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

White matter of the brain and spinal cord is susceptible to anoxia and ischemia. Irreversible injury to this tissue can have serious consequences for the overall function of the CNS through disruption of signal transmission. Myelinated axons of the CNS are critically dependent on a continuous supply of energy largely generated through oxidative phosphorylation. Anoxia and ischemia cause rapid energy depletion, failure of the Na(+)-K(+)-ATPase, and accumulation of axoplasmic Na+ through noninactivating Na+ channels, with concentrations approaching 100 mmol/L after 60 minutes of anoxia. Coupled with severe K+ depletion that results in large membrane depolarization, high [Na+]i stimulates reverse Na(+)-Ca2+ exchange and axonal Ca2+ overload. A component of Ca2+ entry occurs directly through Na+ channels. The excessive accumulation of Ca2+ in turn activates various Ca(2+)-dependent enzymes, such as calpain, phospholipases, and protein kinase C, resulting in irreversible injury. The latter enzyme may be involved in "autoprotection," triggered by release of endogenous gamma-aminobutyric acid and adenosine, by modulation of certain elements responsible for deregulation of ion homeostasis. Glycolytic block, in contrast to anoxia alone, appears to preferentially mobilize internal Ca2+ stores; as control of internal Ca2+ pools is lost, excessive release from this compartment may itself contribute to axonal damage. Reoxygenation paradoxically accelerates injury in many axons, possibly as a result of severe mitochondrial Ca2+ overload leading to a secondary failure of respiration. Although glia are relatively resistant to anoxia, oligodendrocytes and the myelin sheath may be damaged by glutamate released by reverse Na(+)-glutamate transport. Use-dependent Na+ channel blockers, particularly charged compounds such as QX-314, are highly neuroprotective in vitro, but only agents that exist partially in a neutral form, such as mexiletine and tocainide, are effective after systemic administration, because charged species cannot penetrate the blood-brain barrier easily. These concepts may also apply to other white matter disorders, such as spinal cord injury or diffuse axonal injury in brain trauma. Moreover, whereas many events are unique to white matter injury, a number of steps are common to both gray and white matter anoxia and ischemia. Optimal protection of the CNS as a whole will therefore require combination therapy aimed at unique steps in gray and white matter regions, or intervention at common points in the injury cascades.
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PMID:Anoxic and ischemic injury of myelinated axons in CNS white matter: from mechanistic concepts to therapeutics. 942 2

Heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) is an immune-mediated response to the administration of heparin that results in life-threatening thrombosis. The pathophysiology of HITTS remains controversial. The onset of clinical symptoms and laboratory changes is usually delayed 1-2 weeks after exposure to heparin. Thrombosis occurs in both the arterial and venous circulation with significant morbidity and mortality. Complications include deep venous thrombosis, pulmonary embolus, stroke, myocardial infarction, chronic venous insufficiency, extremity ischemia, gangrene, and death. Diagnostic criteria for HITTS include thrombocytopenia during heparin exposure, exclusion of other causes such as sepsis or medications, resolution of thrombocytopenia after withdrawal of heparin, demonstration of in vitro heparin-dependent platelet antibodies, and development of vascular thrombosis. Despite having several disadvantages, the carbon-14-serotonin release assay is the most sensitive and specific test for HITTS. Angiography as an adjunct to other imaging modalities can document the presence, location, and extent of thrombus. Optimal treatment has not yet been defined but should include immediate discontinuation of use of all heparin products and heparin-coated catheters. In addition, alternate methods of antithrombotic therapy should be considered. In severe cases, thrombolysis or thrombectomy may be warranted. Familiarity with the pathophysiology, clinical manifestations, complications, diagnostic criteria, and treatment options associated with HITTS will enable timely recognition and facilitate prompt and effective treatment.
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PMID:Heparin-induced thrombocytopenia and thrombosis syndrome. 946 Jan 12

Nitrates are commonly used for rapid relief of ischemia in the initial management of unstable angina. However, their optimal dosage, route of administration, and therapeutic goals have not been fully established. This study was conducted to determine the optimal dosage and mode of administration (intravenous bolus versus sublingual spray) of nitrates and the therapeutic goals of their use in the immediate management of unstable angina. In a single-center prospective trial, 72 consecutive patients with unstable angina accompanied by typical ST-segment depression on electrocardiogram were randomly assigned to receive isosorbide dinitrate either as repeated intravenous boluses or as sublingual sprays while being delivered to the hospital by a mobile intensive care unit. Optimal nitrate dosage was tailored to pain relief while monitoring mean blood pressure reduction to an optimal range (5% to 20%) without dosage restriction. The mean nitrate dosage needed for ischemia control during the first hour of treatment was 7.8 +/- 3.8 mg. Optimal blood pressure reduction was achieved by significantly more intravenously treated patients than sublingually treated patients (68% v 41%, P = .037). Intravenously treated patients also experienced a more pronounced therapeutic effect, as assessed by reduction in chest pain score (67% v 39%, P = .0004) and decrease in ST-segment depressions (57% v 27%, P = .004). These results show that higher doses of nitrates than previously recommended are required for ischemia control during the initial management of unstable angina. The use of repeated intravenous boluses is safe and more easily controlled and, therefore, more efficacious than sublingual sprays in inducing the maximal anti-ischemic effect while avoiding significant hypotension.
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PMID:High-dose nitrates in the immediate management of unstable angina: optimal dosage, route of administration, and therapeutic goals. 959 18

