syndrome-like blood parameters in rabbits.
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PMID:HELLP syndrome-like biochemical parameters obtained with endothelin-1 injections in rabbits. 833 Jul 62

Endothelium-derived vasoactive factors are produced by the endothelium activated by effective stimulus, and with paracrine regulatory activity of the tone/proliferation of the vascular smooth muscle and platelet function. They are divided in two groups: endothelium-derived relaxing and contracting factors. Among the endothelium-derived relaxing factors, PG I2, EDRF (NO or other nitrous compound) and EDHF (still unidentified) have been considered Synthetized by the endothelium after stimulation by plasmatic, platelet-derived and endothelium-derived substances and mechanisms, towards the vascular smooth muscle (myorelaxing/cytostatic) and the platelets (antiaggregation). The endothelium-derived contracting factors include the EDCF1 (endothelins, 21 amino acids peptides), EDCF2 (O2-) and TxA2. Its production, induced by stimulus similar to those for relaxing factors, promotes constriction/mitogenesis of the vascular smooth muscle and platelet aggregation. Probably, endothelin-1 has indirect actions over hormonal mechanisms of cardiovascular and renal regulation. The vascular system establishes a tight regulation over the production of these endothelium-derived vasoactive factors. Its loss (usually due to alteration of endothelial responsiveness to stimulation) allows local or generalized modifications of the vascular tone. These can depend on hypertension, atherosclerosis, ischemia-reperfusion lesion, diabetes, inflammation and situations of farmacotoxicity (all developing vasoconstriction/vasospasm) or by septicemia (leading to vasodilation). This disregulation is also involved in the pathogenesis of hypertension, atherosclerosis and ischemia-reperfusion. The vascular tone regulation by endothelium also leads to systemic consequences. Essentially by decreasing cardiac, cerebral and renal blood flow it implies morphologic and functional modifications of these organs.
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PMID:[Vasoactive endothelial factors]. 833 93

Endothelin-1 may function pathophysiologically as a counterregulatory vasoconstrictor peptide that is modified in its activity by the opposing action of endothelium-derived relaxing factor(s) (EDRF). The present study determined in part the integrated cardiorenal and endocrine actions of pathophysiologic plasma concentrations of endothelin in the anesthetized dog. In addition, nitroglycerin, which inhibits vascular smooth muscle contraction by increasing cGMP in a mechanism similar to EDRF, acts like an endogenous nitrovasodilator. Therefore, we tested the hypothesis that nitroglycerin would effectively antagonize the cardiac and renal actions of exogenous endothelin. The results confirm that endothelin-1-mediated vasoconstriction in vivo is heterogenous with a greater renal than coronary action. Further, nitroglycerin effectively blocked endothelin-1-mediated coronary flow reductions, but only partially antagonized reductions in renal blood flow. Endothelin-1-induced reduction in cardiac output also was not antagonized by nitroglycerin despite its effects to preserve coronary blood flow. Nitroglycerin did, however, antagonize endothelin-induced elevations in plasma epinephrine, norepinephrine, and aldosterone. These results would suggest that in pathophysiologic states where endothelin-1 is elevated, such as hypertension or congestive heart failure, there is a major compromising of renal function, and also the production of cardiac ischemia. Since exogenous nitroglycerin is relatively ineffective in antagonizing the renal vasoconstrictive effects of endothelin, it may be that the endogenous vasodilating systems, such as ERDF and prostacyclin, are inadequate in such pathologic states to counter the vasoconstrictor effects of endothelin.
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PMID:Endothelin-mediated cardiorenal hemodynamic and neuroendocrine effects are attenuated by nitroglycerin in vivo. 838 58

1. The effect of transient forebrain ischemia on endothelin-1 (ET-1) and endothelin-3 (ET-3) production in the hippocampus of stroke-prone spontaneously hypertensive rats (SHRSPs) was investigated using immunohistochemical techniques. 2. In SHRSPs subjected to 10-min bilateral carotid occlusion, neuronal degeneration in the CA1 pyramidal cell layer of the hippocampus was detectable at 4 days and remarkable at 7 days after reperfusion. 3. Coinciding with neuronal degeneration, ET-1- and ET-3-like immunoreactivities were intense in the CA1 pyramidal-cell layer, the stratum lacunosum moleculare, and the CA4 subfield of the hippocampus. Almost all of the immunostained cells had morphological characteristics of astrocytes. 4. The possibility that ET has a role in the development of neuronal cell death following transient forebrain ischemia warrants further attention.
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PMID:Increased production of endothelins in the hippocampus of stroke-prone spontaneously hypertensive rats following transient forebrain ischemia: histochemical evidence. 845 60

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