Effects of anti-toxic agents in septic shock

From 1975 to 1987, we had 56 patients of septic shock in the Department of Surgery. Multiple organ failure occurred in many septic patients. Glucocorticoids inhibited the secretion of chemical mediators (histamine, serotonin and bradykinin) and then prevented septic shock. Intravenous administration of dexamethasone showed no change in amounts of leukotrienes (LTC4, LTD4, LTE4) in venous blood in peritonitis rats. Dexamethasone treatment of septic rats corrected FDP and nearly normalized PEP values. When glucocorticoid was given intravenously at the time of cecal incision, PFKase, PKase, G6Pase and PEPCK were stimulated, respectively. Protease inhibitor FUT-175 was infused in 5% dextrose (0.1mg/ml/hr) in septic rats. Survival time was 12.1 +/- 2.3 hour in FUT-175 group and 6.6 +/- 1.1 hr without FUT-175. In FUT-175 injected rats G6P decreased by 20%, FDP increased 50% and lactate doubled. PEP levels increased 30% above peritonitis values. The amounts of leukotrienes (LTC4, LTD4, LTE4) in venous blood were gradually decreased by pretreatment with the specific 5-lipoxygenase inhibitor AA-861 after peritonitis. Specific treatments in septic shock should be instituted administration of glucocorticoid, antibiotics, protease inhibitor and lipoxygenase inhibitor. The importance of septic shock as a factor contributing to organ failure must be acknowledge. We believe that the prompt and efficacious treatment of septic shock is the best therapy.     

Liver gluconeogenic metabolites in young and old rats during septic shock

Aged individuals have diminished resistance to severe sepsis and septic shock. Previous studies in young animals showed that the liver's gluconeogenic capacity was an important determinant of survival in shock states. This study compared hepatic carbohydrate intermediates from young rats and old rats to correlate changes during peritonitis septic shock with known differences in survival times. Old control rats had glucose 6-phosphate (G6P) concentrations two-fold higher than young controls, 354 +/- 49 nanomole/g wet liver vs 180 +/- 41, suggesting a reduced ability to convert hexose monophosphate precursor into blood sugar. There was a 53% increase in G6P levels in the peritonitis livers, to 540 +/- 155 nanomole/g liver while in young septic rats the G6P decreased 33 per cent. These opposite, highly significant changes in shock (P = 0.01) show the reduced ability of old animals to mobilize gluconeogenic precursors. Fructose 1,6-biphosphate (FBP) in old control liver was 14 +/- 3 nanomole/g liver and did not change in shock; in young rats, FBP was 7.0 +/- 3 nanomole and increased 230 per cent in shock, showing a different metabolic response in young and old animals. These data suggest older animals may be more vulnerable to shock because of lower gluconeogenic potential.     

Regulation of glucose metabolism in livers and kidneys of NOD mice.

Measurements were made of the levels of metabolic intermediates and activities of enzymes of the glycolytic route, pentose phosphate pathway, and polyol pathway in livers and kidneys of NOD mice. A 34% decrease in UDP-glucose, a 40% decrease in glucose-6-phosphate (G6P) and fructose-6-phosphate, and a 75% decrease in fructose-2,6-bisphosphate (F2,6P) were found in the livers of NOD mice. The fall in the level of F2,6P (the important regulator of glycolysis) is accompanied by a 20% reduction in the activity of phosphofructokinase. These changes are in agreement with previously reported liver depletion of glycogen and reduced synthesis of proteins and nucleic acids in the diabetic state. In the kidney, the increase in hexokinase activity is consistent with increased levels of G6P and glycogen content of kidney in diabetes. The decreased level of phosphoribosyl pyrophosphate was reported to be a regulator of kidney growth in the initial period of diabetes but can still be found in NOD mice 6 wk after development of hyperglycemia. The reported changes are similar to those seen in alloxan- or streptozocin-induced diabetic animals, but certain changes are more marked in NOD mice, especially those directed to increase nucleic acid and protein synthesis in the diabetic kidney.     

