{"title":"Nonsuppressible insulinlike activity (NSILA) and the glucose dyshomeostasis of agonal sepsis.","authors":"R E Viray, J P Filkins","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Peritonitis was induced through the ligation and puncture of rat ceca. The rats were divided into three groups: 1) rats whose ceca were ligated and punctured (CLP); 2) rats whose ceca were isolated and replaced without being tied or perforated (SHAM); and 3) rats which were fasted but not subjected to surgery (FC). Plasma glucose levels, serum insulin content, basal and stimulated glucose oxidation rates of adipose tissue, and nonsuppressible insulinlike activity were measured at the time of death or sacrifice. CLP rats were hypoglycemic (35.9 +/- 2.7 mg/dl) at death whereas both FC and SHAM groups were normoglycemic at 101 +/- 1.6 mg/dl and 94.3 +/- 3.9 mg/dl, respectively. Terminal serum immunoreactive insulin content for the three groups did not vary from each other. The oxidation of 14C-glucose to 14CO2 by the septic rats' epididymal fat pads was significantly greater than either SHAM or FC (56.3 +/- 6.4 vs 35.0 +/- 3.3 or 24.5 +/- 2.4 X 10(3) 14CO2 dpm/g/h). When a suprastimulatory concentration of insulin (1 mU/ml) was added in vitro, the septic rats' fat pads were further stimulated to a greater glucose oxidation rate than either SHAM or FC group. Finally, nonsuppressible insulinlike activity (NSILA) was assessed by the addition of guinea pig antiinsulin serum (GPAIS) and rat sera to the in vitro preparations. CLP sera demonstrated a significantly greater NSILA level than either control group. The gathered data suggest that enhanced peripheral tissue glucose oxidation in late sepsis is associated with elevated NSILA.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"9 ","pages":"31-41"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17410049","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}
F W Schmahl, R W Wabnitz, G Rox, K Drysch, G Richardt, E Poetter
{"title":"Effects of gabexate mesilate on the reactions of lipid metabolism in endotoxic shock.","authors":"F W Schmahl, R W Wabnitz, G Rox, K Drysch, G Richardt, E Poetter","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Endotoxic shock was induced in rabbits of either sex by IV injection of 50 micrograms/kg endotoxin (ET) extracted from E coli O-55 by Boivin's method. A polyvinyl catheter was introduced into the superior vena cava under local anesthesia 1 day prior to the experiments. We observed a rise of plasma-free fatty acids (FFA) from an initial mean value of 190 muEq/liter to a level of 290 muEq/liter within 6 h after injection of endotoxin. The increase of FFA was followed by a rise of plasma triglycerides (TG) and an increase of very low-density lipoproteins (VLDL), beginning 1-2 h later. The rise of FFA and the following increase of TG and VLDL were significantly reduced by infusion of 14 micrograms/kg X min gabexate mesilate (GM). Our results indicate that GM--in addition to its well-known proteinase inhibitory action--effects fatty acid metabolism.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"9 ","pages":"43-7"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17469653","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}
J Tanaka, T Sato, I K Berezesky, R T Jones, B F Trump, R A Cowley
{"title":"Effect of hypothermia on survival time and ECG in rats with acute blood loss.","authors":"J Tanaka, T Sato, I K Berezesky, R T Jones, B F Trump, R A Cowley","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effects of hypothermia on survival time and ECGs were investigated in hemorrhagic-shocked rats. Acute blood loss corresponding to LD84 was achieved within 1 min through cannulation of the carotid artery. Immediately following the hemorrhagic episode, extracorporeal cooling was performed by placing the animals, with ice packs attached to their lateral sides, in a cold water bath. Rewarming was achieved by removing the ice packs and resetting the temperature of the water bath to 37 degrees C. With this system, the survival time of the hemorrhagic rats was lengthened from 40 to 60 min without rewarming and to 123 min with rewarming. ECGs showed sinus bradycardia, prolonged PR and QRS intervals, AV block, and finally ventricular fibrillation in both the control and hemorrhagic groups during extracorporeal cooling. During rewarming, the above ECG changes returned to normal in the control group as did body temperature. In contrast, animals in the hemorrhagic group did not survive. Body temperature in this group began to rise toward normal, and above ECG changes showed slight but not complete improvement. It is concluded that extracorporeal cooling can lengthen the survival time of hemorrhagic-shocked rats and that recovery of the disturbed conduction system is a prerequisite for survival from severe hypothermia.