Effects of continuous venovenous hemofiltration on cardiopulmonary function in a porcine model of endotoxin-induced shock.

OBJECTIVE: To determine whether continuous venovenous hemofiltration, proposed to remove inflammatory mediators from circulation, would resolve cardiopulmonary derangements in a model of established endotoxic shock. ANIMALS: 16 clinically normal pigs. PROCEDURE: Endotoxin was infused, IV, into anesthetized pigs for a total of 50 minutes. Thirty minutes after termination of the infusion period, extracorporeal circulation was initiated through a 50-kd diafilter, or past the filter without ultrafiltrate formation. Cardiac and respiratory variables were monitored for a period of 4 hours. RESULTS: Infusion of lipopolysaccharide resulted in a severe hypodynamic circulatory state, with significant decreases in mean arterial pressure and cardiac output concurrent with a significant increase in pulmonary arterial pressure. Hemofiltration was not associated with any correction of lipopolysaccharide-induced cardiopulmonary derangements. CONCLUSIONS: Continuous venovenous hemofiltration, as used in this acute experiment, did not improve cardiopulmonary dysfunction during endotoxic shock. CLINICAL RELEVANCE: Continuous venovenous hemofiltration needs further investigation before it can be recommended as a clinically effective treatment.

Piroxicam therapy in 34 dogs with transitional cell carcinoma of the urinary bladder.

Thirty-four dogs with histopathologically confirmed, measurable, nonresectable transitional cell carcinoma of the urinary bladder were treated with piroxicam (0.3 mg/kg PO sid) and were evaluated for tumor response and drug toxicity. Dogs were evaluated at the Purdue University Veterinary Teaching Hospital by means of physical examination, thoracic and abdominal radiography, cystography, complete blood count, serum biochemistry profile, and urinalysis. In selected cases, prostaglandin E2 (PGE2) concentrations in plasma and in supernatants of stimulated monocytes, and natural killer cell activity were quantified. Dogs were evaluated before therapy and at 28 and 56 days after initiation of therapy. Dogs with stable disease or remission at 56 days remained on the study and were evaluated at 1 to 2 months intervals. Tumor responses were 2 complete remissions, 4 partial remissions, 18 stable diseases, and 10 progressive diseases. The median survival of all dogs was 181 days (range, 28 to 720+ days), with 2 dogs still alive. Piroxicam toxicity consisted of gastrointestinal irritation in 6 dogs and renal papillary necrosis (detected at necropsy) in 2 dogs. Monocyte production of PGE2 appeared to decrease with therapy in dogs whose tumors were decreasing in size, and increased in dogs with tumor progression. A consistent pattern in natural killer cell activity was not observed. In vitro cytotoxicity assays against 4 canine tumor cell lines revealed no direct antitumor effects of piroxicam. In summary, antitumor activity, which was not likely the result of a direct cytotoxic effect, was observed in dogs with transitional cell carcinoma of the bladder treated with piroxicam.

Ultracentrifugal and electrophoretic characteristics of the plasma lipoproteins of miniature schnauzer dogs with idiopathic hyperlipoproteinemia.

To better characterize the idiopathic hyperlipoproteinemia of Miniature Schnauzer dogs, the plasma lipoproteins of 20 Miniature Schnauzers (MS) and 11 dogs of other breeds (DOB) were evaluated by ultracentrifugation, electrophoresis, and biochemical tests. Seventeen MS were healthy; 3 had diabetes mellitus. Plasma from 6 of 17 healthy and all 3 diabetic MS was visibly lipemic. Lipemia was slight to marked in healthy lipemic MS, and marked in diabetic ones. All DOB had clear plasma; 8 were healthy and 3 had diabetes. All healthy lipemic MS and diabetic lipemic MS had hypertriglyceridemia associated with excess very low density lipoproteins. Chylomicronemia was present in 4 of 6 healthy lipemic MS and all 3 diabetic lipemic MS. Lipoproteins with ultracentrifugal and electrophoretic characteristics of normal low density lipoprotein were lacking in 4 of 6 healthy lipemic MS. The lipoprotein patterns of 4 of 11 healthy nonlipemic MS were characterized by mild hypertriglyceridemia associated with increased very low density lipoproteins and a lack of lipoproteins with characteristics of normal low density lipoproteins. Lipoprotein patterns of diabetic DOB closely resembled those of healthy DOB; those of diabetic lipemic MS resembled those of markedly lipemic healthy lipemic MS. In conclusion, the hyperlipoproteinemia of Miniature Schnauzers is characterized by increased very low density lipoproteins with or without accompanying chylomicronemia; some affected dogs may have decreased low density lipoproteins.

