naloxone and Escherichia-coli-Infections

To clarify the relationship between changes in haemodynamics, liberation of tumour necrosis factor and generation of plasma kallikrein, and to see if treatment with a combination of drugs was successful in preventing activation of tumour necrosis factor and plasma kallikrein in experimental endotoxic shock.. Controlled study.. 22 juvenile pigs.. 15 animals received 0.01 mg/kg endotoxin infusion, the rest being given the same volume of saline. 10 received no treatment, and 5 were given a combination of methylprednisolone, naloxone, ketanserin, promethazine, C1 esterase inhibitor, antithrombin III and aprotinin.. Assessment of the liberation of tumour necrosis factor, generation of plasma kallikrein, and haemodynamic and cellular effects of endotoxaemia.. There was a linear statistical relationship between decreases in cardiac output and increases in packed cell volume, and between increases in packed cell volume and plasma kallikrein activity. The combination treatment totally blocked all the effects of the infusion of endotoxin.. Endotoxin affects several mediators, but combination treatment can prevent some of these effects.

Topics: Animals; Disease Models, Animal; Drug Therapy, Combination; Escherichia coli Infections; Hemodynamics; Kallikreins; Ketanserin; Methylprednisolone; Naloxone; Promethazine; Protease Inhibitors; Shock, Septic; Swine; Tumor Necrosis Factor-alpha

Changes in plasma catecholamine levels in response to the induction of shock and following treatment with buprenorphine or naloxone were determined in a porcine model of Escherichia coli septicaemia. Thirty animals were anaesthetised with alpha-chloralose and infused with live E. coli over 2 hr. One hour after starting the infusion, cardiac index, mean arterial pressure, and pH had decreased significantly (P < 0.001), and there was a significant increase in mixed venous blood lactate concentrations (P < 0.001). This was associated with significant increases in plasma concentrations of adrenaline and noradrenaline (P < 0.001). There was a strong correlation between the extent of the increase in circulating catecholamines and the severity of shock (as reflected by haemodynamic changes and lactic acidosis) as well as significantly higher peak plasma catecholamine concentrations (P < 0.01) and dramatic terminal increases in circulating catecholamines in nonsurviving animals. Animals were randomly divided into three groups and received either naloxone or buprenorphine or an equivalent volume of normal saline and were monitored for a further 3 hr. Both naloxone and buprenorphine produced significant improvements in cardiac index (P < 0.05) and limited the development of acidosis (P < 0.05). This was not associated with any further increase in plasma catecholamine concentrations; indeed, catecholamine levels tended to decrease in treated animals but continued to increase in controls. In summary, we have shown a correlation between the increase in plasma catecholamines and the severity of shock in this model. In addition, we observed that the beneficial effects of treatment with buprenorphine or naloxone were not accompanied by any further increase in plasma catecholamine concentrations.

Topics: Animals; Buprenorphine; Catecholamines; Escherichia coli Infections; Female; Hemodynamics; Naloxone; Survival Analysis; Swine

Little is known of the endorphins' role in sepsis-induced respiratory distress and naloxone's effect as a treatment of it. Thirteen piglets were infused with live Escherichia coli at a rate of 2 to 10 x 10(8) colony-forming units per hour for six hours or until death and were divided into two groups: the septic control group (n = 8), and the naloxone-treated group (n = 5), which received 8 mg/kg/h of naloxone by continuous infusion. The results showed a significant reduction of QS/QT, VD/VT, and arterial carbon dioxide pressure at one hour and a significant increase of arterial carbon dioxide pressure and minute ventilation at 1, 3, and 4 hours in the naloxone-treated group, compared with the untreated septic group. None of the piglets in the naloxone-treated group developed ventilatory depression, while 75% of those in the untreated septic group did. Among the latter ficial effects of naloxone are likely related to its action on the central and peripheral respiratory regulatory mechanisms. A transient protection of the cardiac output and relatively decreased extravascular lung water with naloxone treatment may also, in part, improve the ventilation-perfusion maldistribution and secondarily reduce QS/QT and VD/VT.