Continuous veno-venous haemofiltration attenuates myocardial mitochondrial respiratory chain complexes activity in porcine septic shock

Increasing evidence indicates that mitochondrial dysfunction plays an important role in modulating the development of septic shock. In the present study, we investigated whether continuous veno-venous haemofiltration (CVVH) with high-volume might improve myocardial mitochondrial dysfunction in a porcine model of peritonitis-induced septic shock. Sixteen male Landrace pigs weighing 31 +/- 5 kg were randomly assigned to normal control group (n = 4), peritonitis group (n = 6) and peritonitis plus CVVH group (n = 6). All animals were anaesthetised and mechanically ventilated. After baseline examinations, the peritonitis group and the peritonitis plus CVVH group underwent induction of peritonitis. One hour later, the animals in the peritonitis plus CVVH group received treatment with high-volume CVVH. Twelve hours after treatment, the animals were sacrificed. Animals in the peritonitis group were killed 13 hours after induction of peritonitis. Peritonitis challenge induced septic shock associated with increased blood lactate and high-volume CVVH improved lactate acidosis. Compared with the peritonitis group, cardiac output, stroke volume and mean arterial pressure were better maintained in peritonitis plus CVVH group. More importantly, high-volume CVVH improved myocardial mitochondrial complex I activity (0.22 +/- 0.03 vs. 0.15 +/- 0.04, P = 0.04). These results suggest that high-volume CVVH improves haemodynamics and heart dysfunction in septic shock and the improvement may be attributed to amelioration of myocardial mitochondrial dysfunction.     

Inhibitory effect of dimethyl sulfoxide on nuclear factor-kappa B activation and intercellular adhesion molecule 1 gene expression in septic rats

Antioxidants are potent radical scavengers that protect against endotoxemia and septic shock in animal models. Using a rat model of peritonitis sepsis induced by cecal incision we studied the effect of the free radical scavenger dimethyl sulfoxide (DMSO) on hepatic nuclear factor kappa B (NF-kappa B) activation, hepatic intercellular adhesion molecule 1 (ICAM-1) gene expression, serum tumor necrosis factor alpha (TNF) formation, and serum glucose concentration. Five groups of rats (N = 5) were treated as follows: (1) untreated control (Untreated), (2) sham operated with laparotomies (Sham), (3) pretreated with 6 ml/kg DMSO followed by sham operation (DMSO/Sham), (4) cecal incision (Sepsis), and (5) pretreated with DMSO followed by cecal incision (DMSO/Sepsis). In the DMSO/Sham group, DMSO did not affect NF-kappa B activation, ICAM-1 gene expression, and TNF formation. At 3 h postcecal incision, DMSO inhibited sepsis-induced hepatic NF-kappa B activation and hepatic ICAM-1 gene expression to control levels and suppressed serum TNF by 75%. In the late (6 h) septic phase, DMSO inhibited NF-kappa B activation (32%), ICAM-1 gene expression (27%), and TNF formation (71%). These findings suggest that the protective mechanism of antioxidants in septic rats may be partly due to the inhibition of NF-kappa B activation and NF-kappa B-mediated events.     

Effective renal blood flow and renal energy charge in murine peritonitis

The temporal sequence of physiological derangements preceding acute renal failure (ARF) observed in overwhelming bacterial septicemia remains controversial. In order to examine the relationship of renal circulatory alterations and cellular dysfunction in murine sepsis, effective renal plasma flow (ERPF), renal tissue metabolites, and energy charge ratios were determined in Sprague-Dawley rats at 10 and 20 hours following induction of peritonitis by cecal ligation and perforation (CLP) or cecal manipulation alone (sham). Tissue levels of adenine nucleotides, lactate, and pyruvate were assayed after freeze-clamping kidneys unilaterally followed by enzymatic determinations. Cardiac outputs were determined by thermodilution and ERPF by p-aminohippuric acid (PAH) clearance. Results indicate in this model, despite an increase in cardiac output (P less than 0.05), ERPF was significantly decreased at both 10 hours (P less than; 0.05) and 20 hours (P less than 0.01) following induction of peritonitis. Further, although tissue pyruvate/lactate ratios showed significant decreases by 10 hours (P less than 0.05), diminished energy charge ratios were not observed until 20 hours following septic insult. These findings support the hypothesis of diminished renal perfusion as contributory and antecedent to cellular dysfunction in septicemic ARF.     

