Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

To assess possible coronary vasoconstriction in patients with ischemic heart disease, we measured coronary vascular resistance in 12 patients with normal hearts and 12 with coronary disease before and during the initial 50 seconds of cold pressor test, a stimulus known to produce systemic vasoconstriction. Control coronary vascular resistance was similar in the two groups, and although it did not change in patients with normal vessels, it rose by 27 per cent (P less than 0.005) in the group with coronary disease during the cold pressor test. In three of 12 patients with coronary disease coronary flow actually declined despite an increase in arterial pressure; in four, angina was precipitated. Phentolamine abolished increases in arterial pressure and coronary vascular resistance during the test in three patients with coronary disease. Adrenergically mediated coronary vascular tone may be an important determinant of coronary blood flow and may contribute to ischemia in patients with coronary disease.
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PMID:Reflex increase in coronary vascular resistance in patients with ischemic heart disease. 1 May 27

Cerebral cortical ischemia was induced in anesthetized rats by occlusion of the middle cerebral artery (MCA). Cerebral blood flow (CBF) was measured with the H2 clearance technique in the center and periphery of the ischemic territory. A decrease of CBF to about 50% of pre-occlusion values was observed in both areas. Administration of Physostigmine, a cholinesterase inhibitor, at a dose of 0.15 mg/Kg by intravenous route, induced an increase of CBF in the ischemic cortex. This change in CBF reached 120% of pre-occlusion level in the periphery and 80% of pre-occlusion value in the center of the area of distribution of the occluded artery. Although Physostigmine induced an increase in arterial blood pressure, the cerebral hyperemia observed both in normal and ischemic cortex could still be demonstrated after blockade of the pressor effect by bleeding or Phentolamine administration.
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PMID:Physostigmine induced reversal of ischemia following acute middle cerebral artery occlusion in the rat. 376 45

Graded doses of norepinephrine and methoxamine were given to rabbits over a standard 90-minute infusion period to assess their potential for inducing myocardial injury. Lesions of myofiber necrosis and leukocytic infiltration were graded semiquantitatively in animals killed 2 days later. A close correlation was found between the dose of norepinephrine and the histological score (r = 0.912, P less than 0.001). Mean arterial pressure rose from 100 mm Hg to a maximum of 129 mm Hg, and averaged 115 mm Hg during infusion of 2 micrograms/min per kg. However, heart rate fell from 287 beats/min to average 208 beats/min. The pressure-rate product, an index of metabolic demand, showed no significant change and did not differ from saline-infused controls. Beta-adrenergic blockade with practolol (4 mg/kg) or propranolol (1 mg/kg) failed to significantly reduce cardiac injury with norepinephrine. However, alpha-adrenoceptor blockade with phentolamine (10 mg), alone or in combination with either of the beta-antagonists, markedly reduced lesion formation as reflected by the histological score (P less than 0.02). Administration of the alpha-agonist methoxamine produced dose-related increases in the intensity of myocardial injury (r = 0.938, P less than 0.01), morphologically identical with those resulting from norepinephrine. Hemodynamic changes also were comparable. Phentolamine markedly reduced methoxamine injury. It may be concluded from these studies that norepinephrine cardiomyopathy results in large part from activation of the alpha-adrenergic system in the rabbit model. Ischemia or a supply-demand mismatch are unlikely mechanisms. We speculate that alterations in myofiber Ca++ translocation, uptake, and binding induced by alpha 1-receptor activation may contribute to membrane damage.
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PMID:Contribution of alpha-adrenoceptor activation to the pathogenesis of norepinephrine cardiomyopathy. 613 55

Reperfusion of ischemic myocardium is associated with increases in total myocardial calcium (Ca+2), which may influence the ultimate extent of ischemic damage as well as the development of arrhythmias. Since reperfusion is also associated with enhanced alpha-adrenergic responsivity, this study was performed to determine the potential interactions between alpha-adrenergic receptors and myocardial calcium during reperfusion. Cats were subjected to 35 min of left anterior descending coronary artery occlusion and 10 min of reperfusion. Total myocardial calcium was measured by atomic absorption spectrometry. Intracellular calcium was calculated from measurements of extracellular space [( 3H]inulin). In control animals with reperfusion, total calcium increased from 0.32 +/- 0.03 to 0.65 +/- 0.05 mmol/100 g dry tissue (P less than 0.0001), while intracellular calcium increased from 0.15 +/- 0.03 to 0.40 +/- 0.05 mmol/100 g dry tissue (P less than 0.001). Pretreatment with the alpha-adrenergic blocking agents phentolamine or prazosin prevented the increase in total and intracellular calcium. Phentolamine and the aqueous soluble alpha 1-adrenergic antagonist BE-2254 administered as late as 2 min before reperfusion similarly attenuated the increase in tissue calcium. Although administration of BE-2254 2 min before reperfusion failed to block the reperfusion-induced increase in extracellular space, the increase in calculated intracellular calcium was prevented. beta-Adrenergic blockade with propranolol partially attenuated but did not prevent an increase in total tissue calcium. Labetalol, a combined alpha- and beta-adrenergic blocking agent completely blocked the increase in tissue calcium during reperfusion. Additional experiments performed after 70 min of ischemia with reperfusion demonstrated a 49% attenuation of the increase in tissue calcium with alpha-adrenergic blockade. Electron microscopy with pyroantimonate and x-ray microprobe analysis demonstrated a large increase in calcium precipitate in mitochondria after reperfusion in untreated animals. Though alpha-adrenergic blockade prevented the calcium deposition in mitochondria, other criteria of ischemia persisted. Thus, alpha-adrenergic blockade specifically prevents the increase in intracellular calcium during reperfusion in reversibly injured tissue, independent of alterations in extracellular space and tissue water.
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PMID:Alpha adrenergic-mediated accumulation of calcium in reperfused myocardium. 613 27

