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 endothelin-1 (ET-1) on the blood flow contributions of the pulmonary and systemic circulations to the trachea and main bronchi were measured in anesthetized dogs by injecting 15-microns radiolabeled microspheres into the right and left heart, respectively. After the microsphere injections the animals were killed, and the tracheal cartilage, tracheal muscle mucosa, and main bronchi were excised and collected for radioactive counting. The results of this study showed that under normal conditions tracheal blood flow was primarily systemic (> 95% of total tracheal blood flow) averaging 25-50 ml/min/100 g, whereas both the pulmonary (9-10 ml/min/100 g) and systemic circulations (19-20 ml/min/100 g) contributed substantially to main bronchi blood flow. Administration of ET-1 i.v. decreased systemic tracheal cartilage blood flow from 25.3 +/- 3.8 to 14.5 +/- 2.8 ml/min/100 g, systemic tracheal mucosal blood flow from 50.0 +/- 7.0 to 25.0 +/- 7.0 ml/min/100 g, and systemic main bronchi blood flow from 19.4 +/- 4.6 to 11.6 +/- 3.4 ml/min/100 g (p < 0.05). These results indicate that ET-1 is a potent constrictor of the airway circulation and may contribute to airway ischemia seen in different airway disease states.
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PMID:Effect of endothelin-1 on canine airway blood flow. 750 64

The role of endogenous endothelin-1 (ET-1) in myocardial infarction was investigated in a rabbit ischemia-reperfusion model and in rabbit Langendorff hearts. AwETN40, a monoclonal antibody against ET-1, at 10 mg/kg i.v. inhibited hypertension and hypotension induced by ET-1 (0.3 nmol/kg i.v.): about 70-100% inhibition lasted for 24 h. In a coronary occlusion (30 min)-reperfusion (24 h) model, AwETN40 (10 mg/kg i.v.) reduced the infarct size from 60.9 +/- 4.6% (infarct region/ischemic region in weight, IgG1 kappa control; n = 5) to 37.1 +/- 5.2% (n = 5, p < 0.05). Plasma ET-1 levels were increased significantly by coronary occlusion-reperfusion and returned to control level 24 h after reperfusion. Effects of ET-1 on the coronary vessels and cardiac contractility were studied in the Langendorff heart. ET-1 increased the perfusion pressure from concentrations as low as 10 pM, whereas the developed left ventricular pressure was not altered. These results suggest that ET-1 decreases oxygen supply to the cardiac muscles by constricting coronary vessels and that this, in turn, worsens the ischemic condition of the heart to extend the infarct size.
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PMID:Role of endogenous endothelin in extension of rabbit myocardial infarction. 750 81

Using an isolated rat heart preparation and 31P magnetic resonance spectroscopy, we studied the effects of endothelin-1 (ET-1) and U-46619, a thromboxane-A2 analogue, on coronary flow (CF), left ventricular developed pressure (LVP), and high-energy phosphate metabolism under control conditions (normal myocardium) and during postischemic reperfusion (reperfused myocardium). The selected doses of ET-1 and U-46619 reduced CF in the normal myocardium to a similar extent (47.8 +/- 1.5% and 48.7 +/- 4.6%, respectively). In contrast to ET-1, U-46619 induced a depression of LVP (20.2 +/- 6.9% versus 6.8 +/- 4.7%; p < 0.05) which was accompanied by an intracellular acidosis, indicating that a low-flow ischemia occurred. In reperfused hearts, the ET-1-induced decrease in CF was more pronounced compared to U-46619 (79.5 +/- 1.6% versus 59.0 +/- 5.9%; p < 0.05) and to ET-1-induced decrease in CF in the normal myocardium (74.0 +/- 7.9% versus 32.4 +/- 6.3%; p < 0.05). This was accompanied by a large decrease in LVP and in levels of high-energy phosphate compounds. Therefore, the effects of ET-1 but not of U-46619 are enhanced in reperfused hearts. This may contribute to the delayed recovery of the postischemic reperfused myocardium.
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PMID:Differential effects of endothelin-1 on normal and postischemic reperfused myocardium. 750 89

