{"title":"Arachidonic acid metabolism in endotoxin tolerance.","authors":"W C Wise, J A Cook, P V Halushka","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The arachidonic acid metabolites thromboxane A2, a potent platelet aggregator, and prostacyclin, a potent vasodilator, are released early in endotoxin shock and may contribute to its pathologic sequelae. Plasma levels of thromboxane (Tx) A2 and prostacyclin were measured via radioimmunoassay of their stable metabolites immunoreactive (i) TxB2 and i6-keto-PGF1 alpha in tolerant and nontolerant rats after endotoxin. Long-Evans rats were made tolerant to endotoxin by four daily IV injections of S enteritidis (endotoxin) (0.1, 0.5, 1, and 5 mg/kg). In normal rats (N = 15) given LPS (IV, 15 mg/kg), only 11% survived at 24 h; in contrast, tolerant rats (N = 13) all survived even at a dose of 50 mg/kg. At 1 h, after endotoxin (15 mg/kg) IV, plasma i6-keto-PGF1 alpha in nontolerant rats was 1,005 +/- 149 pg/ml (N = 14) and continued to rise to 4,209 +/- 757 pg/ml (N = 5) (P less than 0.001) after 4 h. In tolerant rats, given endotoxin (15 mg/kg), plasma i6-keto-PGF1 alpha at 1 h was 800 +/- 203 pg/ml (N = 5) and was not significantly different (734 +/- 254 pg/ml) at 4 h. Plasma iTxB2 at both 1 and 4 h was significantly (P less than 0.01) lower in tolerant than nontolerant rats. Both iTxB2 and i6-keto-PGF1 alpha were significantly (P less than 0.01) lower in tolerant rats given 50 mg/kg IV endotoxin than nontolerant rats. Endotoxin-induced elevation in fibrin degradation products was significantly decreased (P less than 0.05) during endotoxin tolerance although there was no difference in the severity of thrombocytopenia. These composite observations demonstrate that endotoxin tolerance in the rat is associated with altered arachidonic acid metabolism.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"10 ","pages":"131-42"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17469651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Influence of septic peritonitis on circulating fibronectin, immunoglobulin, and complement: relationship to reticuloendothelial phagocytic function.","authors":"M H McCafferty, T M Saba","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This study was designed to quantify the changes in the major serum opsonins--ie, fibronectin, IgG, and C3--during Staphylococcus aureus and Escherichia coli peritonitis as they may functionally relate to RES phagocytic function. Both forms of peritonitis were characterized by acute depletion of fibronectin, IgG, and C3 within 6 h. By 24 h, C3 levels had returned to control levels in both groups. IgG levels remained depressed 24 h following the induction of E coli peritonitis but had normalized by 24 h after Staph aureus challenge. In contrast, fibronectin was markedly elevated by 24 h with both E coli and Staph aureus peritonitis. Hepatic RES phagocytic function was significantly stimulated following induction of either Staph aureus or E coli peritonitis. The rapid increase in fibronectin as well as RES activation during septic peritonitis may represent a generalized host-defense response.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"9 ","pages":"241-55"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17410048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of lidocaine on hepatic prostanoid production in vitro following 2,4-dinitrophenol administration.","authors":"J T Flynn","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The uncoupling of oxidative phosphorylation with 2,4-dinitrophenol (DNP) stimulates prostacyclin production in the isolated, perfused rabbit liver. This study determines the effect of a clinically used drug, lidocaine, on DNP induced cellular injury and prostanoid biosynthesis in vitro. Livers were perfused with buffer alone, buffer containing 10 microM DNP or lidocaine, or buffer containing both 10 microM DNP and 10 microM lidocaine. DNP treatment significantly increased lactic dehydrogenase and acid phosphatase activity in the effluent perfusate, indicating a moderate degree of cellular injury. These enzyme changes were exacerbated by lidocaine. The rate of release of thromboxane B2 by the perfused liver was not significantly affected by DNP or lidocaine treatment. In contrast, DNP significantly stimulated 6-keto PGF1 alpha production from a control period value of 177 +/- 40 to 2,938 +/- 979 picograms/min/g wet weight after 180 minutes of perfusion. The addition of 10 microM lidocaine to the DNP treatment resulted in a significant attenuation in the rate of endogenous 6-keto PGF1 alpha release to values not different from those of the sham plus vehicle-treated group. In livers receiving lidocaine alone, there was a slight but significant increase in the rate of 6-keto PGF1 alpha synthesis. These data demonstrate that lidocaine can inhibit injury related activation of the arachidonic acid cascade in hepatic tissue. The addition of lidocaine to the perfusate of the injured livers also resulted in a more severe degree of cellular injury. The relationship between these two events remains to be determined.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"10 ","pages":"149-59"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17410178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L T Archer, S D Kosanke, B K Beller, R B Passey, L B Hinshaw
