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)

Although rare, exertional collapse and sudden death are the most serious potential complications of sickle cell trait. Studies suggest that this condition may occur in susceptible persons when poor physical conditioning, dehydration, heat stress or hypoxic states precipitate sickling of the abnormal erythrocytes. Sickling leads to endothelial damage, which can cause vasoconstriction, disseminated intravascular coagulation and local tissue damage. Cardiac effects include acute ischemia and arrhythmias. Muscle damage results in acute compartment syndromes and release of myoglobin into the circulation. Acute renal failure is possible. Diagnosis is based on a high index of suspicion, and characteristic presentation and laboratory findings, including myoglobinuria, hyperkalemia, hypocalcemia, hyperphosphatemia and elevated creatine kinase levels. The differential diagnosis includes pulmonary embolism, acute cardiac events, anaphylaxis and heat stroke. Management is based on stabilization, rehydration, and the treatment and prevention of complications.
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PMID:Exertional collapse and sudden death associated with sickle cell trait. 904 99

A case of thrombotic microangiopathy presenting as a hemolytic uremic syndrome complicated by untreatable hypertension and ultimately requiring bilateral nephrectomy is discussed. Severe hypertension and renal failure may complicate the course of vascular diseases of the kidney, including thrombotic microangiopathy, chronic hypertension, and scleroderma. Toxins, pressure stress, and immune material may trigger the initial injury to vascular endothelium. The malignant course of these renal vascular diseases seems linked to the severity of vascular injury. Endothelial injury manifests with swelling and detachment of endothelial cells from the basement membrane, expansion of the subendothelial space, and newly formed basement membrane-like material. In arterioles, endothelial injury precedes myointimal swelling and proliferation, leading to vascular lumina narrowing or obliteration and secondary glomerular ischemia, with glomerular tuft collapse and garland-like wrinkling and thickening of the capillary wall. Endothelial cell injury is very likely the common determinant of a cascade of events that lead to irreversible renal failure. When the initial insult (toxins, mechanical stress, antibodies) is promptly removed, lesions are self-limiting and the patient usually recovers. However, a severe insult persisting for some time can lead to chronic and irreversible vascular lesions that, through renal ischemia, trigger maximal activation of the renin angiotensin system with a brisk elevation in arterial blood pressure that may combine to further vascular injury and renal ischemia. Moreover, enhanced shear stress in the severely narrowed microcirculation, through abnormal von Willebrand factor processing, can also favor endothelial injury and platelet aggregation, which may further worsen the vascular lesions and sustain the microangiopathic process. Plasma manipulation, arteriolar vasodilators, and angiotensin-converting enzyme inhibitors normally control the vicious circle, but in few severe cases bilateral nephrectomy remains the last chance to save the patient's life.
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PMID:Malignant vascular disease of the kidney: nature of the lesions, mediators of disease progression, and the case for bilateral nephrectomy. 867 55

Release of met-enkephalin-like immunoreactivity (MLI) into the circulation was investigated during feline intestinal ischemia-reperfusion in relation to the mass of ischemic tissue and in correlation to the sympathoadrenergic, response as gauged by plasma norepinephrine (NE) and epinephrine (E) levels. Chloralose anesthetized cats were randomized to a control group (C, n = 7), 20 cm segmental (S, n = 7), or complete intestinal ischemia (l, n = 7) for 90 min followed by reperfusion for 180 min. MLI and NE/E concentrations were assayed by radioimmunoassay and chromatography, respectively. Severe mucosal lesions and cardiovascular decompensation were observed in l animals in association with increased MLI and NE levels in femoral venous and portal venous plasma, whereas no such responses were observed in the S or C groups. MLI and NE concentrations were consistently higher in portal venous than in femoral venous plasma in 1 animals and correlations between MLI and NE levels were found during reperfusion in the portal, but not the systemic, circulation. Concentrations of E remained unchanged in all groups and did not correlate to MLI release. We conclude that: 1) intestinal MLI release and sympathetic activation occur only when the ischemic insult is sufficient to cause circulatory collapse, characteristic of an "on-off" rather than a "dose-response" pattern; and 2) intestinal MLI and NE release at reperfusion are correlated whereas MLI and E release do not appear to be related events.
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PMID:Met-enkephalin and catecholamine release during feline intestinal ischemia-reperfusion. 879 56

