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)

Following liver transplantation, the decision to retransplant in cases in which graft function is marginal must be taken early. Plasma coagulation factor monitoring was evaluated as an early predictor of graft failure requiring retransplantation in the first posttransplant week. Plasma levels of fibrinogen, factors V, VII, VIII, IX, antithrombin III, protein C, and plasminogen were measured in all patients at 0, 12, 24, 48, 72, 96, and 120 hours posttransplant in 46 patients who received 56 grafts and results were compared between livers that failed early (group 1) and those that functioned adequately (group 2). Six grafts were included in group 1: one patient died before retransplantation, four were retransplanted once, and one patient was retransplanted twice. Three grafts had primary nonfunction (PNF), 2 had obstructed portal veins, and 1 had a long period of warm ischemia during the initial transplant. In group 1, plasma levels of factor V were significantly lower than in group 2 at 24, 48, and 72 hours posttransplant (21.2% +/- 14.2%, 12.4% +/- 4.5%, and 13.0% +/- 5.0% v 39.1% +/- 23.9%, 48.8% +/- 31.9%, and 60.9% +/- 25.9%; P less than .05, P less than .01, and P less than .005, respectively). Similarly, plasma levels of factor VII were significantly lower in group 1 over the same period of time (7.3% +/- 2.7%, 4.2% +/- 1.8%, and 4.7% +/- 2.5% v 27.4% +/- 17.1%, 34.1% +/- 21.6%, and 34.8% +/- 18.6%, respectively; P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coagulation plasma factor levels are early indicators of graft nonfunction following liver transplantation in children. 150 Oct 1

Controversy persists regarding which oxygen metabolites are cytotoxic. Although the combination of superoxide dismutase (SOD) and catalase has been shown to attenuate postischemic myocardial dysfunction ("stunning"), it is unknown whether this beneficial effect is due to scavenging of O2-., H2O2, or both. Accordingly, 85 open-chest dogs underwent a 15-min occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. In phase A, dogs received an intravenous infusion of saline (group I), SOD (5 mg/kg, group II), catalase (12,000 U/kg, group III), or the combination of SOD and catalase (same doses, group IV). Recovery of regional myocardial function (assessed as systolic wall thickening) after reperfusion was significantly improved by the combination of SOD and catalase but not by SOD alone or catalase alone. To determine whether higher doses of enzymes are more effective, in phase B dogs received an intracoronary infusion of normal saline (group V), SOD in low dose (1.5 mg/kg, group VI), SOD in high dose (6.3 mg/kg plus 1.5 mg/kg iv, group VII), catalase in low dose (18,000 U/kg, group VIII), or catalase in high dose (240,000 U/kg plus 40,000 U/kg iv, group IX). Despite the fact that the local plasma levels of enzymes were considerably higher than those achieved in phase A, none of the treatments in phase B significantly enhanced recovery of contractile function. This study demonstrates that the combination of SOD and catalase is more effective than either enzyme alone in attenuating postischemic myocardial dysfunction and that increasing the doses of SOD or catalase does not provide additional protection. The results suggest that both O2-. and H2O2 contribute significantly to the pathogenesis of myocardial stunning after regional ischemia in the intact animal. Furthermore, the data imply that if SOD and catalase are to be used clinically to prevent postischemic dysfunction, protection may be achieved most effectively by combining the two enzymes.
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PMID:Effect of superoxide dismutase and catalase, given separately, on myocardial "stunning". 239 95

As brain capillaries do various works necessary for maintaining the homeostasis of neurons, their disruptions may play an important role in the establishment of ischemic brain damage. It is also said that brain capillaries response to ischemia more functionally than structurally and their microstructural features remain unchanged for a long time of ischemia. Therefore, a new method is expected to be introduced that can evaluate the ischemic changes of endothelial cells on a histological level more sensitively than conventional histological methods. In the present study we investigated immunohistochemical reactivity of factor VIII related antigen (F VIII RAg), a specific and representative marker of vascular endothelial cells, in normal and ischemic brains. In the experiment, cerebral ischemia was induced by occlusion of the unilateral common carotid artery in adult mongolian gerbils. The periods of occlusion were 1, 2, 3, 6, 12, and 24 hours, in five animals respectively. After occlusion each brain was obtained by decapitation and quickly frozen at -80 degrees C and 5-6 micron sections were cut in a cryostat at -20 degrees C and dried at 37 degrees C. The staining for F VIII RAg was done by the peroxidase-antiperoxidase method using specific antiserum to human F VIII RAg. In normal gerbil's brains, the positive staining for F VIII RAg was observed in endothelial cells of arteries, veins and capillaries. In major vessels the staining was intense, but neurons and glia were not stained.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Brain ischemia and endothelial cell damage--immunohistochemical study using factor VIII related antigen as a marker]. 245 25

