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L T Archer

Publications and source records attributed to L T Archer.

At least 55 records · Page 3Linked to original sources
PubMed1979

Recovery from endotoxin shock after extracorporeal perfusion without anticoagulation.

The purpose of this study was to determine the effect of an extracorporeal nonanticoagulated perfusion system on survival from endotoxin shock in anesthetized closed-chest dogs. Dogs weighing approximately 18 kg were perfused four hours or used as nonperfused controls. In the perfused animals, blood was diverted from the distal aorta via plastic tubing at 1,000 ml/min into a reservoir and returned by means of a roller-type pump to the femoral veins. Whole blood clotting times increased from a control value of seven minutes to greater than 24 hours within 45 minutes of perfusion in the absence of exogenous anticoagulation. After blood became incoagulable, animals were infused with 3 mg/kg Escherichia coli endotoxin during a 30-minute period. Systemic pressures declined during the initial period but returned to base-line values; glucose remained at normal levels and all six dogs thus treated remained healthy survivors after seven days. On the other hand, animals infused with endotoxin without extracorporeal perfusion demonstrated hypotension, hypoglycemia, and diarrhea, and five of six dogs died within 36 hours.

Animals↗
PubMed1978

Reversal of myocardial dysfunction in endotoxin shock with insulin.

Recent data reported from this laboratory have documented myocardial functional depression in endotoxin shock. The purpose of the present study was to determine the effects of insulin on the dysfunctioning canine myocardium subjected to lethal endotoxin shock. Experiments were conducted on isolated working left ventricular preparations in which LD90-100 endotoxin was administered prior to, or following, isolation of the heart. Determinations of myocardial performance were conducted under the conditions of controlled mean aortic pressure and cardiac output. Myocardial dysfunction occurred between 2 and 6 h postendotoxin, as evidenced by significantly increased left ventricular end-diastolic pressure, decreased power, and depressed negative dP/dt, although blood glucose concentrations were maintained at control values. Intraatrial infusions of insulin at rates of 6 U/min reversed all signs of myocardial dysfunction. During insulin infusion, heart rates decreased (p less than 0.02) and myocardial lactate uptake increased (p less than 0.02), while oxygen uptake and coronary blood flow were insignificantly altered.

Animals↗
PubMed1978

Escherichia coli shock in the baboon and the response to adrenocorticosteroid treatment.

Results of recent studies from this laboratory have demonstrated that methylprednisolone sodium succinate increases the survival rate of dogs given LD100 Escherichia coli endotoxin. This study was undertaken to determine the effects of methylprednisolone on the baboon infused with live Escherichia coli organisms. Awake baboons were paired by infusing intravenously comparable doses of Escherichia coli during a five hour period. Baboons given methylprednisolone received bolus injections of 30 milligrams per kilogram at 15 minutes after beginning the infusion of Escherichia coli and two hour infusions of 15 milligrams per kilogram at two hour intervals until death or for a 24 hour period. The mortality was unaltered by methylprednisolone. Six of seven baboons that were dying became progressively hypoglycemic, while hypoinsulinemia occurred in all baboons within six hours and was sustained until death. Systemic hypotension was observed. although pressures were variable. Potassium and lactate concentrations increased, while pH remained relatively constant in most baboons. Serum glutamic-pyruvic transaminase and arginase concentrations rose in most baboons dying with 18 hours. Results of morphologic studies revealed the presence of fibrin thrombi in the liver, kidney and adrenal tissue in most baboons. No significant differences in physiologic, metabolic, hematologic or morphologic parameters were observed between treated and untreated baboons.

Animals↗
PubMed1978

Prolonged shock in the baboon subjected to infusion of E. coli endotoxin.