This report is the first to correlate data concerning intraoperative somatosensory evoked potentials (SSEPs) and local spinal cord blood flow (ISCBF) in patients with syringomyelia. In a consecutive study, bilateral median nerve SSEPs were recorded intraoperatively in 13 patients undergoing a syrinx shunt to the posterior fossa cisterns (syringocisternostomy). ISCBF was measured in five of these patients using laser doppler flowmetry (LDF) calibrated in arbitrary units (AU). SSEP recordings obtained 30 min after syrinx decompression demonstrated a slight but consistent reduction of N20 latencies (mean change: 0.53 ms right, p < 0.003; 0.58 ms left, p < 0.001) concurrent with a similar but less consistent increase of N20 amplitudes (0.16 mV right, p = 0.256; 0.29 mV left, p = 0.03). Prior to shunting, LDF recordings from the spinal cord overlying syrinxes revealed very low ISCBF values in five of five patients (mean LDF, 13.2 AU +/- 15.3 SD). Immediately after shunting, there was a dramatic rise of ISCBF (mean LDF, 241.2 AU +/- 106.3 SD) associated with visualized hyperemia of the spinal cord and pial vessels. The ISCBF fell to intermediate levels after 2 min (157.2 AU +/- 33.0 SD) and remained at these levels during the interval of recording (5 min). Hyperventilation testing in two patients prior to shunting revealed no change in ISCBF consistent with a loss of CO2 vascular reactivity and a paradoxical increase of ISCBF in one patient 5 min after shunting. Each patient in this study experienced neurological improvement in the immediate postoperative period associated with collapse or disappearance of the syrinx on magnetic resonance imaging scans. Because syrinx shunting results in an acute decompression of the distended spinal cord, it is possible that the rapid improvement of SSEPs reflects a relief of mechanical factors such as stretching and compression of nervous tissue. However, the LDF findings in this study suggest that distended spinal cord cavities are also capable of producing regional ischemia. A significant reduction of ISCBF is a possible contributing cause of neurological injury and SSEP abnormalities. Intraoperative improvement of SSEPs and ISCBF were found to correlate well with neurological recovery following syringocisternostomy. Our results indicate that SSEP monitoring can provide useful information during surgical procedures for syringomyelia and that further experience with LDF monitoring may provide insights into the pathophysiology of this condition.
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PMID:Intraoperative improvement of somatosensory evoked potentials and local spinal cord blood flow in patients with syringomyelia. 880 32

Cells can die by two distinct pathways: apoptosis or necrosis. Necrosis is associated with rapid metabolic collapse that leads to cell swelling, early loss of plasma membrane integrity, and ultimate cell rupture. Cytosolic contents leak from the necrotic cell causing injury and inflammation to surrounding tissue. In contrast, apoptosis is an energy-requiring, gene-directed process, which, when activated, results in cell "suicide." The morphological and biochemical characteristics of cells dying by apoptosis differ markedly from those of cells dying by necrosis. During apoptosis, cells decrease in size and round up. The nuclear chromatin undergoes condensation and fragmentation. The apoptotic cell then breaks apart into many plasma membrane-bound vesicles called "apoptotic bodies," which contain fragments of condensed chromatin and morphologically intact organelles such as mitochondria. Apoptotic cells and bodies are rapidly phagocytosed, thereby protecting surrounding tissues from injury. The rapid and efficient clearance of apoptotic cells makes apoptosis extremely difficult to detect in tissue sections. Recent studies show that multiple cytotoxic stimuli well known to cause necrosis can lead to apoptosis instead when cells are exposed to the same noxious agents at lower concentrations. This insight has led to an interest in the role of apoptosis in the pathogenesis of renal diseases that result primarily from injury to renal tubular epithelial cells. These diseases include acute and chronic renal failure from exposure of the kidney to ischemia or to cytotoxic agents. In this review we discuss some relevant aspects of the differences between necrotic and apoptotic cell death. We also present evidence to support the hypothesis that apoptosis is an important pathogenic mechanism in those forms of acute and chronic renal failure in which the renal tubular epithelial cell is the primary target of ischemic or toxic injury.
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PMID:Mechanisms of apoptosis and its potential role in renal tubular epithelial cell injury. 885 9

