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)

The effect of nimodipine on cerebral metabolism during ischemia and reflow was studied in female mongolian gerbils. Animals were divided into three experimental groups. Group 1 received 1 mg/kg nimodipine i.p. 1 h prior to ischemia. Group 2 received an injection of the vehicle, 5% polyethylene glycol 400. Group 3 received an equal volume of normal saline. Cerebral ischemia was induced by bilateral common carotid artery occlusion for 1, 2, or 5 min. Recirculation was established for 0, 1, or 5 min. Sham-operated animals served as nonischemic controls. Gerbils were killed by microwave irradiation. Regional levels of ATP, phosphocreatine, glucose, glycogen, cyclic AMP, and cyclic GMP were measured in brain extracts using standard assay techniques. Levels of metabolites in sham-operated animals did not differ among Groups 1, 2, and 3. At 1 min of ischemia, cortical and striatal ATP levels were highest in Group 1 (p less than 0.05 and p less than 0.01, respectively). After 5 min of recirculation, cortical and striatal glucose levels were highest in Group 1 (p less than 0.005). Regional levels of the metabolites measured at other times did not differ significantly among the three groups. Pretreatment with nimodipine thus retards the fall in ATP and facilitates the recovery of glucose in mongolian gerbils subjected to common carotid artery occlusion. A regional variability of this effect was observed.
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PMID:Effect of nimodipine on cerebral metabolism during ischemia and recirculation in the mongolian gerbil. 299 44

When dehydration, infection, and mechanical trauma are prevented, procedures (such as cooling and/or oral antithromboxane) designed to diminish ischemia in experimental zone-of-stasis burns have been associated with no or only minor improvement in wound healing. To test the hypothesis that ongoing skin damage occurring postburn (PB) may in part be due to release of oxygen-derived free radicals during the 16-hour through 4-day PB period of reperfusion in such burns, beginning immediately and for a period of 5 days PB, equal numbers of guinea pigs received: allopurinol 150 mg/kg PO q 6 h vs. placebo, dimethylsulfoxide (DMSO) 75% applied topically q 12 h vs. placebo, or yeast-derived superoxide dismutase coupled with polyethylene glycol (PEG-SOD, Pharmacia) 10,000 U (Fridovich) given IV q 8 h producing a concentration of 16 U/cc of plasma 8 hr after injection vs. placebo. Gross and histologic examination of wounds by a 'blinded' investigator at 1 week and 3 weeks PB revealed no difference between treatment and control groups when rates of re-epithelialization and frequencies of hair-follicle retention were compared. Using the dosages, routes, and model described, treatment of a zone-of-stasis burn with PO allopurinol (a xanthine oxidase inhibitor), topical DMSO (a scavenger of the hydroxyl radical), or IV PEG-SOD (a scavenger of the superoxide radical) during the first 5 days PB was associated with no increase in the rate of re-epithelialization or frequency of hair follicle retention at 1 and 3 weeks PB when compared with controls.
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PMID:Oxygen-derived free radical inhibition in the healing of experimental zone-of-stasis burns. 302 94

Cytotoxic oxygen metabolites may contribute to skeletal muscle damage associated with ischemia and reperfusion. This study utilized a rat hindlimb ischemia model to investigate the effect of pretreatment with oxygen free radical scavengers superoxide dismutase (SOD) and catalase (CAT) on skeletal muscle Ca2+ uptake by sarcoplasmic reticulum (SR) in limbs subjected to periods of ischemia and reperfusion. SOD and CAT were conjugated to polyethylene glycol to prolong their half lives. Anesthetized rats (ca. 350 g) received an iv injection of either conjugated SOD (2 mg/kg) plus CAT (3.5 mg/kg) (n = 6, Treated Group) or 0.9 saline (4 ml/kg) (n = 6, Control Group) 5 min before unilateral hindlimb tourniquet ischemia of 3 hr duration. After 19 hr of reperfusion, muscle from each lower leg was excised and homogenized. Skeletal muscle SR was isolated by differential centrifugation. ATP-dependent Ca2+ uptake by the SR was then measured with dual wavelength spectrophotometry and used as an index of muscle function. Pretreatment with SOD and CAT maintained higher rates of Ca2+ uptake by SR of skeletal muscle from postischemic reperfused limbs (Treated Group 2.29 +/- 0.21 vs Control Group, 1.61 +/- 0.06 mumole Ca2+/mg protein/min). These results implicate cytotoxic oxygen metabolites in the pathogenesis of ischemic reperfusion skeletal muscle injury.
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PMID:Effect of superoxide dismutase plus catalase on Ca2+ transport in ischemic and reperfused skeletal muscle. 380 51