This study was designed to examine the response of the baboon during a 24-hour period following Escherichia coli endotoxin infusion. Experiments were conducted on young adult baboons, unrestrained and maintained at a light plane of anesthesia induced with pentobarbital sodium. Light and electron microscopic studies on lung, heart, liver, and kidney were conducted; hematologic changes and physiologic responses were measured. The efficacy of heparin to prevent the coagulopathy and increase survivability was assayed. Hepatic sinusoidal fibrin thrombi with underlying hepatocyte cellular damage was seen in the endotoxin-treated group. In contrast, the experimental group receiving heparin showed no sinusoidal fibrin thrombi but demonstrated hepatocellular damage. Liver dysfunction was indicated by elevation of blood levels of enzymes. Glomerular fibrin thrombi were not present. Although heparin prevented the formation of hepatic thrombi in endotoxin-treated baboons, it did not increase survival. Platelet and complement levels decreased in both experimental groups, while wide variations in white blood cell and fibrinogen levels were observed. Polymorphonuclear leukocyte-platelet aggregations previously reported in the pulmonary vasculature during acute shock were not observed in the present study, and their absence may have been related to the longer time of survival.

Animals↗
PubMed1978

In vitro effects of methyprednisolone sodium succinate and E coli organisms on neutrophils in baboon blood.

The corticosteroid methylprednisolone sodium succinate (MP) has been observed to prevent hypoglycemia in experimental septic shock; however, detrimental actions of various corticosteroids on polymorphonuclear leukocyte function have been reported. The present study was designed to determine if MP depresses glucose metabolism of leukocytes or adversely affects neutrophil survival, or whether it modifies the mortality rate of live E coli in baboon blood in vitro. Results show that therapeutically effective concentrations (13 micrograms/ml blood) and high doses (130 micrograms/ml blood) of MP exert no detrimental influences on glucose utilization or survival of neutrophils in the absence or presence of E coli organisms in concentrations of 4.2 x 10(7) and 2.3 x 10(8) organisms per milliliter blood. However, E coli organisms increase neutrophil mortality rate and glucose uptake of the blood. These findings support the view that MP does not adversely influence leukocyte metabolism and survival, nor does it modify the mortality rate of live E coli.

Animals↗
PubMed1978

Preserved liver function and leukocyte response in superlethal endotoxic shock.

Recent studies reveal that endotoxin-pretreated awake dogs become markedly leukocytotic and survive superlethal endotoxin challenge without hypoglycemia. The purpose of this study was to determine if an association exists between leukocytosis, liver function, and survival in endotoxin shock. Studies were conducted on awake, conditioned adult dogs, with the experimental group (N= 5) injected intravenously with 1/1,000 LD100 E. coli endotoxin on Days 1 and 2, LD100 on Day 3, and 2 x LD100 on Day 4. A control group (N = 6) received equal volumes of saline on Days 1, 2, and 3, but on Day 4 received 2 x LD100 endotoxin. All saline-pretreated dogs died within seven hours following superlethal endotoxin challenge. Each animal in the experimental group was sacrificed at the time of its paired saline control's death for a comparison of liver pathology, since in parallel studies all endotoxin-pretreated dogs (N = 11) survived for 30 days. Animals in the experimental group exhibited a marked leukocytosis of 39,000/cu mm (mature neutrophils, 28,000/cu mm, immature neutrophils, 8,300/cu mm (P is less than 0.001) on Day 4 compared with saline-pretreated controls. At the time of death the liver enzymes, arginase, and SGPT were significantly elevated in the saline-pretreated controls compared with endotoxin-pretreated dogs (P is less than 0.02). Liver pathology in endotoxin-pretreated dogs consisted of mild necrosis, while saline-pretreated animals demonstrated massive hepatocellular necrosis. Results support the view that increased numbers of neutrophils protect liver function and enhance survival in endotoxin shock.

Alanine Transaminase↗
PubMed1977

Glucose utilization and role of blood in endotoxin shock.

The present study was conducted to explore influences modifying glucose uptake in canine blood administered LD100 E. coli endotoxin. Particular emphasis was given to assay the role of the white blood cell (WBC) in glucose utilization. Significant increases in glucose uptake and lactic acid production, attributed to increased activity of the WBC, were observed 1-3 h after endotoxin was added to blood in vitro. Although a net increase in glucose utilization was noted, endotoxin simultaneously exerted adverse effects by depressing glucose uptake below predicted values (Q10 = 2.12 with LD100 endotoxin vs. 2.78 in saline controls) and increasing WBC mortality rate. Blood from dogs pretreated with sublethal doses of endotoxin in vivo utilized glucose at an accelerated rate when subjected to endotoxin in vitro. Excess glucose was consumed because of elevated numbers of white blood cells although additional glucose requirements after endotoxin were independent of temperature between the ranges of 34-41 degrees C. All animals pretreated with daily sublethal injections of endotoxin for 3 days survived superlethal doses of endotoxin.