The mechanism leading to changes in the superstructure of endothelial cells exposed to ischemia and reperfusion remains uncharacterized. We show that in post-hypoxic endothelial cells, the simple re-addition of oxygen induces a profound reorganization of the actin cytoskeleton. The total filamentous actin pool increases by 41% and translocation of actin filaments to the submembranous network is observed. Concurrent with the actin polymerization, increased tyrosine phosphorylation of endothelial cell substrates is detected on Western blots. Overexpression of superoxide dismutase using replication incompetent adenovirus inhibits the actin and tyrosine phosphorylation responses to reoxygenation. Inhibition of tyrosine kinases with the isoflavone genistein also suppressed the actin polymerization response to reoxygenation, but unlike superoxide dismutase, genistein also induced the collapse of the superstructure of endothelial cells upon reoxygenation. These experiments support the concept that reoxygenation following a period of hypoxia can induce the remodeling of the actin cytoskeleton in endothelial cells. Such a response requires the intact coupling of superoxide producing pathway(s) with tyrosine kinase pathway(s).
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PMID:Superoxide-mediated actin response in post-hypoxic endothelial cells. 890 Jan 69

Starling forces and hemodynamics in the digits of 5 horses were studied during early laminitis induced by oral administration of an aqueous extract of black walnut (Juglans nigra). The black walnut extract was prepared from heartwood shavings and was administered by nasogastric tube. Heart and respiratory rates, rectal temperature, central venous and arterial pressures, digital pulses, and signs of lameness were monitored. Blood samples were collected for determination of WBC count, hemoglobin concentration, and PCV and for endotoxin and tumor necrosis factor assays. Total WBC count and central venous pressure were monitored until they decreased by 30 or 20%, respectively. These decreases in WBC count and central venous pressure were observed 2 to 3 hours after dosing with black walnut extract. Respiratory and heart rates, body temperature, systolic and diastolic blood pressures, PCV, and hemoglobin concentration did not change significantly. Anesthesia was induced, heparin (500 IU/kg of body weight) was administered IV, and a pump-perfused extracorporeal digital preparation was established. Digital arterial and venous pressures were maintained at 100 and 30 mm of Hg, respectively. Blood flow, capillary pressure, lymph and plasma protein concentrations, and weight of the isolated digit during rapid increase in venous pressure were measured. Isogravimetric capillary filtration coefficient, vascular compliance, vascular and tissue oncotic pressures, tissue pressure, osmotic reflection coefficient, and precapillary and postcapillary resistances were calculated. Mean digital blood flow was 14 ml/min/100 capillary pressure was 52 mm of Hg, and vascular compliance was 0.06 ml/mm of Hg. The vascular and tissue oncotic pressures were 21.49 and 4.93 mm of Hg, respectively. The osmotic reflection coefficient was 0.71, and tissue pressure was 41 mm of Hg. The precapillary and postcapillary resistances were 7 and 2 mm of Hg/ml, respectively. Capillary permeability to proteins was not significantly different from that previously measured in healthy horses, suggesting that the increased capillary filtration coefficient reflected increased capillary hydrostatic pressure and perfusion of previously nonperfused capillaries. Neither endotoxin nor serum tumor necrosis factor activity was detected in any samples. The hemodynamic and Starling forces observed in this study were similar to those observed after laminitis was induced by administration of a carbohydrate gruel. Significant differences between the 2 models were detected for total vascular resistance, postcapillary resistance, and capillary filtration coefficient. It is likely that these differences were identified because the horses administered the black walnut extract were at an earlier stage in the disease process. The findings of this study suggest that the increase in capillary pressure causes transvascular fluid movement, resulting in increased tissue pressure and edema. We hypothesize that further increases in tissue pressure may collapse capillary beds and lead to tissue ischemia.
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PMID:Digital Starling forces and hemodynamics during early laminitis induced by an aqueous extract of black walnut (Juglans nigra) in horses. 892 52

Nourishment of arteries is accomplished by diffusion from the lumen of the vessel and from vasa vasorum. Most normal arteries have an extensive network of vasa in the adventitia that arise from branch points of parent arteries. When the thickness of arteries exceeds the ability of simple diffusion of nutrients from the lumen (larger muscular of atherosclerotic arteries), vasa extend into the media and intima. Vasa in the intima-media arise predominantly from adventitial vasa, but can arise from the lumen in vascular grafts and recanalized arteries after thrombosis. Vasa respond to vasoactive stimuli, and can regress after they vascularize arterial grafts and in response to regression of the atherosclerotic lesions. Therefore, vasa can increase blood flow to the artery wall by dilation of existing arteries or by formation of new vessels (neovascularization). Conversely, vasa can reduce blood flow to the artery wall by active constriction or by regression (involution) of existing vasa. The pathophysiological significance of vasa vasorum in normal and diseased arteries is related to their structure. Vasa in the intima-media are thin-walled endothelial cell tubes with thin or absent medial smooth muscle cells. Therefore, they are prone to collapse and rupture in response to arterial pressure, mechanical forces in the artery, necrotic substances found in diseased arteries, and vasospasm. Vasa also provide the artery with a vast absorptive endothelial surface that may have important implications for arterial lipid kinetics, and delivery and removal of neurohumoral agents from the artery wall. These properties have lead to speculation about their role in the pathogenesis of atherosclerosis, plaque rupture and thrombosis, medial ischemia leading to arterial dissection and aneurysm, restenosis after angioplasty, and post-stenotic dilatation. Finally, larger veins also have an extensive network of vasa that have been implicated in the pathogenesis of venous thrombosis and varicose veins.
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PMID:[The vasa vasorum of the arteries]. 898 46

