A crude, whole-body extract of female or male heartworms was injected IV into 28 dogs with and 22 dogs without heartworm (HW) infection. The female HW extract caused shock in 22 of 24 dogs with and 12 of 20 dogs without HW infection. The male HW extract induced shock in 4 of 4 dogs with and 1 of 2 dogs without HW infection. Prevalence of shock caused by female HW extract was significantly (P < 0.05) higher in dogs with than without HW infection; shock developed 5 to 30 minutes after HW injection. These signs were observed: marked decrease in blood pressure; collapse (initial collapse); paleness of mucous membranes; weak heart sounds; dyspnea; skin coldness; intestinal hyperperistalsis, and defecation; increases in RBC count, serum total protein concentration, serum osmolality, serum Na and blood glucose concentrations; and decreases in neutrophil, eosinophil, and platelet counts. Alanine transaminase, alkaline phosphatase, and lactate dehydrogenase activities increased substantially from the time of initial collapse to 24 hours after HW injection. Of 39 dogs with shock, 29 recovered from initial collapse, but 5 of the 29 subsequently collapsed again (secondary collapse), with bloody diarrhea followed by death. Of these 39 dogs, 6 died during initial collapse without bloody diarrhea, and 4 were euthanatized during initial collapse. It was confirmed that HW extract had, in fact, induced shock. These clinical, hematologic, and biochemical findings were fundamentally similar to those associated with shock resulting from administration of drugs, such as diethylcarbamazine and milbemycin D, in microfilaremic dogs with HW infection.

The effects of hypertonic saline solution (HTSS) combined with colloids on hemostatic analytes were studied in 15 dogs. The analytes evaluated included platelet counts, onestage prothrombin time, activated partial thromboplastin time, von Willebrand's factor antigen (vWF-Ag), and buccal mucosa bleeding times. The dogs were anesthetized, and jugular phlebotomy was used to induce hypovolemia (mean arterial blood pressure = 50 mm of Hg). Treatment dogs (n = 12) were resuscitated by infusion (6 ml/kg of body weight) of 1 of 3 solutions: HTSS combined with 6% dextran 70, 6% hetastarch, or 10% pentastarch. The control dogs (n = 3) were autotransfused. Hemostatic analytes were evaluated prior to induction of hypovolemia (baseline) and then after resuscitation (after 30 minutes of sustained hypovolemia) at 0.25, 0.5, 1, 6 and 24 hours. All treatment dogs responded rapidly and dramatically to resuscitation with hypertonic solutions. Clinically apparent hemostatic defects (epistaxis, petechiae, hematoma) were not observed in any dog. All coagulation variables evaluated, with the exception of vWF:Ag, remained within reference ranges over the 24-hour period. The vWF:Ag values were not statistically different than values from control dogs, and actual values were only slightly lower than reference ranges. Significant (P less than or equal to 0.04) differences were detected for one-stage prothrombin time, but did not exceed reference ranges. The results of this study suggested that small volume HTSS/colloid solutions do not cause significant alterations in hemostatic analytes and should be considered for initial treatment of hypovolemic or hemorrhagic shock.

The cardiopulmonary effects of thiopental sodium were studied in hypovolemic dogs from completion of until 1 hour after administration of the drug. Hypovolemia was induced by withdrawal of blood from dogs until mean arterial pressure of 60 mm of Hg was achieved. After stabilization at this pressure for 1 hour, 8 mg of thiopental/kg of body weight was administered IV to 7 dogs, and cardiopulmonary effects were measured. After blood withdrawal and prior to thiopental administration, heart rate and oxygen utilization ratio increased, whereas mean arterial pressure, mean pulmonary arterial pressure, central venous pressure, pulmonary wedge pressure, cardiac index, oxygen delivery, mixed venous oxygen tension, and mixed venous oxygen content decreased from baseline. Three minutes after thiopental administration, heart rate, mean arterial pressure, mean pulmonary arterial pressure, pulmonary vascular resistance, and mixed venous oxygen tension increased, whereas oxygen utilization ratio and arterial and mixed venous pH decreased from values measured prior to thiopental administration. Fifteen minutes after thiopental administration, heart rate was still increased; however by 60 minutes after thiopental administration, all measurements had returned to values similar to those obtained prior to thiopental administration.