Studies were performed to evaluate the effect of solute permeability and extracellular osmolality in protecting against ischemic acute renal failure. The functional protective effect of a 1-min intrarenal perfusion (prior to intrarenal norepinephrine 0.75 micrograms . kg-1 . min-1) of a hypertonic permeant solute (hypertonic saline, 1,400 mosmol/kg H2O) and an isotonic impermeant solute (isotonic mannitol, 280 mosmol/kg H2O or isotonic polyethylene glycol, IPEG, 300 mosmol/kg H2O) was evaluated. Three hours after ischemia, the glomerular filtration rate was significantly lower in hypertonic saline group vs. either the isotonic mannitol- or IPEG-treated animals (2.4 vs. 8.9 and 10.4 ml/min, respectively; both P less than 0.05). Mean renal blood flow was similar in all three groups. The effects of hypertonic saline and IPEG on glomerular filtration pressure and tubular obstruction were also evaluated. Stop-flow pressure, as an index of glomerular filtration pressure, was higher in the IPEG- vs. the hypertonic saline-treated animals (40 vs. 35 mmHg, P less than 0.001). Although proximal tubular pressure was increased in both groups, transglomerular hydrostatic pressure was higher in the IPEG vs. the hypertonic saline group (13 vs. 6 mmHg, P less than 0.01). Tubular microperfusion studies demonstrated increases in proximal tubular pressure in the hypertonic saline but not the IPEG studies. The present results indicate that isotonic, impermeant solutes provide functional protection against ischemic acute renal failure. The beneficial effect of impermeant solute is mediated, at least in part, by better maintenance of transglomerular hydrostatic pressure and prevention of secondary tubular obstruction.
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PMID:Prevention of ischemic acute renal failure with impermeant solutes. 640 34

Acute renal failure in dogs occurs following 40 min of total renal ischemia induced by a 40-min infusion of norepinephrine (NE; 0.75 micrograms/kg/min) into the renal artery. Similar functional impairment is seen following 50 min of bilateral renal pedicle clamping in the rat. Attending these renal ischemic insults a progressive increase in mitochondrial (Mito) calcium (Ca++) accumulation occurs during reflow. Although Mito respiration and Mito Ca++ kinetics (uptake and release) are abnormal during ischemia, prior to reflow, as are tissue ATP levels, reflow in the first 1-3 h after ischemia is associated with recovery of these measurements to almost normal levels. Between 3 and 24 h of further reflow, however, Mito functional deterioration is again observed. Verapamil (5 micrograms/kg/min) infused intrarenally for 2 h after NE or for 30 min prior to NE protected kidneys from the low glomerular filtration rate which follows renal ischemia in untreated dogs. Since mannitol and polyethylene glycol, two solutes with relatively high reflection coefficients, also exert protection in this model, it may be that Ca++ leak into the cytosol of ischemically damaged kidney cells eventually aborts the Mito recovery which accompanies reflow; these impermeant solutes (by preventing cell swelling) and the Ca++ blocker Verapamil may work by different mechanisms to prevent increased cytosolic Ca++ after renal ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ischemic acute renal failure--pathogenetic steps leading to acute tubular necrosis. 665 80

In order to study the relationship between cell swelling and cell death due to ischemia, we have developed an in vitro model by using primary cultures of renal tubular epithelial cells. With this model, we have studied two components of ischemia--namely, anoxia along with substrate deprivation. After 2 hr of anoxia in the absence of substrate, the cultured cells swelled and blebbed. Cells similarly treated in the presence of 8% polyethylene glycol, an oncotic agent, did not swell and bleb, and when cells were counted 18 hr later, similar numbers of cells were seen as in the untreated cultures. However, tubule cells exposed to anoxia without 8% polyethylene glycol had 50% fewer cells 18 hr later. Therefore, if cell swelling is prevented during 2 hr of anoxia, cell viability is improved.
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PMID:Protection of cultured renal tubular epithelial cells from anoxic cell swelling and cell death. 693 64

The identification of ischemia as a central mechanism of cell injury within the nervous system has resulted in a commonality of interests of neurosurgeons, neurologists and basic scientists interested in head injury, subarachnoid hemorrhage and stroke. This, in turn, has led to a certain synergy between the development of new agents and the availability of interested and committed investigators so that these agents can be tested under appropriate clinical conditions. In head injury, major sources of focus have been the membrane damage resulting from the free-radical cascade and the disruption in cellular ionic homeostasis resulting from the excitotoxic effects of pathologic release of amino acid neurotransmitters. At present, the final analyses of phase III trials of the antagonism of the initiation and propagation of the free-radical cascade by tirilazad and polyethylene glycol-bound superoxide dismutase are nearing completion. Data on the efficacy of these agents in improving outcome from moderate and severe head injury should be available within the next 6 months. In addition, worldwide trials of glutamate antagonists are presently being initiated in severe head injury, with results anticipated in late 1997 or early 1998. In subarachnoid hemorrhage, calcium has been hypothesized to play a role in mediating vasospasm-induced ischemia as well as in promoting intracellular damage. Trials of calcium-channel blockade have demonstrated a reduction in mortality, but no improvement in the quality of survival over other methods of managing these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacologic therapy: promising clinical investigations. 749 69

