UMLS:C0022116 - FACTA Search

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

A two-center elective coronary angioplasty experience with intra-aortic balloon pump support for patients with severe left ventricular dysfunction is reported. To prevent hemodynamic collapse, an intra-aortic balloon pump was inserted percutaneously before coronary angioplasty in 97 patients with a left ventricular ejection fraction less than 35% (26% of whom had ejection fractions less than 25%). The cohort was predominantly male (71%) with a mean age of 64 +/- 9 years. Angioplasty was successfully performed in 83 (85.6%) patients and 80 (82.5%) of these successful patients were discharged from the hospital. Seven patients had unsuccessful angioplasty without a major cardiac event. Seven patients (7.2%) suffered a major cardiac event; 4 had emergent coronary bypass surgery with q-wave infarction, 2 had uneventful emergency coronary bypass surgery, and one patient died in the operating room after a failed angioplasty. Using logistic regression analysis, the presence of multivessel disease and a history of prior myocardial infarction were associated with more complications during angioplasty (p less than 0.05). Intra-aortic balloon pump placement did not interfere with the angioplasty procedure. Two patients had limb ischemia which resolved when the intra-aortic balloon pump was removed. Of the 80 successful patients discharged, 72 were followed for a mean of 22 months. At the latest follow-up, 52 had not suffered a myocardial infarction and were alive. Of the 20 late deaths, 16 were cardiac and 4 non-cardiac.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intra-aortic balloon counterpulsation support for elective coronary angioplasty in the setting of poor left ventricular function: a two center experience. 1014 78

Mitochondrial membrane potential (delta psi(m)) was determined in intact isolated nerve terminals using the membrane potential-sensitive probe JC-1. Oxidative stress induced by H2O2 (0.1-1 mM) caused only a minor decrease in delta psi(m). When complex I of the respiratory chain was inhibited by rotenone (2 microM), delta psi(m) was unaltered, but on subsequent addition of H2O2, delta psi(m) started to decrease and collapsed during incubation with 0.5 mM H2O2 for 12 min. The ATP level and [ATP]/[ADP] ratio were greatly reduced in the simultaneous presence of rotenone and H2O2. H2O2 also induced a marked reduction in delta psi(m) when added after oligomycin (10 microM), an inhibitor of F0F1-ATPase. H2O2 (0.1 or 0.5 mM) inhibited alpha-ketoglutarate dehydrogenase and decreased the steady-state NAD(P)H level in nerve terminals. It is concluded that there are at least two factors that determine delta psi(m) in the presence of H2O2: (a) The NADH level reduced owing to inhibition of alpha-ketoglutarate dehydrogenase is insufficient to ensure an optimal rate of respiration, which is reflected in a fall of delta psi(m) when the F0F1-ATPase is not functional. (b) The greatly reduced ATP level in the presence of rotenone and H2O2 prevents maintenance of delta psi(m) by F0F1-ATPase. The results indicate that to maintain delta psi(m) in the nerve terminal during H2O2-induced oxidative stress, both complex I and F0F1-ATPase must be functional. Collapse of delta psi(m) could be a critical event in neuronal injury in ischemia or Parkinson's disease when H2O2 is generated in excess and complex I of the respiratory chain is simultaneously impaired.
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PMID:Depolarization of in situ mitochondria due to hydrogen peroxide-induced oxidative stress in nerve terminals: inhibition of alpha-ketoglutarate dehydrogenase. 1038 74

