Hemodynamic response of endotoxemic calves to treatment with small-volume hypertonic saline solution

The hemodynamic effects of hypertonic saline solution (HSS) resuscitation on endotoxic shock were examined in pentobarbital-anesthetized calves (8 to 20 days old). Escherichia coli (055:B5) endotoxin was infused IV at dosage of 0.1 microgram/kg of body weight for 30 minutes. Endotoxin induced large decreases in cardiac index, stroke volume, maximal rate of change of left ventricular pressure (+dP/dtmax), femoral and mesenteric arterial blood flow, glomerular filtration rate, urine production, and mean aortic pressure. Severe pulmonary arterial hypertension and increased pulmonary vascular resistance were evident at the end of endotoxin infusion. Treatment with HSS (2,400 mosm of NaCl/L, 4 ml/kg) or an equivalent sodium load of isotonic saline solution (ISS: 300 mosm of NaCl/L, 32 ml/kg) was administered 90 minutes after the end of endotoxin administration. Both solutions were infused IV over a 4- to 6-minute period. Administration of HSS induced immediate and significant (P less than 0.05) increase in stroke volume and central venous pressure, as well as significant decrease in pulmonary vascular resistance. These effects were sustained for 60 minutes, after which all variables returned toward preinfusion values. The hemodynamic response to HSS administration was suggestive of rapid plasma volume expansion and redistribution of cardiac output toward splanchnic circulation. Plasma volume expansion by HSS was minimal 60 minutes after resuscitation. Administration of ISS induced significant increase in cardiac index, stroke volume, femoral arterial blood flow, and urine production. These effects were sustained for 120 minutes, at which time, calves were euthanatized. Compared with HSS, ISS induced sustained increase in mean pulmonary arterial pressure and only a small increase in mesenteric arterial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dobutamine-induced augmentation of cardiac output does not enhance respiratory gas exchange in anesthetized recumbent healthy horses

The influence of pharmacologic enhancement of cardiac output on the alveolar-to-arterial oxygen tension (difference (P[A-a]O2), physiologic right-to-left shunt fraction (Qs/Qt), and physiologic dead space-to-tidal volume ratio (VD/VT) ws studied in halothane-anesthetized horses in left lateral, right lateral, and dorsal recumbencies. Adult horses were anesthetized, using xylazine (2.2 mg/kg, IM), guaifenesin (50 mg/kg, IV), thiamylal (4.4 mg/kg, IV), and halothane (1.5% to 2% inspired) in 100% O2. Mechanical ventilation was controlled to maintain arterial eucapnia (PaCO2) 35 to 45 mm of Hg) for a period lasting at least 1 hour. Dobutamine was administered at dosages of 1, 3, and 5 micrograms/kg/min, IV, on a randomized basis. The P(A-a)O2, Qs/Qt, and VD/VT were calculated during equilibration and after each dobutamine infusion was given. The P(A-a)O2 and Qs/Qt were significantly (P less than 0.05) greater and VD/VT tended to be greater in horses in dorsal recumbency, compared with those values in horses in left lateral or right lateral recumbency. Cardiac output was similar in all horses, regardless of body position (recumbency). The qualitative relationship between horses in the 3 recumbent positions were not altered by dobutamine. Cardiac output was significantly (P less than 0.05) increased by 3 or 5 micrograms of dobutamine/kg/min in all horses, whereas P(A-a)O2, Qs/Qt, and VD/VT were not significantly altered by dobutamine. The results of the present study failed to substantiate our clinical observations of decreased P(A-a)O2 and Qs/Qt in anesthetized compromised horses given dobutamine.     

Effect of intravenous infusion of a 7.2% hypertonic saline solution on serum electrolytes and osmotic pressure in healthy beagles.

