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Biomedical subjects

B K Beller

Publications and source records attributed to B K Beller.

At least 19 recordsLinked to original sources
PubMed1988

Evaluation of naloxone therapy for Escherichia coli sepsis in the baboon.

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.

Animals↗
PubMed1986

Treatment of LD100 Escherichia coli septic shock with netilmicin and methylprednisolone in baboons.

Treatment efficacy with netilmicin sulphate/methylprednisolone sodium succinate in a severe septic shock baboon model, using an LD100 of live Escherichia coli, was evaluated. All the animals treated with both netilmicin and methylprednisolone were permanent (greater than or equal to 7 days) survivors, whereas none of the untreated baboons lived more than 24 hours. These results indicate that, in a baboon model, netilmicin is an effective alternative to gentamicin (with methylprednisolone) in the treatment of severe septic shock.

Animals↗
PubMed1986

Tobramycin therapy for lethal sepsis in the dog.

Antimicrobial effectiveness and effect on survival of single-dose vs. multiple-dose aminoglycoside antibiotic therapy (with and without steroid) for lethal sepsis were evaluated. Adult dogs of either sex were anesthetized, divided into five groups, and infused iv for one hour with Escherichia coli. Group A was given no drug. Group B was given a 45-mg/kg, 10-min iv injection of tobramycin (TOB) at 65 min. Group C was given a 3-mg/kg, 10-min TOB injection at 65 min, followed by an 8.25-mg/kg iv infusion for 285 min, and three 11.25-mg/kg intramuscular injections at 6, 12, and 18 h (total 45 mg/kg). Group D was given the same TOB regimen as B, plus a 30-mg/kg iv injection and 30-mg/kg iv infusion of methylprednisolone sodium succinate (MPSS) from 15 to 360 min. Group E was given the same TOB regimen as C, plus the same MPSS regimen as D. Treated dogs also received 11.25 mg/kg of TOB daily for 4 days. The percent surviving more than 7 days was 0, 0, 17%, 83%, and 83%, for groups A through E, respectively. By 4 h, TOB-treated groups had significantly (p less than .05) lower E. coli blood levels than group A. Also E. coli levels in group B were significantly (p less than .05) lower than those in groups C, D, or E. High trough serum TOB concentrations were associated with death and very low levels with recovery. Serum urea nitrogen and creatinine concentrations increased in all groups, but returned to normal by 7 days in survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Effects of prior administration of steroids upon recovery from lethal sepsis.

The effects upon survival of large doses of steroid administered to dogs prior to challenging them with lethal sepsis was evaluated in this study. Dogs were given 30 milligrams per kilogram of body weight per day of methylprednisolone sodium succinate for one, two or eight days and then were infused with 9.72 +/- 0.35 X 10(9) Escherichia coli per kilogram of body weight. All dogs in group 1 (n equals six) not given steroid died within 25 hours. Of the dogs in group 2 (n equals 12) given one or two doses of steroid previously, 42 per cent permanently survived (more than seven days). All dogs in group 3 (n equals five) given eight daily doses of steroid prior to infusion of Escherichia coli died within 17 hours. Dogs in group 4 (n equals six) were given eight daily doses of steroid prior to infusion of Escherichia coli and treated on the day of infusion of Escherichia coli with a regimen of methylprednisolone and gentamicin sulfate which results in a 100 per cent survival rate when given to dogs that have not received prior treatment with steroid. Thirty-three per cent of the dogs in group 4 permanently survived. One or two daily large doses of steroid did not detrimentally affect survival of the dogs. Eight days of steroid administration suppressed endogenous cortisol production. When the dogs were treated with six hours of steroid-antibiotic therapy, survival benefits were limited.

Adrenal Cortex Hormones↗
PubMed1985

Corticosteroid/antibiotic treatment of adrenalectomized dogs challenged with lethal E. coli.

Adrenalectomized animals are extremely sensitive to endotoxin and die quickly when given small doses. A six hour administration of the corticosteroid, methylprednisolone sodium succinate (MPSS), combined with the antibiotic, gentamicin sulfate (GS), promotes complete recovery of dogs with intact adrenals administered LD100 E. coli. The aim of the present study was to determine if this early administered treatment would protect adrenalectomized dogs from overwhelming lethal doses of E. coli. Dogs were infused with MPSS from fifteen minutes to six hours after the onset of E. coli administration and with GS after administration of all E. coli. Animals given only E. coli died in 2.6 (+/- 0.3) hours, while those given no E. coli, or E. coli plus steroid/antibiotic, survived longer than 100 hours. Arterial pressure, pH, pO2, hematocrit, lactate, and glucose concentrations were maintained near control values in animals receiving steroid/antibiotic infusions. Adrenalectomized dogs infused with corticosteroid/antibiotic recovered completely from shock even though the treatment period was limited to the first 6 hours after lethal E. coli infusion. Findings indicate that animals treated with MPSS/GS after E. coli ultimately succumbed to adrenal insufficiency rather than from the E. coli insult and thus recovery from shock itself was complete.

Adrenal Cortex Hormones↗
PubMed1984

A model for thrombin protection against endotoxin.

