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

The effect of different processing factors on tissue valve calcification were studied in the subdermal rat model. Factors evaluated, were the influence of tissue ischaemia (4 degrees and 25 degrees C), different blocking reagents (KH2PO4, T6, MgCl2 and AlCl3), fixation pressures (0, 10 and 20 mmHg) and the pH (3.72 and 7.40) of the fixative. Tensile strength tests performed, showed that all blocking reagents tend to weaken valve tissue. Histologically calcification originated mainly in the spongiosa of the valve leaflets. Tissue ischaemia at 4 degrees C significantly (p less than 0.05) decreased the calcification potential of the valve tissue. Ischaemia at 25 degrees C significantly (p less than 0.05) increased this process. Blocking reagents KH2PO4, T6 and MgCl2 significantly (p less than 0.05) reduced calcification of valve tissue. AlCl3 pretreatment virtually prevented it to such an extend that the calcification process was down to 92% of the control group. Different fixation pressures had no influence on the calcification potential of the tissue. AlCl3 was dependent on a low pH (3.72) to act as a blocking reagent on tissue calcification. It is concluded that certain processing factors do influence the calcification potential of valve tissue. These factors should be considered when constructing bioprostheses with glutaraldehyde-treated porcine valves.
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PMID:Processing factors as determinants of tissue valve calcification. 153 9

Cardiac metabolism changes in response to oxygen and substrate availability during development. The fetus is relatively more dependent on anaerobic glycolysis, using glucose as its major substrate during hypoxia, lactate when well-oxygenated. The mature heart is almost exclusively aerobic, with nonesterified fatty acids as the predominant substrate. During hypoxia and ischemia, shifting the heart to carbohydrate metabolism has oxygen-sparing effects. Blocking lipolysis or carnitine palmityl transferase activity prevents accumulation of potentially toxic long-chain esters during hypoxia/ischemia, thereby reducing the risk of electrophysiologic disturbance and membrane disruption. Knowledge of developmental cardiac metabolism may aid in the development of therapeutic strategies to preserve the myocardium during hypoxia and ischemia.
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PMID:Developmental cardiac metabolism in health and disease. 267 17

We evaluated the hypothesis that postischemic renal failure is caused primarily at reperfusion by oxygen-derived free radicals in a swine model designed to realistically mimick human cadaveric renal transplantation. Both kidneys were removed, flushed with Euro-Collins solution, stored 24 hr at 4 degrees C, and then transplanted to a second pig. Experiments were paired, each pig receiving one treated and one control kidney. All pigs received the optimal conventional regimen of hydration, phenoxybenzamine, furosemide, and mannitol to allow assessment of free radical treatment superimposed thereupon. Two days later creatinine clearance (CCR) was measured from each kidney via separate ureterostomies. Untreated kidneys developed severe functional impairment, CCR falling from a normal level of 25.5 +/- 6.3 ml/min (n = 8) to 7.7 +/- 0.9 ml/min (n = 14, P less than .05 vs. control). The infusion of 20 mg of the free radical scavenger superoxide dismutase (SOD) into the renal artery at reperfusion substantially ameliorated this injury (CCR = 15.9 +/- 1.7 ml/min, n = 18, P less than 0.05 vs. control). A dose-response curve to SOD showed no effect of doses of 0.2 mg (CCR = 8.0 +/- 1.1 ml/min, n = 4) or 2 mg (CCR = 7.7 +/- 0.9, n = 5), and no greater benefit from 100 mg (CCR = 16.1 +/- 2.1 ml/min, n = 3, P less than 0.05 vs. control). Blocking the generation of superoxide radicals from xanthine oxidase with allopurinol (50 mg/kg) afforded similar protection (CCR = 18.2 +/- 1.8; n = 11, P less than 0.01 vs. control). On the other hand, following an 18-hr period of cold ischemia, little damage was sustained by the untreated (control) kidneys (CCR = 22.1 +/- 0.6 ml/min). Consequently, under these conditions the ablation of free radical generation with allopurinol provided no significant benefit. These findings suggest that after a critical period of cold ischemic preservation, metabolic changes take place within the kidney that lead to free radical generation and consequent tissue injury upon reperfusion, despite optimal preservation by conventional methods. This damage can be prevented by simple nontoxic measures--which, therefore, show great promise for use in the prevention of early renal failure following cadaveric renal transplantation.
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PMID:The role of oxygen free radicals in mediating the reperfusion injury of cold-preserved ischemic kidneys. 390 28