Animals↗
PubMed1977

Leukocyte response and hypoglycemia in superlethal endotoxic shock.

This laboratory has documented a progressively developing hypoglycemia associated with systemic hypotension, hepatosplanchnic pathology, and death in endotoxin-shocked dogs. Recent data documented accelerated uptake of glucose in blood following endotoxin, with certain components of the buffy coat responsible for the increased uptake. The present study utilizing the awake dog assayed a possible protective role of leukocytes against the lethal effects of endotoxin. Animals were divided into paired groups: saline controls (Group I) and endotoxin experimentals (Group II). Group II animals were injected intravenously with sublethal doses of E. coli endotoxin on 2 successive days (Days 1 and 2), LD100 on the third day, and 2 X LD100 on Day 4. The control group received equal volumes of saline on Days 1, 2, and 3, but on Day 4 received a superlethal dose of endotoxin identical to the experimental group. The awake dog became febrile and exhibited initial leukopenia with subsequent marked leukocytosis in response to endotoxin. Lethal hypoglycemia was not seen in animals demonstrating initial leukocytosis (zero time) on the day of superlethal endotoxin challenge, while animals with initial normal leukocyte counts died with low glucose concentrations (mean, 40 mg%). Results suggest that an initial leukocytosis and sustained gluconeogenic function are important factors in survivability to endotoxin shock.

Animals↗
PubMed1976

Renal gluconeogenesis and increased glucose utilization in shock.

The roles of renal gluconeogenesis and glucose utilization in control, hemorrhaged, and endotoxin-injected animals were investigated using anesthetized, eviscerated, nonnephrectomized and nephrectomized dogs. Results demonstrate an increased glucose utilization in both hemorrhagic and endotoxic shock which was marked after endotoxin. Since blood glucose values dropped more in nephrectomized, hemorrhaged animals, in contrast to the nonnephrectomized, hemorrhaged dogs, the kidneys were assumed to perform a significant gluconeogenic role. The kidneys did not appear to perform gluconeogenesis in endotoxin shock since blood glucose levels were comparable in eviscerated, endotoxin-treated animals whether nephrectomized or not. To ascertain the tissue responsible for the increased glucose utilization in endotoxin shock, a study was performed with endotoxin added to blood in vitro (estimated LD100 concentration). The endotoxin-treated blood (n = 7) demonstrated an increased glucose utilization compared with saline controls (n = 7) (P less than or equal 0.02). Acclerated glucose utilization rates were comparable between the eviscerated, nephrectomized animals and in vitro experiments. These data suggest that excessive glucose demand by certain blood components may partially explain the lethal hypoglycemia of endotoxin shock.

Animals↗
PubMed1976

Effects of glucose or insulin on myocardial performance in endotoxin shock.

Past studies reported by this laboratory have documented myocardial dysfunction and progressively developing hypoglycemia in canine endotoxin shock. The purpose of the present study was to determine the effects of glucose concentrations and insulin infusions on myocardial performance following endotoxin administration. Experiments were carried out on isolated, working canine left ventricular heart preparations exchanging blood with intact dogs. Myocardial function was evaluated following endotoxin and correlated with concentrations of glucose and effects of insulin infusion. Cardiac dysfunction occurred within 2-4 hr postendotoxin and the degree of malfunction was not related to arterial blood glucose concentrations. Maintaining blood glucose at control, preshock, levels by infusion of 50% glucose did not prevent myocardial dysfunction as evidenced by elevations of left ventricular end diastolic pressure, and depressed power. Infusions of insulin reversed cardiac failure and maintained normal performance in spite of wide ranges in glucose concentration (5-120 mg%). Findings suggest that myocardial dysfunction is not precipitated or enhanced by the hypoglycemia of endotoxin shock. The beneficial actions of infused insulin on cardiac performance appear to be elicited on the basis of mechanisms other than myocardial glucose transport.