Local anesthetics reduce mortality and protect against renal and hepatic dysfunction in murine septic peritonitis

BACKGROUND: Mortality from sepsis frequently results from multiple organ injury and dysfunction. Cecal ligation and puncture is an established murine model of septic peritonitis that produces septic shock characterized by an initial hyperinflammatory response. In addition to their anesthetic properties, local anesthetics have been shown to attenuate inflammatory responses both in vivo and in vitro. In the current study, the ability of local anesthetic infusions to protect against sepsis-induced mortality, as well as renal and hepatic dysfunction after cecal ligation and puncture, was investigated. METHODS: C57BL/6 mice received mini-osmotic pumps containing saline (vehicle), 10% lidocaine, or 1% bupivacaine and were subjected to cecal ligation and puncture. Twenty-four hours after cecal ligation and puncture, renal and hepatic functions were assessed as well as markers of inflammation (proinflammatory cytokine protein and mRNA concentrations and myeloperoxidase activity). Renal apoptosis and 7-day survival was also assessed. RESULTS: Mice treated with lidocaine or bupivacaine infusion showed improved survival and had significantly lower plasma creatinine, aspartate aminotransferase, and alanine aminotransferase concentrations compared with mice receiving vehicle alone. Significant reduction in plasma tumor necrosis factor-alpha and keratinocyte-derived chemokine, as well as reductions in myeloperoxidase activity, intracellular adhesion molecule-1 protein expression, mRNA concentrations of proinflammatory markers, and apoptosis were observed in renal cortices from both local anesthetic groups. CONCLUSIONS: The current data demonstrate that local anesthetic infusions confer a protective effect in mice from septic peritonitis by attenuating the hyperacute inflammatory response. This suppression resulted in improved mortality and less progression to acute kidney and liver injury and dysfunction.     

Therapeutic effect of dimethyl sulfoxide on ICAM-1 gene expression and activation of NF-kappaB and AP-1 in septic rats

BACKGROUND: Dimethyl sulfoxide (DMSO) is a potent antioxidant which protects against endotoxemia and septic shock in animal models. We investigated the therapeutic effect of DMSO on intercellular adhesion molecule 1 (ICAM-1) gene expression and activation of nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) in a rat model of peritonitis sepsis. This postchallenge model simulates the clinical treatment of ruptured viscus peritonitis. MATERIALS AND METHODS: Peritonitis was produced by subjecting rats to laparotomy, followed by a 1-cm cecal incision (CI) to produce fecal soilage of the peritoneum. Rats were subjected to laparotomy only for the sham-operated group. For the protection study, DMSO (6 ml/kg) was injected ip at 30, 60, or 90 min post-CI surgery. The levels of ICAM-1 mRNA expression and activation of NF-kappaB and AP-1 in livers were determined at 3 and 6 h post-CI. RESULTS: At 3 h post-CI surgery (early sepsis), DMSO treatment at 30 and 60 min post-CI surgery significantly inhibited sepsis-induced ICAM-1 mRNA expression and activation of NF-kappaB and AP-1. DMSO has no effect on ICAM-1 gene expression and activation of NF-kappaB and AP-1 when administered at 90 min post-CI surgery. At 6 h post-CI surgery (late sepsis), DMSO administered at 30, 60, or 90 min post-CI surgery significantly inhibited ICAM-1 mRNA expression and NF-kappaB activation but not AP-1 activation. CONCLUSIONS: Therapeutic treatment of DMSO inhibited sepsis-induced activation of NF-kappaB and AP-1, resulting in the suppression of ICAM-1 gene expression in the livers of peritonitis septic rats. This finding suggests that reactive oxidants are involved in the signal transduction pathways for activation of NF-kappaB and AP-1. Thus, antioxidants which inhibit NF-kappaB and AP-1 activation may be beneficial in treating sepsis and septic shock.     