We investigated the contribution of the rate of vascular collapse to the early contractile failure and decreased diastolic stiffness induced by ischemia. Isolated rat hearts (n = 8/group), perfused at 37 degrees C with blood through a roller pump and paced at 320 beats/min, were subjected to global ischemia either by switching off the roller pump (slow vascular collapse-group 1) or by reversing the direction of the roller pump for 5 s prior to switch-off (rapid vascular collapse-group 2). In group 1, residual coronary pressure declined progressively over the first 20 s of ischemia whereas in group 2 the pressure had fallen to zero within 2 s. The profile of ischemia-induced contractile failure was however, similar in both groups. Thus, after 2 s of ischemia, when residual perfusion pressure had declined by only 10% in group 1 (60.0 +/- 0.0 to 54.9 +/- 0.8 mmHg) but was virtually non-existent in group 2 (60.0 +/- 0.0 to 0.4 +/- 12.7 mmHg), left ventricular developed pressure had fallen to a similar extent in both groups (86 +/- 2% and 84 +/- 3%, respectively). Curve-fitting analysis for individual hearts showed that the profile of contractile failure was described by a double exponential process that was not significantly affected by the rapid vascular collapse. Left ventricular end-diastolic pressure in group 1 hearts progressively declined over the first 20 s of ischemia, the profile paralleling that of the dissipation of perfusion pressure. In contrast, in group 2 hearts, left ventricular end-diastolic pressure rose rapidly and leaked at 5 s, a period that coincided with the reversed direction of the perfusion pump. Similarly, in a separate study, the analysis of ventricular diastolic stiffness (n = 6/group) showed a rapid decline during the first 20 s of ischemia: this decline could be inhibited by the use of rapid vascular collapse. In additional experiments, hearts (n = 8/group) were paced at 220, 320 or 420 beats/min and ischemia was induced by reversing (5 s) and then stopping the perfusion pump. Myocardial oxygen consumption increased in parallel with heart rate and was matched by commensurate increases in the rate of contractile failure. Curve-fitting analysis showed that slow stimulation rates (220 beats/ min) significantly delayed contractile failure during the first 60 s of ischemia (first time constant = 14.5 +/- 4.1 s compared with 8.1 +/- 1.1 s at 320 beats/min and 6.3 +/- 1.1 s at 420 beats/min; P < 0.05 in both instances). In conclusion, vascular collapse associated with ischemia may contribute to the initial decrease in ventricular diastolic stiffness; however, it does not play a major role in determining the rate of acute contractile failure. Metabolic processes as reflected by oxygen consumption do however, appear to be important.
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PMID:The role of the rate of vascular collapse in ischemia-induced acute contractile failure and decreased diastolic stiffness. 901 35

To test the role of inorganic phosphate (Pi) in downregulation of myocardial contractile force at the onset of ischemia, Pi of rat hearts was determined with 31P nuclear magnetic resonance spectroscopy. Forty cycles of brief hypoperfusion (30% of baseline flow for 33 s) were used to achieve a time resolution of 0.512 s for comparing dynamic changes in Pi and contractile force. Initial control values of left ventricular developed pressure (LVP), heart rate, and oxygen consumption were 136 +/- 11 mmHg, 236 +/- 4 beats/min, and 95 +/- 3 microl O2 x min(-1) x g(-1); these values were unchanged at the end of the experiment. During the first 10 s of hypoperfusion, Pi increased at a rate (percentage of the total observed change) faster than the decrease in LVP; Pi and LVP then changed at the same rate during the remainder of the hypoperfusion. ADP did not change in advance of LVP. Intracellular pH did not change. The results indicate that Pi plays an important role in initiating the downregulation of myocardial contractile force at the onset of ischemia. Perfusion pressure also declined faster than LVP at the onset of ischemia, indicating potential importance of vascular collapse in contractile downregulation during early ischemia.
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PMID:Correlation between myocardial contractile force and cytosolic inorganic phosphate during early ischemia. 908 9


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