The effect of an intravenous (i.v.) infusion of hypertonic saline solution (HSS; 7.2%, 2,400 mOsmol/kg.H2O) was evaluated by serum electrolyte concentrations and osmotic pressure in the anesthetized beagles. Sixteen beagles were assigned to 3 experimental groups (2.5, 5 or 15 ml/kg of HSS i.v. infusion) or a control group (5 ml/kg of isotonic saline solution (ISS) i.v. infusion) and were monitored for 120 min after the initiation of fluid infusion. The relative plasma volume (rPV) in the 5 ml/kg and 15 ml/kg HSS groups progressively expanded to 143.1 +/- 7.4% at 3 min and 156.4 +/- 5.9% at 5 min after the initiation of the fluid infusion, respectively. Significant increases were not produced by ISS and 2.5 ml/kg HSS infusion. The serum sodium and chloride concentrations in the ISS group were not altered. The 5 ml/kg HSS infusion induced transient high osmotic and sodium levels, and the serum sodium concentration remained under the 160 mM/l after the completion of the HSS infusion. However, the 15 ml/kg HSS infusion induced a constant high osmotic level (340.5-352.8 mOsmol/kg.H2O) and hypernatremia (161.4-174.5 mM/l) from 10 to 90 min after the initiation of the fluid infusion. The 15 ml/kg HSS infusion induced significant decreases in the partial pressure of oxygen (PaO2), reaching 63.7 +/- 8.0 mmHg at 120 min after the initiation of the fluid infusion compared with an immediately before fluid infusion value. On the basis of these findings, 5 ml/kg HSS infusion can be safely administered to healthy beagles for expanding the plasma volume without inducing hypernatremia. A 5 ml/kg HSS infusion is thus recommended for the initial field resuscitation of dogs.     

Cardiovascular effects of enoximone in isoflurane anaesthetized ponies

OBJECTIVE: Enoximone is a phosphodiesterase III inhibitor frequently used to improve cardiac output (CO) in man. As the use of enoximone has not been reported in horses, the effects of this inodilator were examined in isoflurane anaesthetized ponies. STUDY DESIGN: Prospective, randomised, experimental study. ANIMALS: Six healthy ponies, weighing 286 (212-367) +/- 52 kg, aged 5.0 +/- 1.6 years (4-6.5). METHODS: After sedation with romifidine [80 microg kg(-1) intravenously (IV)], general anaesthesia was induced with midazolam (0.06 mg kg(-1) IV) and ketamine (2.2 mg kg(-1) IV) and maintained with isoflurane in oxygen (Et Iso 1.7%). The ponies were ventilated to maintain eucapnia (PaCO(2) 4.66-6.00 kPa). Each pony was anaesthetized twice with an interval of 3 weeks; receiving enoximone 0.5 mg kg(-1) IV (E) or saline (S) 90 minutes post-induction. Heart rate (HR), arterial (AP) and right atrial pressure (RAP) were measured before treatment, every 5 minutes between T0 (treatment) and T30 and then every 10 minutes until T120. Cardiac output measurements (lithium dilution technique) and blood gas analysis (arterial and central venous samples) were performed before T0 and at T5, T10, T20, T40, T60, T80, T100 and T120. Stroke volume (SV), systemic vascular resistance (SVR), venous admixture (Qs/Qt) and oxygen delivery (DO(2)) were calculated. RESULTS: Enoximone induced significant increases in HR, CO, SV, Qs/Qt and DO(2) and a significant decrease in RAP. No significant differences were detected for AP, SVR and blood gases. No cardiac arrhythmias or other side effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE: The present results suggest that in isoflurane anaesthetized ponies, enoximone has beneficial effects on CO and SV without producing significant changes in blood pressure. Despite an increase in Qs/Qt, DO(2) to the tissues was improved.     