The effects of recombinant soluble P-selectin glycoprotein ligand-1 (rsPSGL.Ig) were studied after 120 min of splanchnic artery occlusion and 120 min of reperfusion (SAO/R). SAO/R rats administered a low-affinity mutant form of rsPSGL.Ig exhibited signs of severe circulatory collapse with marked hypotension, a survival time of only 37+/-16 min, and significant increases in intestinal myeloperoxidase (MPO) activity (P<0.01). In addition, SAO/R rats given rsPSGL.Ig low-affinity mutant showed severe endothelial dysfunction characterized by a blunted vasorelaxation to the endothelium-dependent vasodilator acetylcholine in comparison to sham-operated controls (30+/-9% vs. 97+/-3%). Administration of rsPSGL.Ig (0.5 mg/kg) significantly improved mean arterial blood pressure and increased survival time to 107+/-13 min (P <0.01). rsPSGL.Ig treatment also resulted in a significant attenuation in both intestinal MPO activity as well as the SAO/R-induced decline in endothelium-dependent vasorelaxation of superior mesenteric artery rings (P<0.01). In addition, rsPSGL.Ig attenuated in vitro neutrophil adherence to thrombin-stimulated superior mesenteric artery endothelium to a comparable degree as a P-selectin monoclonal antibody. These data suggest that rsPSGL.Ig provides beneficial effects by preserving endothelial function and attenuating neutrophil-endothelial cell interactions in the splanchnic circulation following ischemia-reperfusion.
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PMID:Acute mesenteric ischemia and reperfusion: protective effects of recombinant soluble P-selectin glycoprotein ligand-1. 1048 98

Ischemia is accompanied by mitochondrial dysfunction, as assessed by measurements of mitochondrial respiratory activities in vitro. Following brief periods of ischemia, mitochondrial function is usually normalized during reperfusion. However, particularly after ischemia of longer duration, reperfusion may be accompanied by secondary mitochondrial failure. After short periods of ischemia this is observed in selectively vulnerable areas and, after intermediate to long periods of ischemia, in other areas as well. However, it has remained unsettled if the mitochondrial dysfunction is the result or the cause of cell death. Although it has been commonly assumed that such failure is secondary to cell injury by other mechanisms, recent results suggest that mitochondrial dysfunction may be the cause of cell death. Indirect evidence for this postulate is provided by experiments showing that cyclosporin A (CsA), when allowed to cross the blood-brain barrier, is a potent neuroprotectant. CsA is a virtually specific blocker of the mitochondrial permeability transition (MPT) pore, a voltage-gated channel allowing molecules and ions with a mass < 1500 Daltons to pass the inner mitochondrial membrane. Experiments on isolated cells in vitro demonstrate that cell calcium accumulation or oxidative stress triggers the assembly of an MPT pore, which leads to collapse of the mitochondrial membrane potential, to ATP hydrolysis, to enhanced production of reactive oxygen species (ROS), and to cell death. The beneficial effect of CsA could thus be related to its ability to block the MPT pore. Longer periods of ischemia, such as occurs after transient middle cerebral artery (MCA) occlusion, lead to pan-necrotic lesions (infarction). In the rat, recirculation following 2 h of MCA occlusion leads to partial normalization of the bioenergetic state but this is followed within 4-6 h by secondary bioenergetic failure. The latter seems unrelated to blockade of the microcirculation, but correlates to secondary mitochondrial failure. The brain damage incurred is ameliorated by the spin trap alpha-phenyl-N-butyl nitrone (PBN) and by the immunosuppressant FK506 even when given 1-3 h after the start of recirculation. The two drugs also prevent the secondary mitochondrial failure during early recirculation, suggesting that such failure is pathogenetically important. Probably, though, the mitochondrial dysfunction involves not only the assembly of an MPT pore but also other mechanisms. Since recirculation is associated with release of mitochondrial proteins it is not unlikely that such proteins, e.g. cytochrome c, trigger cascades of events leading to cell death.6.
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PMID:Role and mechanisms of secondary mitochondrial failure. 1049 35