The respiratory, renal, hematologic, and serum biochemical effects of hypertonic saline solution (HSS) treatment were examined in 12 endotoxic, pentobarbital-anesthetized calves (8 to 20 days old). Escherichia coli endotoxin (055:B5) was infused IV at a rate of 0.1 microgram/kg of body weight over 30 minutes. Endotoxin induced severe respiratory effects, with marked hypoxemia and increases in arterial-alveolar O2 gradient (P[A-a]O2), physiologic shunt fraction (Qs/Qt), and physiologic dead space to tidal volume ratio (Vd/Vt). Oxygen consumption was decreased, despite an increase in the systemic O2 extraction ratio. Peak effects were observed at the end of endotoxin infusion. The renal response to endotoxemia was characterized by a decrease in free-water reabsorption and osmotic clearance, as well as a decrease in sodium and phosphorus excretion. Endotoxemia induced leukopenia, thrombocytopenia, hyperphosphatemia, hypoglycemia, acidemia, and increased serum alkaline phosphatase concentrations. Calves were treated with HSS (2,400 mosm/L of NaCl, 4 ml/kg, n = 4) or an equivalent sodium load of isotonic saline solution (ISS; 300 mosm/L of NaCl, 32 ml/kg, n = 4) 90 minutes after the end of endotoxin administration. Both solutions were infused over a 4- to 6-minute period. A control group (n = 4) was not treated. Infusion of HSS or ISS failed to induce a significant change in PaO2, P(A-a)O2, (Qs/Qt), (Vd/Vt), or oxygen consumption. Both solutions increased systemic oxygen delivery to above preendotoxin values. Hypertonic saline infusion induced significant (P < 0.05) increases in serum Na and Cl concentrations and osmolality, whereas ISS induced a significant increase in serum Cl concentration and a significant decrease in serum phosphorus concentration. Both HSS and ISS reversed the endotoxin-induced changes in renal function, with increases in free water reabsorption and osmotic clearance, as well as increases in sodium and phosphorus excretion. Sodium retention was greater following HSS administration. On the basis of these findings, hypertonic saline solutions can be rapidly and safely administered to endotoxic calves.

The relationship between the palpebral conjunctival oxygen index, mixed venous oxygen tension, and cardiac index were compared, using a canine hemorrhagic shock model. The cardiac output was reduced by reducing the blood volume in 5% increments until the initial cardiac output was reduced by one half. In each of 7 dogs, the palpebral conjunctival oxygen index and mixed venous oxygen tension were found to have good correlation with cardiac index; however, the correlation coefficients were markedly reduced when the data from all of the dogs were combined. It was concluded that the palpebral conjunctival oxygen index provides an excellent means of assessing changes in cardiac index over time in the same dog; however, it cannot be used to estimate cardiac index in an individual dog with a degree of accuracy that would be clinically significant.

The effects of coliform endotoxin (E) and recombinant ovine tumor necrosis factor a (TNF) were compared with respect to clinical signs of disease and changes in plasma metabolite and pituitary and pancreatic hormone concentrations in calves. In addition, changes in plasma TNF concentration during each challenge exposure were quantitated by use of radioimmunoassay. Healthy Holstein bull calves with mean body weight of 90 kg were each given, in order, on different days, saline solution (5.0 ml, IV, day 1, n = 4), E (type 055:B5, 1.0 microgram/kg of body weight IV, day 2, n = 4) and TNF (5.0 microgram/kg IV, day 9, n = 3). Jugular venous blood samples, rectal temperature reading, and PCV were obtained at hourly intervals before (2 hours) and after challenge exposure. The PCV increased (P < 0.05) after E and TNF administrations for the first 5 hours, then returned to normal in calves given E, but decreased and remained low in calves given TNF through 24 hours. Plasma triglyceride and nonesterified free fatty acids concentrations were increased through 10 hours (P < 0.05) after E administration, whereas triglyceride and nonesterified free fatty acids concentrations were not significantly affected by TNF administration. Increase in blood glucose concentration at 1 hour after administration of E and TNF was followed by prolonged hypoglycemia that lasted through 6 hours. Changes in plasma insulin concentration paralleled the observed changes in glucose concentration, initially increased at 2 hours after E and TNF (P < 0.05) administrations, but then tended to decrease below control values thereafter. Plasma growth hormone and luteinizing hormone concentrations decreased after E and TNF administrations to almost nondetectable values through 4 hours after dosing, returning to normal values by 8 hours. The data indicate similarities in physiologic response of calves to E and TNF and suggest a role for acute production of TNF as a mediator of E responses.