Effect of hypertonic vs isotonic saline solution on responses to sublethal Escherichia coli endotoxemia in horses

Cardiovascular responses to sublethal endotoxin infusion (Escherichia coli, 50 micrograms/ml in lactated Ringer solution at 100 ml/h until pulmonary arterial pressure increased by 10 mm of Hg) were measured 2 times in 5 standing horses. In a 2-period crossover experimental design, horses were either administered hypertonic (2,400 mosm/kg of body weight, IV) or isotonic (300 mosm/kg, IV) NaCl solution after endotoxin challenges. Each solution was administered at a dose of 5 ml/kg (infusion rate, 80 ml/min). Complete data sets (mean arterial, central venous, and pulmonary arterial pressures, pulmonary arterial blood temperature, cardiac output, total peripheral vascular resistance, heart rate, plasma osmolality, plasma concentration of Na, K, Cl, and total protein, blood lactate concentration, and PCV) were collected at 0 (baseline, before endotoxin infusion), 0.25, 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after initiation of the endotoxin infusion. Blood constituents alone were measured at 0.5 hour and cardiovascular variables alone were evaluated at 0.75 hour. By 0.25 hour, endotoxin infusion was completed, a data set was collected, and saline infusion was initiated. By 0.75 hour, saline solutions had been completely administered. Mean (+/- SEM) cardiac output decreased (99.76 +/- 3.66 to 72.7 +/- 2.35 ml/min/kg) and total peripheral resistance (1.0 +/- 0.047 to 1.37 +/- 0.049 mm of Hg/ml/min/kg) and pulmonary arterial pressure (33.4 +/- 0.86 to 58.3 +/- 1.18 mm of Hg) increased for both trials by 0.25 hour after initiation of the endotoxin infusion and prior to fluid administration. For the remainder of the protocol, cardiac output was increased and total peripheral resistance was decreased during the hypertonic, compared with the isotonic, saline trial.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of two different methods for dead space measurements in ventilated dogs

The aim of the study was to compare two methods of measuring physiological dead space/tidal volume ratio (Vd /Vt ) and alveolar dead space (Vd _ALV). Measurements were obtained by automated single breath CO₂ analysis (Ventrak 1550/Capnoguard 1265 (V&C)) and classical calculations were carried out using the Enghoff–Bohr equation in anaesthetized dogs. The V&C consists of a mainstream capnometer, a pneumotachometer, a signal processor, and computer software to determine continuous single‐breath CO₂ analysis (SBT‐CO₂). Eleven dogs of mixed breed (five female, six male) mean body mass 35 ± 10 kg, aged 9 months to 8 years were studied. Pre‐anaesthetic medication was acepromazine (0.03 mg kg^?1) and methadone (0.1 mg kg^?1). Anaesthesia was induced with propofol given to effect and maintained with propofol (10 mg kg^?1 hour^?1) and fentanyl (0.02 mg kg^?1 hour^?1) by infusion. The dog's trachea were intubated and the carbon dioxide and flow sensor were placed between the tube and the Y‐piece of a circle system (Fi O₂ = 1.0). Controlled ventilation was started (tidal volume 10–15 mL kg^?1) and settings were not changed throughout the measurement period. Mixed expired PCO₂ (P e ?CO₂) was measured by analyzing expired gas collected in a mixing box in the expiratory limb of the circle system. The dorsal pedal artery was cannulated for arterial blood sampling and analysis. Measurements were done every 15 minutes for 1 hour. The Vd /Vt was automatically calculated and displayed from the SBT‐CO₂ analysis and also obtained using the Enghoff modification of the Bohr equation (Vd /Vt = (PaCO₂ ? P e ?CO₂)/PaCO₂). Alveolar dead space was determined by calculating the physiological dead space (Vd phys = expired volume × (Vd /Vt )) and subtracting the anatomical dead space measured by SBT‐CO₂. Values for Vd /Vt and Vd _ALV obtained with both methods were compared using Students t‐test. The mean values from the automatic dead space calculation (Vd /Vt : 0.62–0.63; Vd _ALV: 56.1–64.3 mL) did not differ significantly from those calculated arithmetically (Vd /Vt : 0.62–0.63; Vd _ALV: 54.09–66.31 mL). The mean differences and standard deviation in Vd /Vt was 0.63 ± 0.00 and in Vd _ALV 58.98 ± 4.28 mL for the two measurement techniques. Our data indicate that V&C can be used for accurate noninvasive online Vd /Vt and Vd _ALV measurements in anaesthetized ventilated dogs.     