Effect of severe hemorrhage on rat hepatic glycolytic intermediates

The concentrations of key hepatic glycolytic intermediates were determined at different time intervals in fasted adult male rats following the removal of 40% of the estimated blood volume. This procedure lowered arterial pressure to 40–45 mm Hg. Frozen liver samples taken immediately after bleeding showed an 87% decrease of phosphoenolpyruvate (PEP), a critical high-energy metabolite, while glucose 6-phosphate (G6P) was reduced 67% compared to controls. Liver lactate increased 2.5-fold and fructose 1,6-diphosphate (FDP) was doubled, indicating the rapid onset of hypoxic conditions and the simultaneous decline of gluconeogenesis. Within 15 min, however, homeostatic mechanisms had restored PEP levels to normal and at 1 hr to supernormal concentrations. G6P rose almost to the control range in 1 hr and was 100% overcompensated at 3 and 5 hr. Liver lactate and FDP were normalized at 3 and 5 hr. The data reveal the great sensitivity of the glycolytic cycle to the hypovolemia and hypoxia of severe hemorrhage and, additionally, the remarkable capacity of the liver to promptly restore depleted substrates. Theoretically significant was the fact that the hepatic metabolite pattern differed completely from previous findings on endotoxic and septic livers studied at 5 hr. This difference in metabolic pattern suggests that the changes in endotoxemic and septic liver are not caused by circulatory deficits and that the hypoglycemia of terminal infective states results from some other factor.     

Hepatic glycolytic intermediates in fed and fasted rats after severe hemorrhage

The responses of key liver carbohydrate intermediates to severe hemorrhage were investigated in fed and fasted young adult male rats. Forty per cent of intravascular blood was withdrawn and liver was sampled by freeze-clamp at 0, 0.25, 1.0, 3.0, and 4.0-5.0 hours. Fed rats with abundant glycogen showed a threefold increase in glucose-6-phosphate (G6P) concentration, and fasted rats showed a 75% decline in G6P immediately after hemorrhage. This significant difference in response traces to the fact that G6P is one of the first catabolites in fed liver formed by glycogenolysis but is the last intermediate of the gluconeogenic pathway in fasted animals. Phosphoenolpyruvate (PEP), the high-energy intermediate, was markedly depleted in both fed and fasted rats at zero time. In the fasted animal, however, the PEP was rapidly restored, and by 1.0 hour was threefold above normal. The ability of fasted rats to rapidly synthesize glucose from accumulated lactate is attributed to increased amount of gluconeogenic enzymes induced by fasting. In prolonged shock states, this synthetic capacity plays a protective role. Contrariwise, in brief shock states such as hemorrhage, the immediate availability of glucose from stored glycogen appears to be a more important determinant of survival. In the present experiments, fed rats were more resistant to the hemorrhage protocol.     

Alterations in glucose-6-phosphatase gene expression in sepsis

BACKGROUND: The influence of sepsis on the expression and activity of hepatic glucose-6-phosphatase (Glu-6-Pase) was examined during the early hyperglycemic phase and the later hypoglycemic phase. METHODS: Sepsis was induced in anesthetized, fasted rats by cecal ligation and puncture, and liver samples were taken at 0, 0.5, 1, 1.5, and 20 hours after cecal ligation and puncture. RESULTS: The mRNA abundance of hepatic Glu-6-Pase increased fourfold at 0.5 hours over healthy control values, two-fold after 1 hour, and returned to normal after 1.5 hours. This finding was followed by a corresponding increase in Glu-6-Pase activity and was coincident with increased plasma glucose levels and decreased liver glucose-6-phosphate (Glu-6-P) at 0.5 and 1 hours. Plasma insulin and glucagon levels remained unchanged during this period, whereas corticosterone levels increased 2.5-fold over control values. At 20 hours cecal ligation and puncture, plasma glucose levels returned to normal, coincident with a 90% reduction in Glu-6-Pase mRNA abundance. Glu-6-Pase activity and Glu-6-P concentration returned to normal levels, while insulin, glucagon, and corticosterone levels increased significantly, i.e., 40-fold, 6.5-fold, and 6-fold, respectively. CONCLUSION: The initial rise and subsequent decline in blood glucose correlate very well with a corticosterone-dependent induction of hepatic Glu-6-Pase, mRNA, and protein, followed by an insulin-dependent suppression of its expression.     