Serum triiodothyronine, total thyroxine, and free thyroxine concentrations in horses.

The objectives of this experiment were to determine serum concentrations of triiodothyronine (T3), thyroxine (T4), and free thyroxine (fT4) at rest, following thyroid-stimulating hormone (TSH) administration, and following phenylbutazone administration in healthy horses. This was done to determine which available laboratory test can best be used for diagnosis of hypothyroid conditions in horses. Serum T3, T4, and fT4 concentrations in serum samples obtained before and after TSH stimulation and following phenylbutazone administration for 7 days were determined. Baseline values ranged from 0.21 to 0.80 ng of T3/ml, 6.2 to 25.1 ng of T4/ml, and 0.07 to 0.47 ng of fT3/dl. After 5 IU of TSH was administered IV, serum T3 values increased to 6 times baseline values in 2 hours. Thyroxine values increased to 3 times baseline values at 4 hours and remained high at 6 hours. Free T4 values increased to 4 times baseline values at 4 hours and remained high at 6 hours. Administration of 4.4 mg of phenylbutazone/kg, every 12 hours for 7 days significantly decreased T4 and fT4 values, but did not significantly affect serum T3 concentrations. It was concluded that a TSH stimulation test should be performed when hypothyroidism is suspected. Measurement of serum fT4 concentrations, by the single-stage radioimmunoassay, does not provide any additional information about thyroid gland function over that gained by measuring T4 concentrations. Phenylbutazone given at a dosage of 4.4 mg/kg every 24 hours, for 7 days did significantly decrease resting T4 and fT4 concentrations, but did not significantly affect T3 concentrations in horses.

The effect of starting time on dexamethasone suppression test results in horses.

This study was conducted to investigate the effect of starting time on dexamethasone suppression test results in horses. Eight adult horses were used throughout the trial. Baseline cortisol levels were established by collecting cortisol levels twice daily, at 8:00 A.M. and 8:00 P.M. for 4 consecutive days. Morning baseline cortisol levels were 46.3 +/- 5.94 ng/ml, and evening baseline cortisol levels were 32.8 +/- 5.59 ng/ml. Although lower, the evening cortisol levels were not statistically different (P = 0.154) from the morning levels. Dexamethasone suppression tests initiated at either 9:00 A.M. or 9:00 P.M. were performed by collected a control blood sample, administering either 0.044 mg/kg dexamethasone or its vehicle intravenously and then collecting additional blood samples at 6, 12, 24, 36, and 48 hr after treatment. Mean cortisol levels at hr 0, 6, 12, 24, 36, and 48 after a dexamethasone injection given at 9:00 A.M. were 55.6 +/- 3.08, 6.4 +/- 2.05, 0.73 +/- 0.48, 11.0 +/- 5.82, 12.6 +/- 4.30, and 40.5 +/- 5.38 ng/ml respectively. Mean cortisol levels at hr 0, 6, 12, 24, 36, and 48 hr after a dexamethasone injection given at 9:00 P.M. were 45.0 +/- 6.03, 4.5 +/- 1.28, 0.20 +/- 0.12, 4.5 +/- 2.49, 23.4 +/- 5.88, and 29.5 +/- 6.61 ng/ml respectively. There was no statistical difference in cortisol values between A.M. and P.M. initiated tests at any hour post dexamethasone administration. There was no decrease in cortisol level after administration of dexamethasone vehicle.

Serial thyroid hormone concentrations in healthy euthyroid dogs, dogs with hypothyroidism, and euthyroid dogs with atopic dermatitis.