{"title":"Prevention or amelioration of morphologic lesions in LD100 E coli-shocked baboons with steroid/antibiotic therapy.","authors":"L T Archer, S D Kosanke, B K Beller, R B Passey, L B Hinshaw","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have documented the effectiveness of methylprednisolone sodium succinate (MPSS) and gentamicin sulfate (GS) therapy for LD100 E coli-induced shock in the baboon. We sequentially delayed initiation of MPSS infusion from 30 to 120 min and then to 240 min after onset of a 2-h E coli infusion. Treatment resulted in 100%, 85%, and 65% survival respectively. In this study we evaluated tissue taken at autopsy in the three MPSS/GS treatment studies including untreated baboons and those treated with GS only. When animals died (3-49 h) or were sacrificed (7-71 days), tissues were removed, coded, and prepared for histopathologic evaluation by light microscopy. On the basis of morphologic changes animals split into two groups: baboons with little or no tissue alterations (survivors), and those with multiple organ damage (nonsurvivors). Combinations of mild to massive congestion, edema, hemorrhage, fibrin thrombi, increased numbers of polymorphonuclear leukocytes (PMNs), and necrosis of the adrenal glands, liver, kidneys, lungs, and spleen of nonsurvivors were prevented or ameliorated in the MPSS/GS-treated surviving baboons. Data demonstrate the MPSS/GS therapy prevents or reverses the multiple organ damage and increases survival in lethal septic shock.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"10 ","pages":"195-215"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17410182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Peripheral effects of opiate antagonists in shock.","authors":"A M Lefer, M T Curtis","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"10 ","pages":"83-6"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17369624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of endogenous opiates in shock: experimental and clinical studies in vitro and in vivo.","authors":"I S Weissglas","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"10 ","pages":"87-94"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17369625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D L Traber, J Jinkins, K Rice, L Sziebert, T Adams, N Henriksen, L D Traber, P D Thomson
{"title":"Role of lymphocytes in the ovine response to endotoxin.","authors":"D L Traber, J Jinkins, K Rice, L Sziebert, T Adams, N Henriksen, L D Traber, P D Thomson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The involvement of thymocytes in the cardiopulmonary response to endotoxin was studied in chronically instrumented sheep. Four hours after the administration of 0.75 microgram/kg of endotoxin the blood levels of thymocytes were less than 25% of the control value, at a time when there was a marked fall in the cardiac index and a rise in pulmonary lymph flow. In a second series of experiments sheep were depleted of their thymocytes by the administration of antithymocyte serum. When endotoxin was given to these animals the cardiac output did not fall to the same extent, nor did the hematocrit rise as much as it did in the intact animal. It thus appears that the thymocyte may play a contributing role in the cardiopulmonary response to endotoxin.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"9 ","pages":"257-63"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17660263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L Sziebert, P D Thomson, J Jinkins, K Rice, T Adams, N Henriksen, L D Traber, D L Traber
