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)

Ischemia of the intestines damages the permeability of the intestinal wall, allowing lipopolysaccharide (LPS) (endotoxin) to leak from the gut lumen into the blood circulation, causing shock and death. We measured LPS levels associated with corticosteroid treatment vs. no treatment in cats whose superior mesenteric artery had been occluded for 60 min. In untreated cats, the preocclusion mean plasma LPS concentration remained stable at 0.069 +/- 0.015 ng/ml. Toward the end of the occlusion period, mean plasma LPS rose to 0.239 +/- 0.032 ng/ml (p less than .01). Release of the clamp and reperfusion with oxygenated blood was followed within 20 min by a large rise in plasma LPS concentration to 0.825 +/- 0.11 ng/ml (p less than .01), which had returned to preocclusion levels about 80 min later. Methylprednisolone (30 mg/kg) was infused into a second group of cats 1.5 h before SMA occlusion. In these cats there was a complete inhibition of the LPS rise both during and after occlusion. These data suggest that the reported beneficial effect of corticosteroids in the treatment of septic shock may be mediated, in part, by reducing LPS leakage from the gut.
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PMID:Effect of corticosteroid prophylaxis on lipopolysaccharide levels associated with intestinal ischemia in cats. 375 30

The most important concept emerging from the management of complex hepatic trauma is that direct suture ligation of severed blood vessels and bile ducts is the most effective treatment. Three essential maneuvers are necessary: (1) the use of the finger fracture technique to expose the laceration widely, so that individual ligation of severed blood vessels and bile ducts can be accomplished under direct vision; (2) occluding the portal triad for 20 to 60 minutes; (3) closure of the hepatic incision over a viable omental pedicle. Two hundred consecutive patients with hepatic injuries were treated at the Trauma and Shock Unit of Bellevue Hospital between July 1976 and January 1982. One hundred and twenty-five injuries (63%) could be managed by superficial suture and drainage alone; 75 (37%) more extensive injuries required additional therapy; 47 of the 75 injuries required inflow occlusion for periods of up to 60 minutes, with the mean occlusion time of 30 minutes. All patients were pretreated with 30 to 40 mg/kg of Solu-Medrol prior to cross-clamping the portal triad. In addition, the liver was cooled to 27-32 degrees C topically by pouring 1 liter of iced Ringer's lactate directly on the liver surface, monitoring the temperature with an intra-hepatic probe. Ischemia time exceeded 20 minutes in 70%, 30 minutes in 40% and 60 minutes in 7% of patients. This approach, with complex hepatic trauma, has been dramatically effective. There were only four deaths (5.3%). One (1.3%) patient required reoperation for bleeding; three patients (4%) developed perihepatic abscesses; and two patients (3%) developed biliary fistulae that spontaneously closed. An extended right hepatectomy was necessary in the one patient who required reoperation for bleeding. This represents the only case of a formal hepatic resection in this series. Hepatic artery ligation was not employed in any case. These experiences strongly endorse the direct approach to the treatment of major hepatic lacerations by opening a lacerated liver sufficiently to ligate lacerated blood vessels and bile ducts, followed by closure over an omental pedicle. The wide-spread adoption of this technique will probably lower the mortality from massive liver injuries to 5-10%.
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PMID:Experience with the finger fracture technique to achieve intra-hepatic hemostasis in 75 patients with severe injuries of the liver. 634 18

The ability of a single large intravenous dose of methylprednisolone sodium succinate (MPSS: 15, 30, or 60 mg/kg) to modify the evolution of lumbar spinal cord ischemia in cats undergoing a contusion injury of 500 gm-cm is examined. Repeated measurements of spinal cord blood flow (SCBF) in the dorsolateral funiculus were made via the hydrogen clearance technique before and for 4 to 5 hours after injury. The mean preinjury SCBF for all animals was 12.29 +/- 0.77 ml/100 gm/min. Following injury, SCBF began to decrease progressively in vehicle-treated animals to a level of 7.71 ml/100 gm/min, a fall of 37.3%. In contrast, cats that received a 30-mg/kg intravenous dose of MPSS at 30 minutes after injury maintained SCBF within normal limits (p less than 0.05 at 3 and 4 hours after contusion). A 15-mg/kg MPSS dose was less effective at preventing posttraumatic white matter ischemia, and a 60-mg/kg dose was essentially ineffective. It was determined that the 30-mg/kg MPSS dose was optimal for supporting SCBF when the drug was given at 30 minutes after spinal trauma, and a second series of experiments was carried out to examine the ability of this dose, when given at longer latencies, to improve decreased flow. Methylprednisolone given at 1 1/2 hours after injury in four cats produced a slight (12.7%) but transient improvement in SCBF, and when administered at 4 1/2 hours in another three animals was totally ineffective. These results show that MPSS in a 30-mg/kg dose can prevent posttraumatic spinal cord ischemia. However, it would appear that the ability of the steroid to reverse the ischemia once it has developed is limited, and probably lost, within a few hours of onset. This further suggests that the ischemic process is irreversible and underscores the need for early treatment with a large MPSS dose in order to prevent full development of ischemia and to promote neurological recovery.
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PMID:Effects of a single large dose of methylprednisolone sodium succinate on experimental posttraumatic spinal cord ischemia. Dose-response and time-action analysis. 637 68