Infusion of dogs with thrombin (0.5 U/kg/min) for 90 minutes significantly increased percent survival following infusion of endotoxin (0.06 mg/kg/min) for 30 minutes. Nine of fourteen dogs infused with thrombin survived seven days (permanent survivors), whereas thirteen of fourteen dogs infused with saline died within 36 hours. Those dogs which survived responded immediately to endotoxin with enhanced anticoagulant and fibrinolytic activity as measured by the Xa one-stage and fibrin degradation product assays, respectively. Those dogs receiving saline instead of thrombin did not respond with anticoagulant or fibrinolytic activity until the end of the study. We concluded that thrombin in the correct amounts protected dogs from endotoxin and that this protection was associated with an early anticoagulant and fibrinolytic response to endotoxin infusion.

Animals↗
PubMed1984

Evaluation of naloxone for therapy of Escherichia coli shock. Species differences.

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.

Animals↗
PubMed1983

Effectiveness of modified steroid-antibiotic therapies for lethal sepsis in the dog.

Dogs permanently recover (survive at least seven days) from lethal doses of Escherichia coli when treated early with intravenous (IV) intermittent infusions of methylprednisolone sodium succinate and gentamicin sulfate. We evaluated the therapeutic effectiveness of constant or bolus IV infusion of methylprednisolone combined with gentamicin or netilmicin sulfate. Four groups of anesthetized dogs were infused for one hour with E coli and treated as follows (% survival indicated): no treatment (0%); constant infusion of methylprednisolone and gentamicin (100%); bolus infusion of methylprednisolone and gentamicin (57%); and constant infusion of methylprednisolone and netilmicin (83%). Constant or bolus infusion of methylprednisolone was begun 15 minutes after E coli infusion was started. Gentamicin or netilmicin administration was begun when all organisms had been infused. The probability of recovery from shock was significantly increased when dogs were treated with constant infusion of methylprednisolone and intermittent infusions of gentamicin or netilmicin, but was only moderately increased when treated with intermittent bolus infusions of methylprednisolone and intermittent infusions of gentamicin.

Animals↗
PubMed1983

Detection of the 'hyperdynamic state' of sepsis in the baboon during lethal E. coli infusion.

This study was designed to document the early responses of the baboon to LD100 E. coli infusion with an emphasis on cardiovascular, respiratory, and metabolic alterations. Adult baboons were anesthetized, catheterized aseptically to monitor cardiopulmonary and systemic parameters, and infused with LD100 E. coli intravenously for 2 hours. Cardiac output was determined with an Edwards Laboratory Thermodilution Cardiac Output Computer. Oxygen contents of systemic and pulmonary artery blood were determined with a Van Slyke Manometric Apparatus. Results demonstrate early significant increases in cardiac output, oxygen uptake, heart rate, rectal temperature, respiratory rate and minute volume, and decreases in mean systemic arterial pressure and total peripheral resistance. Pulmonary vascular resistance remained relatively constant. In conclusion, an early 'hyperdynamic state' has been detected in the baboon during lethal E. coli infusion (similar to that documented in humans with sepsis) characterized by compensatory alterations in cardiovascular hemodynamics, respiration, and metabolism.

Animals↗
PubMed1983

Relationship of serum gentamicin levels and methylprednisolone sodium succinate treatment in baboons challenged with Escherichia coli LD100.

Serum gentamicin bioassay determinations were performed on 15 adult baboons that had been challenged with an infusion of live Escherichia coli sufficient to kill all of the individuals (LD100) and then treated with either methylprednisolone sodium succinate (MPSS) (administered early in some animals and late in others) and gentamicin sulfate (GS) or with GS only. Initial peak gentamicin levels in all three groups were similar; however, subsequent valley levels revealed that when MPSS treatment was delayed or omitted, gentamicin concentrations remained elevated.

Animals↗
PubMed1983

Prevention or amelioration of morphologic lesions in LD100 E coli-shocked baboons with steroid/antibiotic therapy.

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.

Adrenal Glands↗
PubMed1983

Preventing versus delaying death in shock therapy studies: evaluating "survival".

When results from a short-term experimental study of septic shock indicate that a therapy increases survival time (i.e., delays death), should the reader conclude that the therapy ultimately will increase the percentage of permanent survivors (i.e., prevent death)? If not, how long must animals be observed after lethal sepsis to reasonably validate that a therapy can be used to effect complete recovery? To help answer these questions, we reevaluated survival data from the symposium that entailed the largest number of separate shock therapy studies ever performed on a homogeneous group of dogs in one place at one time with a single lot of endotoxin. Twenty-eight scientists studied the responses of 115 treated and 38 untreated dogs given LD80 endotoxin by bolus injection to compare 15 therapies (most previously reported to have "increased survival"): the numbers of dogs alive were recorded at 0, 0.5, 1, 2, 4, and 7 days. Chi-square analysis indicated significantly more treated than untreated dogs alive only at 24 hr and significantly fewer treated dogs alive on day 7 than on day 2. Individual comparison of the proportion of animals alive in each of the 15 treated groups with the untreated group showed more dogs alive (P less than 0.05) in 3 treated groups at day 1 and in 1 treated group at day 2 and 4; so, four therapies appeared to "increase survival." However, by day 7 no therapy group had statistically more survivors than the untreated group. This evaluation indicates that in order to make a clear distinction between increasing survival time and increasing the percentage of permanent survivors, both treated and untreated dogs should be observed and compared after septic challenge until the percentage of survivors in both groups attains a steady state.

Animals↗
PubMed1979

Extracorporeal perfusion without anticoagulation and the response to endotoxin.

The results of this study show that an extracorporeal perfusion system without anticoagulation can be established in the dog under certain conditions. The exact mechanisms merit further investigation. It also points to a model to study the effects of endotoxin without heparin interference and as another model for studying the canine blood coagulation system.

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↗