We have demonstrated previously that oxygen-derived free radicals are important mediators of tissue injury following ischemia (total venous occlusion) and reperfusion in small (3 cm X 6 cm) island skin flaps in rats. In this study, we evaluated extension of this concept to regional ischemia in large (8 cm X 8 cm) acute island skin flaps which were constructed to exceed their sole blood supply via unilateral inferior epigastric vessels. Under normal (control) circumstances, a significant portion of the flap would undergo necrosis at the periphery, mimicking the corresponding clinical situation. Blocking the generation of superoxide radicals from xanthine oxidase with a single dose of allopurinol prior to flap elevation significantly improved the area of flap viability from 34 +/- 12% to 57 +/- 6% (p less than 0.01) in the random portion of the flap, contralateral to the source of blood supply. Similarly, the detoxification of superoxide radicals with a single dose of superoxide dismutase improved viability from 41 +/- 6% to 58 +/- 7% (p less than 0.01). Similar results were obtained when either of these agents were administered 60 minutes after flap elevation. These findings suggest that oxygen-derived free radicals play an important role in the development of tissue necrosis in the critical transition zone between well-vascularized and devascularized skin.
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PMID:Effects of superoxide dismutase and allopurinol on the survival of acute island skin flaps. 397 40

A 72-year-old man suffering from arthritis received a total dose of 500 mg sodium aurothiomalate during a period of 5 months. His clinical state then deteriorated and he had to be hospitalized. Upon admission he was bedridden, his level of consciousness was slightly impaired, he was confused and respiration was laboured. Continuous muscle activity was noted on all extremities and at first, erroneously, fasciculations were diagnosed. The EMG exhibited continuous muscle fibre activity consisting of duplets, triplets and multiplets. The discharges occurred in an irregular pattern; when various muscles were examined at the same time no synchronicity could be observed between muscle discharges. In the left m. deltoideus an increased percentage of polyphasic potentials was found, whereas mean duration of motor unit potentials was normal. Spontaneous activity remained unchanged during sleep and administration of intravenous diazepam or phenytoin. Blocking of ulnar nerve at either elbow or wrist level did not stop spontaneous activity in m. abductor digiti quinti. Ischaemia increased the amount of discharges after 7 min. Within 4 months after termination of gold therapy the patient's condition improved and he was discharged from hospital. Regular EMG follow-up after 8 months showed complete cessation of abnormal spontaneous activities. Nerve conduction velocities were normal except for markedly reduced compound action potential in peroneal nerves. Continuous muscle fibre activity as a side-effect of gold therapy is described.
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PMID:The syndrome of continuous muscle fibre activity following gold therapy. 644 Sep 53

Single or multiple brief periods of ischemia (preconditioning, PC) have been shown to protect the myocardium from infarction during a subsequent more prolonged ischemic insult. To test the hypothesis that opening of ATP-sensitive potassium channels (KATP) is involved in this mechanism, either bimakalim, a KATP channel opener, or glibenclamide, a KATP channel blocker, were administered to mimic or to block preconditioning protection in barbital-anesthetized pigs. PC was elicited by a single period of 10 min left anterior descending coronary artery (LADCA) occlusion followed by 15 min of reperfusion before the LADCA was reoccluded for 60 min. Instead of PC, bimakalim infusion was started 15 min before the 60 min LADCA occlusion (TCO) and stopped with the onset of ischemia. Glibenclamide was administered either for 10 min prior to the PC protocol, before bimakalim infusion, or before TCO. Regional wall function was quantified with ultrasonic crystals aligned to measure wall thickening (% delta WT). At the end of the protocol, infarct size was determined by incubating myocardium with p-nitrobluetetrazolium. In seven preconditioned pigs, infarct size was 9.9 +/- 5.1% of the risk region compared with 65.9 +/- 6.0% in the seven control pigs subjected to 60 min of ischemia only (p < 0.001). In seven pigs treated with bimakalim, infarct size was reduced to 35.3 +/- 6.6 (p < 0.05 vs. controls). Blocking ATP-sensitive potassium channels with glibenclamide prior to PC abolished its protective effect (infarct size, 62.2 +/- 4.5%; p < 0.001 vs. PC alone). Glibenclamide also antagonized the protective effect of bimakalim (infarct size, 55.2 +/- 4.0%), but did not affect infarct size, when solely administered prior to the prolonged ischemic period (62.2 +/- 4.3%). We conclude that in swine myocardium KATP channels are involved in the protective effect of ischemic preconditioning, since glibenclamide completely abolished the protective effect of preconditioning, while bimakalim could--at least in part--mimic it.
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PMID:Involvement of ATP-sensitive potassium channels in preconditioning protection. 770 45

