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

We explored the role of polymorphonuclear leukocytes (PMN) in the genesis of contractile dysfunction (myocardial "stunning") and of vascular abnormalities after reversible ischemia. Open-chest dogs underwent a 15-min coronary occlusion and 4 h of reperfusion (REP); treated animals (n = 16) received intravenous goat antiserum against canine PMN, whereas controls received nonimmune goat serum (n = 10) or saline (n = 15). In treated dogs, the average blood PMN levels were 10% of those in saline controls. During ischemia, collateral flow tended to be higher, and paradoxical systolic wall thinning tended to be less in neutropenic dogs, but despite this, recovery of wall thickening after REP was not enhanced in these animals. Similarly, arrhythmias during ischemia or REP did not differ among the three groups. Four hours after REP, both resting and minimal coronary resistance (the latter assessed by adenosine infusion) were higher in the stunned compared with the nonischemic myocardium; these vascular derangements, however, were similar in all three groups. Thus profound neutropenia failed to attenuate mechanical dysfunction, to reduce arrhythmias, and to prevent vascular abnormalities after a 15-min coronary occlusion. Although previous studies have suggested that neutrophils mediate cell death during prolonged ischemia, the present findings suggest that PMN do not contribute importantly to the damage associated with brief, reversible ischemia. The duration of flow reduction may be a critical factor determining whether PMN exacerbate ischemic injury.
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PMID:Influence of neutrophil depletion on myocardial function and flow after reversible ischemia. 291 69

Oxygen free radicals have been implicated in postischemic renal injury. However, the source of these oxygen free radicals has not been well defined. One potential source is activated neutrophils. Neutrophil depletion was produced in rats by using two different techniques, and the effect on ischemic injury was examined. Rabbit anti-rat neutrophil serum was prepared by immunizing a rabbit with a Percoll gradient centrifugation-purified (approximately 90%) suspension of rat neutrophils. Rats received antineutrophil serum in one of four protocols and were subsequently subjected to 40 minutes of renal artery occlusion. Control animals received nonimmune rabbit serum. The serum creatinine levels 24 hours after ischemia were not different between control and immune serum-treated rats in any of the protocols despite significant reductions in absolute neutrophil count. In a separate study, nitrogen mustard was administered 40 hours before ischemia. Nitrogen mustard-treated rats developed moderate neutropenia and 24 hours after ischemia had lower serum creatinine levels and higher inulin clearance. However, nitrogen mustard-treated rats lost 31.5 +/- 5 gm body weight in the 2 days after nitrogen mustard administration, whereas control animals gained 5.9 +/- 5.9 gm during the same interval. Furthermore, among nitrogen mustard-treated rats there was no correlation between neutrophil count and postischemic renal function. It is thus possible that the beneficial effects of nitrogen mustard were caused by a mechanism other than neutrophil depletion. In summary, in four protocols that used antineutrophil serum, neutropenia did not protect against ischemic injury. Nitrogen mustard provided protection, but probably by a neutrophil-independent mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of neutrophil depletion on ischemic renal injury in the rat. 292 43

Predictive indexes for atherosclerotic risk are imperfect, suggesting that there are predictive factors not commonly considered. Such a factor may be the white blood cell (WBC) count. Epidemiologic studies have shown correlations between the WBC count and the risk of myocardial infarction and stroke. The risk of acute myocardial infarction is approximately four times as great in persons with WBC counts high in the normal range (greater than 9000/microL [9 X 10(9)/L]) as in persons with WBC counts low in the normal range (less than 6000/microL [6 X 10(9)/L]); only 50% to 65% of the excess risk of the high-count individuals is explainable by tobacco smoking (which covaries with WBC count). A high WBC count also predicts greater risk of reinfarction and of in-hospital death. Less rigorously studied, the constitutional neutropenia of Yemenite Jews appears to afford protection against atherosclerotic disease. Among WBC types, the strongest epidemiologic association has been with the neutrophil count. Such a predictive value of WBC count is plausible and satisfying, because WBCs make a major contribution to the rheologic properties of blood; alter adhesive properties under stress--including the stress of ischemia, enhancing their rheologic importance; and participate in endothelial injury, both acutely and chronically, by adhering to endothelium and damaging it with toxic oxygen compounds and proteolytic enzymes. Techniques newly developed or under development may allow us to refine the predictive value of the WBC count by combining it with measures of cell activation and/or activatability.
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PMID:Leukocytes and the risk of ischemic diseases. 355 28