Lumbar sympathectomy, which is usually indicated in the arteritic patient in cases of severe ischemia and occlusion of leg arteries when bypass surgery is not feasible, can be performed surgically or by scanner-guided phenolization. Surgical sympathectomy was performed by resection of the 2nd, 3rd, 4th and 5th lumbar ganglia under general anesthesia by a retroperitoneal route. Chemical sympathectomy involved scanner-guided injection of phenol diluted 6.7% into the sympathetic nervous system at L3 and L4 level. This act, performed on outpatients, required no anesthesia. Prospective study of the early results (within one month) obtained with these two techniques in 428 patients indicates that rates of death, amputation and noteworthy complications for those less than 70 yr (table IV, VI and VIII) were respectively 4.7%, 8.5% and 7.4% for surgery, and 2.5%, 5% and 0% for phenolization; for those greater than 70 yr the rates were respectively 12%, 11% and 10% for surgery, and 10%, 9% and 8% for phenolization. It may be concluded that phenolization of the sympathetic nervous system provides the same results as surgical sympathectomy but has the advantage of lower morbidity and shorter hospitalization (24 h vs 10 days). The results of these two techniques in terms of limb conservation are disappointing and markedly poorer than those of distal bypass surgery.
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PMID:[Lumbar sympathectomy in the aged subject: surgery or phenolization? Prospective study of early results]. 258 90

To test the hypothesis that plasma contains native constituents capable of impairing microcirculatory flow in zones of acute ischemic tissue damage, we performed 14C-antipyrine autoradiographic blood flow studies in splenectomized dogs subjected to 35 min of cerebrospinal fluid compression ischemia followed by 30 min of recirculation to the neuraxis. The animals were anticoagulated with heparin and were divided into 4 groups by exposure to various measures before induction of ischemia. Groups 1 and 2 served for comparison with the other groups and underwent, respectively, no glass-wool filtration and glass-wool filtration via an arteriovenous shunt. Post-ischemic brain blood flows in Group 1 were low and focal zones of greatly impaired reperfusion were present. In Group 2, post-ischemic brain blood flows were high and focal perfusion impairment did not occur. Group 3 received homologous purified factor VIII/von Willebrand factor protein (F VIII/vWF) after glass-wool filtration but before induction of ischemia; Group 4 received F VIII/vWF-poor cryoprecipitate at the same time point. The purpose of administering the plasma preparations was to check for the presence of activity that nullified the enhancement of post-ischemic reperfusion expected after exposure to glass-wool. The results indicate that activity deleterious to post-ischemic reperfusion primarily resides in the F VIII/vWF fraction of cryoprecipitate. The F VIII/vWF-poor cryoprecipitate infusate, containing 250 to 800-fold more protein than the F VIII/vWF fraction, produced an intermediate reduction of blood flow.
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PMID:Influence of factor VIII/von Willebrand factor protein (F VIII/vWF) and F VIII/vWF-poor cryoprecipitate on post-ischemic microvascular reperfusion in the central nervous system. 678 87

Open-chest dogs (total number used, 117) underwent 10 5-min coronary occlusions (O) interspersed with 10 min of reperfusion (R). When systolic thickening fraction was measured 9 min after each R, the first O-R cycle was found to cause the largest decrement, with only a slight additional loss during the next four cycles and no further loss during the last five cycles (group IV), suggesting that the first few episodes of ischemia preconditioned the myocardium against the stunning induced by the last five episodes. However, different results were obtained when the total deficit of wall thickening during the final 4-h R interval was measured. The total deficit was similar after one and three 5-min O (groups V and VI, respectively), indicating that the first ischemic episode did precondition against the next two episodes; however, it was approximately 2.5-fold greater after 10 O (group IV) than after 3, indicating that the first 3 episodes failed to precondition against the next 7. Thus, at some point between the 4th and 10th O, the preconditioning effect was lost and recurrent ischemic episodes started to have a cumulative effect. Measurements of free radicals with alpha-phenyl N-tert-butyl nitrone (PBN) demonstrated a burst of free radical generation immediately after the 1st, 5th, and 10th R (group VIII). The total cumulative release of PBN adducts during the initial 5 min of reflow was 58% less after the 5th R than after the 1st (P < 0.05) but did not differ significantly between the 1st and 10th R. When administered throughout the 10 O-R cycles, the .OH scavenger mercaptopropionyl glycine significantly enhanced the recovery of function (group I) and markedly suppressed the formation of free radicals (group VII). However, the beneficial effects of mercaptopropionyl glycine were completely, or largely, lost if the drug was discontinued after the first five (group II) or eight (group III) O-R cycles, respectively, implying that (a) the oxidative stress associated with the last five, or even two, cycles was sufficient to cause severe postischemic dysfunction, and (b) the cumulative injury caused by repetitive ischemic episodes is mediated by recurrent oxidative stress. This study provides direct in vivo evidence that oxygen radicals play an important role in the pathogenesis of myocardial stunning after repetitive ischemia, and implicates .OH as a primary culprit. Taken together, the data indicate that recurrent brief ischemic episodes result in recurrent bouts of oxyradical-mediated injury that have a cumulative effect on contractility, a situation that could lead to protracted or even chronic myocardial stunning.
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PMID:Recurrent ischemia in the canine heart causes recurrent bursts of free radical production that have a cumulative effect on contractile function. A pathophysiological basis for chronic myocardial "stunning". 763 43