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"9 ","pages":"219-32"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17931687","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":"Metabolism of prolonged shock.","authors":"A M Daniel, M E Taylor, B Kapadia, L D MacLean","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Dogs in shock due to controlled cardiac tamponade for 4 or 12 h were studied to determine which of the metabolic changes characteristic of early shock persisted if the shock state was prolonged. Moderate hyperglycemia and severe lactacidemia were present in the first few hours but the levels returned to near normal values by the end of 12 h. The entry rate of lactic acid into the circulation as well as the rate of glycogenolysis was high in the first 4 h but decreased thereafter even though skeletal muscle glycogen stores were not exhausted. In early but not in late shock glycogen accumulated in the heart. Glucose entry and exit rates were significantly elevated in early shock only. Increased protein utilization and decreased fatty acid mobilization persisted throughout the experimental period. Both in early and late shock the incorporation of labeled free fatty acid into tissue lipids was decreased in most organs. In the diaphragm free fatty acid incorporation only decreased in late shock. In the heart and lung, incorporation was higher than normal in the early stages but was at control levels after 12 h of shock.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"9 ","pages":"19-30"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17931688","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 a new synthetic complement inhibitor on hepatic glycolytic intermediates in septic rats.","authors":"T Ebata, R E Kuttner, F O Apantaku, W Schumer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Peritonitis and endotoxemia produce similar derangements in carbohydrate metabolism, indicating a common mechanism of action. Endotoxin activates the complement chain by the alternate pathway with the release of chemical mediators. These mediators may be responsible for the changes occurring in hepatic metabolite pools during endotoxemia. This hypothesis was tested with FUT-175, a complement inhibitor, (2-(6-amidino)naphthyl-4-guanidinobenzoate 2HC1). Peritonitis was induced by cecal incision in fasted male rats. FUT-175 was infused in 5% dextrose at a dose of 0.1 mg/ml/h. Survival time was 12.1 +/- 2.3 h in the FUT-175 group and and 6.6 +/- 1.1 h without FUT-175. Three peritonitis groups received either 5% dextrose alone; FUT-175 2.5 mg/100 g by IP injection, or FUT-175 0.1 mg/ml/h by infusion. Liver was sampled at 5 h by freeze-clamping, and metabolites were assayed by UV spectrophotometry. Peritonitis caused 33% decrease in glucose-6-phosphate (G6P), a 2.5-fold increase in fructose diphosphate (FDP), and 3.5-fold increase in lactate. In FUT-175-injected rats, G6P was decreased by 20%, FDP increased only 50%, and lactate doubled. Phosphoenolpyruvate (PEP) levels were increased 30% above peritonitis values. The drug produced a partial normalization of liver metabolites. The data suggest that the anticomplement action prevented the release of potent mediators which otherwise cause physiological changes leading to the metabolic imbalance of septic shock.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"9 ","pages":"275-82"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17931690","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":"Isotopic approaches to the estimation of protein requirements in burn patients.","authors":"R R Wolfe, R D Goodenough, M H Wolfe","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Determination of the protein requirement of the severely burned patient has been hampered by the lack of an appropriate means of evaluating the effects of various levels of intake. We have used two new isotopic techniques in an attempt to assess the effects of two levels of protein intake in six severely burned adult patients. A crossover experimental design enabled us to study each patient at the end of two 3-day dietary regimens. All diets were isocaloric and provided approximately 25% more calories than the measured energy expenditure (means = 40 Kcal/kg X day). In one regimen, each patient received 2.2 g protein/kg X day; during the other treatment period they received 1.4 g protein/kg X day. The patients were studied in the fed state and after 10-12 h of fasting. Leucine kinetics were determined by means of the primed-constant