Hypothermia is commonly used to prevent ischemic renal damage during complex nephron-sparing surgical procedures requiring temporary renal artery occlusion. We developed a novel Cooling Sheath device, which is compatible with laparoscopy, to protect the kidney hypothermically during 60 minutes of temporary arterial occlusion in a laparoscopic swine model. Comparison of temperature curves and histology to control groups undergoing open slush surface cooling and laparoscopic warm ischemia for similar time periods was performed. Optimal hypothermic temperatures were reached rapidly and maintained with the use of the Cooling Sheath. Ischemic damage, present in all kidneys subjected to warm ischemia, was not found on histopathologic examination of the cooled kidneys. This new device provides hypothermic protection of the kidney during ischemia. The use of the Cooling Sheath combined with temporary arterial occlusion will allow more complex nephron-sparing renal surgery to be performed using laparoscopy.
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PMID:The laparoscopic cooling sheath: novel device for hypothermic preservation of kidney during temporary renal artery occlusion. 960 43

Optimal management of dyspnea in terminal cancer patients requires an understanding of the responsible pathophysiological mechanisms. This prospective study assessed visual analogue scales (VAS) of shortness of breath (SOB) and anxiety, bedside spirometry, maximum inspiratory pressure (MIP), chest radiography, arterial blood gases, hemoglobin, and electrocardiogram, if indicated, in 100 terminally ill cancer patients. Forty-nine percent of the patients had lung cancer. The median VAS scores for SOB and anxiety were 53 mm and 29 mm, respectively. Spirometry was abnormal in 93% of patients, with 5% having obstructive, 41% restrictive, and 47% mixed patterns. The median MIP was 16 cm H2O. Sixty-five percent of the patients had parenchymal or pleural involvement on chest radiograph. Twenty-nine percent had evidence of cardiac ischemia, recent or current myocardial infarction or atrial fibrillation. Patients had a median of five different abnormalities that could have contributed to their shortness of breath. Only anxiety (p = 0.001), a history of smoking (p = 0.02), and pCO2 levels were statistically significantly correlated with SOB VAS scores. The potentially correctable causes of dyspnea included hypoxia (40%), anemia (20%), and bronchospasm (52%). The finding of very low MIPs suggests severe respiratory muscle weakness may contribute significantly to dyspnea in this patient population. Further studies are needed to confirm this finding and characterize the underlying pathophysiology.
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PMID:Dyspnea in the advanced cancer patient. 1058 52

Nearly 25% of patients with sickle cell disease (SCD) experience central nervous system morbidity involving both large and small vessel disease. Optimal imaging methods for determining the extent of ischemia are not known. Positron emission tomography (PET) has the unique ability to show tissue function as well as structure. Reports concerning patients with non-SCD neurodegenerative disorders suggest PET may be useful in determining prognosis. We compared magnetic resonance imaging, magnetic resonance angiography, and neuropsychological testing with PET prospectively. Six patients with SCD and a history of stroke, aged 10 to 28, were enrolled. PET studies were performed on an ECAT HR 47 scanner (Siemens/CTI, Knoxville, TN) using 18-F-fluorodeoxyglucose as a tracer. PET interpretations were conducted in blinded fashion. MRI studies found two patients with only small vessel disease and four with both large and small vessel disease. In two of four subjects with large vessel disease, PET showed a corresponding metabolic abnormality and also identified an area of hypometabolism extending beyond the anatomical lesion as shown by MRI. PET did not demonstrate an abnormality corresponding with small vessel disease. Detailed neuropsychological testing demonstrated cognitive dysfunction in all cases. For some patients, PET may add sensitivity in detecting impaired metabolism in the area surrounding a major vessel infarct. However, the technique does not appear to be generally useful in characterizing small watershed or deep white matter infarcts. Larger studies, to include control subjects and carefully selected untransfused SCD patients, are needed. A combination of conventional imaging and neuropsychological testing remains the preferred evaluation for most SCD patients with neurologic symptoms.
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PMID:Role of positron emission tomography in determining the extent of CNS ischemia in patients with sickle cell disease. 1020 99