Flow cytometric analysis of peripheral blood mononuclear cells induced by experimental endotoxemia in horse

Cellular activation and functional cell surface markers were evaluated during experimentally-induced endotoxemia in healthy horses. Eight healthy adult horses were infused a low dose of endotoxin (lipopolysaccharide from Escherichia coli O26: B6, 30 ng/kg of body weight, IV) and five control horses were given an equivalent volume of sterile saline solution. Venous blood samples were collected for flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and to measure plasma endotoxin concentrations. Clinical signs of endotoxemia were recorded at 10, 20, 30, 40, 50 min, 1, 2, 3, 4, 8, 16, 24 and 48 hr after endotoxin or saline solution administration. Clinical findings characteristic of endotoxemia (tachycardia, tachypnea, increased rectal temperature, and leukopenia) occurred transiently in all horses administered endotoxin; however, plasma endotoxin concentrations were detectable in only 50% (4/8) of the endotoxin-infused horses. The percentage of CD4(+), CD5(+), and CD8(+) cells decreased while the percentage of CD14(+), IgM(+), and MHC class II(+) cells increased significantly after endotoxin infusion. Alterations in the immunophenotype of PBMCs from horses with experimentally-induced endotoxemia were associated with changes in vital signs, indicating that endotoxin altered the immuno balance.     

Haemodynamic, pathological, haematological and behavioural changes during endotoxin infusion in equine neonates

The purpose of this study was to evaluate the effects of experimentally induced sublethal endotoxaemia in equine neonates. Four foals, between two and five days of age, were infused intravenously with 0.5 microgram/kg bodyweight of Salmonella typhimurium endotoxin (LPS) over a 5 h period. A four-day-old and a five-day-old foal, similarly infused with sterile isotonic saline, served as controls. Clinical signs were monitored, blood samples obtained for evaluation of selected haematological and biochemical parameters; and haemodynamic parameters were recorded hourly during the infusion, as well as 6 and 24 h post infusion. Depression, anorexia, increased rectal temperature, leucopenia followed by leucocytosis, hypoglycaemia, increased prothrombin time, partial thromboplastin time (APTT), pulmonary artery pressure, pulmonary artery wedge pressure, right atrial pressure, pulmonary and systemic vascular resistance and mild hypoxaemia were consistent findings in the foals receiving endotoxin. There was marked variation over time in the above parameters, during the infusion. Shock was not induced, and the foals appeared to be healthy shortly after the infusion was discontinued. The return to baseline values of body temperature (3 of 4 foals), APTT (1 of 4 foals) and neutrophil count (2 of 4 foals), during endotoxin infusion, suggests induction of early tolerance. The control foals remained alert and the temperature, prothrombin time and fibrinogen remained stable during the study. Hyperglycaemia, transient increased APTT and variations in selected haemodynamic parameters were recorded in the control foals during the infusion.     

Effects of flunixin meglumine on selected clinicopathologic variables, and serum testosterone concentration in stallions after endotoxin administration

Four clinically normal stallions were infused intravenously with endotoxin (LPS) from Escherichia coli 055:B5 at a dose of 0.3 microg/kg b.w. and four stallions were treated with flunixin meglumine (FM) as a single intravenous injection at a dose of 1.1 mg/kg b.w., 5 min after the infusion of LPS. In response to endotoxin infusion, stallions' reaction was fever (increased rectal and scrotal skin temperature), increased heart rate (HR) and leucopenia. Administration of endotoxin also influenced the level of testosterone (decrease at 3-24 h and increase at 48-72 h after LPS administration) in the blood serum. FM treatment prevented an endotoxin-induced increase in rectal and scrotal skin temperature, HR, with no influence on the decrease of leucocytes. Administration of FM only had a significant effect on the latter changes (at 24-72 h) of serum testosterone concentration after addition of endotoxin.     