Animals↗
PubMed1976

Physiopathologic responses of the rhesus monkey to live Escherichia coli.

The present study was designed to develop an animal model applicable to the clinical patient in the investigation of the pathogenesis of septic shock. The model currently described is a lightly anesthetized, unrestrained monkey, carefully monitored during a 24 hour observation period. Varying doses of live Excherichia coli organisms were infused intravenously during a 30 minute period, and a variety of hemodynamic, respiratory and metabolic parameters were monitored. Doses of organisms varied between 7.6X10(9) and 3.0X10(11) organisms per kilogram of body weight, and there was no obvious correlation between size of dose and survival time. Two of nine experimental monkeys survived the Excherichia coli, while times of death of the remaining monkeys varied between three and 27 hours. Two control monkeys, not administered organisms, survived the 24 hour period with minimal changes in all measured parameters. Results reveal two patterns in response to organism administration. These were early acute death, after three to four hours, and prolonged life, death after 20 to 27 hours. The acute response was characterized by marked systemic hypotension, hypoglycemia, hypoinsulinemia, increased lactate level, decreased pH or respiratory depression. The other type of response involved profound sustained hypotension with hypoglycemia and hypoinsulinemia in most monkeys and elevations in lactate, blood urea nitrogen potassium creatinine, serum glutamicoxalacetic, lactic dehydrogenase and fractionatedlactic dehydrogenase levels. Depressions in respiration were not evident in the group which survived a longer period of time. Renal fibrin thrombi, prominent in baboons administered Escherichia coli, were absent in the rhesus monkey regardless of the size of the dose of organisms. The results of this study suggest the operation of a multifactiorial mechanism in septic shock with interactions between hemodynamic and metabolic factors varying within the species.

Animals↗
PubMed1975

Myocardial failure with altered response to adrenaline in endotoxin shock.

1 There is a growing concensus that myocardial performance in the early stages of experimental endotoxic and septic shock is relatively normal; however, recent reports have identified an intermediate phase of shock when myocardial dysfunction is clearly apparent.2 The mechanism of dysfunction has become a subject of intense investigation. A current view is that altered myocardial responsiveness to circulating catecholamines may play an important role in the dysfunction observed after endotoxin administration. The present studies, in which an isolated working heart preparation of the dog was used, were designed to test this hypothesis. This particular experimental preparation was selected to provide an adequate interpretation of results; cardiac output, afterload, and concentrations of adrenaline reaching the coronary vascular bed were controlled in all experiments. Responses to infusions of adrenaline were recorded in the ;steady-state' condition. Control (non-shocked) heart responses to adrenaline were highly reproducible in terms of inotropic, chronotropic and coronary vascular behaviour.3 Results from the study document myocardial dysfunction within 4-6 h following an LD(70) endotoxin administration on the basis of increased left ventricular end diastolic pressure (LVEDP), decreased cardiac power and myocardial efficiency, and depressed negative and positive dP/dt parameters.4 Findings suggest significantly altered responsiveness of the myocardium to infused adrenaline at rates of 1, 2, and 5 mug/min with concentrations between 10 and 1 ng/ml blood. LVEDP was elevated while calculated power and efficiency parameters remained significantly below control values during infusion of adrenaline in endotoxin-treated hearts. Depressions of responsiveness were interpreted to occur on the basis of failure to restore positive and negative dP/dt to normal values and depressed coronary blood flow responses during adrenaline administration. Increases in coronary flow were regularly less in experimental hearts than the controls. Heart rate responses to adrenaline in both failing and non-failing hearts were identical.5 In conclusion, it is suggested that myocardial contractile and relaxation characteristics and coronary vascular responses to adrenaline infusion are depressed in endotoxin shock during the period of demonstrated myocardial dysfunction. No distinct causal relationships were observed between the altered myocardial responsiveness and pathogenesis of heart dysfunction since myocardial dysfunction and altered responsiveness to adrenaline were generally observed together. Myocardial oedema formation after endotoxin as previously reported by this laboratory may bear a relationship to the depressed negative dP/dt response to adrenaline.

Animals↗