The therapeutic efficacy of intrathecally administered MK-801 (dizocilpine maleate), a noncompetitive receptor antagonist of N-methyl-D-aspartate receptor complex, was investigated in a rabbit spinal cord ischemia model. Normal saline, 0.3 ml (control, n = 4) or MK-801, 150 micrograms in 0.3 ml of saline, was administered intrathecally at the level of the lumbar enlargement, 30 min before (pretreatment, n = 7) or in the first min after (post-treatment, n = 4) 30 min of aortic occlusion followed by 2-h reperfusion. Nauta silver method was used for histopathological evaluation of lumbosacral segments. The degree of gray matter damage (argyrophilic neurons) was evaluated in three areas: A1, Rexed's laminae I-VI; A2, laminae VII and X; and A3, laminae VIII-IX. Pre- and post-treatment with MK-801 decreased the number of argyrophilic neurons (P < 0.05) in all areas examined. The number of argyrophilic neurons in A1, A2, and A3 was reduced by 59, 28, and 29%, respectively, by MK-801 pretreatment and by 87, 66, and 46%, respectively, by MK-801 post-treatment. Our results show that with single bolus intrathecal administration the efficacy of MK-801 was greater with post- compared to pretreatment and most dramatic in Rexed's laminae I-VI compared to laminae VII-X. Intrathecal administration of MK-801 prior to or at the beginning of the recirculation diminishes the extent of postischemic neuronal spinal cord damage at early postreperfusion period.
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PMID:Intrathecal administration of dizocilpine maleate (MK-801) attenuates ischemic damage in the rabbit spinal cord. 786 63

Among a total of 220 liver transplants, reduced-size liver was used in 21 cases due to discrepancies in size between recipient and donors in 19 patients. In the case of two adult patients suffering from fulminant hepatic failure and in a critical condition, only one donor organ became available, so that the graft was divided to give the two recipients an equal opportunity. The two patients with fulminant hepatic failure were admitted to the ICU requiring mechanical respiration almost at the same time. Hepatitis serologies were HBcAb+, HBsAb+, and VCA+ in one and negative in the second. They had different blood groups (A.Rh+, O.Rh-), and the only donor available was located in Milan, Italy. The graft perfused with UW. was divided into two (right side, segments IV, V, VI, VII, and VIII, and left side, segments I, II and III). The recipients were transplanted 50 and 48 hours after admission. The cold ischemia time was 7.10 and 16.50 hours. The first patient, who received the right lobe, was extubated at 48 hours and discharged on the 40th postransplant day. The second patient remained unconscious with progressive deterioration; an EEG on the 4th day revealed absence of higher cortical function.
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PMID:Utilization of split liver grafts in orthotopic liver transplantation. 846 22

