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

Optimal treatment for ST-segment elevation myocardial infarction depends on early diagnosis and rapid selection of the appropriate reperfusion strategy. Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy at PCI-capable hospitals. For hospitals without PCI capability, there are 2 reperfusion strategies, primary PCI and thrombolytic therapy, which are both supported by clinical evidence and national guidelines. Transferring patients for primary PCI may cause delays and requires established, proven protocols, systems, and networks to achieve minimal door-to-balloon times. The authors review the available data and present a systematic, evidence-based approach in a simple framework to enable noncardiovascular and cardiovascular physicians to select the optimal reperfusion strategy. The framework is based on available data from clinical trials and local circumstances from clinical practice by incorporating duration of symptoms (fixed ischemia time) and anticipated transport delays to a PCI-capable facility (incurred ischemia time).
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PMID:Narrative review: reperfusion strategies for ST-segment elevation myocardial infarction. 1704 42

Optimal timing of therapeutic hypothermia for cardiac ischemia is unknown. Our prior work suggests that ischemia with rapid reperfusion (I/R) in cardiomyocytes can be more damaging than prolonged ischemia alone. Also, these cardiomyocytes demonstrate protein kinase C (PKC) activation and nitric oxide (NO) signaling that confer protection against I/R injury. Thus we hypothesized that hypothermia will protect most using extended ischemia and early reperfusion cooling and is mediated via PKC and NO synthase (NOS). Chick cardiomyocytes were exposed to an established model of 1-h ischemia/3-h reperfusion, and the same field of initially contracting cells was monitored for viability and NO generation. Normothermic I/R resulted in 49.7 +/- 3.4% cell death. Hypothermia induction to 25 degrees C was most protective (14.3 +/- 0.6% death, P < 0.001 vs. I/R control) when instituted during extended ischemia and early reperfusion, compared with induction after reperfusion (22.4 +/- 2.9% death). Protection was completely lost if onset of cooling was delayed by 15 min of reperfusion (45.0 +/- 8.2% death). Extended ischemia/early reperfusion cooling was associated with increased and sustained NO generation at reperfusion and decreased caspase-3 activation. The NOS inhibitor N(omega)-nitro-L-arginine methyl ester (200 microM) reversed these changes and abrogated hypothermia protection. In addition, the PKCepsilon inhibitor myr-PKCepsilon v1-2 (5 microM) also reversed NO production and hypothermia protection. In conclusion, therapeutic hypothermia initiated during extended ischemia/early reperfusion optimally protects cardiomyocytes from I/R injury. Such protection appears to be mediated by increased NO generation via activation of protein kinase Cepsilon; nitric oxide synthase.
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PMID:Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling. 1717 66

In complex coronary artery disease, it is sometimes difficult to determine which lesions are associated with reversible ischemia and should be stented. Fractional flow reserve (FFR) is an established objective methodology to indicate which lesions produce ischemia. Despite this, the selection of lesions to be stented is often based on the subjectively interpreted angiogram alone. The aim of this study in patients admitted for elective percutaneous intervention (PCI) was to evaluate the change in strategy if the decision to intervene was based on FFR measurement rather than on angiographic assessment. Two hundred fifty consecutive patients (471 arteries) scheduled for PCI were included in this study. All stenoses >or=50% by visual estimation and initially selected to be stented by 3 independent reviewers were assessed by FFR measurements. If FFR was <0.75, stenting was performed; if FFR was >or=0.75, no interventional treatment was given. Optimal pressure measurements were obtained in 452 lesions (96%). Diameter stenosis was 62 +/- 12%, and FFR was 0.67 +/- 0.17 for the entire group. In 68% of the stenoses, initial strategy as assessed from the angiogram was followed, and in 32%, there was a change in the planned approach based on FFR. In 48% of the patients, there was >or=1 lesion in which the treatment decision was changed after physiologic measurements. In conclusion, in this prospective, nonselective, but complete study representing the real world of PCI, 32% of the coronary stenoses and 48% of patients would have received a different treatment if the decision had been based on angiography only, stressing the utility of physiologic assessment in refining decision making during PCI.
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PMID:Influence of routine assessment of fractional flow reserve on decision making during coronary interventions. 1729 94