An experimental model of acute mesenteric ischemia following 85 minutes of superior mesenteric artery (SMA) occlusion in male Wistar rats was used in this investigation. Untreated control animals had a 48-hour survival rate of 38% (n = 26), whereas sham laparotomy resulted in a 100% 48-hour survival rate (n = 10). Study groups received intravenous infusions of normal saline solution (16.6 ml/kg/hr; n = 26) or similar volumes of normal saline solution with the addition of glucagon (1.6 micrograms/kg/min; n = 26), dopamine (3.2 micrograms/kg/min; n = 26), or prostacyclin (PGI2) (10.7 ng/kg/min; n = 26). Infusions were begun 15 minutes after initiating 85 minutes of SMA occlusion and were continued for a total of 90 minutes. Glucagon increased the 48-hour survival rate to 85%, significantly greater than both control survival (p less than 0.001) and normal saline solution group survival rates (p less than 0.025). Neither normal saline solution alone nor dopamine significantly increased the 48-hour survival rate, which was 54% in both groups. The PGI2 group survival rate, 65% at 48 hours, was significantly greater than the control rate (p less than 0.05), was not statistically different from the normal saline solution group survival rate, and was 20% less than the glucagon group survival rate, the latter difference approaching statistical significance (p = 0.10). Methylprednisolone (40 mg/kg; n = 26) administered as an intravenous bolus 15 minutes after initiating SMA occlusion significantly increased the 48-hour survival rate to 73% (p less than 0.01), whereas neither intravenous heparin (150 U/kg; n = 26) nor superoxide dismutase (11,900 U/kg; n = 26) were beneficial. Glucagon, methylprednisolone, and PGI2 improved the survival rate in this model of acute mesenteric ischemia.
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PMID:Pharmacologic interventions in acute mesenteric ischemia: improved survival with intravenous glucagon, methylprednisolone, and prostacyclin. 638 66

Thirty minutes after experimental spinal cord contusion (500 gm-cm) injury, cats were treated with an initial intravenous dose of either vehicle (V) or 30 mg/kg of Solu-Medrol sterile powder (methylprednisolone sodium succinate; MPSS). Two hours later, cats received a second intravenous injection of either V or 15 mg/kg MPSS, giving three treatment groups: V/V; MPSS/V; MPSS/MPSS. At 4 1/2 hours following injury of the cat lumbar spinal cord, the gray and white matter neurofilament protein content was reduced by over 70% within the injured segment of V/V-treated animals. The three major cat spinal cord neurofilament protein subunits of 200,000, 152,000, and 76,000 daltons were reduced in parallel by the injury. Treatment of cats with a single 30-mg/kg dose of MPSS (MPSS/V) provided a clear, although not significant, protection against neurofilament degradation compared with V/V-treated cats when measured at 4 1/2 hours after injury. The lactic acid content of the injured spinal cord segment at 4 1/2 hours after injury was significantly elevated in both V/V- and MPSS/V-treated cats, while the adenosine triphosphate (ATP) content, total adenylates, and energy charge were significantly reduced. The administration of a second intravenous 15-mg/kg dose of MPSS 2 hours after the initial 30-mg/kg dose (MPSS/MPSS) provided complete (p less than 0.01) preservation of neurofilaments within the injured spinal cord segment measured at 4 1/2 hours after injury. The levels of lactate, ATP, total adenylates, and tissue energy charge in MPSS/MPSS-treated cats were not different from those of uninjured spinal cords following laminectomy. The (Na+ + K+)-ATPase activity in the injured spinal segment was enhanced, although highly variable, in MPSS/V-treated animals. On the other hand, spinal cord enzyme activity was significantly and consistently elevated in the MPSS/MPSS-treated group. The results demonstrate that a 30-mg/kg dose of MPSS followed at 2 hours by a 15-mg/kg dose provides significantly better protection against injury-induced ischemia and Ca++-dependent neurofilament degradation than a single 30-mg/kg dose. These findings are in agreement with the spinal cord tissue pharmacokinetics and time-action characteristics of methylprednisolone observed in earlier studies.
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PMID:Effects of multi-dose methylprednisolone sodium succinate administration on injured cat spinal cord neurofilament degradation and energy metabolism. 653 14