We used three interventions to test critically the theory that ischemic preconditioning is the result of translocation of cytosolic protein kinase C (PKC) into the membranes where it can be activated. If that theory were true then kinase activity should not be necessary during the preconditioning ischemia and thus blocking kinase activity at this time should not block protection. Secondly, since most translocation processes in the cell are accomplished by cytoskeletal microtubules, disrupting them with colchicine should also block protection from preconditioning. Finally, translocating PKC by transient exposure to PMA, should still require adenosine receptor activation to reactivate the PKC pathway during the subsequent ischemia. Blocking kinase activity with staurosporine during a 30 min insult completely blocks protection in preconditioned hearts but when staurosporine treatment was confined to the preconditioning episode protection was not blocked in five of the eight hearts studied. Microtubule disruption with colchincine did block the protective effect of preconditioning (38.3 +/- 1.9% infarction v 40.6 +/- 4.1% in non-preconditioned). Colchicine had no effect on infarct size in the non-preconditioned group. Five min PMA treatment plus 10 min washout significantly limited infarct size in isolated rabbit hearts subjected to 30 min regional ischemia (5.9 +/- 1.1% v 31 +/- 3.5% infarction in control). PMA's protection was blocked by adding the adenosine receptor blocker, SPT, during the sustained ischemia (38.1 +/- 6.1% infarction). All three of these experiments strongly support the translocation theory of ischemic preconditioning.
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PMID:Evidence that translocation of protein kinase C is a key event during ischemic preconditioning of rabbit myocardium. 807 20

Leukocytes can produce vascular injury following ischemia and reperfusion of tissue resulting in thrombosis, edema and necrosis. Leukocyte adhesion to endothelial cells allows formation of a protected microenvironment where inflammatory molecules can exceed anti-inflammatory molecules thus resulting in injury. Blocking adherence with monoclonal antibodies to adherence molecules can prevent reperfusion injury to a variety of organs. In particular, antibodies to CD18 and P-selectin have been shown to be effective in ameliorating injury.
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PMID:The role of adhesion molecules in reperfusion injury. 831 35

Adenosine is a potent endogenous antiinflammatory agent released by cells under metabolically unfavorable conditions. Its effects on the production of IL-10 by human monocytes were presently investigated. Pre-incubation with adenosine dose-dependently enhanced IL-10 release by TNF stimulated human monocytes (+29, +58, and +116% at 1, 10, and 100 muM, respectively.) Adenosine also significantly enhanced IL-10 production after hydrogen peroxide and LPS stimulation and dose-dependently inhibited TNF secretion. Pre-incubation was not mandatory to achieve these effects, since addition of adenosine at the time of or 30 min after the stimulus led to the same results. Blocking IL-10 with anti-IL-10 mAbs partially restored adenosine-induced TNF inhibition. The enhanced IL-10 production was not observed when cells were preincubated with adenosine A1 or A2 receptor agonists (R-phenylisopropyladenosine, 5'-N-ethylcarboxamido-adenosine, and 2-chloroadenosine) and was not affected by pretreatment with theophyllin, an antagonist of both A1 and A2 receptors, or with dipyridamole, an inhibitor of adenosine cellular uptake. In conclusion, adenosine, in the submillimolar concentration range, increases IL-10 secretion by stimulated monocytes. This phenomenon participates in TNF inhibition, a known property of adenosine, but is not mediated through the occupancy of A1 or A2 receptors. This may represent a novel antiinflammatory property of adenosine by which it could modulate inflammation and limit ischemia-reperfusion injury.
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PMID:Adenosine enhances IL-10 secretion by human monocytes. 866 14

The selectins are carbohydrate-binding cell adhesion molecules acting in the vascular system. They mediate the docking of leukocytes to the blood vessel wall and the rolling of these cells along the endothelial cell surface. These adhesion phenomena initiate the entry of leukocytes into sites of inflammation as well as the migration of recirculating lymphocytes into secondary lymphoid tissues. Blocking selectin function with antibodies or oligosaccharides has proven to be beneficial in various animal models of inflammation and models of ischemia/reperfusion damage. This has raised much interest in the identification of the physiological ligands of the selectins. Several glycoprotein ligands have been identified, some of which can even be selectively isolated from cellular detergent extracts using a selectin as an affinity probe. Four of these "high affinity" ligands have been cloned. The structural requirements of their interaction with the selectins is discussed.
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PMID:Ligand-specificity of the selectins. 880 82


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