Seventy-four conscious rabbits undergoing a sequence of six 4-minute coronary occlusion/4-minute reperfusion cycles for 3 consecutive days (days 1, 2, and 3) were assigned to nine groups. In group I (controls, n = 8), the recovery of systolic wall thickening (WTh) after the sixth reperfusion was markedly improved on days 2 and 3 compared with day 1, indicating late preconditioning (PC) against myocardial stunning; the total deficit of WTh after the sixth reperfusion was reduced by 56% on day 2 and 50% on day 3 compared with day 1 (P < .01). Administration on day 2 of the nonselective NO synthase (NOS) inhibitor N omega-nitro-L-arginine (L-NA) (group II, n = 8) or of the selective inducible NOS inhibitors aminoguanidine (AG) (group IV, n = 8) and S-methylisothiourea sulfate (SMT) (group VI, n = 6) completely abrogated late PC against stunning on day 2. On day 3, the expected PC effect became manifest in all groups. Administration of L-NA, AG, or SMT on day 1 (groups III [n = 7], V [n = 6], and VII [n = 5], respectively) had no discernible effect on the deficit of WTh on day 1, indicating that these agents do not augment the severity of myocardial stunning in nonpreconditioned myocardium. In group VIII (n = 7), the abrogation of late PC by SMT on day 2 was completely reversed by the concomitant administration of L-arginine (595 mg/kg IV), indicating that it was not due to nonspecific NOS-unrelated actions. Administration of L-arginine alone on day 2 (group IX [n = 5]) had no effect on the deficit of WTh. Furthermore, administration of L-NA on day 1 (group III) prevented the appearance of the PC effect on day 2, whereas AG (group V) and SMT (group VI) did not, suggesting that the development of late PC on day 1 is triggered by the endothelial (type III) isoform of NOS. This study demonstrates that three structurally different NOS inhibitors (L-NA, AG, and SMT), given 24 hours after the PC ischemia, consistently abrogate late PC against myocardial stunning in conscious rabbits, indicating that this cardioprotective effect is mediated by the activity of NOS. The results obtained with AG and SMT specifically implicate the inducible (type II) isoform as the mediator of the protection on day 2. Previous studies have shown that NO triggers the development of late PC. The present results indicate that NO plays a dual role in late PC against stunning, acting initially as the trigger and subsequently as the mediator of the protection.
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PMID:The protective effect of late preconditioning against myocardial stunning in conscious rabbits is mediated by nitric oxide synthase. Evidence that nitric oxide acts both as a trigger and as a mediator of the late phase of ischemic preconditioning. 940 Mar 91

Brief ischemic episodes confer marked protection against myocardial stunning 1-3 d later (late preconditioning [PC] against stunning). The mechanism of this powerful protective effect is poorly understood. Although protein kinase C (PKC) has been implicated in PC against infarction, it is unknown whether it triggers late PC against stunning. In addition, the entire PKC hypothesis of ischemic PC remains controversial, possibly because the effects of PKC inhibitors on PC protection have not been correlated with their effects on PKC activity and/or translocation in vivo. Thus, conscious rabbits underwent a sequence of six 4-min coronary occlusion (O)/4-min reperfusion (R) cycles for three consecutive days (days 1, 2, and 3). In the control group (group I, n = 7), the recovery of systolic wall thickening after the six O/R cycles was markedly improved on days 2 and 3 compared with day 1, indicating the development of late PC against stunning. Administration of the PKC inhibitor chelerythrine at a dose of 5 mg/kg before the first O on day 1 (group II, n = 10) abrogated the late PC effect against stunning, whereas a 10-fold lower dose (0.5 mg/kg; group III, n = 7) did not. Administration of 5 mg/kg of chelerythrine 10 min after the sixth reperfusion on day 1 (group IV, n = 6) failed to block late PC against stunning. When rabbits were given 5 mg/kg of chelerythrine in the absence of O/R (group V, n = 5), the severity of myocardial stunning 24 h later was not modified. Pretreatment with phorbol 12-myristate 13-acetate (4 microg/kg) on day 1 without ischemia (group VI, n = 11) induced late PC against stunning on day 2 and the magnitude of this effect was equivalent to that observed after ischemic PC. In vehicle-treated rabbits (group VIII, n = 5), the six O/R cycles caused translocation of PKC isoforms epsilon and eta from the cytosolic to the particulate fraction without significant changes in total PKC activity, in the subcellular distribution of total PKC activity, or in the subcellular distribution of the alpha, beta1, beta2, gamma, delta, zeta, iota, lambda, and mu isoforms. The higher dose of chelerythrine (5 mg/kg; group X, n = 5) prevented the translocation of both PKC epsilon and eta induced by ischemic PC, whereas the lower dose (0.5 mg/kg; group XI, n = 5) prevented the translocation of PKC eta but not that of epsilon, indicating that the activation of epsilon is necessary for late PC to occur whereas that of eta is not. To our knowledge, this is the first demonstration that a PKC inhibitor actually prevents the translocation of PKC induced by ischemic PC in vivo, and that this inhibition of PKC translocation results in loss of PC protection. Taken together, the results demonstrate that the mechanism of late PC against myocardial stunning in conscious rabbits involves a PKC-mediated signaling pathway, and implicate epsilon as the specific PKC isoform responsible for the development of this cardioprotective phenomenon.
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PMID:Direct evidence that protein kinase C plays an essential role in the development of late preconditioning against myocardial stunning in conscious rabbits and that epsilon is the isoform involved. 959 74


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