Serum thyroxine (T4) and 3,5,3'-triiodothyronine (T3) concentrations were determined every 3 h for 12 h beginning at 8 a.m. in 20 healthy euthyroid dogs, 19 dogs with hypothyroidism, and 18 euthyroid dogs with atopic dermatitis. Status of thyroid function was based on history, physical findings, results of thyrotropin response testing, and requirement for thyroid hormone replacement therapy. Mean serum T4 and T3 concentrations did not vary significantly between blood samplings within each of the three groups of dogs. Between groups of dogs, mean serum T4 concentration was significantly (P less than 0.05) higher at each blood sampling time in healthy euthyroid dogs and euthyroid dogs with atopic dermatitis when compared to dogs with hypothyroidism. There was no significant difference in mean serum T4 concentration at any blood sampling time between healthy euthyroid dogs and euthyroid dogs with atopic dermatitis or in mean serum T3 concentrations at any blood sampling time between any of the three groups of dogs. Random fluctuation in serum T4 and T3 concentrations was found in dogs in all three groups. Random fluctuations were more common with serum T3 versus T4 concentrations. Consequently, sensitivity (0.88 versus 0.52), specificity (0.73 versus 0.45), predictive value for a positive test (0.75 versus 0.32), predictive value for a negative test (0.87 versus 0.65), and accuracy (0.80 versus 0.47) were better for serum T4 concentration than serum T3 concentration, respectively, when all blood samples were analysed. Measurement of serum T4 concentration was more accurate than serum T3 concentration in assessing the status of thyroid gland function.

Effects of flunixin meglumine on dogs with experimental gastric dilatation-volvulus.

Gastric dilatation-volvulus (GDV) was created experimentally and maintained for 90 minutes in 16 anesthetized, mixed-breed dogs. After the GDV was corrected, normal saline solution (0.044 mL/kg intravenously [IV]) was administered to eight dogs (controls), and flunixin meglumine (2.2 mg/kg IV) was administered to eight dogs. Microspheres labeled with radioactive cobalt, scandium, tin, or niobium were injected intravenously at baseline (before GDV) and minutes 90, 100, and 270, respectively, to determine tissue blood flows. Plasma endotoxin and prostacyclin were measured at the same intervals. Electrocardiogram, mean arterial pressure, portal pressure, and cardiac output were recorded continuously. Dogs were euthanatized at minute 270 and necropsied. There was no significant difference between treatment groups for any measured variable at any time. Endotoxin levels increased significantly during GDV. Prostacyclin levels were lower in dogs treated with flunixin meglumine than in controls at minutes 210 and 270. Histopathologic findings were similar for all dogs and consistent with those associated with endotoxemia. Flunixin meglumine treatment did not alter cardiac indices or tissue blood flows significantly. However, elevation of prostacyclin was inhibited by flunixin meglumine, which suggested that continued effects of endotoxic damage might be attenuated or inhibited.

Phase I trial of piroxicam in 62 dogs bearing naturally occurring tumors.

Piroxicam, a nonsteroidal antiinflammatory drug, was given to 62 dogs bearing naturally occurring tumors in a phase I clinical trial. Dose escalation was performed, with oral doses ranging from 0.5 mg/kg every 48 h (q48h) to 1.5 mg/kg q48h being tested. Dose-limiting gastrointestinal irritation/ulceration occurred in all four animals that received 1.5 mg/kg q48h. The maximum tolerated dose was 1 mg/kg q48h. Subclinical renal papillary necrosis occurred in two dogs (initial dosages, 1 and 1.5 mg/kg q48h, respectively). Following dose escalation, an additional group of dogs was treated with 0.3 mg/kg piroxicam q24h per os, the accepted canine dosage prior to this trial. Inclusion of this treatment group enabled evaluation of the toxicity of and tumor response to a daily dosage regimen. No complete remissions occurred in this trial. Partial remission was documented in three of ten dogs exhibiting transitional-cell carcinoma, in three of five animals bearing squamous-cell carcinoma, in one of three dogs displaying mammary adenocarcinoma, and in the one dog that exhibited a transmissible venereal tumor. The results of this study support the additional evaluation of piroxicam in a phase II clinical trial in dogs bearing naturally occurring tumors.

Effects of dietary fiber supplementation on glycemic control in dogs with alloxan-induced diabetes mellitus.