Experiments were performed in the dog to examine the effects of neutropenia on ultimate infarct size resulting from short (90 minutes) or prolonged (4 hours) circumflex coronary artery occlusion. Sheep antiserum to canine neutrophils was used to produce neutropenia. Control animals received nonimmune serum. Neutrophil infiltration into myocardial infarcts was examined using histopathologic techniques and a semiquantitative scoring system. In 90-minute occlusions with 24-hour reperfusion, neutropenia was associated with the development of significantly smaller infarcts: normopenic group, 43.2% +/- 3.3% (n = 7) vs. neutropenic group, 26.6% +/- 3.7% (n = 10) of the area at risk, means +/- SEM. However, in 4-hour occlusion with 6-hour reperfusion experiments, the tendency of neutrophil depletion to reduce infarct size did not reach statistical significance (46.4% +/- 7.2% vs. 31.5% +/- 6.0% of the area at risk, normopenic vs. neutropenic) despite differences in neutrophil infiltration into the reperfused region. The observed differences in ultimate infarct size could not be attributed to differences in myocardial oxygen consumption. The results suggest that a significant amount of myocardial infarction induced by a limited duration of coronary artery occlusion followed by reperfusion is neutrophil dependent and appears to be less important in determining the fate of myocardium subjected to more prolonged periods of ischemia followed by reperfusion.
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PMID:Reduction of myocardial infarct size by neutrophil depletion: effect of duration of occlusion. 376 67

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein that regulates the proliferation and maturation of hematopoietic progenitor cells and modulates the function of mature neutrophils. The responses to administration of G-CSF alone, and in combination with antimicrobials, were studied in an equine model of ascending colon ischemia. Complete segmental colonic ischemia (3.75 hours) with pelvic flexure enterotomy was created in four treatment groups. Group 1 horses received recombinant canine G-CSF (10 micrograms/kg, every 24 hours, intramuscularly), gentamicin sulfate (2.2 mg/kg, every 8 hours, intravenously), and potassium penicillin G (40,000 IU/kg, every 6 hours, intravenously). Group 2 horses were treated with the G-CSF vehicle and antimicrobials as for group 1. Group 3 horses received G-CSF and the antimicrobial drug vehicles, and group 4 horses served as the untreated control receiving G-CSF vehicle and antimicrobial vehicles. The results for 20 horses, five horses in each group, were compared. Treatment with G-CSF was associated with an increased concentration of white blood cells, band neutrophils, neutrophils, lymphocytes, and monocytes in the peripheral blood after surgery. Antimicrobial administration had no detectable effect on cell concentrations after surgery. Administration of G-CSF was associated with an increased concentration of nucleated cells in the peritoneal fluid including neutrophils, small mononuclear cells and large mononuclear cells. Horses that developed incisional infections had lower neutrophil concentrations in the peripheral blood on postoperative day 2 than horses without infected incisions. These results suggested that the prophylactic administration of G-CSF may be useful in the treatment of patients at risk for developing neutropenia after surgery.
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PMID:Effects of perioperative granulocyte colony-stimulating factor on horses with ascending colonic ischemia. 769 19

Using a rat lung model, we sought to characterize the time course for ischemia-reperfusion injury and the role of neutrophils in the development of injury. Adult male Long-Evans rats underwent left thoracotomy with dissection and clamping of the left pulmonary artery, bronchus, and vein for 90 min, resulting in complete left lung ischemia. The lungs were then ventilated and reperfused for up to 4 hr. Time-matched sham animals underwent the identical thoracotomy and hilar dissection, but the lungs were not rendered ischemic. Using vascular permeability of 125I-labeled bovine serum albumin as a measure of reperfusion injury, a bimodal pattern of injury was observed. Compared to sham controls, animals undergoing ischemia-reperfusion demonstrated a significant early phase of lung injury at 30 min of reperfusion (P < 0.0001), followed by partial recovery. A second peak of lung injury was noted after 4 hr of reperfusion (P < 0.001). Myeloperoxidase activity in reperfused lung tissue, a measure of neutrophil sequestration, increased during the reperfusion time course. To determine the role of neutrophils in the development of lung reperfusion injury, additional animals undergoing the identical ischemia-reperfusion protocol received either rabbit anti-rat neutrophil serum or preimmune serum the day prior to operation. Profound neutropenia (< 75/mm3 blood) was confirmed by differential leukocyte counts. Neutropenia had no protective effect against microvascular permeability at 30 min of reperfusion, but there was a significant reduction in lung injury at 4 hr (P < 0.005). We conclude that, during lung ischemia-reperfusion, there is a bimodal pattern of injury, consisting of both neutrophil-independent and neutrophil-mediated events.
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PMID:Pattern of injury and the role of neutrophils in reperfusion injury of rat lung. 779 51