The role of decreased luteal activity in embryonic loss after induced endotoxemia was studied in mares 21 to 35 days pregnant. Fourteen pregnant mares were treated daily with 44 mg of altrenogest to compensate for the loss of endogenous progesterone secretion caused by prostaglandin F2 alpha, (PGF2 alpha) synthesis and release following intravenous administration of Salmonella typhimurium endotoxin. Altrenogest was administered daily from the day of endotoxin injection until day 40 of gestation (group 1; n = 7), until day 70 (group 2; n = 5), or until day 50 (group 3; n = 2). In all mares, secretion of PGF2 alpha, as determined by the plasma 15-keto-13,14-dihydro-PGF2 alpha concentrations, followed a biphasic pattern, with an initial peak at 30 minutes followed by a second, larger peak at 105 minutes after endotoxin injection. Plasma progesterone concentrations decreased in all mares to values < 1 ng/ml within 24 hours after endotoxin injection. In group 1, progesterone concentrations for all mares were < 1 ng/ml until the final day of altrenogest treatment. In 6 of 7 mares in group 1, the fetuses died within 4 days after the end of treatment, with progesterone concentrations < than 1 ng/ml at that time. In the mare that remained pregnant after the end of treatment, plasma progesterone concentration was 1.6 ng/ml on day 41 and increased to 4.4 ng/ml on day 44. In group 2, all mares remained pregnant, even though plasma progesterone concentrations were < 1 ng/ml in 4 of 5 mares from the day after endotoxin injection until after the end of altrenogest treatment. One group-2 mare appeared to develop a secondary corpus luteum before day 70, with progesterone concentrations greater than 1 ng/ml from day 36 through day 70. Daily altrenogest administration consistently prevented pregnancy loss, which usually follows induced endotoxemia. Altrenogest administration offers a reliable and practical treatment for the prevention of fetal loss following endotoxemia in mares < 2 months pregnant. One group-3 mare remained pregnant, and in the other mare, fetal death was diagnosed 8 days after endotoxin administration, although this mare was still being treated with altrenogest. In that case fetal death was believed to be unrelated to the treatment.

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. Cardiac output was decreased and total peripheral resistance was increased during the isotonic saline trial, compared with baseline values. Both trials were associated with increased blood lactate concentration, but lactate values during the isotonic saline trial were greater and remained increased above baseline values for a longer period (4 hours) than during the hypertonic saline trial (2.5 hours). It was concluded for this model of endotoxemia, that IV administered hypertonic saline solution was associated with more-desirable cardiovascular and metabolic responses than was an equal volume of isotonic saline solution.

Serum tumor necrosis factor (TNF) activity wasquantitated in 8 horses given an IV infusion of endotoxin (0.03 microgram of lipopolysaccharide/kg of body weight, from Escherichia coli 55:B5) in 0.9% NaCl solution over 1 hour. Serum TNF activity was likewise measured in 6 horses given only 0.9% sterile NaCl solution at the same rate. The duration of serum TNF activity was determined, and serum TNF activity was correlated with clinical and laboratory changes during the induced endotoxemia. Horses had no serum TNF activity prior to endotoxin administration, but geometric mean serum TNF activity was significantly higher from 1 to 4 hours after the start of the infusion. In response to endotoxin, horses seemed depressed, had signs of mild to moderate abdominal pain, developed tachycardia and fever, and had leukopenia followed by leukocytosis. Association between serum TNF activity and temperature, heart rate, attitude abnormality score, and WBC count of horses given endotoxin was significant. Serum TNF activity had a significant positive linear correlation with attitude abnormality and heart rate and a negative linear correlation with the WBC count during endotoxemia. Geometric mean serum TNF activity peaked approximately 1.5 hours prior to mean peak fever, and these data were significantly correlated. Results of this study suggest that TNF is an important mediator of endotoxemia in horses.

We evaluated the hemodynamic effects of IV and intraaortic (aortic root) administation of 7.5% NaCl solution on hemodynamic in anesthetized cats with severe hypovolemia. Hypovolemic shock was induced by exsanguinating cats to a mean arterial blood pressure of 50 mm of Hg, which was maintained for 30 minutes prior to treatment. Shed blood volume was 38.4 +/- 2.1 ml/kg of body weight. The cats were treated with a small volume (4 ml/kg) of 0.9% NaCl solution IV, 7.5% NaCl solution IV, or 7.5% NaCl solution administered into the aortic root. The IV administration of 0.9% NaCl aolution did not improve hemodynamics. The IV administration of 7.5% NaCl solution induced rapid restoration of arterial blood pressure, aortic blood flow, and cardiac contractility. Total peripheral vascular resistance decreased. The administration of 7.5% NaCl solution into the aortic root induced a further deterioration in hemodynamics resulting in death in 3 cats and a marked improvement in hemodynamics similar to that observed after IV administration of 7.5% NaCl solution in 2 cats. The duration of the beneficial hemodynamic effects after IV or intra-aortic administration of 7.5% NaCl solution did not exceed 60 minutes. Results of these studies suggested that either the IV or intra-aortic administration of 7.5% NaCl solution in cats can induce beneficial hemodynamic effects that may be of value in the field resuscitation of hypovolemic patients.