Effects of small- and large-volume resuscitation on coagulation and electrolytes during experimental endotoxemia in anesthetized horses

BACKGROUND: Small-volume resuscitation (SVR) has been advocated in place of large-volume isotonic resuscitation for the treatment of endotoxemia in horses. The effects of this type of therapy during experimental endotoxemia on electrolytes and coagulation have not been evaluated in the horse. As part of a larger project, the objective of this study was to determine the effects of SVR (hypertonic saline solution [HSS] plus hetastarch [HES]) on coagulation and serum electrolytes concentration, and to compare SVR with large- and small-volume isotonic resuscitation during experimental endotoxemia in anesthetized horses. HYPOTHESIS: SVR does not affect coagulation parameters or serum electrolyte concentrations when compared with either small- or large-volume isotonic crystalloids. ANIMALS: Horses were randomly assigned to 1 of 3 groups. Under halothane anesthesia, endotoxemia was induced by administering 50 microg/kg Escherichia coli endotoxin i.v. The horses were treated for 30 minutes with 15 mL/kg of balanced polyionic crystalloid solution (control), 60 mL/kg of balanced polyionic crystalloid solution (ISO), or 5 mL/kg of HSS followed by 10 mL/kg HES (HSS-HES). METHODS: Prospective randomized trial. RESULTS: Significant differences in coagulation parameters were not found among the groups. Thrombocytopenia was severe in all 3 groups. Serum ionized calcium concentration significantly decreased from baseline in control and ISO groups but not in the HSS-HES group. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that the HSS-HES combination, at the dosage used in this study had no adverse effects on coagulation beyond those produced by endotoxemia. HSS-HES may have a protective effect against endotoxemia-induced ionized hypocalcemia.     

Gentamicin pharmacokinetics in horses given small doses of Escherichia coli endotoxin

The pharmacokinetics of gentamicin (3 mg/kg of body weight) were evaluated in 6 healthy horses and in 6 horses after they were given Escherichia coli endotoxin (0.113 microgram/kg). In the horses given endotoxin, there were a maximum temperature increase of 1.97 +/- 0.44 degrees (C) and a fever index (between the 2 groups) of 8.754 units. Other mild signs of endotoxemia also occurred. Statistically significant changes were not observed in the rate constants for distribution (alpha) or elimination (beta) or in body clearance (ClB) of gentamicin in the 2 groups of horses. In the horses given endotoxin, significant (P less than 0.05) increases were found in the serum concentration data (A, B, and CoS), and significant decreases were found in the apparent volume of distribution [Vd(area)] and in the volume of the central compartment (Vc). The alterations in gentamicin kinetics in the horses given endotoxin are believed to result from the decrease in Vc. This indicates that the extracellular fluid volume available for gentamicin distribution may be reduced by endotoxin.     

Dexamethasone-induced attenuation of cardiopulmonary dysfunction in endotoxemic calves

Effects of dexamethasone on pulmonary hemodynamics, pulmonary mechanics, and gas exchange were determined in anesthetized (pentobarbital sodium) and paralyzed (pancuronium bromide) calves (9.4 +/- 0.4 weeks old) during 5 hours of endotoxemia. Escherichia coli endotoxin (055-B5) was infused IV at 20 micrograms/kg the 1st hour, followed by a continuous infusion at 10 micrograms/kg/hour for the following 4 hours. Dexamethasone (5 mg/kg) was given IV 18 hours and 1 hour before endotoxin administration, and was also administered IV (1 mg/kg/hr) during endotoxemia. Endotoxin induced large increases in pulmonary artery pressure, pulmonary vascular resistance, alveolar-arterial O2 gradient, alveolar dead-space ventilation, postmortem gravimetric lung weight of bloodless lung, albumin and total protein concentrations in bronchoalveolar lavage fluid, and the number of neutrophils recovered from bronchoalveolar lavage fluid. Endotoxin induced decreases in the cardiac index, dynamic lung compliance, and PaO2. Dexamethasone attenuated most of the cardiopulmonary responses induced by endotoxin, especially during the first 3 hours of endotoxemia. Dexamethasone blocked endotoxin-induced increases in bronchoalveolar lavage albumin, total protein, and neutrophil content. Therefore, glucocorticoids modify endotoxin-induced pulmonary injury in calves, possibly by limiting mobilization of endogenous arachidonic acid.     