Effect of sepsis on tissue adenine nucleotide levels.

Tissue adenine nucleotides were measured in rats to determine if there is depletion of energy stores associated with sepsis. Peritonitis was produced by cecal ligation and cecal puncture. At 16 to 24 hours after ligation, rats which were lethargic but still normotensive (late sepsis) and showed clinical and laboratory confirmation of peritonitis-sepsis were stunned by a blow on the head, and small pieces of tissue were removed and frozen. Adenine nucleotides were measured enzymatically. In late sepsis adenosine triphosphate (ATP) levels in liver and kidney decreased significantly; however, no significant decreases were observed in the diaphragm or gastrocnemius muscle. Hydrogen polarograph measurements of hepatic blood flow indicated that flow was decreased markedly at this stage of peritonitis. A second group of rats was prepared in the same manner, except they were studied 10 hours after ligation (early sepsis). Most rats at this stage of sepsis appeared to be only mildly ill; however, blood cultures obtained from six rats so prepared all were positive. These rats did not show any decrease in either hepatic blood flow or tissue adenine nucleotides. Thus the changes in adenine nucleotides observed in late sepsis (lpw-flow septic rats) are similar to those seen during early hemorrhagic shock and suggest inadequate perfusion associated with peritonitis as the cause.     

Inhibition by AICA riboside of gluconeogenesis in isolated rat hepatocytes.

5-Amino-4-imidazolecarboxamide (AICA) riboside, the nucleoside corresponding to AICA ribotide (AICAR or ZMP), an intermediate of the de novo pathway of purine biosynthesis, was found to exert a dose-dependent inhibition on gluconeogenesis in isolated rat hepatocytes. Production of glucose from lactate-pyruvate mixtures was half-maximally inhibited by approximately 100 microM and completely suppressed by 500 microM AICA riboside. AICA riboside also inhibited the production of glucose from all other gluconeogenic precursors investigated, i.e., fructose, dihydroxyacetone, and L-proline. Measurements of intermediates of the glycolytic-gluconeogenic pathway showed that AICA riboside provoked elevations of triose phosphates and fructose-1,6-bisphosphate and decreases in fructose-6-phosphate and glucose-6-phosphate. The effects of AICA riboside persisted when the cells were washed 10 min after its addition but were suppressed by 5-iodotubercidin, an inhibitor of adenosine kinase. AICA riboside provoked a dose-dependent buildup of normally undetectable Z nucleotides. After 20 min of incubation with 500 microM AICA riboside, ZMP, ZTP, and ZDP reached 3, 0.3, and 0.1 mumol/g cells, respectively. Concentrations of ATP were not significantly modified by addition of up to 500 microM AICA riboside when the cells were incubated with lactate-pyruvate but decreased with fructose or dihydroxyacetone. The activity of rat liver fructose-1,6-bisphosphatase was inhibited by ZMP with an apparent Ki of 370 microM. It is concluded that AICA riboside exerts a suppressive effect on gluconeogenesis because it provokes an accumulation of ZMP, which inhibits fructose-1,6-bisphosphatase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Severe sepsis induces deficient interferon-gamma and interleukin-12 production, but interleukin-12 therapy improves survival in peritonitis.