This century brings a pandemic of diabetes mellitus, with marked increases in early-accelerated atherosclerosis. When asymptomatic patients with diabetes present for evaluation, they have more extensive coronary atherosclerosis, lower ejection fractions, higher rates of previous cardiac events, and more silent ischemia than the normal population. The challenge faced by clinicians is to accurately identify asymptomatic patients with diabetes who have significant coronary ischemia that would benefit from revascularization. Diabetic endovascular disease has all the high-risk features to promote atherosclerosis and coronary occlusion: hyperglycemia-induced endothelial dysfunction, impaired fibrinolysis, increased platelet aggregation, plaque instability, dysfunctional arterial remodeling, and fibrotic and calcified coronary arteries. The optimal revascularization strategy for patients with diabetes is an ongoing debate. The advent of drug-eluting stents has changed the landscape, and some have suggested that the current role of coronary artery bypass grafting may be reduced by as much as 46%. Unfortunately, there is limited evidence from randomized, controlled trials that reflects current practice and could guide clinicians in making the best choices for patients with diabetes and coronary disease. It is hoped that ongoing trials--including Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D), Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM), and Coronary Artery Revascularisation in Diabetes (CARDia)--will answer many of the remaining questions. Still, the best treatment includes lifestyle modification and early prevention strategies with global risk reduction.
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PMID:Diabetic endovascular disease: role of coronary artery revascularization. 1730 63

Ultrasound provides a diagnostic modality that allows a whole-body approach at the bedside of a critically ill patient in the search for infectious foci. Both common sites of infection, such as the lung and pleura, central veins, and maxillary sinuses, and also less common sites, such as gastrointestinal perforation, sepsis due to mesenteric ischemia, or even meningitis, provide characteristic ultrasound patterns. Optimal use of ultrasound also combines bedside diagnosis with subsequent interventional procedures that can decrease the need for transfer to other imaging and interventional suites. Experience has shown that fevers of unknown origin in the critical care unit often have ultrasound equivalents. Thus, if a comprehensive ultrasound examination is negative, it is now appropriate to speak of fever of unknown sonographic origin.
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PMID:Point-of-care ultrasound: Infection control in the intensive care unit. 1744 86

Erythropoietin is known to stimulate red cell production and has recently been shown to protect the heart against injury from ischemia/reperfusion. However, it is unknown whether darbepoetin alfa (Dpa), a long-acting analog of erythropoietin, can play a protective role against myocardial infarction. We assessed the potential protective role of Dpa in an in vivo rat model of myocardial ischemia/reperfusion and the underlying mechanisms. We found that a single intravenous Dpa treatment immediately before 30 minutes of regional ischemia reduced myocardial necrosis following 120 minutes of reperfusion in a dose-dependent manner. Optimal protection with Dpa against myocardial infarction was manifest at a dose of 2.5 microg/kg. Dpa conferred cardioprotection when administered after the onset of ischemia and at the start of reperfusion. Dpa (2.5 microg/kg) also reduced infarct size and Troponin I leakage 24 hours after reperfusion. Inhibition of p42/44 MAPK (PD98059), p38 MAPK (SB203580), mitochondrial ATP-dependent potassium (KATP) channels (5-HD), sarcolemmal KATP channels (HMR 1098), but not phosphatidylinositol-3 (PI3) kinase/Akt (Wortmannin and LY 294002) abolished Dpa-induced cardioprotection. Dpa confers immediate and sustained cardioprotection in rats, suggesting a potential therapeutic role of this long-acting erythropoietin analog for the treatment of acute myocardial infarction.
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PMID:Darbepoetin alfa protects the rat heart against infarction: dose-response, phase of action, and mechanisms. 1757 97

Ischemic tissues require mechanisms to alert the immune system of impending cell damage. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from ischemic cells. We elucidate the mechanism by which HMGB1, one of the key alarm molecules released during liver ischemia/reperfusion (I/R), is mobilized in response to hypoxia. HMGB1 release from cultured hepatocytes was found to be an active process regulated by reactive oxygen species (ROS). Optimal production of ROS and subsequent HMGB1 release by hypoxic hepatocytes required intact Toll-like receptor (TLR) 4 signaling. To elucidate the downstream signaling pathways involved in hypoxia-induced HMGB1 release from hepatocytes, we examined the role of calcium signaling in this process. HMGB1 release induced by oxidative stress was markedly reduced by inhibition of calcium/calmodulin-dependent kinases (CaMKs), a family of proteins involved in a wide range of calcium-linked signaling events. In addition, CaMK inhibition substantially decreased liver damage after I/R and resulted in accumulation of HMGB1 in the cytoplasm of hepatocytes. Collectively, these results demonstrate that hypoxia-induced HMGB1 release by hepatocytes is an active, regulated process that occurs through a mechanism promoted by TLR4-dependent ROS production and downstream CaMK-mediated signaling.
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PMID:HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. 1798 3