The authors undertook a study to test the feasibility and efficacy of doxorubicin (Dox) administered as continuous infusion (c.i.) in the treatment of advanced breast cancer patients. All patients were previously treated as first line chemiotherapy with bolus-administered Dox; then they received a second line treatment without Dox. Patients were eligible if they had advanced measurable breast cancer, resistant to first and second line chemotherapy regimens, and if previous Dox treatment had been performed more than one year before, and after ECG and cardiac echographic controls were performed. A dose of 4.5 mg/m2/day of Dox was planned for 10 consecutive days in c.i. through a central venous catheter, repeated at 28 day intervals, for a maximum of 10 cycles. Among the 71 patients, 56 received 3 or more treatment courses; 10 patients refused further therapy after the first cycle. Objective responses were achieved in 25 patients (35%), 3 complete and 22 partial remissions. Stabilization was obtained in 11 patients (16%). The median time to progression was 9.3 months. Obviously, haematological toxicity was the major problem; in the 71 patients, 376 courses were administered (mean number of courses per patient: 5.3): grade 4 neutropenia (WHO system) occurred in 2 patients, and grade 3 in 9 patients; while one patient died of gastric haemorrhage. Severe cardiac toxicity occurred in only one patient who died 24 hours after the beginning of therapy, with ECG lateral ischemia. Grade 4 stomatitis was observed in only one patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Continuous infusion of doxorubicin for 10 days as third-line chemotherapy in metastasized breast tumors. Initial observations]. 792 81

Neutrophils accumulate during the acute inflammatory response to brain injury, but their role in the injury process remains controversial. We tested the hypothesis that neutrophils contribute to cerebral edema, tissue injury, and disturbed cerebral blood flow (CBF) (hyperemia or ischemia) during the first 24 h after traumatic brain injury. Wistar rats (n = 51) were injected with either vinblastine sulfate to induce neutropenia or the saline vehicle. Five days later, under halothane anesthesia, right hemispheric trauma was produced by weight drop (10 g x 5 cm) onto exposed dura. At 24 h after trauma, brain water (wet-dry weight), traumatic infarct size (percent of hemispheric section infarcted), or local CBF (lCBF, 14C-iodoantipyrine autoradiography) was assessed. Vinblastine treatment produced profound neutropenia on the day of trauma (absolute neutrophil count 0.024 +/- 0.008 x 10(9)/L vs 1.471 +/- 0.322 x 10(9)/L, p < 0.05 in neutropenic vs saline, respectively, mean +/- SEM). Neutropenia did not reduce the development of brain edema in the injured hemisphere (brain water 82.38 +/- 0.29% vs 82.73 +/- 0.37% in neutropenic and saline, respectively, mean +/- SEM) or traumatic infarct size (34.5 +/- 3.3% vs 33.2 +/- 2.1% in neutropenic vs saline respectively). In contrast, neutropenic rats exhibited 52%, 41%, and 57% reductions in lCBF in the frontal cortex, parietal cortex, and amygdala, respectively, of the injured hemisphere 24 h after trauma (all p < 0.05 vs nonneutropenic controls). These data suggest that neutrophils and the acute inflammatory process contribute to the level of CBF observed 24 h after trauma, but effects on edema or early posttraumatic infarct size could not be demonstrated.
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PMID:Effects of neutropenia on edema, histology, and cerebral blood flow after traumatic brain injury in rats. 799 84

Hepatic ischemia-reperfusion injury is reported to be modulated by neutrophils (PMNs). The adhesion and emigration of PMNs that precede tissue inflammation and necrosis in other organs are mediated, in part, by the leukocyte adhesion complex CD11/CD18. In this study, the role of PMN adhesion via CD11/CD18 in isolated liver ischemia-reperfusion injury was examined in rabbits using a blocking monoclonal antibody (mAb 60.3) specific for the CD18 receptor. Vinblastine-induced neutropenia provided significant protection, confirming participation of neutrophils in the pathogenesis of hepatic injury. Inhibition of PMN adherence with mAb 60.3 did not ameliorate injury, as measured by aminotransferase concentrations or a histologic scoring system for injury severity. Histologic sections were scored for pattern and extent of injury as well as neutrophil association with injury. These results suggest a CD18-independent mechanism of neutrophil adhesion in the evolution of isolated hepatic ischemia-reperfusion injury.
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PMID:Neutrophils contribute to hepatic ischemia-reperfusion injury by a CD18-independent mechanism. 809 14

Cases of neutropenic enterocolitis associated with Clostridium septicum infection have been reported with increasing frequency in the past decade. We report two such cases involving unusual hosts and briefly discuss possible pathogenetic mechanisms such as ischemia, mucosal damage related to chemotherapy and neutropenia, and immunosuppression. One case involved a young man with chronic Epstein-Barr infection who developed extensive gas gangrene of the right side of his trunk and thigh and who died within 12 hours of presentation to the emergency department. Diagnosis was only made at postmortem examination. The second, middle-aged patient was admitted with an acute abdomen shortly after he completed chemotherapy for pleural mesothelioma. A right hemicolectomy was performed, but the patient developed antibiotic-associated pseudomembranous colitis and died. These cases indicate that neutropenic enterocolitis may arise in a variety of underlying conditions and that prompt diagnosis and therapy will be required to salvage more patients with this disorder.
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PMID:Neutropenic enterocolitis. Two unusual cases with review of the literature. 848 43


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