The effect of a high insoluble-fiber (IF) diet containing 15% cellulose in dry matter, high soluble-fiber (SF) diet containing 15% pectin in dry matter, and low-fiber (LF) diet on glycemic control in 6 dogs with alloxan-induced insulin-dependent diabetes mellitus was evaluated. Each diet contained greater than 50% digestible carbohydrate in dry matter. A crossover study was used with each dog randomly assigned to a predetermined diet sequence. Each dog was fed each diet for 56 days. Caloric intake was adjusted weekly as needed to maintain each dog within 1.5 kg of its body weight measured prior to induction of diabetes mellitus. All dogs were given pork lente insulin and half of their daily caloric intake at 12-hour intervals. Mean (+/- SEM) daily caloric intake was significantly (P less than 0.05) less when dogs consumed the IF diet vs the SF and LF diets (66 +/- 3 kcal/kg, 81 +/- 5 kcal/kg, and 79 +/- 4 kcal/kg, respectively). Serum alkaline phosphatase activity was significantly (P less than 0.05) higher when dogs consumed the LF diet vs the IF and SF diets (182 +/- 37 IU/L, 131 +/- 24 IU/L, and 143 +/- 24 IU/L, respectively). Mean postprandial plasma glucose concentration measured every 2 hours for 24 hours, beginning at the time of the morning insulin injection, was significantly (P less than 0.05) lower at most blood sampling times in dogs fed IF and SF diets, compared with dogs fed the LF diet.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of dietary n-3 and n-6 fatty acids on tumor necrosis factor-alpha production and leucine aminopeptidase levels in rat peritoneal macrophages.

The purpose of this study was to determine the effect of dietary n-3 and n-6 fatty acids on tumor necrosis factor-alpha (TNF-alpha) production and macrophage (MO) activation state. Rats were fed diets containing 12.5% linseed oil (LO) or corn oil (CO) that are high in n-3 and n-6 fatty acids respectively. The LO diet resulted in a significant increase in basal and endotoxin (LPS)-induced levels of TNF-alpha from resident MO cultured in vitro. There was no difference between the diets in LPS-induced TNF-alpha production by complete Freund's adjuvant (CFA) elicited macrophages. Variable responses were also observed between LO and CO MO in response to prostaglandin E2, indomethacin (INDO), and the prostaglandin E receptor antagonist SC-19220. This may indicate differences in signal transducing secondary messengers due to different activation states, receptor expression or ligand binding. Fluorescence due to leucine aminopeptidase (LAP) staining was determined by flow cytometry. Resident LO MO had a 15% increase in LAP fluorescence compared to CO MO. In CFA-elicited MO, the CO MO had a 43% increase in fluorescence compared to LO MO. Resident LO MO increased in LAP fluorescence by 35% to the activated state whereas resident CO MO increased in LAP fluorescence by 93%. The smaller window of activation for the LO MO may explain some of the antiinflammatory properties of dietary n-3 fatty acids.

Serum glucose and insulin responses to an insulin-containing ophthalmic solution administered topically in clinically normal cats.

Serum glucose and immunoreactive insulin concentrations were monitored after topical administration of an insulin-containing ophthalmic solution in 20 clinically normal cats. Three ophthalmic surface-acting agents, benzalkonium chloride, dimethyl sulfoxide, and proparacaine hydrochloride, were evaluated individually for their effectiveness in enhancing absorption of topically applied insulin. The ophthalmic effects of insulin-containing ophthalmic preparations were assessed by complete ophthalmic examination before and at the conclusion of each test period. Withholding of food overnight (12 hours) preceded each topical application of insulin-containing ophthalmic solution (12.25 to 26.4 U/cat), either alone or in combination with surface-acting agents, after which blood samples were drawn serially from an indwelling IV catheter over a period of 8 hours. Baseline serum insulin concentration, after food was withheld for 12 hours, in nonstressed cats was 6.0 microU/ml (geometric mean), and an exponentiation of the logarithmic quantity (mean +/- SD) yielded values of 1.5 to 23.0 microU/ml. All ophthalmic solutions tested failed to significantly lower serum glucose concentration or increase serum insulin concentration. Solutions used did not induce deleterious effect on ocular structures. Results indicate that topical administration of insulin-containing ophthalmic solution, either alone at the concentrations used or in combination with surface-acting agents, did not result in effective absorption of insulin across the conjunctival and lacrimal nasal mucosa in biologically relevant quantities. Thus, this route of insulin administration, under these specific conditions, is not an effective alternative or adjunct to SC administration of insulin for treatment of cats with insulin-dependent diabetes mellitus or severe noninsulin-dependent diabetes mellitus.