Endotoxemia in neonatal calves given antiserum to a mutant Escherichia coli (J-5)

Endotoxemia was characterized in neonatal calves given a small amount of colostrum and smooth Escherichia coli endotoxin by small-dosage (0.5 microgram/kg of body weight), slow (5-hour) IV infusion to mimic natural conditions. Responses were compared among 22 calves freely allotted to groups treated with saline solution (group I), preimmunization plasma (PP, group II), or antiserum to the rough mutant of E coli O111:B4 (J-5, group III) before endotoxin was infused. Bovine J-5 antiserum was produced by immunization of 4 cattle with J-5 boiled cell bacterin. The antiserum titers of immunoglobulin (Ig) M, IgG1, and IgG2 to the J-5 boiled cells, as determined by enzyme-linked immunosorbent assay, were 240, 7,680, and 960, respectively. The PP had enzyme-linked immunosorbent assay titers to J-5 of 240, 480, and 60 of IgM, IgG1, and IgG2, respectively. Endotoxemia in the 3 groups was characterized by significant (P less than 0.05) time-related changes in rectal temperature, heart rate, respiratory rate, capillary refill time, oral mucous membranes, nose moistness, scleral injection, attitude, PCV, total plasma protein concentration, WBC count and differential, plasma glucose, and lactate concentrations. The only significant treatment effects on clinical or laboratory values were higher mean total plasma protein concentrations in groups II and III 10 to 30 hours after endotoxin infusion was started than that in group I and increasing mean most-severe attitude abnormality score in groups I, III, and II (P less than 0.05). The administration of bovine J-5 antiserum to neonatal calves resulted in significantly higher serum IgG1 and IgG2 titers to J-5 boiled cells (P less than 0.05), and cross-reactive IgG2 to the challenge endotoxin (P less than 0.01) than did treatment with PP or saline solution; however, this antiserum did not mitigate the effects of sublethal endotoxemia. There was a significant negative correlation between IgG2 to J-5 at base line and the mean attitude abnormality score at 4.5 hours after infusion was started (P less than 0.05).     

Endotoxin-induced bovine mastitis: immunoglobulins, phagocytosis, and effect of flunixin meglumine

Milk whey immunoglobulins (Ig) and phagocytosis of staphylococci by milk polymorphonuclear neutrophilic leukocytes (PMN) were measured in 12 cows (allotted to 6 pairs) during acute bovine mastitis induced by intramammary inoculation of endotoxin. Six of these cows (or 1 in each pair) were treated with flunixin meglumine and were compared with the others (given only saline solution). The endotoxin inoculation comprised 10 micrograms of Escherichia coli O26:B6 lipopolysaccharide injected into one of the rear quarters (mammae). Flunixin meglumine was administered parenterally at a dosage of 1.1 mg/kg every 8 hours (total of 7 doses) beginning at 2 hours after endotoxin was injected. Milk samples were obtained, and whey samples were prepared from each quarter of each cow 3 times before inoculation and at 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 336 hours after endotoxin was inoculated. Significant increases (P less than 0.05) in milk whey IgG1, IgG2, IgM, and IgA concentrations were observed in whey samples from endotoxin-inoculated quarters. Greatest relative increase was seen for IgG2. Increased whey Ig concentrations were not observed in quarters which were not inoculated with endotoxin. Concentrations of whey IgG1 and IgM in endotoxin-inoculated quarters were significantly (P less than 0.05) decreased in flunixin meglumine-treated cows, compared with those in saline solution-treated cows. Significant increases in phagocytosis of staphylococci by milk PMN were observed in whey samples from endotoxin-inoculated quarters. Significant differences in PMN phagocytosis were not found in whey samples from cows given flunixin meglumine when compared with whey samples from cows given saline solution.     