Cardiogenic shock is a state of inadequate tissue perfusion due to cardiac dysfunction, which is most commonly caused by acute myocardial infarction. The pathophysiology of cardiogenic shock is characterized by a downward spiral: ischemia causes myocardial dysfunction, which, in turn, augments the ischemic damage and the energetical imbalance. With conservative therapy, mortality rates for patients with cardiogenic shock are frustratingly high reaching more than 80%. Additional thrombolytic therapy has not been shown to significantly improve survival in such patients. Emergency cardiac catheterization and coronary angioplasty, however, seem to improve the outcome in shock-patients, which most probably is due to rapid and complete revascularization generally reached by angioplasty. In addition to interventional therapy with rapid coronary revascularization, the use of mechanical circulatory support may interrupt the vicious cycle in cardiogenic shock by stabilizing hemodynamics and the metabolic situation. Different cardiac assist devices are available for cardiologists and cardiac surgeons: 1. intraaortic balloon counterpulsation (IABP), 2. implantable turbine-pump (Hemopump), 3. percutaneous cardiopulmonary bypass support (CPS), 4. right heart, left heart, or biventricular assist devices placed by thoracotomy, and 5. intra- and extrathoracic total artificial hearts. Since percutaneous application is possible with IABP, Hemopump and CPS, these devices are currently used in interventional cardiology. The basic goals of the less invasive intraaortic balloon counterpulsation (IABP; Figure 1) are to stabilize circulatory collapse, to increase coronary perfusion and myocardial oxygen supply, and to decrease left ventricular workload and myocardial oxygen demand (Figure 2). Since the advent of percutaneous placement, IABP has been used by an increasing number of institutions (Figure 3). In addition to cardiogenic shock, the system may be of use in a variety of other indications in the catheterization laboratory and intensive care unit, including weaning from percutaneous cardiopulmonary bypass, in ischaemic left ventricular failure, in unstable angina, in high risk PTCA, and in prophylactic support in patients with myocardial infarction and successful revascularization. Animal experimental data showed that IABP may improve success of thrombolysis and recent clinical data suggest that survival is enhanced and transfer for revascularization is facilitated when patients with myocardial infarction and cardiogenic shock undergo thrombolysis and IABP rather than thrombolysis alone. A lot of studies had demonstrated before, that combined use of counterpulsation and revascularization therapy (i.e. coronary bypass surgery or angioplasty) may improve prognosis in patients with myocardial infarction complicated by cardiogenic shock (Table 1). In such patients, early treatment with IABP is most important: Multivariate analysis identified early IABP-support with a duration of shock to IABP-treatment of > or = 4 hours as an independent predictor of a positive short-term outcome. In shock-patients with postinfarction ventricular septal defect, IABP provides a marked hemodynamic improvement, and a significant decrease in shunt-flow (Figure 5). However, despite initial stabilization with IABP, such patients need immediate surgical repair of the septal defect to avoid hemodynamic deterioration. The rate of complications related to percutaneous IABP was significantly attenuated by employing catheters of reduced size. Using 9.5-F catheters, a long duration of counterpulsation emerged as the most significant factor associated with complications. In our hospital, those patients with 9.5-F catheters in whom counterpulsation did not exceed 48 hours had a low complication rate of 3.9%. The Hemopump is a catheter-mounted transvalvular left ventricular assist device intended for surgical placement via the femoral artery (Figures 6 and 7). (ABSTRACT TRUNCATED)
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PMID:[Reperfusion therapy and mechanical circulatory support in patients in cardiogenic shock]. 1054 49

Up to 10% of patients who arrive at the hospital with acute myocardial infarction (AMI) present with or develop cardiogenic shock. Some patients, despite inotropes and intra-aortic balloon pump (IABP) placement, are not hemodynamically stable enough to undergo emergent revascularization. The use of percutaneous extracorporeal life support (ECLS) can stabilize patients to allow effective therapy. In a retrospective review of the first 100 patients emergently placed on ECLS by a nurse-supported physician insertion technique at Sharp Memorial Hospital, 10 patients underwent placement of ECLS after out-of hospital AMI. All AMI patients required intubation for respiratory failure and temporary CPR for cardiovascular collapse before initiation of ECLS. Of the 10 AMI patients placed on ECLS, four (40%) are currently long-term survivors (5.1 +/- 4.2 years; range, 6 months to 11 years). All survivors underwent successful revascularization after placement on ECLS. The cause of death in the other six patients was neurologic insufficiency in two, ineffective ECLS in two, and recurrent cardiovascular collapse after weaning from bypass in two. Total CPR time before initiation of cardiopulmonary bypass was 17 +/- 10.3 minutes for the survivors and 54.2 +/-11.1 minutes for the nonsurvivors (p < 0.001). The average time on ECLS was 29 +/- 26 hours for the survivors and 30 +/-67 hours for the nonsurvivors (p = NS). Leg complications were common among long-term survivors, associated with the use of ECLS (three ischemia, one infection). After AMI and cardiovascular collapse, insertion of ECLS may permit long-term patient survival.
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PMID:Long-term survival with use of percutaneous extracorporeal life support in patients presenting with acute myocardial infarction and cardiovascular collapse. 1059 95