The aim of the study was to investigate the cytoprotective effect of a calcium channel blocker, nicardipine, on altered renal function due to cold ischemia for 72 h. The experiments were performed on isolated perfused kidneys from adult rabbits. Kidneys were perfused with either standard Euro-Collins (EC) solution (n = 7) or EC containing nicardipine (n = 6) and then incubated with the same preservation solutions in a beaker exposed to cold ischemia for 72 h at +4 degrees C. In the control group the same procedure was applied to untreated kidneys (n = 6) which were exposed to cold ischemia for 30 min. Vascular responses and urinary output to noradrenaline, angiotensin II, endothelin-1, acetylcholine and sympathetic stimulation were assessed as the functional activities of the kidney. The responses of the preserved kidneys were compared following cold ischemic conditions. The results indicate that the addition of nicardipine to EC solution protects the vascular endothelial regulatory function and urine excretion; therefore, dihydropyridine calcium channel blockers might be useful for kidney preservation.
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PMID:The effect of nicardipine on renal functions following 72-hour cold ischemia. 758 2

The effects of intravenous (i.v.) infusions of exogenous endothelin-1 (ET-1, 0.05 and 0.1 nmol/kg/min) on incidence and severity of ventricular arrhythmias during 30-min period of acute myocardial ischemia were assessed in anesthetized rats. We examined the role of ETA-receptors in the proarrhythmic effects of both exogenous and endogenous ET using the ETA-receptor antagonist, BQ123. Exogenous ET-1 increased the severity and incidence of ischemic arrhythmias dose dependently. Both doses increased the total incidence of ventricular fibrillation (VF: from 30% in controls to 100 and 88% in rats given 0.05 and 0.1 nmol/kg/min ET-1, respectively); the higher dose also increased total arrhythmia count and duration of ventricular tachycardia (VT). BQ123 (10 micrograms/kg/min) completely abolished this proarrhythmic effect of exogenous ET-1. To assess the role of endogenous ET-1 in the genesis of ischemic arrhythmias, we studied the effects of a range of doses of BQ123 (5-100 micrograms/kg/min) on ischemic arrhythmias. Only one dose of BQ123 (10 micrograms/kg/min) attenuated arrhythmias by reducing total ventricular ectopic count (from 1,423 +/- 112 in controls to 677 +/- 159). The highest dose of BQ123 tested (100 micrograms/kg/min) increased arrhythmias by significantly increasing the incidence of irreversible VF (from 25 to 75%). These results suggest that exogenous ET-1 can aggravate ischemia-induced arrhythmias, an effect that is sensitive to ETA-receptor blockade. However, although endogenous ET-1 may make some contribution to the genesis of arrhythmias resulting from coronary occlusion through an action at ETA receptors, the observed proarrhythmic effect of BQ123 at high doses suggests that this may unmask an effect of ET-1 at other receptors.
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PMID:Effects of endothelin-1 and the ETA-receptor antagonist, BQ123, on ischemic arrhythmias in anesthetized rats. 759 33

Hypertension is a complex disease, the treatment of which should not only lower systolic and diastolic blood pressure but also attenuate the secondary consequences of the disease. These include vascular injury (including atherosclerosis), stroke, left ventricular hypertrophy, and renal damage. To establish whether the long-acting, vascular-selective calcium antagonist amlodipine attenuates some of these secondary consequences of hypertension, 5-week-old stroke-prone hypertensive and 8-week-old spontaneously hypertensive rats were treated (orally) with 5 mg/kg/day and 10 mg/kg/day amlodipine, respectively, for 30 weeks. The treatment resulted in a significant lowering of systolic blood pressure, accompanied by reduced cardiac hypertrophy and prolonged survival. Evidence for a protective effect of amlodipine on the vasculature was obtained by treating cholesterol-fed rabbits with 1-5 mg/kg/body weight/day. This resulted in a reduction in vascular Ca2+ overloading and a reduced incidence of sudanophilic lesion formation. Protection against ischemia-induced changes in the myocardium included a reduction in the ischemia-induced externalization of endothelin-1 binding sites.
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PMID:End-organ involvement and calcium antagonist therapy: animal studies. 760 72