Cardiovascular and pulmonary effects of hetastarch plus hypertonic saline solutions during experimental endotoxemia in anesthetized horses

BACKGROUND: Small volume resuscitation has been advocated as a beneficial therapy for endotoxemia in horses but this therapy has not been investigated in a prospective manner. The objective of this study was to determine the cardiopulmonary effects of small-volume resuscitation using hypertonic saline solution (HSS) plus Hetastarch (HES) during experimental endotoxemia in anesthetized horses. HYPOTHESIS: Treatment of horses with induced endotoxemia using HES-HSS does not alter the response of various cardiopulmonary indices when compared to treatment with either small- or large-volume isotonic crystalloid solutions. ANIMALS: Eighteen healthy horses were randomly assigned to 1 of 3 groups. Anesthesia was maintained with halothane. Endotoxemia was induced by administering 50 microg/kg of Escherichia coli endotoxin IV. The horses were treated over 30 minutes with 15 mL/kg of balanced polyionic crystalloid solution (control), 60 mL/kg of balanced polyionic crystalloid solution (ISO), or 5 mL/kg of HSS followed by 10 mL/kg of HES (HSS-HES). METHODS: Prospective randomized trial. RESULTS: Cardiac output (CO) after endotoxin infusion increased significantly (P < .05) from baseline in all groups, whereas mean central venous pressure increased significantly (P < .05) in the ISO group only. Mean pulmonary artery pressure increased from baseline (P < .05) in horses treated with isotonic fluids and HSS-HES. There was no effect of treatment with HSS-HES on CO, systemic vascular resistance (SVR), mean arterial pressure, blood lactate concentrations, or arterial oxygenation. CONCLUSIONS AND CLINICAL IMPORTANCE: The use of HSS-HES failed to ameliorate the deleterious hemodynamic responses associated with endotoxemia in horses. The clinical value of this treatment in horses with endotoxemia remains unconfirmed.     

Effects of endotoxin on lung water, hemodynamics, and gas exchange in anesthetized ponies

Effects of endotoxemia on lung water, hemodynamics, and gas exchange were determined in ponies breathing a mixture of halothane and 100% O2. Escherichia coli endotoxin was infused IV at 20 micrograms/kg of body weight for 1 hour followed by 10 micrograms/kg/hr the subsequent 4 hours. By 0.25 hour, endotoxin increased mean pulmonary artery pressure and pulmonary vascular resistance; this was followed by a return to base-line values by 0.5 and 1 hour, respectively. A 2nd increase in pulmonary vascular resistance occurred by 5 hours of endotoxemia. During the last 2 hours of endotoxin infusion, cardiac index was significantly (P less than 0.05) decreased. Hematocrit was increased from 1 to 5 hours of endotoxemia, whereas, the plasma protein concentration was increased from 2 to 4 hours, indicating a loss of plasma volume. The PaO2 and PaCO2 were unchanged. After 5 hours of endotoxemia, lung extravascular thermal volume, postmortem bronchoalveolar lavage albumin content, and extravascular lung water/extravascular dry weight ratio of bloodless lungs were not increased, indicating no increase in alveolar-capillary permeability or pulmonary edema.     

The effect of 7.2% hypertonic saline solution with 6% dextran 70 on cardiac contractility as observed by an echocardiography in normovolemic and anesthetized dogs

We studied the effect of a small volume of 7.2% hypertonic saline solution (HSS) or HSS with 6% dextran 70 (HSD) on hemodynamic status, especially on cardiac contractility, in anesthetized dogs using the left ventricular end-systolic volume index (ESVI) and ejection fraction (EF), which can be obtained in noninvasive echocardiography. In the present study, the mean values of ESVI were unaffected by HSS and HSD infusion, whereas the left ventricular end-diastolic volume index (EDVI) was markedly and significant increased. As a result of the changes in EDVI but not in ESVI, EF increased transiently and significantly in the HSS and HSD group, whereas no such significant change was observed in the dogs that received isotonic saline solution. In addition, as a result of the increases in cardiac index but not arterial pressure, system vascular resistances (SVR) decreased transiently and significantly in the HSS and HSD groups, whereas no such significant change was observed in the ISS group. Therefore, the positive inotropic effects of HSS and HSD may be attributable to the increase in left ventricular preload and decreases in SVR rather than direct changes in myocardial contractility.     