The effects of soman poisoning in combination with hypovolemic shock.

Hemorrhage is a cause of death in both combat and civilian injuries. The specific objectives of this research were: (1) to determine the pathophysiologic effects of combined injuries from sublethal amounts of an organophosphate (soman) along with hypovolemic shock, and (2) to determine the efficacy of atropine sulfate and pralidoxime (2-PAM) therapy for organophosphate poisoning when combined injuries occur. Four groups of six beagle dogs/group were used: Group V/H, vehicle administration followed by hemorrhage; Group S/H, soman administration followed by hemorrhage; Group S/A/H, soman followed by antidote (atropine and 2-PAM) and then hemorrhage; and Group S, soman only. Acetylcholinesterase (AChE) activity, hemodynamic parameters, regional blood flow, plasma enzyme, and hematological changes were monitored. Soman rapidly decreased AChE activity in RBCs, plasma, and brain tissue. Treatment with atropine and 2-PAM resulted in only slight reactivation of AChE; they helped maintain blood gases, cortisol, plasma enzymes, inspiratory volume, and blood pressure nearer baseline values. The effects of combined injuries appear to be greater than those of either injury alone. This was indicated by increased plasma lactate, plasma enzymes indicative of tissue damage (aspartate amine transferase and creatine kinase), and increased lethality in dogs subjected to both soman and hemorrhage (5/12 died). All dogs subjected to only one insult survived the 6-hr experiment.

Serum free thyroxine concentration in healthy dogs, dogs with hypothyroidism, and euthyroid dogs with concurrent illness.

Serum free thyroxine (fT4), thyroxine (T4), and 3,5,3'-triiodothyronine (T3) concentrations were determined in 62 healthy dogs, 51 dogs with hypothyroidism, and 59 euthyroid dogs with concurrent dermatopathy or concurrent illness for which hypothyroidism was a diagnostic consideration. Status of thyroid function was based on history, physical findings, results of thyrotropin response testing, requirement for thyroid hormone replacement therapy, and in 31 dogs, on results of histologic examination of a thyroid gland biopsy specimen. Serum fT4 concentration was determined, using a single-stage radioimmunoassay. Mean (+/- SD) serum fT4 concentration was significantly (P less than 0.05) greater in healthy dogs vs dogs with hypothyroidism (0.51 +/- 0.27 ng/dl vs 0.10 +/- 0.07 ng/dl). Significant difference in mean serum fT4 concentration was not evident between dogs with hypothyroidism and euthyroid dogs with hyperadrenocorticism (0.16 +/- 0.13 ng/dl) or peripheral neuropathy (0.19 +/- 0.10 ng/dl). Mean serum fT4 concentration in all other groups of euthyroid dogs with concurrent illness was similar to values in healthy dogs and was significantly (P less than 0.05) greater, compared with values in dogs with hypothyroidism. Similar results were found for mean serum T4 concentration. Comparison of serum fT4 vs T4 concentration revealed: sensitivity, 0.97 vs 0.98; specificity, 0.78 vs 0.73; predictive value for a positive test result, 0.79 vs 0.80; predictive value for a negative test result, 0.97 vs 0.97; and accuracy, 0.78 vs 0.86, respectively. Ten (17%) and 12 (20%) of 59 serum fT4 and T4 concentrations, respectively, were inappropriately low in euthyroid dogs with concurrent illness.(ABSTRACT TRUNCATED AT 250 WORDS)

Leukotriene C4 disposition and metabolism in the anesthetized and endotoxemic dog.