Hypoxic-ischemic (HI) brain injury is the most common cause of encephalopathy and seizures in term newborn infants. There is no single, valid test for birth asphyxia leading to HI brain injury, and thus this disorder is often poorly characterized, and the timing and etiology of the injury can be difficult to ascertain. Optimal management of HI brain injury involves prompt resuscitation, careful supportive care including prevention of hyperthermia and hypoglycemia, and treatment of clinical and frequent or prolonged subclinical seizures. Recent evidence suggests that therapeutic hypothermia by selective head or whole-body cooling administered within 6 hours of birth reduces the incidence of death or moderate/severe disability at 12 to 22 months. Hypothermia is a promising new therapy that physicians should consider within the context of a registry or study. Optimal seizure treatment remains controversial because the most widely used drug, phenobarbital, has limited efficacy, and the value of monitoring and treating subclinical seizures is uncertain. There is compelling need for well-designed clinical trials to address treatment of ongoing brain injury in the setting of hypoxia-ischemia and seizures. Emerging evidence from preclinical studies suggests that future therapy for HI brain injury and neonatal encephalopathy will combine novel neuroprotective and anti-seizure agents. Pilot clinical trials of newer anticonvulsants are ongoing and will provide critical information for care of neonatal seizures.
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PMID:Treatment of hypoxic-ischemic encephalopathy in newborns. 1817 41

The best management strategy for symptomatic vertebrobasilar ischemia is currently not well-defined. Noninvasive Optimal Vessel Analysis (NOVA, VasSol, Inc.) is computer software that, using quantitative magnetic resonance (MR) angiography technology, represents the only commercially available means of noninvasively measuring blood flow within the human vasculature. The author used quantitative MR angiography to study cerebral blood flow in 2 patients who underwent angioplasty and stenting for medically refractory extracranial cervical vertebral artery (VA) stenosis using the recently Food and Drug Administration-approved WingSpan stent (Boston Scientific, Target). WingSpan stents were successfully placed after balloon angioplasty in both patients without complications. At the 5-month clinical follow-up examination, 1 patient was symptom free and the other had had a possible transient ischemic attack without sequelae. The WingSpan stent may represent an alternative management scheme for symptomatic vertebrobasilar ischemia from extracranial VA stenosis. Quantitative MR angiography can readily measure blood flow in the vertebrobasilar system, and these values correlated with the angiographic outcomes in the 2 patients treated in the present study.
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PMID:Wingspan stenting of symptomatic extracranial vertebral artery stenosis and perioperative evaluation using quantitative magnetic resonance angiography: report of two cases. 1827 90

Optimal retinal neuronal cell function requires an appropriate, tightly regulated environment, provided by cellular barriers, which separate functional compartments, maintain their homeostasis, and control metabolic substrate transport. Correctly regulated hemodynamics and delivery of oxygen and metabolic substrates, as well as intact blood-retinal barriers are necessary requirements for the maintenance of retinal structure and function. Retinal blood flow is autoregulated by the interaction of myogenic and metabolic mechanisms through the release of vasoactive substances by the vascular endothelium and retinal tissue surrounding the arteriolar wall. Autoregulation is achieved by adaptation of the vascular tone of the resistance vessels (arterioles, capillaries) to changes in the perfusion pressure or metabolic needs of the tissue. This adaptation occurs through the interaction of multiple mechanisms affecting the arteriolar smooth muscle cells and capillary pericytes. Mechanical stretch and increases in arteriolar transmural pressure induce the endothelial cells to release contracting factors affecting the tone of arteriolar smooth muscle cells and pericytes. Close interaction between nitric oxide (NO), lactate, arachidonic acid metabolites, released by the neuronal and glial cells during neural activity and energy-generating reactions of the retina strive to optimize blood flow according to the metabolic needs of the tissue. NO, which plays a central role in neurovascular coupling, may exert its effect, by modulating glial cell function involved in such vasomotor responses. During the evolution of ischemic microangiopathies, impairment of structure and function of the retinal neural tissue and endothelium affect the interaction of these metabolic pathways, leading to a disturbed blood flow regulation. The resulting ischemia, tissue hypoxia and alterations in the blood barrier trigger the formation of macular edema and neovascularization. Hypoxia-related VEGF expression correlates with the formation of neovessels. The relief from hypoxia results in arteriolar constriction, decreases the hydrostatic pressure in the capillaries and venules, and relieves endothelial stretching. The reestablished oxygenation of the inner retina downregulates VEGF expression and thus inhibits neovascularization and macular edema. Correct control of the multiple pathways, such as retinal blood flow, tissue oxygenation and metabolic substrate support, aiming at restoring retinal cell metabolic interactions, may be effective in preventing damage occurring during the evolution of ischemic microangiopathies.
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PMID:Regulation of retinal blood flow in health and disease. 1844 80


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