Serum endothelin levels increase during sepsis, ischemia, reperfusion, pulmonary operations, and systemic hypertension after surgery. Despite extensive study, the site and extent of action of endothelin on the pulmonary microcirculation are not well established. To assess the effect of endothelin on the pulmonary vasculature, especially the veins, the circulation of the lung was cast with methyl methacrylate 10 minutes after endothelin-1 was given intravenously to rats. Endothelin-1, at concentrations of 0.1, 1.0, and 10.0 micrograms/kg of body weight, increased the mean systemic arterial blood pressure 8%, 7%, and 17% (p < 0.01) and mean pulmonary arterial blood pressure 15%, 28%, and 53%, respectively (p < 0.01). The proportional increases in the pulmonary pressures were greater than those of the systemic pressures (p < 0.01). Scanning electron microscopy of cast blood vessels showed more contraction of the veins than the arteries. For doses of 0, 0.1, 1.0, and 10.0 micrograms/kg, the respective focal contraction of small veins was 6.7% (+/- 4.4), 15.4% (+/- 9.1), 23.3% (+/- 10.1), and 14.4% (+/- 9.0) of the vessel diameter (p < 0.01). In addition, the diameter of capillaries increased (p < 0.01) and the capillary interspaces decreased (p < 0.01) after endothelin administration, but not in a linear dose-dependent manner. The dose of endothelin correlated with the change in the mean systemic (r = 0.82, p < 0.01) and the mean pulmonary (r = 0.80, p < 0.01) blood pressures. The mean pulmonary pressure change correlated with the focal venous contraction on the casts (r = 0.35, p < 0.01), capillary diameter (r = 0.64, p < 0.01), and capillary interspace distance (r = -0.34, p < 0.01). The venous contraction was related to the capillary diameter (r = 0.26, p < 0.01). The most notable effect of endothelin-1 in rat pulmonary microcirculation is focal constriction of small veins. Because this effect may lead to pulmonary edema, endothelin antagonists may be of benefit in a variety of clinical situations.
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PMID:Endothelin-1 focally constricts pulmonary veins in rats. 760 38

Adult respiratory distress syndrome (ARDS) often occurs in response to sepsis, shock, or ischemia/reperfusion (I/R) of a remote organ and is a frequent cause of mortality in the ICU patient. Pulmonary vascular resistance (PVR) increases during ARDS, yet direct observations of the pulmonary microcirculation are needed to characterize the vascular response. The purpose of this study was to quantitate the changes in hemodynamic variables, subpleural arteriolar diameters (AD), and alveolar cross-sectional areas (ACSA) during intestinal I/R-induced lung injury in rats, using a new method of in vivo videomicroscopy. Sprague-Dawley rats were anesthetized and cannulated, and superior mesenteric arteries were looped. A thoracotomy was performed with animals ventilated with air with 1 cm PEEP. Hemodynamic and videomicroscopic data were obtained before and during 45 min of SMA occlusion and after reperfusion, up to 120 min. Maximal vessel dilation was measured using topical 10(-5) M nitroprusside. The ability of vessels to constrict was confirmed by applying topical 10(-6) M endothelin-1. Intestinal I/R produced decreases in arterial pH, mean arterial pressure, and cardiac output. Despite these alterations, subpleural AD remained maximally dilated. Arterioles maintained the ability to constrict as demonstrated by the response to topical endothelin-1. ACSA did not change, indicating a uniform inflation of the lung. Using a unique method of in vivo pulmonary videomicroscopy, we have shown that AD do not change following 120 min of intestinal I/R, despite systemic hemodynamic instability. It appears that pulmonary arteriolar vasoconstriction does not contribute to increased PVR during the early phase of lung injury.
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PMID:Pulmonary subpleural arteriolar diameters during intestinal ischemia/reperfusion. 763 Jan 36