Decreasing progressive dermal ischemia after burning could theoretically limit the amount of skin necrosis to the zone of coagulation. Methylprednisolone, aspirin, indomethacin, imidazole, dipyridamole, and methimazole have been shown to prevent dermal ischemia, suggesting that prostaglandins and/or thromboxanes may play a role in its pathogenesis. Specific antiprostaglandin antibodies (anti-PgE2, PgF2 alpha, PgI2, and TxA2) were reacted with tissue biopsies of burned guinea pig skin at various time intervals postburn. An immunoperoxidase technique with goat anti-rabbit immunoglobulin and horseradish peroxidase demonstrated the presence of the specific arachidonic acid metabolites. The burned tissue showed high levels of PgE2 and TxA2. The effects of three thromboxane inhibitors, imidazole, methimazole, and dipyridamole, on dermal ischemia were studied. Xenon133 washout studies were performed in burned and unburned areas. Tissue half-life of Xenon was prolonged in burned, untreated areas but this rapidly decreased in antithromboxane-treated burns. Repeated antiprostaglandin and antithromboxane antibody-immunoperoxidase studies on tissue from the thromboxane inhibitor-treated animals showed that PgE2, PgF2 alpha, and PgI2 were at the same levels as in untreated animals, but thromboxane (TxA2) was essentially absent, suggesting that thromboxane may be responsible for the progressive dermal ischemia after burning and that decreasing its production can increase dermal perfusion.
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PMID:Increasing dermal perfusion after burning by decreasing thromboxane production. 699 4

The effect of methylprednisolone on the distribution of myocardial flow during ischemia and after reperfusion was determined in 10 treated and 11 control dogs. Methylprednisolone, 30 mg/kg, was administered iv after occlusion. Transmural blood flow and the endo/epicardial ratio in the normal and ischemic zones was measured by injecting 141Ce- and 85Sr-labelled microspheres after 90 min of ischemia and 30 min after reperfusion, respectively. During ischemia, transmural blood flow (ml g-1 min-1) in the ischemic zone was higher in treated animals than in controls (0.25 +/- 0.04 vs 0.15 +/- 0.03; P less than 0.05) but not different in the normal zone for both groups (1.36 +/- 0.14 vs 1.15 +/- 0.10; P greater than 0.05). The endo/epicardial ratio of the ischemic zone was low but similar for both groups during ischemia (0.43 +/- 0.07 vs 0.40 +/- 0.09; P greater than 0.05). After reperfusion, transmural blood flow increased significantly in treated (0.25 +/- 0.13 vs 1.36 +/- 0.13; P less than 0.0005) as well as in control animals (0.15 +/- 0.03 vs 1.63 +/- 0.14; P greater than 0.0005), reaching similar values (1.36 +/- 0.13 vs 1.63 +/- 0.14; P greater than 0.05). The endo/epicardial ratio also increased during reperfusion in both treated (0.43 +/- 0.07 vs 1.12 +/- 0.12; P less than 0.0005) and control animals (0.40 +/- 0.90 vs 1.03 +/- 0.19; P less than 0.025). These data show that although methylprednisolone-treated dogs had higher myocardial blood flow during ischemia, after reperfusion the increase in flow in the ischemic zone of treated and control dogs was of the same magnitude.
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PMID:Experimental myocardial infarction: effect of methylprednisolone on myocardial blood flow after reperfusion. 718 24