BACKGROUND: After severe sepsis, there is an increase of Th2 cytokine and a decrease in Th1 cytokine that may account for impaired cellular immunity. The aim of this study is to evaluate the Th1, Th2 cytokine balance in the serum, peritoneal lavage fluid (PLF) and liver mononuclear cells (MNC) of experimental peritonitis mice, and determine the effect of interleukin-12 (IL-12), a cytokine stimulating Th1 cytokine production, when administered to septic mice. METHODS: Experimental bacterial peritonitis mice was induced by cecal ligation and puncture (21-gauge needle, mild peritonitis) or cut (5 mm, severe peritonitis). Serum and PLF levels and liver MNC production of interferon (IFN)-gamma, IL-10, and IL-12 were measured after the procedure. Mild and severe peritonitis mice were treated intraperitoneally with recombinant IL-12 (r-IL-12) either 6 hours before or 6 and 24 hours after the procedure. The survival rates were then compared with nontreated mice. RESULTS: Serum and PLF IFN-gamma, IL-12 levels in severe peritonitis mice were significantly lower than those in mild peritonitis mice at 6 and 12 hours after the procedure. On the other hand, serum and PLF IL-10 levels in severe peritonitis mice were significantly higher than those in mild peritonitis mice at 6 hours after the procedure. Furthermore, liver MNC IFN-gamma production in severe peritonitis mice was significantly higher than that in mild peritonitis mice at 6 hours after the procedure, but liver MNC IL-12 production in severe peritonitis mice was significantly lower than that in mild peritonitis mice at 12 hours after the procedure. Severe peritonitis mice treated with r-IL-12 at 6 hours before the procedure improved survival rate, and mild peritonitis mice treated with r-IL-12 at 24 hours after the procedure showed significantly improved survival rates. CONCLUSIONS: Change in the Th1, Th2 cytokine balance in peritonitis mice might induce a shift toward a Th2 dominant phenotype according to the severity of peritonitis, and the capacity to produce IFN-gamma and IL-12 by liver MNC is reduced. Therapies designed to augment the production of Th1 cytokines, such as IL-12, may thus prove to be beneficial in the treatment of severe sepsis after peritonitis.     

Local Anesthetics Reduce Mortality and Protect against Renal and Hepatic Dysfunction in Murine Septic Peritonitis

Background: Mortality from sepsis frequently results from multiple organ injury and dysfunction. Cecal ligation and puncture is an established murine model of septic peritonitis that produces septic shock characterized by an initial hyperinflammatory response. In addition to their anesthetic properties, local anesthetics have been shown to attenuate inflammatory responses both in vivo and in vitro. In the current study, the ability of local anesthetic infusions to protect against sepsis-induced mortality, as well as renal and hepatic dysfunction after cecal ligation and puncture, was investigated.

Methods: C57BL/6 mice received mini-osmotic pumps containing saline (vehicle), 10% lidocaine, or 1% bupivacaine and were subjected to cecal ligation and puncture. Twenty-four hours after cecal ligation and puncture, renal and hepatic functions were assessed as well as markers of inflammation (proinflammatory cytokine protein and mRNA concentrations and myeloperoxidase activity). Renal apoptosis and 7-day survival was also assessed.

Results: Mice treated with lidocaine or bupivacaine infusion showed improved survival and had significantly lower plasma creatinine, aspartate aminotransferase, and alanine aminotransferase concentrations compared with mice receiving vehicle alone. Significant reduction in plasma tumor necrosis factor-[alpha] and keratinocyte-derived chemokine, as well as reductions in myeloperoxidase activity, intracellular adhesion molecule-1 protein expression, mRNA concentrations of proinflammatory markers, and apoptosis were observed in renal cortices from both local anesthetic groups.     

Metabolism of red blood cells in chronic renal failure. I. Glycolytic enzyme levels.

This paper starts a series on red blood cell (RBC) metabolism in patients with chronic renal failure (CRF). The glycolytic enzyme levels and in vitro half-lives of these patients' RBCs were determined. A number of enzymes (hexokinase, glucose-6-phosphate isomerase, fructose-6-phosphate kinase, aldolase, glyceraldehyde-3-phosphate dehydrogenase and lactate dehydrogenase) showed higher activities than in normal control RBCs. Other enzyme activities were normal. These results were discussed and several possible mechanisms considered. We favour the point of view of a shortened life span of the RBCs in CRF, making the most unstable enzymes of the glycolytic sequence appear increase as compared with normal controls.     

