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)

Cell transplantation has been proposed as a future therapy for various myocardial diseases. It is unknown, however, whether the encouraging results obtained in animal models of ischemia and reperfusion, cryoinjury or cardiomyopathy can be reproduced in the setting of permanent coronary artery occlusion and extensive myocardial infarction (MI). Embryonic cardiac cells were isolated and cultured for 3 days to confirm viability, morphology and to label cells with BrdU or the reporter gene LacZ. Seven days after extensive MI, rats were randomized to cell (1.5x10(6)) transplantation (n=11) or culture medium injection (n=16) into the myocardial scar. Echocardiography study was performed before and 53+/-3 days after implantation to assess left ventricular (LV) remodeling and function. During follow-up, there was no mortality among cell-treated rats v 4 of 16 control rats (P=0.12). X-gal staining, BrdU and alpha -SMA immunohistochemistry identified the engrafted cells 1 week, 4 weeks and 8 weeks after transplantation, respectively. Antibodies against alpha -SMA, connexin-43, fast and slow myosin heavy chain revealed grafts in various stages of differentiation in 10 of 11 cell-treated hearts. Many of them, however, kept their embryonic phenotype and were isolated from the host myocardium by scar tissue. Serial echocardiography studies revealed that cell transplantation prevented scar thinning, LV dilatation and dysfunction while control animals developed scar thinning, significant LV dilatation accompanied by progressive deterioration in LV contractility. Transplantation of embryonic cardiomyocytes after extensive MI in a rat model attenuate LV dilatation, infarct thinning, and myocardial dysfunction. Still, many grafts remain isolated and do not differentiate into an adult phenotype, even when studied 2 months after grafting.
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PMID:Influence of embryonic cardiomyocyte transplantation on the progression of heart failure in a rat model of extensive myocardial infarction. 1143 38

Dobutamine increases oxygen demand in the myocardium and is used in conjunction with echocardiography to detect coronary artery disease. Beta blockers (BB) are partial antagonists of dobutamine and, therefore, offset dobutamine effects. Still, the impact of BB therapy on dobutamine stress echocardiography is not clear. One hundred forty-one dobutamine-atropine echocardiographic studies have retrospectively been analyzed: 27 patients were on BB (19%; group I); and 114 off BB (81%; group II). Coronary angiography was performed in a similar percentage of patients (97% and 85%, respectively; P = NS). No differences in clinical and angiographic profile were found between the groups. Sensitivity (83% vs 71%; P = NS) and specificity (100% vs 95%; P = NS) for coronary artery disease were similar in both groups. Atropine was infused more frequently to patients from group I (67% vs 46%; P = 0.04). Limiting side effects and prolonged ischemia presented with the same frequency in both groups. When the dobutamine test was positive, severe extent of ischemia appeared more often in patients from group I than in patients from group II (66% vs 33%; P = 0.03). The majority of patients from group I (55%) with severe extent of ischemia and only 12% from group II received atropine (P = 0.02). No differences were found in dobutamine time and extent of ischemia in patients from group I who had a positive response to dobutamine. On the contrary, patients from group II with one vessel disease had a dobutamine time longer (10.5 +/- 3.8 vs 7.8 +/- 3.7 min; P < 0.05) and extent of ischemia smaller (1.8 +/- 0.4 vs 2.6 +/- 0.5 segments; P < 0.05) than patients from group II with multivessel disease. We conclude that: 1) sensitivity of dobutamine-atropine echocardiography for diagnosis of coronary artery disease remains even if patients are on BB; 2) patients with significant coronary artery disease who are taking BB often develop severe myocardial ischemia during dobutamine-atropine stress echocardiography; and 3) BB therapy precludes stratification of a positive echocardiographic response. These conclusions should be confirmed in a prospective study to be considered as definitive. (ECHOCARDIOGRAPHY, Volume 13, July 1996)
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PMID:Impact of Beta Blockers on Dobutamine-Atropine Stress Echocardiography. 1144 43

The surgical approach to ischemic mitral regurgitation (IMR) remains a topic of considerable controversy. Will coronary artery bypass alone suffice, or should the valve be intervened upon? The poor late survival of patients with IMR is well recognized, but it remains unknown if this can be altered by addressing the valve directly. And if surgery is undertaken, should the valve be repaired or replaced? The underlying mechanisms of IMR remain incompletely understood, and although current theory focuses on the role of alterations in ventricular geometry in its pathogenesis, IMR is most often addressed by annuloplasty alone. Is this sufficient, or does the ventricle itself require "remodeling?" The debate is confounded by imprecise terminology that fails to distinguish between acute and chronic disease, and active ischemia from completed infarction. Available clinical information is from retrospective studies with all of their inherent limitations and potential for bias. Still, progress is being made as increasing attention is focused on this clinically important entity.
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PMID:Trends in the surgical management of ischemic mitral regurgitation. 1258 54