{"title":"Effect of naloxone treatment on the cardiopulmonary response to endotoxin in sheep.","authors":"L Sziebert, P D Thomson, J Jinkins, K Rice, T Adams, N Henriksen, L D Traber, D L Traber","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The administration of small dosages of endotoxin to sheep results in cardiopulmonary changes characterized by an elevation in pulmonary lymph flow, vascular resistance, and hemoconcentration, and a reduction in cardiac output. These changes are not as great when the narcotic antagonist, naloxone (2 mg/kg/h for 5 h), is infused prior to and during the endotoxin response. The present study evaluates the ovine response to endotoxin when naloxone is administered 1 h after the endotoxin infusion. Sheep were prepared by implanting cardiopulmonary and lung lymphatic catheters. One week following the last surgical procedure, the sheep, in the awake state, were given 0.75 micrograms/kg of endotoxin and the variables were measured. Three days later, a second dose of endotoxin was administered and variables were again measured. An infusion of naloxone was given with one of the dosages of lipopolysaccharide. Two dosages of the narcotic antagonist were used. One group received 2 mg/kg bolus + 2 mg/kg/h for 5 h; another group was given twice this amount. Both dosages were started 1 h after endotoxin. The response to endotoxin was essentially the same whether or not the sheep were treated with naloxone. If naloxone pretreatment is effective and posttreatment is not, then it is possible that an opiatelike substance might be released by endotoxin which in turn results in the ultimate release of the lesion-producing substance.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"10 ","pages":"121-8"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17931010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protons and glucose metabolism in shock.","authors":"P W Hochachka","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>When oxygen is limiting, animals can ferment glucose via several metabolic pathways varying in energetic efficiency and leading to various end products (such as lactate, succinate, or propionate). Because the pH dependence of H+ production by fermentation is opposite to that by hydrolysis of adenosine triphosphate formed in the fermentation, the total number of moles of protons generated is always two per mole of fermentable substrate. However, two and three times more adenosine triphosphate can be turned over per mole of protons produced in succinate and propionate fermentations, respectively, than in lactate fermentation. At its limit, this advantage would achieve the same balance between H+ production and H+ consumption during ATP cycling that is observed in aerobic metabolism, a situation observed in certain alcohol fermentations. Since proton balance during anaerobiosis is clearly adaptable, we consider possible impact and functions of net H+ accumulation during carbohydrate metabolism in endotoxin shock.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"9 ","pages":"49-65"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17369626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The influence of glucocorticoids on hepatic glycolytic intermediates in fed peritonitis rats.","authors":"R E Kuttner, T Ebata, F O Apantaku, W Schumer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Earlier work on fasted endotoxemic and septic rats suggested that glucocorticoid pretreatment improved survival by promoting gluconeogenesis. The possible mechanism of this therapeutic effect was investigated in fed peritonitis septic rats, which are in a predominantly glycolytic mode of metabolism. Fed adult male rats (185-255 g) received cecal incisions or sham operations under ether with or without simultaneous IV injection of dexamethasone (DMS) (1.0 mg/100 g rat). Liver was sampled by freeze-clamping at 5 h, and glycolytic intermediates were determined by UV spectrophotometry. The high-energy intermediate, phosphoenol-pyruvate (PEP), fell 57% to 76 +/- 83 nmole/g wet liver (+/- 1 SD) in the fed peritonitis group; nine of 13 rats had PEP values at least 50% below mean control concentrations. Fasted septic rats (N = 26) do not have decreased PEP levels. Glucocorticoids were protective in the fed septic rats; only five of 17 DMS-pretreated rats had PEP fall below 50% of the fed normals. A significant finding was the decline in fructose diphosphate (FDP) from 32 +/- 9 nmole in fed shams (N = 12) to 21 +/- 11 nmole/g wet liver with DMS-pretreated fed shams (N = 15). This suggests that DMS may be inhibiting the glycolytic enzyme, phosphofructokinase, and thereby enhancing gluconeogenesis by sparing hexose monophosphates. Lactate in fed sham liver was 1,869 +/- 336 nmole/g, a concentration twofold greater than in fasted liver. This difference may contribute to the increased vulnerability of fed rats to septic shock. It is concluded that glucocorticoids tend to normalize Embden-Meyerhof pathway intermediates in both fed and fasted rat livers.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"10 ","pages":"175-82"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17742573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}