The metabolism and disposition of tritiated leukotriene C4, [3H]-LTC4, were studied in control dogs and endotoxin-treated dogs. Radioactivity was monitored in plasma, bile, and urine for 4.5 hr after an IV bolus of [3H]-LTC4. A decreased recovery of radioactivity in bile and urine was observed in the endotoxin-treated dogs. Cumulative [3H]-LTC4 metabolic patterns in bile and urine were determined by reverse-phase high-performance liquid chromatography (RP-HPLC) separation. Three primary metabolites, [3H]-LTD4, [3H]-LTE4, and a polar metabolite, (0.15-0.19)LT, accounted for most of the total bile radioactivity. The same primary metabolites were found for endotoxin-treated dogs and in similar relative amounts. [3H]-LTE4 and the polar metabolite (0.15-0.21)LT were the primary metabolites found in urine, but no N-acetyl LTE4 was found in bile or urine for either group. Plasma incubation of [3H]-LTC4 revealed heat-sensitive dipeptidase and glutamyl transpeptidase activity with significant production of [3H]-LTD4 and [3H]-LTE4 after 5- and 30-min incubation. Pharmacokinetic analysis using the two-compartment open model revealed an increased distribution phase rate constant (alpha) and distribution phase half-life [t1/2(alpha)], and decreased clearance (ClB), volume of distribution [Vd(ss) and Vd(area)] and elimination rate microconstant (Kel) of tritiated leukotrienes for endotoxin-treated dogs. This analysis along with the maintained higher plasma levels of tritiated leukotrienes, [3H]-LTs, in endotoxin-treated dogs suggests that endotoxin caused a decreased body clearance and less peripheral tissue penetration of [3H]-LTs. Collectively, these results indicate that the metabolism of LTC4 to LTD4 and LTE4, but not N-acetyl LTE4, in dogs was similar to that reported for man, pig, and monkey but dissimilar to rat. Endotoxin did not affect the types or relative amounts of metabolites found in bile or urine but appears to affect the disposition of [3H]-LTs by decreasing clearance and distribution.

Plasma concentrations of endotoxin following jugular or portal injections of endotoxin and following gastrointestinal ischemia due to hemorrhage.

Endotoxin (LPS) was quantitated in canine plasma using the Limulus amebocyte lysate (LAL) chromogenic testing procedure. The assay was validated for sensitivity (25 pg/ml), recovery (90-110%), intra-assay precision (CV = 5.5), interassay precision (CV = 10), and stability of diluted, heat-treated, frozen samples (greater than or equal to 60 days). Canine plasma samples were analyzed for endotoxin following sublethal IV injections (cephalic and portal, bolus and slow infusion) of LPS. Pharmacokinetic analysis using the two-compartment open model on plasma LPS levels was possible for portal bolus, cephalic bolus, and portal slow infusion dogs. The results revealed that LPS given via cephalic bolus route had a lower clearance rate than LPS given via portal bolus route. Slow infusion of LPS into the portal vein revealed an increased distribution phase t1/2 in plasma and a slower elimination kel and beta rate than observed following a portal bolus injection of LPS. During a clinical endo(to)xemia, LPS enters the circulation slowly, and is therefore probably cleared more slowly; the prolonged low level of LPS may be responsible for many pathophysiological changes observed. Low levels of endotoxin were detected in plasma following hemorrhage, indicating that intestinal ischemia results in low levels of LPS leaking into the circulation.

Absorption kinetics of regular insulin in dogs with alloxan-induced diabetes mellitus.

The absorption kinetics of porcine regular insulin following IV, IM, and SC administration were evaluated in 10 dogs with alloxan-induced diabetes mellitus. Plasma immunoreactive insulin (IRI) concentrations were evaluated immediately prior to and at 10, 20, 30, 45, 60, 90, 120, 180, and 240 minutes following IV administration; and immediately prior to and every 30 minutes for 2 hours and then every hour for 6 hours following IM and SC administration of 0.55 U of porcine regular insulin/kg of body weight. Model-independent pharmacokinetic analysis was performed on each data set. Plasma IRI concentration declined rapidly after IV administration of regular insulin and then returned to baseline IRI concentration by 3.2 +/- 0.8 hours. The absorption kinetics following IV administration of regular insulin were similar to those found in earlier studies in healthy dogs and human beings. The IM and SC routes of regular insulin administration resulted in a pharmacologic concentration of IRI at 30 minutes. The peak mean (+/- SD) plasma IRI concentration was significantly (P less than 0.05) greater following SC administration than it was following IM administration of regular insulin (263 +/- 185 and 151 +/- 71 I microU/ml, respectively). The time of the peak plasma IRI concentration (68 +/- 31 minutes and 60 +/- 30 minutes) and the time to return to baseline plasma IRI concentration (5.8 +/- 1.2 hours and 5.8 +/- 1.3 hours) were not significantly different following SC and IM administration of regular insulin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acute alcohol intake on tolerance to hypotension.