Acute phase response in reindeer after challenge with Escherichia coli endotoxin

The serum concentrations of two acute phase proteins (APPs), haptoglobin (Hp) and serum amyloid-A (SAA), were monitored in reindeer after challenge with endotoxin. Four adult female reindeer received either 0.1 μg/kg Escherichia coli 0111:B4 lipopolysaccharide B or saline solution intravenously. At the second challenge, the treatments were reversed. In addition to the APPs, changes in blood chemistry and rectal temperature were monitored. The endotoxin challenge caused a significant increase in SAA (peak 48 h) and a sharp decrease (8–12 h) of serum iron concentrations in all animals. The mean Hp concentration increased at 8 h and remained elevated until 48 h, but no statistically significant differences were found. This investigation demonstrates that challenge with a single-bolus dose of E. coli endotoxin can activate the acute phase response (APR) and SAA appears to be a more sensitive indicator of the APR than Hp during bacterial infection in reindeer.     

Influence of endotoxin on the disposition kinetics and dosage regimens of oxytetracycline in calves

The influence of endotoxin on the disposition kinetics of oxytetracycline (OTC) (10 mg/kg) was investigated in five healthy ruminating male crossbred calves. The serum concentration-time data of OTC before and after endotoxin challenge were best described by a two-compartment open model. Repeated administration of Escherichia coli endotoxin (1 microg/kg, i.v.) at an interval of 12 h up to 48 h produced a clear rise in the body temperature and an increase in the pulse and respiration rates. Endotoxin caused a significant reduction in mean transit time in tissue compartment (MTTT) (P < or = 0.05), mean residence time in the peripheral tissue compartment (MRTT) (P < or = 0.05), mean residence time in the body (MRTB) (P < or = 0.05), elimination half-life (t1/2lambda2) (P < or = 0.05) and distribution space in tissues (VT) (P < or = 0.01) and at steady-state (Vd(ss)) (P < or = 0.01). Endotoxin had no effect on the distribution clearance (ClD), systemic clearance (Cl) and distribution half-life of OTC, while the values of first order rate constant of transfer of drug from tissue to central compartment (K21) and the zero time intercept at terminal phase (C2) were significantly high. The drug dosage regimens to maintain serum OTC concentrations of 0.5, 1, 2, 4, 6 and 8 microg/mL were also determined in febrile and clinically healthy animals.     

Kinetics, dose response, tachyphylaxis and cross-tachyphylaxis of vascular leakage induced by endotoxin, zymosan-activated plasma and platelet-activating factor in the horse

Vascular leakage induced by intradermal injection of endotoxin, zymosan-activated plasma (ZAP) and platelet-activating factor (PAF) was measured in nine Thoroughbreds using 125-iodine human serum albumin (¹²⁵I-HSA) as a marker in the blood. ZAP and PAF produced dose-dependent increases in vascular permeability with the maximum occurring within the first 15 min after injection. The vascular leakage induced by endotoxin was also dose-dependent, but the maximum occurred 2 h after intradermal injection. Intradermal sites previously injected with endotoxin were refractory to a second injection of endotoxin for up to 5 days. However, sites injected with endotoxin and re-injected with either ZAP or PAF remained responsive with increased vascular leakage compared to saline injected control sites re-injected with either ZAP or PAF. Diminished response to endotoxin challenge may contribute to the poor prognosis of endotoxaemia in the horse.