Rejection crises after kidney transplantation could be associated with individual variability of pharmacokinetic parameters of steroids. We therefore investigated the individual pharmacokinetics of methylprednisolone on day 2 (60 mg intravenously) and day 4 (60 mg per os) in 40 patients after kidney transplantation. Methylprednisolone was determined in serum by HPLC. Within 6 months, all rejection episodes were recorded and confirmed by kidney transplant biopsy. Values are given as nonparametric medians with the 95% confidence interval (0.95 CI). The 7 patients with a rejection within the first 10 days had a methylprednisolone clearance of 437 ml/min (162-756) that was significantly higher than the 220 ml/min (121-604) in the 22 patients without a rejection episode (P = 0.04). In the complete group of 18 patients having a transplant rejection episode within 6 months, the methylprednisolone elimination half-life after oral dosage was 2.5 hr (1.6-3.9) and significantly shorter than 2.9 hr (1.7-4.0) in 22 patients without rejections (P = 0.03). No differences were seen for body weight, number of mismatches, cold ischemia time, immunosuppressive regimens, and other pharmacokinetic parameters of methylprednisolone (e.g. bioavailability, distribution volume, trough levels). We conclude that pharmacokinetic variability may contribute to the lack of immunosuppressive efficacy in patients with a short halflife of steroids. Therefore, a twice daily dose fraction might be useful for low-dose steroid regimens in kidney transplantation.
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PMID:Pharmacokinetics of methylprednisolone and rejection episodes in kidney transplant patients. 765 60

Only limited therapeutic measures are currently available for the treatment of spinal cord injury. This review describes the pathologic mechanisms of trauma-induced spinal cord injury in rats, which will contribute to new understanding of the pathologic process leading to spinal cord injury and to further development of new therapeutic strategies. Spinal cord injury induced by trauma is a consequence of an initial physical insult and a subsequent progressive injury process that involves various pathochemical events leading to tissue destruction; the latter process should therefore be a target of pharmacological treatment. Recently, activated neutrophils have been shown to be implicated in the latter process of the spinal cord injury in rats. Activated neutrophils damage the endothelial cells by releasing inflammatory mediators such as neutrophil elastase and oxygen free radicals. Adhesion of activated neutrophils to the endothelial cell could also play a role in endothelial cell injury. This endothelial cell injury could in turn induce microcirculatory disturbances leading to spinal cord ischemia. We have found that some therapeutic agents that inhibit neutrophil activation alleviate the motor disturbances observed in the rat model of spinal cord injury. Methylprednisolone (MPS) and GM1 ganglioside, which are the only two pharmacological agents currently clinically available for treatment of acute spinal cord injury, do not inhibit neutrophil activation in this rat model. Taken together, these observations raise a possibility that other pharmacological agents that inhibit neutrophil activation used in conjunction with MPS or GM1 ganglioside may have a synergistic effect in the treatment of traumatic spinal cord injury in humans.
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PMID:Spinal cord injury in the rat. 977 Feb 43

To study the efficacy of methylprednisolone/vitamin E in reducing cerebral edema and improving the ultimate neuropathological outcome in perinatal cerebral hypoxia-ischemia, 40 seven-day postnatal rats were subjected to right common carotid artery ligation followed by exposure to 8% oxygen at 37 degrees C for 3 h. The animals were divided into groups. Twenty rat pups received an intraperitoneal injection of 30 mg/kg body weight methylprednisolone and vitamin E (100 U/kg) immediately following cerebral hypoxia-ischemia. Control animals received either no therapy (n = 10) or an equivalent volume of normal saline (n = 10). After 72 h of recovery from hypoxia-ischemia, the animals were killed and their brains were examined to measure the water contents in the right and left hemispheres (29 rat pups), whereas the others were killed at 21 days for neuropathological examination. Methylprednisolone/vitamin E-treated rats had significantly less water content in the right hemisphere (87.08 +/- 0.28%, mean +/- S.E.M.) than saline-treated animals (89.07 +/- 0.37%, mean +/- S.E.M., P < 0.0001). Methylprednisolone/vitamin E significantly reduced water content in the right hemisphere of the brain. Neuropathological study was performed on nine rat pups. The brains of four methylprednisolone/vitamin E- and five saline-treated pups were examined at the end of the 21-day recovery period. Two groups of the right cerebral cortex included thinning of the cortex. Significantly less damage was seen in the methylprednisolone/vitamin E-treated pups. Our study suggests that trials of methylprednisolone/vitamin E might be effective if they are given to the mother at risk of fetal hypoxia during labor or to the hypoxic infant right after delivery in preventing hypoxic brain damage.
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PMID:Methylprednisolone and vitamin E therapy in perinatal hypoxic-ischemic brain damage in rats. 1040 17


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