The specific aim of this research was to test the hypothesis that intoxication with alcohol results in poor tolerance to hemorrhage. This was evaluated on the basis of blood pressure, cardiac output respiratory rate, blood flow to organs, and survival for 4 hr after hemorrhage. Four groups of six swine per group were used (control, intoxicated, hemorrhage, and intoxicated-hemorrhage). The results revealed that blood alcohol concentrations near 0.1% greatly reduced tolerance to hemorrhage. Intoxicated animals subjected to hemorrhage were unable to maintain an adequate cardiac output, blood pressure, or respiratory rate to sustain life. Pigs tolerated higher blood alcohol concentrations, up to 0.35%, when not exposed to hemorrhage. Also, unintoxicated pigs were able to compensate for severe hemorrhage. Only one of the six pigs in the intoxicated-hemorrhage group survived for 4 hr after hemorrhage. In conclusion the body's ability to compensate and recover from hemorrhage was greatly reduced during intoxication. It is logical to assume that the ability to overcome numerous other stressors may also be reduced during intoxication.

Glucose tolerance and insulin response in normal-weight and obese cats.

Glucose tolerance and insulin response were evaluated in 9 normal-weight and 6 obese cats after IV administration of 0.5 g of glucose/kg of body weight. Blood samples for glucose and insulin determinations were collected immediately prior to and 2.5, 5, 7.5, 10, 15, 30, 45, 60, 90, and 120 minutes after glucose infusion. Baseline glucose concentrations were not significantly different between normal-weight and obese cats; however, mean +/- SEM glucose tolerance was significantly impaired in obese vs normal-weight cats after glucose infusion (half time for glucose disappearance in serum--77 +/- 7 vs 51 +/- 4 minutes, P less than 0.01; glucose disappearance coefficient--0.95 +/- 0.10 vs 1.44 +/- 0.10%/min, P less than 0.01; insulinogenic index--0.20 +/- 0.02 vs 0.12 +/- 0.01, P less than 0.005, respectively). Baseline serum insulin concentrations were not significantly different between obese and normal-weight cats. Insulin peak response after glucose infusion was significantly (P less than 0.005) greater in obese than in normal-weight cats. Insulin secretion during the first 60 minutes (P less than 0.02), second 60 minutes (P less than 0.001), and total 120 minutes (P less than 0.0003) after glucose infusion was also significantly greater in obese than in normal-weight cats. Most insulin was secreted during the first hour after glucose infusion in normal-weight cats and during the second hour in obese cats. The impaired glucose tolerance and altered insulin response to glucose infusion in the obese cats was believed to be attributable to deleterious effects of obesity on insulin action and beta-cell responsiveness to stimuli (ie, glucose).

Characterization of release of tumor necrosis factor, interleukin-1, and superoxide anion from equine white blood cells in response to endotoxin.

Direct effects of endotoxin (lipopolysaccharide [LPS]) on equine WBC are known to stimulate the release of a variety of mediators including thromboxane, prostacyclin, and leukotrienes. In this study, 0.1 microgram of LPS/ml stimulated an early increase in tumor necrosis factor, succeeded by an increase in interleukin-1, but concentrations of LPS up to 5.0 micrograms/ml caused no significant increase in superoxide anion release. The concentration of LPS (0.1 microgram/ml) used in this experiment was in the range of concentrations measured in plasma of some horses with gastrointestinal problems. These results indicate that mediators released in response to low concentrations of LPS may be responsible for many of the LPS-induced pathophysiologic effects. This is indicated because concentrations of LPS detected in plasma of some horses with severe gastrointestinal problems are approximately 0.1 microgram/ml, a concentration that will stimulate cells to produce tumor necrosis factor, but will not stimulate any other measurable cytotoxic effect.