A crude, whole-body extract of female heartworms was administered IV to 10 dogs with and 13 dogs without heartworm (HW) infection. Shock developed in 8 of 10 infected dogs and 11 of 13 non-infected dogs, and blood coagulopathy was observed in 12 of 19 dogs with shock. Prevalence and severity of blood coagulopathy were proportionate to prevalence and severity of shock. Platelet count decreased in all dogs with shock with or without blood coagulopathy; thus, the decrease in platelet count might be related to shock. In 4 dogs, activated partial thromboplastin time (APTT) was prolonged--192.0 seconds at 30 minutes after HW injection--and prothrombin time (PT) was increased--13.8 seconds at initial collapse. In 8 dogs, APTT was increased--200 seconds for 2 hours after HW injection--and PT was increased--200 seconds at 30 minutes after the injection. The APTT prolongation might have been caused mainly by decreases in activities of factors VIII, IX, XI, and XII of the intrinsic blood coagulation pathway. In dogs with severely prolonged PT, plasma fibrinogen concentration and factor II activity decreased slightly. Prolonged PT was corrected in vitro by addition of normal plasma at high concentration (> 80%), but prolonged APTT could not be corrected in vitro by addition of 80% normal plasma. Serum fibrin degradation products concentration was < 10 microgram/ml, and soluble fibrin monomer complex was negative in all dogs. Thrombi were not found in blood vessels of any organ at necropsy and after histologic study. Therefore, it was suggested that blood coagulopathy resulting from inhibition of coagulation factor activities might develop in shock induced by HW extract.

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 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 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 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.

We investigated small-volume (5 ml/kg) 7% NaCl in 6% dextran 70 (HS/D70) as an alternative to large-volume (60 ml/kg) 0.9% NaCl for treatment of experimentally induced canine gastric dilatation-volvulus (GDV) shock. The stomach was surgically displaced and then distended with an intragastric balloon in 11 dogs anesthetized with pentobarbital. All dogs were subjected to GDV for 180 minutes before partial decompression and resuscitation. Hemodynamic values, blood gas values, and plasma volume were measured during control, shock, and resuscitation periods. Resuscitation started with 1 group (n = 6) receiving 5 ml of HS/D70/kg, IV, over 5 minutes, and the other group (n = 5) receiving 60 ml of 0.9% NaCl/kg, IV, over 60 minutes. Both groups received a surgical maintenance dosage (20 ml/kg/h of 0.9% NaCl after initial resuscitation. Resuscitative effects of small-volume HS/D70 were similar to large-volume 0.9% NaCl during the first hour of treatment; however, cardiac output was significantly higher in the HS/D70 group for the last 2 hours of resuscitation. Changes in heart rate, left ventricular pressure change, and systemic vascular resistance appeared to be responsible for improved perfusion. Mixed venous oxygen partial pressure data supported improved perfusion in the HS/D70 group. Packed cell volume remained higher in the HS/D70 group, indicating less hemodilution and improved oxygen delivery. Resuscitation of this GDV-induced shock model was better sustained with small-volume HS/D70, compared with conventional large-volume 0.9% NaCl.

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.

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.

Hemorrhagic shock was induced in nonsplenectomized dogs by removing 41% of their blood volume over a 15-minute period. Hemodynamic and metabolic variables were determined prior to and for 3 hours after completion of hemorrhage. One group of 5 dogs was not treated. After the 30-minute sample was collected, a second group of 5 dogs was given lactated Ringer solution (LRS) at 88 ml/kg of body weight, IV. A third group of 5 dogs was given LRS (88 ml/kg, IV) and prednisolone sodium succinate (11 mg/kg, IV) 30 minutes after hemorrhage. The IV administration of LRS was completed within 15 minutes. The glucocorticoid was administered as an IV bolus after 500 ml of LRS had been given. The large volume and administration of LRS significantly (P = 0.05) improved many of the hemodynamic and metabolic effects of acute hemorrhage and hemorrhagic shock. At one time or another during the 2.5-hour observation period after the initiation of treatment, mean arterial pressure, cardiac index, systemic vascular resistance, heart rate, respiratory rate, lactate, glucose, and arterial and venous blood gas values were significantly (P = 0.05) improved, compared with baseline values. The addition of prednisolone sodium succinate to the treatment regimen improved the effectiveness of LRS alone only in some dogs at random sampling times. Significant trends were not observed except, possibly, the improvement of venous pH and A-V pH and P(CO)2 differences.