This study was designed to investigate the changes in plasma and tissue endothelin-1/endothelin-2 (ET) after liver ischemia and to assess the protective effect of anti-ET 1/ET 2 monoclonal antibody (ET antibody) against ischemia-reperfusion injury. The ET levels in the liver tissue, hepatic venous blood of the ischemic and non-ischemic sides, and in the portal venous blood were measured before and after partial liver ischemia for 1 hour in the adult dog. The ET levels in the liver tissue and hepatic venous blood on the ischemic side increased slightly during ischemia and markedly after reperfusion, whereas those on the nonischemic side showed no significant increases. The ET levels in the portal venous blood peaked at 1 to 3 hours after ischemia, which was significantly higher than the levels in the hepatic venous blood on the ischemic side and which correlated with the portal venous pressure elevated because of the partial liver clamping. The administration of antibody (2 mg/kg, intravenous) before reperfusion resulted in a significant inhibition of the postreperfusion elevations of serum-glutamic-oxaloacetic transaminase (GOT), S-glutamic pyruvic transaminase (GPT), and the indocyanine green (ICG) dye retention rate. In conclusion, ET was produced both in the liver tissue exposed to ischemia and in the vascular endothelium of the portal bed exposed to portal congestion. The ET released from the vascular endothelium, including the liver and the portal bed, was found to be a possible factor of ischemia-reperfusion injury.
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PMID:Response of plasma and tissue endothelin-1 to liver ischemia and its implication in ischemia-reperfusion injury. 770 89

A temporary increase in pulmonary vascular resistance is observed during the first 24 hr following lung allotransplantation. We hypothesized that such early vascular changes are secondary to endothelial injury by ischemia-reperfusion, and that this may be mediated by an increased pulmonary endothelin-1 production/release. To test this hypothesis, radioimmunoassay was used to analyze endothelin-1 levels in bronchoalveolar lavage and plasma taken before surgery and at 1 hr, 4 hr, 24 hr, and 1 week after transplantation. The study was carried out on 2 groups of mongrel dogs. One group was subjected to left single-lung allotransplantation and the other to autotransplantation. Endothelin-1 levels in the bronchoalveolar lavage samples from the lung allografts were significantly increased at 1 (0.70 +/- 0.18 pg/ml) and 4 (1.84 +/- 0.65 pg/ml) hr after transplantation compared with the preoperative value (0.14 +/- 0.05 pg/ml), and declined at 24 (0.85 +/- 0.84 pg/ml) hr after transplantation. Similarly, plasma endothelin-1 levels in the allografts were significantly increased at 1 (2.0 +/- 0.80 pg/ml) and 4 (2.0 +/- 0.71 pg/ml) hr after transplant when compared with preoperative levels (0.54 +/- 0.09 pg/ml). Plasma endothelin-1 levels, however, remained significantly high after 24 hr (1.4 +/- 0.4 pg/ml; P < 0.007) and decreased after 1 week after transplant (0.89 +/- 0.32 pg/ml). On the other hand, endothelin-1 levels in bronchoalveolar lavage from the autograft group remained relatively unchanged; however, plasma levels showed a significant increase at 4 hr (6.6 +/- 1.8 pg/ml) after transplantation compared with preoperative levels (2.8 +/- 0.38 pg/ml). Elevation of endothelin-1 levels early after lung transplantation may play an important role in early high pulmonary vascular resistance and temporary graft dysfunction.
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PMID:Alterations in bronchoalveolar lavage and plasma endothelin-1 levels early after lung transplantation. 770 61


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