Resuscitation from circulatory and respiratory failure represent mainstays of emergency and critical care management. Importantly, no amount of resuscitative effort will be successful in promoting patient survival if the primary reason for the shock state is not identified and treated, independent of resuscitation. Having said that, aggressive resuscitation to normal functional levels of blood flow and organ perfusion pressure during the first 6 hours following the development of shock improves outcome both in patients with trauma or sepsis. However, clinical studies have demonstrated that restoration of total blood flow to supranormal levels in subjects with established shock that has been present for over 6 hours does not improve survival. Still, some defined clinical targets are essential in these patients as well to prevent further organ injury due to ischemia and its associated inflammatory response. Thus, the rapid restoration of normal hemodynamics by conventional means, including fluid resuscitation and surgical repair, results in a better log term outcome than inadequate or delayed resuscitative efforts. Clear initial targets for resuscitation are a mean arterial pressure > 60 mm Hg, and a cardiac output and O(2) transport to the body adequate enough to prevent tissue hypoperfusion. The level of cardiac output needed to achieve this goal is probably different among subjects and within subjects over time. Indirect signposts of adequate perfusion, such as venous O2 saturation, mentation, urine output and local measures of tissue blood flow are useful in monitoring this response.
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PMID:Targets for resuscitation from shock. 1276 14

Axillary artery injury from blunt trauma to the shoulder is uncommon. Fracture of the neck of the humerus is a rare cause of injury to the axillary artery. Four cases of axillary artery thrombosis from humeral neck fracture are reported. Each of the first 2 patients presented with a pulseless and acutely ischemic limb after a trivial fall. A repair of the axillary artery with saphenous vein interposition graft was performed in the first patient. The extremity was salvaged, but a residual radial and ulnar neurologic deficit persisted. The second patient presented with a pulseless insensate upper extremity accompanied by motor loss. He underwent primary axillary artery repair. Still early in his postoperative course, he has had global brachial plexopathy and is undergoing intensive physical therapy. The third patient had a delayed presentation of brachial plexopathy and sympathetic reflex dystrophy. Arterial reconstruction was not required owing to excellent collateralization. The fourth patient presented with a cool pulseless extremity. His recovery is nearly complete after bypass of the axillary artery with a reversed saphenous vein graft. In addition, a review of the literature revealed 24 cases of axillary artery injury associated with humeral neck fracture. The mean age was 66.6 years. The most common mechanism of injury was a fall (79%). Thirteen patients (46%) presented with a neurologic deficit. Acute ischemia was present in 68%. Physical examination predicted the arterial injury in all but 1 patient. The injured axillary artery was repaired in 26 cases. Revascularization by an interposition graft was the most common procedure. All grafts and reanastomoses were patent and led to limb salvage. Of 9 primary repairs, 3 amputations were performed. Although limb salvage rate was 89%, a good functional outcome was obtained in only half of the patients. A high index of suspicion is required for early diagnosis of axillary artery injury. Despite excellent results of vascular reconstruction, the outcome remains determined by the excessive neurologic morbidity. Recognition of the associated brachial plexus injury is essential to improve the functional outcome of this unusual arterial injury.
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PMID:Axillary artery injury from humeral neck fracture: a rare but disabling traumatic event. 1506 49

Moderate hypothermia (MH) is neuroprotective in animal models of focal ischemia when it is induced during, or within few hours after, onset of ischemia. In patients with acute stroke, several observational studies suggested normothermia or mild hypothermia as independent prognostic factors for favorable outcome. Currently, mild hypothermia was only examined in one clinical study that showed its feasibility and safety, but was not powered to examine efficacy. Limited clinical data on MH in humans suggest that this treatment probably reduces mortality in patients with malignant middle cerebral artery infarction. Still, MH in humans is associated with several side effects, intensive medical treatment, and a prolonged stay in the neurologic intensive care unit. Use of MH should be limited to specialized units, applying this treatment within research protocols or observational studies.
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PMID:Hypothermia in Acute Stroke. 1567 15