High‐Volume Hemofiltration Reduces the Expression of Myocardial Tumor Necrosis Factor‐Alpha in Septic Shock Pigs

Increasing evidence indicates that the expression of tumor necrosis factor‐α (TNF‐α) in myocardium correlates with the severity of cardiac dysfunction in septic shock. The aim of this study was to investigate the impact of high‐volume hemofiltration (HVHF) on the expression of TNF‐α in myocardium in septic shock pigs. Sixteen male Landrace pigs weighing 31 ± 5 kg were randomly assigned to control group (n = 4), septic shock group (n = 6), and HVHF group (septic shock + HVHF, n = 6). All animals were anesthetized and mechanically ventilated. After baseline examinations, septic shock group and HVHF group underwent induction of peritonitis. One hour later, the animals in HVHF group received treatment with HVHF and the treatment was continued for 12 h. As the control of HVHF group, the animals in septic shock group received the same support but hemofiltration. Twelve hours after HVHF therapy, all the animals were sacrificed. TNF‐α and nitric oxide (NO) levels in both circulation and myocardium were measured. Compared with those of septic shock animals, the levels of cardiac output, stroke volume, and mean arterial pressure were better maintained in HVHF group. The expression of TNF‐α in myocardium in HVHF group was lower than that in septic shock group (44.17 ± 18.70 vs. 92.50 ± 33.89 pg/mg protein, P = 0.015). The difference of TNF‐α in circulation between HVHF group and septic shock group was no significance at different time. However, circulating NO in HVHF group was lower than that in septic shock group. These results suggest that HVHF improves hemodynamics and heart dysfunction in septic shock pigs, which may be attributed to reduction of TNF‐α in myocardium but not in circulation.     

Myocardial glycolytic and gluconeogenic enzyme activity during cardiopulmonary bypass in humans

Through a study of the activity of the regulatory enzyme of glycolysis phosphofructokinase and the regulatory enzyme of gluconeogenesis fructose-1,6-diphosphatase, myocardial metabolism has been evaluated in the human heart during cardiopulmonary bypass. Three ventricular transmural biopsy specimens were obtained at open-heart surgery before cardiopulmonary bypass was instituted and three similar specimens were taken 30 minutes after cardiopulmonary bypass was started. The enzyme assays were performed on the supernatant obtained from myocardial cells disrupted by sonication. The activity of both enzymes increased during the anoxic conditions of cardiopulmonary arrest. The increase in phosphofructokinase activity is likely due to an overall increase in glycolytic activity, but the presence and increased activity of fructose-1,6-diphosphatase was unexpected.     

Planned relaparotomies in the surgical treatment of severe generalized peritonitis from intestinal origin

The evolution of the septic state and the mortality rate are analyzed in a group of 42 selected patients presenting with severe peritonitis from small or large intestinal origin. All patients presented in a septic state with signs of generalized peritonitis for at least 24 hours. Planned relaparotomies are preferable to the conventional surgical approach of peritoneal lavage which frequently must be followed by demand relaparotomies in patients with recurring peritonitis. The mortality rate in the planned relaparotomy group (29%) was significantly lower than in the conventional treatment group (73%). The poor prognosis of persistent or recurrent multisystem failure complicating septic shock is confirmed. The planned relaparotomy tactic should be considered a valuable alternative approach to the treatment of severe forms of peritonitis.     

Early postoperative enteral feeding increases anastomotic strength in a peritonitis model

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) has been shown to decrease collagen synthesis and increase collagenase activity leading to impaired wound healing. Our hypothesis was that immediate postoperative feeding would decrease TNF-alpha, therefore increasing anastomotic healing in a peritonitis model. METHODS: Twelve Sprague-Dawley rats underwent cecal ligation and puncture to induce peritonitis. Six hours after induction of peritonitis an ileocecectomy and ileocolostomy was performed. Group 1 animals (n = 6) had immediate access to food and water, whereas group 2 (n = 6) had free access to water only. At 48 hours, weight loss, nitrogen loss, anastamotic bursting strength (ABS), TNF-alpha, interleukin-6 (IL-6), and IL-10 were measured. RESULTS: Weight loss was similar in the two groups. Group 1 rats had a significantly lower mean TNF-alpha level (17.3 +/- 10 versus 17.3 +/- 10 mcg/Dl, P = 0.05). ABS was also significantly higher in group 1 rats when compared with group 2 rats (81 +/- 34 versus 39 +/- 13 mm HG, P = 0.03). CONCLUSIONS: These data suggest that immediate postoperative feeding results in a beneficial change in the cytokine profile.