Skeletal muscle deterioration is emerging as a limitation to long-term cardiac assist by dynamic cardiomyoplasty. Chronic electrical stimulation of in situ skeletal muscle showed that ischemia, decreased muscle preload, muscle overuse, and chronic electrical stimulation are factors for muscle deterioration. Transposition around the heart has been associated with signs of muscle denervation after chronic electrical stimulation. To evaluate latissimus dorsi muscle neuromuscular function after longterm dynamic cardiomyoplasty, we performed neuromuscular functional analysis and histology on the latissimus dorsi muscle and thoracodorsal nerve of six normal goats and six goats after 6 months of dynamic cardiomyoplasty. Electromyographic analysis showed positive sharp waves and fibrillation potentials in the latissimus dorsi of three goats from the dynamic cardiomyoplasty group. Conduction velocity of the thoracodorsal nerve of goats from the dynamic cardiomyoplasty group (58.32+/-9.80 m/s) was reduced compared to the goats from the control group (71.48+/-5.71 m/s, P = 0.02). Histologic changes in skeletal muscle were compatible with denervation. Loss of myelin sheaths, collapse of endoneurial connective tissue, and solitary foci of axonophagia and myelinophagia further documented severe injury to the thoracodorsal nerve in goats from the dynamic cardiomyoplasty group. The latissimus dorsi muscle wrap was denervated after long-term dynamic cardiomyoplasty. Traction on the neurovascular pedicle at each contraction of the transposed muscle may induce afferent axonal injury of the thoracodorsal nerve resulting in diminished muscular function.
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PMID:Neuromuscular function of the latissimus dorsi muscle in goats after dynamic cardiomyoplasty. 1059 66

Reperfusion of ischemic myocardium is necessary to salvage tissue from eventual death. However, reperfusion after even brief periods of ischemia is associated with pathologic changes that represent either an acceleration of processes initiated during ischemia per se, or new pathophysiological changes that were initiated after reperfusion. This 'reperfusion injury' shares many characteristics with inflammatory responses in the myocardium. Neutrophils feature prominently in this inflammatory component of postischemic injury. Ischemia-reperfusion prompts a release of oxygen free radicals, cytokines and other proinflammatory mediators that activate both the neutrophils and the coronary vascular endothelium. Activation of these cell types promotes the expression of adhesion molecules on both the neutrophils and endothelium, which recruits neutrophils to the surface of the endothelium and initiate a specific cascade of cell-cell interactions, leading first to adherence of neutrophils to the vascular endothelium, followed later by transendothelial migration and direct interaction with myocytes. This specific series of events is a prerequisite to the phenotypic expression of reperfusion injury, including endothelial dysfunction, microvascular collapse and blood flow defects, myocardial infarction and apoptosis. Pharmacologic therapy can target the various components in this critical series of events. Effective targets for these pharmacologic agents include: (a) inhibiting the release or accumulation of proinflammatory mediators, (b) altering neutrophil or endothelial cell activation and (c) attenuating adhesion molecule expression on endothelium, neutrophils and myocytes. Monoclonal antibodies to adhesion molecules (P-selectin, L-selectin, CD11, CD18), complement fragments and receptors attenuate neutrophil-mediated injury (vascular injury, infarction), but clinical application may encounter limitations due to antigen-antibody reactions with the peptides. Humanized antibodies and non-peptide agents, such as oligosaccharide analogs to sialyl Lewis, may prove effective in this regard. Both nitric oxide and adenosine exhibit broad spectrum effects against neutrophil-mediated events and, therefore, can intervene at several critical points in the ischemic-reperfusion response, and may offer greater benefit than agents that interdict at a single point in the cascade. The understanding of the molecular processes regulating actions of neutrophils in ischemic-reperfusion injury may be applicable to other clinical situations, such as trauma, shock and organ or tissue (i.e. vascular conduits) transplantation.
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PMID:The role of neutrophils in myocardial ischemia-reperfusion injury. 1061 13