infusion of (1-13C)-leucine. We were able to distinguish the oxidation of plasma leucine from the oxidation of leucine derived from intracellular protein at the site of the deamination of leucine (predominantly muscle) by simultaneously determining both leucine and alpha-ketoisocaproic acid enrichment. Also, rates of whole-body protein synthesis and catabolism were calculated by means of another stable-isotope technique involving the infusion of (15N2)-urea. Finally, a third means of estimating net protein catabolism based on urinary N-excretion data was used at the same time that the isotopic studies were performed. The 13C-leucine data and the N-excretion data indicated that a balance between protein synthesis and catabolism could be achieved with a protein intake of 1.4 protein/kg X day. When protein intake was increased to 2.2 g protein/kg X day, neither isotopic method indicated a further beneficial effect on net protein synthesis, although the absolute rates of protein synthesis and catabolism were stimulated. The N-excretion data, however, indicated a significant improvement in net protein synthesis with higher protein intake. Regardless of the level of protein intake, the underlying alterations in protein metabolism that occurred as a response to burn injury persisted.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"9 ","pages":"81-98"},"PeriodicalIF":0.0,"publicationDate":"1983-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17929889","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}
J Tanaka, Y Kono, Y Shimahara, T Sato, R T Jones, R A Cowley, B F Trump
{"title":"A study of oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following living Escherichia coli injection.","authors":"J Tanaka, Y Kono, Y Shimahara, T Sato, R T Jones, R A Cowley, B F Trump","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mechanisms of subcellular dysfunction of the liver in sepsis are still obscure. The present study investigates changes in oxidative phosphorylative activity and calcium-induced respiration of rat liver mitochondria following live Escherichia coli injection (E coli, Serotype: 0--18. A 1.25--1.5 X 10(9)/100 gm body wt inoculum of E coli bacteria was injected via the tail vein, causing a 100% mortality rate within 24 hours after injection. In order to determine alteration of liver mitochondrial membrane permeability, serum ornithine carbamoyltransferase activity was measured following E coli injection. This activity increased ten to 100-fold over that of controls with time following injection. However, the yield of liver mitochondria from treated rats, estimated by the amount of collected mitochondrial protein and the recovery rate of succinate dehydrogenase activity in the final mitochondrial suspensions, was not significantly different from that of controls. Mitochondrial oxidative phosphorylative activity measured using glutamate as a substrate was enhanced throughout all period to death (P less than 0.01 at three and six hours, P less than 0.05 in the fatal stage) and was associated with concomitant increases in respiratory control ratios. Similar results were obtained using beta-hydroxybutyrate as a substrate. This enhancement was accompanied by an increase in 2-4-dinitrophenol-stimulated ATPase activity (160% at three hours and 130% in the fatal stage). Calcium-induced stimulation of mitochondrial respiration as well as initial calcium uptake rate linked to respiration, using glutamate as a substrate, were higher in liver mitochondria from rats with E coli treatment than in those of controls throughout all periods (P less than 0.01 or less). These results suggest the coexistence of hyperfunctioning as well as deteriorated mitochondria following lethal treatment with E coli.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"7 ","pages":"77-90"},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17806321","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}
T Sato, T Isoyama, J Tanaka, R T Jones, R A Cowley, B F Trump