Reperfusion after ischemia results in endothelial cell injury and Kupffer cell activation. Inflammatory cytokines thus released can induce major histocompatibility complex antigens and increase the immunogenecity of the graft. An orthotopic rat liver allotransplant model was used to test the hypothesis that prevention of reperfusion injury by infusion of polyethylene glycol superoxide dismutase (PEG-SOD) would result in long-term allograft survival in the presence of subthreshold immunosuppressive dosages. ACI rats were used as donors, and Lewis strain rats as recipients. Orthotopic liver transplantation was initially performed to identify a subthreshold dose of the immunosuppressant FK-506, which would be unable to extend survival longer than control untreated rats with this strain combination. After testing three intramuscular FK-506 doses of 0.04, 0.08, and 0.16 mg/kg, it was observed that an FK-506 dose of 0.04 mg/kg/day for 14 days was unable to extend survival longer than in untreated recipients. This dose of FK-506 was used in combination with PEG-SOD at doses of 1000, 3000, 10,000, or 30,000 units. Recipient animals were treated intravenously with PEG-SOD as a loading dose to facilitate tissue penetration on day 1, and beginning on the day of transplantation, every 2 days for the duration of the study. Results of histologic studies and mean survival time were compared in untreated recipients and in rats treated with PEG-SOD plus 0.04 mg/kg/day FK-506.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction of FK-506 requirements by combination with polyethylene glycol superoxide dismutase in orthotopic rat liver transplantation. 754 Oct 60

This study was performed to determine whether long-chain acylcarnitines, specifically palmitoylcarnitine, could account for the increase in intracellular Na+ ([Na+]i) during ischemia eliciting a secondary increase in intracellular Ca2+ ([Ca2+]i). Accordingly, whole cell voltage-clamp procedures and Na(+)-sensitive electrode recordings were employed simultaneously in isolated adult rabbit ventricular myocytes to assess the relationship between activation of a slow-inactivating Na+ current [INa(s)] and a potential increase in [Na+]i. The [Na+]i increased progressively from 8.4 +/- 1.2 to 22.5 +/- 1.8 mM (n = 8, P < 0.01) on exposure to palmitoylcarnitine (10 microM) accompanied by the activation of INa(s); both effects were reversible. Inhibition of INa(s) by tetrodotoxin (TTX, 10 microM) inhibited the increase in [Na+]i. Increasing [Na+]i to 20 mM without ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) to mimic effects measured with palmitoylcarnitine consistently elicited the transient inward current (Iti) and delayed afterdepolarizations (DADs). The percent inhibition (12.9 +/- 2.8%) of the Na(+)-K(+)-adenosinetriphosphatase pump activity by palmitoylcarnitine (10 microM) was much smaller than that induced by ouabain (10 microM, 90.5 +/- 2.5%), suggesting that this modest effect of palmitoylcarnitine on the pump is unlikely to account for the increase in [Na+]i induced by palmitoylcarnitine. Thus palmitoylcarnitine induces the INa(s) leading to an increase in [Na+]i, which elicits an increase in [Ca2+]i probably via the Na+/Ca2+ exchanger, thereby leading to the development of Iti and DADs.
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PMID:Palmitoylcarnitine increases [Na+]i and initiates transient inward current in adult ventricular myocytes. 761 93

Extended ischemia results in organ infarction which limits the availability of donor hearts. Hypothermic storage extends heart preservation by effectively stopping cellular metabolism, thereby preventing toxic accumulations of metabolic wastes and depletion of energy stores. However, cell swelling as a result of ion concentration changes and cell laceration due to ice crystal growth are consequences of hypothermic ischemia. Supercooling successfully preserves hearts for an extended time without associated myocardial necrosis. The efficacies of four supercooling preservative solutions, containing hypertonic glucose, polyethylene glycol, and or winter flounder antifreeze protein, are assessed using the Langendorff isolated organ perfusion apparatus and transmission electron microscopy. Polyethylene glycol seems the most effective in preventing myocardial necrosis possibly by dehydrating, minimizing cellular ice formation, protecting against cell swelling, and functioning as an antioxidant. Hypertonic glucose seems the most effective in reducing cell swelling; it may also depress solution freezing points, bind water, adjust both intra- and extracellular osmolarities, stabilize proteins, and assist in adenosine triphosphate (ATP) production. Antifreeze protein seems to bind effectively to ice and inhibit its growth; it may also reduce membrane permeabilities to Ca2+ and K+ ions.
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PMID:The effects of supercooling chemicals on myocardial ultrastructure: a transmission electron microscopy case study. 767 97


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