Frostbite causes injury to the tissue by direct ice-crystal formation at the cellular level with cellular dehydration and microvascular occlusion. Muscle that initially appears viable on reperfusion may subsequently become necrotic because of microcirculatory collapse. Since muscle is a sensitive tissue in frostbite injury, we used technetium-99m-sestamibi limb scintigraphy to assess tissue viability in an experimental rabbit model. Twelve rabbits were used for this investigation. The right hind limb of the rabbits was immersed to the ankle joint in a container filled with 90% ethanol at -25 degrees C for 10 min. Frostbitten limbs were allowed to thaw in air at room temperature. Imaging and pathological examination of the affected limbs were performed 2 h, 24 h, 48 h and 72 h after freezing. In 2-h images, initial hypoperfusion was seen that corresponded to circulatory collapse. In 24-h images, there was hyperperfusion (so-called period of temporary reperfusion), corresponding to circulatory restoration. In 48-h images, a second hypoperfusion corresponded to viable but ischaemic tissue. In 72-h images, there was non-perfusion of the limb that correlated with the pathologically determined diagnosis of necrosis. All scintigraphic patterns correlated with pathological findings. We suggest that these scintigraphic patterns in soft tissue may be helpful in distinguishing between frank infarction and reversible ischemia and therefore may be useful in selecting early therapeutic or surgical interventions to salvage bone and soft tissue. Further studies are needed to show the usefulness of 99mTc sestamibi scintigraphy in clinical frostbite cases.
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PMID:Assessment of tissue viability after frostbite injury by technetium-99m-sestamibi scintigraphy in an experimental rabbit model. 1065 45

We have explored the consequences of a [Na(+)](i) load and oxidative stress in isolated nerve terminals. The Na(+) load was achieved by veratridine (5-40 microM), which allows Na(+) entry via a voltage-operated Na(+) channel, and oxidative stress was induced by hydrogen peroxide (0.1-0.5 mM). Remarkably, neither the [Na(+)](i) load nor exposure to H(2)O(2) had any major effect on [Ca(2+)](i), mitochondrial membrane potential (Deltapsim), or ATP level. However, the combination of an Na(+) load and oxidative stress caused ATP depletion, a collapse of Deltapsim, and a progressive deregulation of [Ca(2+)](i) and [Na(+)](i) homeostasis. The decrease in the ATP level was unrelated to an increase in [Ca(2+)](i) and paralleled the rise in [Na(+)](i). The loss of Deltapsim was prevented in the absence of Ca(2+) but unaltered in the presence of cyclosporin A. We conclude that the increased ATP consumption by the Na,K-ATPase that results from a modest [Na(+)](i) load places an additional demand on mitochondria metabolically compromised by an oxidative stress, which are unable to produce a sufficient amount of ATP to fuel the ATP-driven ion pumps. This results in a deregulation of [Na(+)](i) and [Ca(2+)](i), and as a result of the latter, collapse of Deltapsim. The vicious cycle generated in the combined presence of Na(+) load and oxidative stress could be an important factor in the neuronal injury produced by ischemia or excitotoxicity, in which the oxidative insult is superimposed on a disturbed Na(+) homeostasis.
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PMID:Exacerbated responses to oxidative stress by an Na(+) load in isolated nerve terminals: the role of ATP depletion and rise of [Ca(2+)](i). 1070 83

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