The activation of sympathetic nerves plays a significant role in the initiation of acute myocardial ischemia. In this review the effects of sympathetic nerves on coronary blood flow are summarized. Under physiological conditions the increase in myocardial performance during sympathetic activation is accompanied by metabolic coronary vasodilation. The resulting increase in coronary blood flow is limited by about 30% by alpha-adrenergic coronary constriction. Extravascular compression and beta-adrenergic coronary dilation are of minor importance during sympathetic activation. With exhausted coronary reserve distal to severe coronary stenoses metabolic vasodilation during sympathetic activation is not possible any more; an alpha 2-adrenoceptor-mediated coronary vasoconstriction now predominates. This coronary constriction induces ischemia of the post-stenotic myocardium. The alpha-antagonists Phentolamine and Rauwolscine as well as the calcium-antagonist Nifedipine prevent poststenotic coronary constriction and myocardial ischemia. Also in the genesis of coronary arterial spasm the sympathetic nervous system may play an important role; the constriction of epicardial coronary arteries is mediated by alpha 1-adrenoceptors. The sympathetic nervous system is not only involved in the initiation of myocardial ischemia, but is also activated by ischemia. This feedback-activation of sympathetic nerves leads to an aggravation of myocardial ischemia.
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PMID:[Significance of the sympathetic nervous system for the coronary circulation]. 650 39

The gastric microvascular changes in reserpine (RES 6 mg/kg s.c.)-induced ulcer in Wistar male rats were studied. Two kinds of water paints were injected through the superior mesenteric vein and celiac artery. Excised stomachs were frozen instantly by cooled methanol (-70 degrees C) and were put into methylsalicylate after 24 hr in order to make transparent preparations. RES caused constriction of the vein from the middle layer till the muscularis mucosae and congestion with ischemia in the gastric mucosa after 1 hr. Even after 3 hr, these vascular changes remained and were accompanied by erosion. After 6 and 9 hr, the erosion became more severe, while ischemia was no longer found and the vessels were rather dilated. These lesions initiated from the fundic-antral border area in the lesser curvature and gradually extended to the greater curvature. The early changes up to 3 hr were inhibited by phentolamine, isoproterenol, C6, metiamide and methysergide, but not by carbachol, atropine, vagotomy and propranolol. Atropine, vagotomy, isoproterenol, propranolol and C6 inhibited erosion in the late stage. Phentolamine, carbachol, diphenhydramine, metiamide and methysergide were not effective. From these results and the gastric movement caused by RES, it is suggested that the vascular changes of the early stage in RES-induced ulcer are due not only to the autonomic nervous system but also to the endogenous biogenic amines, and the erosions in the late stage depend on the hypermotility of the stomach rather than on the hypersecretion of the stomach.
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PMID:[Changes of gastric mucosal vessels in reserpine-induced ulcer (author's transl)]. 708 19

Multiple extremity gangrene developed in five patients as a complication of dopamine therapy. The clinical conditions were (1) penetrating chest trauma requiring pneumonectomy with postoperative sepsis, (2) cardiac arrest with aspiration pneumonia, (3) lymphoma with sepsis, (4) Klebsiella pneumonia, and (5) myocardial infarction. The development of acrocyanosis leading to gangrene occurred at dopamine dosages of 5.1 to 10.2 micrograms/kg/min. The alpha-adrenergic vasoconstriction effects of dopamine would not be expected from the doses employed in these patients. Thus, other factors beside pure alpha vasoconstriction are responsible for tissue necrosis after the use of dopamine. We believe that the embolic complications of disseminated intravascular coagulation and hypovolemia are serious risk factors in the development of dopamine gangrene. Peripheral vasoconstriction from dopamine, even at low doses, may set the stage for thrombotic complications of disseminated intravascular coagulation and lead to tissue damage. In laboratory models of disseminated intravascular coagulation, an alpha-adrenergic drug is required to produce peripheral ischemic tissue damage. Treatment of tissue ischemia related to dopamine depends on early recognition of acrocyanosis. Phentolamine, an alpha blocker, has been recommended for treating dopamine ischemia, either through local instillation into ischemic tissues or intravenous infusion. We recommend a high index of suspicion for, and early treatment of, underlying consumptive coagulopathy in all patients requiring dopamine.
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PMID:Dopamine gangrene. Association with disseminated intravascular coagulation. 730 16