Optimal treatment of the patient who has sustained an acute ischemic stroke requires rapid assessment and early intervention. The leisurely approach to acute stroke management sometimes taken in the past should be replaced by an approach that treats stroke as a true medical emergency. Thrombolysis with tissue plasminogen activator has been labeled for the treatment of acute ischemic stroke, but it must be given within three hours of stroke onset. However, fibrinolytic therapy can be given safely to only a fraction of patients with acute stroke, and more broadly applicable therapies are needed. Recent evidence does not support the routine use of heparin in patients with acute stroke, and early use of aspirin offers only modest benefit. Neuroprotective therapies designed to interfere with cytotoxic events initiated by ischemia are undergoing clinical trials that should be completed within the next year. At present, only tissue plasminogen activator has been labeled for acute stroke treatment; however, other agents are on the horizon, and much can be done supportively to improve neurologic outcome. Because of the unique susceptibility of neurons to ischemia, minutes count. Thus, hospitals providing care for patients with acute stroke should organize clinical protocols and pathways for effective implementation of therapies.
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PMID:Stroke: part II. Management of acute ischemic stroke. 1034 75

The purpose of this study was to determine the added value of automated QT dispersion and ST-segment measurements to physician interpretation of 12-lead electrocardiograms (ECGs) in patients with chest pain. To date, poor reproducibility of manual measurements and lack of shown added value have limited the clinical use of QT dispersion. Twelve-lead ECGs (n = 1,161) from the Milwaukee Prehospital Chest Pain Database were independently classified by 2 physicians into 3 groups (acute myocardial infarction (AMI), acute cardiac ischemia (ACI), or nonischemic), and their consensus was obtained. QT-end and QT-peak dispersions were measured by a computerized system. The computer also identified ST-segment deviations. Sensitivity, specificity, and positive predictive values (PPVs) and negative predictive values (NPV) for AMI and ACI were evaluated independently and in combinations. For AMI, physicians' consensus classification was remarkably good (sensitivity, 48%, specificity, 99%). Independent classification by QT-end and QT-peak dispersions or ST deviations was not superior to the physicians' consensus. Optimal classification occurred by combining automated QT-end dispersion and ST deviations with physicians' consensus. This combination increased sensitivity for the diagnoses of AMI by 35% (65% vs 48%, P < .001) and ACI by 55% (62% vs 40%, P < .001) compared with physicians' consensus, while maintaining comparable specificity. This study supports a potential clinical role for automated QT dispersion when combined with other diagnostic methods for detecting AMI and ACI.
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PMID:The added diagnostic value of automated QT-dispersion measurements and automated ST-segment deviations in the electrocardiographic diagnosis of acute cardiac ischemia. 1109 58

It may be concluded that treatment of patients with Volkmann's ischemic contracture is complicated and depends on a number of different variables. Optimal treatment of an established contracture requires a through examination of the extent of damage of the ischemia, followed by conservative therapy or operation. The most important measures concerning Volkmann's ischemic contracture, however, involve measures to prevent the contracture. It is poignant that very simple measures, such as monitoring high-risk injuries and immediate vascular repair or decompression if symptoms of a compartment syndrome are present, can prevent this disabling condition. The following summaries hopefully provide guidelines for prevention and treatment of Volkmann's ischemic contracture.
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PMID:Volkmann's ischemic contracture. Prevention and treatment. 1111 54

Avoidance of the clinical syndrome of acute right-sided heart failure after heart transplantation is, unfortunately, not possible. Clinical experience and the literature certainly suggest that a significant factor in the successful management of right ventricular (RV) failure is recipient selection. Moreover, threshold hemodynamic values beyond which RV failure is certain to occur and heart transplantation is contraindicated do not exist. Nor are there values below which RV failure is always avoidable. Acute RV failure will remain a difficult and ever-present clinical syndrome in the transplant recipient. Goals in the treatment of this clinical problem include: 1. Preserving coronary perfusion through maintenance of systemic blood pressure. 2. Optimizing RV preload. 3. Reducing RV afterload by decreasing pulmonary vascular resistance (PVR). 4. Limiting pulmonary vasoconstriction through ventilation with high inspired oxygen concentrations (100% FiO(2)), increased tidal volume and optimal positive end expiratory pressure ventilation. Inhaled nitric oxide is recommended before leaving the operating room in cases where the initial therapies have had little impact. Intra-aortic balloon counterpulsation is employed in patients with impaired left ventricular (LV) function and may be of benefit in patients with RV dysfunction resulting from ischemia, preservation injury or reperfusion injury. Optimal LV function reduces RV afterload and PVR. A proactive decision regarding RV assist device implantation is made before leaving the operating room and is highly dependent upon overall hemodynamics, size and function of the ventricles as seen on transesophageal echocardiography, renal function and surgical bleeding. Only through careful preoperative planning can this life-threatening condition be managed in the postoperative period.
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PMID:The evolving management of acute right-sided heart failure in cardiac transplant recipients. 1158 60


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