Topics: Animals; Bacteremia; Escherichia coli Infections; Naloxone; Respiratory Dead Space; Shock, Septic; Swine; Ventilation-Perfusion Ratio

This study evaluated the effects of naloxone hydrochloride in the treatment of Escherichia coli-induced shock in baboons. The baboons were studied for 12 hours and monitored for survival times. All baboons were intravenously infused for two hours with E coli and treated as follows: group 1, E coli (control); group 2, E coli plus naloxone hydrochloride, 0.5 mg/kg bolus plus 0.5 mg/kg/h for 9.5 hours; and group 3, E coli plus naloxone hydrochloride, 2.0 mg/kg bolus plus 2.0 mg/kg/h for 3.8 hours. Naloxone was administered after arterial pressure had reached the nadir (more than two hours following initiation of E coli infusion). Mean arterial pressure was supported by the lower dose of naloxone; however, sustained leukopenia and neutropenia were not reversed by its infusion. Naloxone prevented the increase in plasma beta-endorphin level and blunted the increase in plasma cortisol level. Despite these effects, naloxone did not prevent multiple-organ disease and did not decrease mortality.

Topics: Animals; beta-Endorphin; Blood Pressure; Blood Urea Nitrogen; Creatinine; Disease Models, Animal; Drug Evaluation, Preclinical; Escherichia coli Infections; Female; Heart Rate; Hydrocortisone; Injections, Intravenous; Male; Monitoring, Physiologic; Naloxone; Papio; Sepsis; Shock, Septic; Time Factors

The cardiovascular and metabolic responses to treatment with naloxone or buprenorphine (a partial opiate agonist) were investigated in a porcine model of septicaemia. Animals anaesthetised with alpha-chloralose were infused with live E. coli over two hours. They were then divided into three groups and received either naloxone (2 mg kg-1 + 1.5 mg kg-1 hr-1) or buprenorphine (0.3 mg kg-1) or an equivalent volume of normal saline. Treatment was started one hour after commencing the infusion, by which time a significant fall in cardiac index (CI), stroke index (SI), mean arterial pressure (MAP), and pH had occurred in all groups, together with a significant rise in mixed venous blood lactate and packed cell volume. Treatment with both naloxone and buprenorphine resulted in significant improvements in CI, pH, and base excess and in a fall in mixed venous lactate and packed cell volume. Although no significant effect on survival was seen at three hours after the start of treatment, buprenorphine may prove to be a suitable alternative to naloxone in the management of septic shock.

Topics: Animals; Blood Pressure; Buprenorphine; Cardiac Output; Disease Models, Animal; Erythrocyte Indices; Escherichia coli Infections; Female; Lactates; Naloxone; Shock, Septic; Swine

Little is known of the endorphins' role in sepsis-induced respiratory distress and naloxone's effect as a treatment of it. Thirteen piglets were infused with live Escherichia coli at a rate of 2 to 10 X 10(8) colony-forming units per hour for six hours or until death and were divided into two groups: the septic control group (n = 8), and the naloxone-treated group (n = 5), which received 8 mg/kg/h of naloxone by continuous infusion. Hemodynamic parameters, the intrapulmonary shunt fraction (QS/QT), physiologic dead space (VD/VT), minute ventilation, and blood gas levels were measured. Lung lymph flow was obtained by cannulating the right lymphatic duct. The extravascular lung water weight was also measured. The results showed a significant reduction of QS/QT, VD/VT, and arterial carbon dioxide pressure at one hour and a significant increase of arterial carbon dioxide pressure and minute ventilation at 1, 3, and 4 hours in the naloxone-treated group, compared with the untreated septic group. None of the piglets in the naloxone-treated group developed ventilatory depression, while 75% of those in the untreated septic group did. Among the latter piglets, three died of apnea within one hour. These beneficial effects of naloxone are likely related to its action on the central and peripheral respiratory regulatory mechanisms. A transient protection of the cardiac output and relatively decreased extravascular lung water with naloxone treatment may also, in part, improve the ventilation-perfusion maldistribution and secondarily reduce QS/QT and VD/VT. We conclude that endorphins play a role in septic ventilatory depression and that naloxone is effective in ameliorating it.

Topics: Animals; Carbon Dioxide; Escherichia coli Infections; Female; Hemodynamics; Leukocyte Count; Lung; Male; Naloxone; Oxygen; Respiration; Respiratory Insufficiency; Shock, Septic; Swine; Ventilation-Perfusion Ratio

To explain the high neonatal mortality from peritonitis-induced septic shock despite current resuscitation practices, the efficacy of dopamine, naloxone, and prostacyclin was evaluated in an experimental neonatal model. Hemodynamics were monitored and survival was measured in anesthetized neonatal swine, which were subjected to fatal fecal-Escherichia coli peritonitis-induced septic shock. All the animals received fluid resuscitation, antibiotics, and bicarbonate to correct acidosis. Pharmacologic resuscitation began when cardiac output dropped below baseline in the experimental groups. Although significant differences were observed between groups in cardiac output, mean arterial and mean pulmonary arterial pressures, left ventricular stroke work, stroke volume, and pulmonary vascular resistance indices (P less than 0.02), and each animal exhibited favorable hemodynamic responses during the first several hours of dopamine and naloxone infusion, these drugs failed to prolong survival. Also, 5 of the 9 naloxone-treated pigs (56%), died with histologically proven intestinal ischemia (P less than 0.02). Thus, dopamine, naloxone, and prostacyclin (at doses commonly recommended for the treatment of septic shock) fail to positively influence the fatal course of this condition, and the use of naloxone in this model is associated with profound intestinal ischemia.