Systemic hypoxia (SHx) produces microvascular inflammation in mesenteric, cremasteric, and pial microcirculations. In anesthetized rats, SHx lowers arterial blood pressure (MABP), which may alter microvascular blood flow and microvascular Po(2) (Pm(O(2))) and influence SHx-induced leukocyte-endothelial adherence (LEA). These experiments attempted to determine the individual contributions of the decreases in Pm(O(2)), venular blood flow and shear rate, and MABP to the hypoxia-induced increase in LEA. Cremaster microcirculation of anesthetized rats was visualized by intravital microscopy. Pm(O(2)) was measured by a phosphorescence-quenching method. SHx [inspired Po(2) of 70 Torr for 10 min, MABP of 65 +/- 3 mmHg, arterial Po(2) (Pa(O(2))) of 33 +/- 1 Torr] and cremaster ischemia (MABP of 111 +/- 7 mmHg, Pa(O(2)) of 86 +/- 3 Torr) produced similar Pm(O(2)): 7 +/- 2 and 6 +/- 2 Torr, respectively. However, LEA increased only in SHx (1.9 +/- 0.9 vs. 11.2 +/- 1.1 leukocytes/100 microm, control vs. SHx, P < 0.05). Phentolamine-induced hypotension (MABP of 55 +/- 4 mmHg) in normoxia lowered Pm(O(2)) to 26 +/- 6 Torr but did not increase LEA. Cremaster equilibration with 95% N(2)-5% CO(2) during air breathing (Pa(O(2)) of 80 +/- 1 Torr) lowered Pm(O(2)) to 6 +/- 1 Torr but did not increase LEA. On the other hand, when cremaster Pm(O(2)) was maintained at 60-70 Torr during SHx (Pa(O(2)) of 35 +/- 1 Torr), LEA increased from 2.1 +/- 1.1 to 11.1 +/- 1.5 leukocytes/100 microm (P < 0.05). The results show a dissociation between Pm(O(2)) and LEA and support the idea that SHx results in the release of a mediator responsible for the inflammatory response.
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PMID:Dissociation between skeletal muscle microvascular PO2 and hypoxia-induced microvascular inflammation. 1259 89

Loss of cardioprotection by adenosine in hearts stressed by transient ischemia may be due to its effects on glucose metabolism. In the absence of transient ischemia, adenosine inhibits glycolysis, whereas it accelerates glycolysis after transient ischemia. Inasmuch as 5'-AMP-activated protein kinase (AMPK) is implicated as a regulator of glucose and fatty acid utilization, this study determined whether a differential alteration of AMPK activity contributes to acceleration of glycolysis by adenosine in hearts stressed by transient ischemia. Studies were performed in working rat hearts perfused aerobically under normal conditions or after transient ischemia (two 10-min periods of ischemia followed by 5 min of reperfusion). LV work was not affected by adenosine. AMPK phosphorylation was not affected by transient ischemia; however, phosphorylation and activity were increased nine- and threefold, respectively, by adenosine in stressed hearts. Phosphorylation of acetyl-CoA carboxylase and rates of palmitate oxidation were unaltered. Glycolysis and calculated proton production were increased 1.8- and 1.7-fold, respectively, in hearts with elevated AMPK activity. Elevated AMPK activity was associated with inhibition of glycogen synthesis and unchanged rates of glucose uptake and glycogenolysis. Phentolamine, an alpha-adrenoceptor antagonist, which prevents adenosine-induced activation of glycolysis in stressed hearts, prevented AMPK phosphorylation. These data demonstrate that adenosine-induced activation of AMPK after transient ischemia is not sufficient to alter palmitate oxidation or glucose uptake. Rather, activation of AMPK alters partitioning of glucose away from glycogen synthesis; the increase in glycolysis may in part contribute to loss of adenosine-induced cardioprotection in hearts subjected to transient ischemia.
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PMID:Effects of adenosine on myocardial glucose and palmitate metabolism after transient ischemia: role of 5'-AMP-activated protein kinase. 1664 81

Vasopressor extravasation is a rare adverse drug reaction that can lead to tissue damage, ischemia, and necrosis of the affected area when vasopressors are administered peripherally. Phentolamine, a nonselective, reversible alpha antagonist, is the current standard treatment for this adverse reaction, but it is often unavailable for use. This review seeks to synthesize the available data in order to recommend alternative pharmacological options for use when phentolamine is not available. After an extensive literature search, 16 publications were reviewed. A treatment algorithm was created that recommends a combination of subcutaneous terbutaline, a selective beta₂ agonist, and topical nitroglycerin, an organic nitrate, for adults; and topical nitroglycerin monotherapy for children younger than 2 years of age. However, further research and case reports are required in order to establish a new standard of care for the treatment of vasopressor extravasation.
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PMID:Alternative Pharmacological Management of Vasopressor Extravasation in the Absence of Phentolamine. 2889 Jun 46


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