{"title":"The pathophysiology of septic shock: changes in hemodynamics in rats following live E coli injection. An application of the thermodilution method for measurement of cardiac output.","authors":"T Sato, T Isoyama, J Tanaka, R T Jones, R A Cowley, B F Trump","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Fifteen anesthetized rats, 273 +/- 9 gm (SEM), were monitored hemodynamically for six hours following an IV injection of a sublethal (4--5) X 10(8) organisms/100 gm body wt, n = 5) or lethal 12--15 X 10(8) organisms/100 gm body wt, n = 5) dose of live Escherichia coli or saline (control, n = 5). A transpulmonary thermodilution method was used for measurement of cardiac output. Changes in the arterial blood temperature and pressure were recorded on a polygraph. In a simulated hydraulic model system, the measured flow rate was well correlated ( r = 0.993, P less than 0.001) with various actual flow readings (30--130 ml/minute). A sublethal dose resulted in a transient hyperdynamic state in the early stage; the cardiac index was increased from the initial rate of 258.2 +/- 9.4 to 312.3 +/- 10.7 ml/minute/kg with a concomitant decrease in the total peripheral resistance from 0.497 +/- 0.019 to 0.367 +/- 0.022 mm Hg/ml/minute/kg which was sustained for 120 minutes after treatment. In contrast, a lethal dose caused a prolonged hyperdynamic state in the early stage followed by a hypodynamic state in the late stage. The cardiac index was increased from 2.54 +/- 4.5 to 306.0 +/- 10.8 ml/minute/kg and the total peripheral resistance was decreased from 0.513 +/- 0.024 to 0.337 +/- 0.015 mm Hg/ml/minute/kg in the early stage, while, in the late stage, the former decreased to 195.0 +/- 13.3 ml/minute/Kg and the latter increased to 0.615 +/0 0.054 m Hg/ml/minute/kg. The mean arterial blood pressure was decreased in both groups in the early stage but maintained above 100 mm Hg. Essentially, no hemodynamic changes were noted in the control group. These results confirm our hypothesis that an injection of live E coli can produce a hyperdynamic state in the early stage as well as hypodynamic state in the late stage, and that serial hemodynamic studies on bacteremia in rats can be done successfully using the thermodilution method.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"7 ","pages":"25-42"},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17806557","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":"Mechanism of forelimb skin and skeletal muscle glucose uptake during Escherichia coli endotoxin shock in the dog.","authors":"M D Karlstad, R M Raymond, T E Emerson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This study was undertaken to investigate mechanisms of increased glucose uptake by forelimb skin and skeletal muscle during endotoxin shock. Anesthetized mongrel dogs were used. Forelimbs were perfused at either natural or constant blood flow. Temperature of the isolated forelimb was maintained at core temperature. Shock was induced by an IV injection of 2 mg/kg Escherichia coli endotoxin. Forelimb skin and skeletal muscle glucose uptake increased by 30 minutes of shock and remained elevated in the natural flow study. In the constant flow study, glucose uptake by both skin and skeletal muscle was increased at 30 minutes of shock but thereafter returned to control. The natural flow forelimbs were ischemic and hypoxic during shock, whereas the constant flow forelimbs were neither ischemic not hypoxic. Progressive hypoglycemia developed in both endotoxin shock groups. These data support the hypothesis that the mechanism of increases in forelimb skin and skeletal muscle glucose uptake during endotoxin shock is related to local tissue hypoxia.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"7 ","pages":"101-15"},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17806622","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}
M F Wilson, D J Brackett, L T Archer, B K Beller-Todd, P Tompkins, L B Hinshaw
{"title":"Survival characteristics during septic shock in 39 baboons.","authors":"M F Wilson, D J Brackett, L T Archer, B K Beller-Todd, P Tompkins, L B Hinshaw","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In septic shock nonsurvival is characterized by failure of multiple organ systems. The design of therapeutic measures to increase survival would be enhanced if critical responses could be identified early. Escherichia coli LD100 was given to 39 baboons by IV infusion over two hours followed by different therapy regimens in 31 [2--4]. There were 18 permanent survivors (seven days or more), all receiving antibiotic/steroid combination therapy. Responses of survivors and nonsurvivors were measured and compared during the first 12 hours from onset of infusion. Changes in blood pressure and acid-base parameters were not significantly different between groups. Five responses indicative of permanent survival were lower heart rates, less elevation of blood urea nitrogen, normal blood glucose at eight hours, hyperglycemia with normal insulin at 12 hours, and lower plasma lactate concentrations beginning at four hours.</p>","PeriodicalId":75453,"journal":{"name":"Advances in shock research","volume":"7 ","pages":"13-23"},"PeriodicalIF":0.0,"publicationDate":"1982-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17806624","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}