Topics: Analysis of Variance; Animals; Animals, Newborn; Dopamine; Drug Evaluation; Epoprostenol; Escherichia coli Infections; Feces; Hemodynamics; Intestinal Perforation; Naloxone; Peritonitis; Resuscitation; Shock, Septic; Swine; Time Factors

The most common sign of febrile diseases is anorexia, which develops at a time when adequate caloric and micronutrient availability may be critical. In order to study the relationship of fever and anorexia, feed intake in dwarf goats was studied under conditions of fever and antipyresis. Furthermore, experiments were done to establish whether a feed intake stimulant would override the anorexia during febrile conditions. Infection with Ehrlichia phagocytophila and i.v. injection of Escherichia coli endotoxin (0(111) B4, 0.1 microgram/kg body weight) both resulted in increased rectal temperatures and significant reductions in feed intake. Administration of the antipyretic drug flurbiprofen (1 mg/kg) to febrile animals inhibited the temperature responses, but food intake was still suppressed. Diazepam (0.06 mg/kg), a feed intake stimulant, did not override the anorexia associated with fever. Blocking the febrile response of E. coli LPS-injected goats with flurbiprofen plus diazepam or with flurbiprofen plus naloxone (0.1 mg/kg) did not antagonise their reduced feed intake either. The effects of these drugs and of endotoxin on rumen motility adds an interesting aspect to their activities in the CNS, since the CNS has been shown to regulate various aspects of forestomach motility, which in turn could alter feeding behaviour. Moreover, our findings are consistent with the hypothesis that the suppression of feed intake might depend on the release of interleukin-1.

Topics: Animals; Anorexia; Diazepam; Drug Therapy, Combination; Eating; Ehrlichia; Endotoxins; Escherichia coli; Escherichia coli Infections; Female; Fever; Flurbiprofen; Goats; Male; Naloxone; Propionates; Rickettsiaceae Infections

Topics: Animals; Escherichia coli Infections; Humans; Infant, Newborn; Naloxone; Shock, Septic; Swine

Acute bacteremia in sheep caused a surge of plasma beta-endorphin/beta-lipotropin (beta-EP/beta-LPH) associated with shivering behavior, tachycardia, hyperthermia, hemoconcentration, and decreased respiration rate. The surge of plasma beta-EP/beta-LPH was immediately followed by increases (P less than 0.05) in plasma prolactin and growth hormone (GH) concentrations and a depression (P less than 0.05) of plasma luteinizing hormone. These changes in pituitary hormone release were consistent with opioid-induced changes described in the literature. To examine possible opioid mediation, naloxone (2.5 mg X kg-1 X h-1) was continuously infused intravenously from 3 h before to 3 h after induction of an E. coli bacteremia. With the exception of plasma GH, naloxone failed to alter any of the hormonal or clinical parameters associated with bacteremia. For plasma GH, naloxone delayed (P less than 0.01) the increase but did not attenuate its magnitude, suggesting that an opioid mechanism may influence the timing of the pituitary GH release resulting from bacteremia. In general, opioid mechanisms sensitive to the present dosage of naloxone do not appear to mediate bacteremia-induced changes in hormonal or clinical parameters.

Topics: Animals; beta-Endorphin; beta-Lipotropin; Endorphins; Escherichia coli Infections; Female; Growth Hormone; Heart Rate; Hematocrit; Luteinizing Hormone; Naloxone; Pituitary Hormones; Prolactin; Radioimmunoassay; Receptors, Opioid; Respiration; Sepsis; Sheep; Shivering; Time Factors