Hypoxic-ischemic (H-I) injury produces extensive damage to the hippocampus of young rats. We have recently shown that administration of 125 mg kg-1 clomethiazole (CMZ), a GABA(A)-agonist, provides complete histological protection against H-I injury if administered 3 h post-H-I (Brain Res 1035 (2005) 194). However, whether that histological protection translates into lasting functional preservation is unclear. To determine whether hippocampal-based circuits remain functionally intact in CMZ-protected H-I rats, we administered 125 mg kg-1 (high dose [CMZ-HD]) or 65 mg kg-1 (low dose [CMZ-LD]) CMZ, 3 h post-H-I, and examined numerous kindling parameters in the dorsal hippocampus 60 days following H-I. Kindling parameters included afterdischarge (AD) thresholds (ADTs), AD durations and kindling rates. Additional groups assessed included vehicle-injected H-I (VIH), hypoxic, ligated and naive rats. VIH, CMZ-HD, CMZ-LD and hypoxic rats all exhibited significantly faster kindling rates than naive rats. Thus, a previous traumatic event, even hypoxia alone, facilitated subsequent seizure propagation. Still, a significantly slower kindling rate was evident in CMZ-HD rats than in hypoxic, VIH or CMZ-LD rats. Moreover, while longer pre-kindling AD durations were observed in the damaged hippocampus of VIH compared with naive rats, this was not true for either CMZ-treated groups, hypoxic or ligated rats. Collectively, these findings suggest CMZ can suppress the epileptogenic effects of H-I. Surprisingly, however, both groups of CMZ-treated rats exhibited a four to nine times greater ADT than any other group and this effect was most profound in the CMZ-protected hippocampus. Thus, CMZ administration protected local neurons against terminal insult and left network excitability relatively normal with respect to seizure offset mechanisms but also caused profound elevation of local ADTs, which suggests a local hypoexcitability/increased inhibition. Finally, this study demonstrates, for the first time, that the kindling model can serve as a sensitive measure of function-related neuroprotective efficacy in animal models of ischemia.
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PMID:Neuro-overprotection? A functional evaluation of clomethiazole-induced neuroprotection following hypoxic-ischemic injury. 1574 33

Glutamate is the principal excitatory neurotransmitter in the mammalian central nervous system. The cellular regulation of glutamate receptor (GluR) ion channel function and expression is important for maintaining or adjusting target cell excitability to meet ever-changing demands, for example, in relation to developmental or use-dependent synaptic plasticity. Dysregulation of GluR function or expression may be a contributing factor in certain forms of epilepsy, stroke/ischemia, head trauma, cognitive impairments, and neurodegenerative disease. Recent years have seen substantial progress in understanding how GluRs operate in terms of their structural and functional properties, their synaptic targeting and membrane anchoring by PDZ-domain proteins, and their activity-dependent cycling at the plasma membrane. Yet precious little is known about the earliest events in GluR biogenesis or the mechanisms in place to ensure the GluRs that reach the cell surface are processed, folded, and oligomerized in an appropriate manner. Indeed, only a minor fraction of the GluR content of cells is expressed at any given time on the cell surface, whereas most of the remaining receptors exist in the endoplasmic reticulum (ER). The functional competence and significance of the ER fraction of receptors are presently unknown, but they are generally thought to represent immature, unassembled, or improperly assembled subunits. Some are ultimately destined for insertion in the plasma membrane. Others may be targeted for proteosomal degradation. Still others might provide a latent pool of fully functional receptors that can be recruited to enhance cell excitability in response to specific signals or under pathological conditions. This review will explore the structural and functional elements that regulate GluR assembly and export from the ER.
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PMID:Glutamate receptors and endoplasmic reticulum quality control: looking beneath the surface. 1668 68

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

Myocardial ischemia leads to an efflux of potassium ions from affected cells. The resulting depolarization of the resting membrane is one of the main features of ischemic myocardium. It has been shown experimentally that a part of the surplus interstitial potassium is transported out of the ischemic zone, even if no coronary blood flow is present in the affected area. We propose to model this transport mechanism mathematically with a diffusion equation. This model explains the measured spatial profiles of extracellular potential and potassium concentration. In addition, it allows a quantitative prediction of the transmembrane current that flows as a result of ischemia-induced depolarization. This current is thought to play a role in arrhythmogenicity, which is an important cause of mortality in acute myocardial infarction. Our model predicts that this current reaches its maximum exactly on the border of the hypoxic area. An important depolarizing current would be present just within the border, where hypoxia is accompanied by a resting membrane potential that is only slightly elevated, due to coupling with the adjacent normal tissue. Still, in the presence of potassium transport the predicted current density is not large enough to explain ectopic activation on the lateral border of the ischemia. This suggests that activation is more likely to occur at the endocardium, where the potassium gradient is steeper.
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PMID:Modeling transport of interstitial potassium in regional myocardial ischemia: effect on the injury current. 1800 69


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