Sepsis remains the most common associated factor in acute respiratory failure (ARF). Endogenous opiates are known to have both respiratory and cardiovascular depressant effects. Because there is a high level of circulating endogenous opiates in sepsis, the possible role of opioids in the ARF syndrome seen in sepsis was studied. Sixteen piglets were infused with an LD100 dose (7.5 X 10(10) organisms/kg) of live Escherichia coli (Type 09-41). The pigs were hemodynamically monitored. Serial blood samples were taken for arterial blood gases and lactate. Serial lung biopsies were taken for determining wet/dry lung weight ratios and for histology. Group I (n = 8): septic shock controls without naloxone; group II (n = 8): naloxone treated, given as 2 mg/kg/hr intravenous boluses, starting within 1 min of E. coli infusion. All animals died of septic shock. Survivors at 150 min in group II had a higher blood pressure than group I (67.7 +/- 5.33 SEM vs 39.0 +/- 9.39) and cardiac output was also greater (1.07 +/- 0.23 vs 0.25 +/- 0.25). By 210 min, group I had no survivors (0/8) while 3/8 in group II survived. Pulmonary vascular resistance in group II at 90 and 120 min (870.8 +/- 274.1 and 942.5 +/- 12.9, respectively) was lower than in group I (2868.3 +/- 843.6 and 4156 +/- 1067). The PO2 was markedly better in group II and at 90 min; controls had a PO2 70.7 +/- 13.0, while group II had a PO2 111.4 +/- 8.4 (P less than 0.05). PCO2 levels showed a progressive rise in group I from 39.25 +/- 1.4 to 49.4 +/- 8.57.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Animals; Drug Evaluation, Preclinical; Endorphins; Escherichia coli Infections; Hemodynamics; Lung; Naloxone; Organ Size; Respiratory Insufficiency; Shock, Septic; Swine; Time Factors

This study was designed to investigate the concept that endogenous opioids are involved in the pathogenesis of septic shock. Infusion of live Escherichia coli (1.0-1.6 X 10(10) organisms/kg) in splenectomized dogs induced profound hypotension (p less than 0.001), peripheral vasodilatation (p less than 0.001), and metabolic acidosis (p less than 0.05) with maintenance of cardiac index as compared to control splenectomized dogs. Treatment with naloxone (3 mg/kg bolus and 2 mg/kg/hr infusion for 2.5 hours), a specific opiate antagonist, during septic shock attenuated the hypotension (p less than 0.002) and systemic acidosis (p less than 0.02) without altering cardiac index or total peripheral resistance. These experimental results indicate that naloxone may be of therapeutic value in the management of the early vasodilatory stage of septicemia.

Topics: Animals; Blood Pressure; Cardiac Output; Disease Models, Animal; Dogs; Escherichia coli Infections; Female; Heart Rate; Hemodynamics; Male; Naloxone; Sepsis; Shock, Septic; Splenectomy; Vascular Resistance

Dogs and baboons were infused intravenously (IV) with Escherichia coli and treated with the opiate antagonist, naloxone hydrochloride, and the antibiotic, gentamicin sulfate, to determine the therapeutic efficacy of naloxone. Naloxone hydrochloride (2 mg/kg) was injected IV when one fourth of the E coli had been infused and then infused at 2 mg/kg/hr (six hours for dogs and 12 hours for baboons). Four of five naloxone-treated dogs survived permanently (greater than seven days), while all dogs that were given only E coli died. Arterial BP, blood glucose levels, PCO2, and PO2 were supported at higher levels and lesions of the gastrointestinal tract were prevented in naloxone-treated dogs. A steady decline in blood glucose levels after an initial hyperglycemia was observed in naloxone-treated baboons, indications of peripheral vasoconstriction were noted, and all baboons died within 42 hours.

Topics: Animals; Blood Pressure; Body Temperature; Dogs; Drug Therapy, Combination; Epinephrine; Escherichia coli Infections; Gentamicins; Naloxone; Norepinephrine; Papio; Shock, Septic

Hypoxia of the superficial gastric epithelium induced by a systemic infusion of live Escherichia coli organisms was mimicked by a local intra-arterial infusion of the naturally occurring opiate beta-endorphin. Naloxone, a specific opiate antagonist, reversed the gastric epithelial hypoxia induced by sepsis and also prevented the development of systemic acidosis. The mean blood pH of septic dogs had declined during the experiment from 7.42 +/- 0.06 to 6.88 +/- 0.17, whereas corresponding values for the naloxone-treated group were 7.38 +/- 0.06 and 7.32 +/- 0.08. These experiments, which support the concept of beta-endorphin involvement in the pathogenesis of septic shock, indicate a direct tissue response to circulatory beta-endorphin and highlight a further beneficial effect of naloxone in the management of sepsis.

Topics: Animals; Blood Pressure; Cardiac Output; Dogs; Epithelium; Escherichia coli Infections; Female; Male; Naloxone; Oxygen; Pressure; Receptors, Opioid; Stomach