Role of histamine in heartworm extract-induced shock in dogs

OBJECTIVE: To determine whether heartworm (HW) extract-induced shock in dogs is consistent with anaphylactic shock by examining the role of histamine. ANIMALS: 6 mixed-breed dogs (3 without and 3 with HW infections) and 4 specific pathogen-free (SPF) Beagles. PROCEDURE: Four experiments were performed as follows: 1) 6 mixed-breed dogs were treated IV with 2 ml of HW extract, and plasma histamine concentrations were determined; 2) 4 SPF dogs were treated IV with 2 ml of HW extract and examined for shock; 3) sera from 6 dogs of experiment 1 and from 4 SPF dogs of experiment 2 that were obtained before HW extract treatment were tested for heterologous passive cutaneous anaphylaxis (PCA), using rabbits during a sensitization period of 48 to 72 hours; and 4) mast cell degranulation by HW extract was tested, using rat mesentery and canine cultured mast cells. RESULTS: Experiment 1: 6 dogs developed shock, and plasma histamine concentrations increased significantly from 0.3 +/- 0.2 (mean +/- SD) ng/ml before HW extract treatment to 44.6 +/- 68.9 ng/ml at the onset of shock; experiment 2: all SPF dogs developed shock and had an increase in plasma histamine concentrations; experiment 3: sera from mixed-breed dogs without HW infection and from SPF dogs had negative PCA reactions; experiment 4: HW extract degranulated rat mesentery mast cells and released histamine directly from canine mast cells. CONCLUSIONS AND CLINICAL RELEVANCE: Results of our study indicate that an unknown mast cell-degranulating substances contained in HW extract may degranulate mast cells directly, consequently releasing histamine that may participate in the onset of shock in HW extract-induced shock in dogs.     

Vasopressin therapy in dogs with dopamine-resistant hypotension and vasodilatory shock

Objective: To describe the therapeutic use of vasopressin in dogs with dopamine‐resistant hypotension and vasodilatory shock. Series summary: We report the effects of intravenous vasopressin therapy on mean arterial blood pressure and central venous pressure (CVP) in 5 dogs with dopamine‐resistant hypotension from vasodilatory shock. All subjects had documented hypotension and vasodilation, despite adequate intravascular volume and catecholamine therapy. There was an increase in mean arterial pressure following vasopressin administration. No cardiac arrhythmias were noted, nor were there clinically significant changes in CVP. New information provided: Mean arterial blood pressure increased following vasopressin therapy in all of the dogs. Vasopressin may prove useful in the treatment of vasodilatory shock, however further research is warranted.     

Osmolal and anion gaps in dogs with acute endotoxic shock

Serum osmolalities, biochemical concentrations, osmolal and anion gaps, blood lactate concentrations, and acid base status were evaluated in anesthetized, healthy control dogs and in dogs with endotoxic shock. The osmolal gap was not affected by endotoxemia. Compared with control dogs, dogs with endotoxic shock had mildly, though insignificantly, increased anion gaps and significantly increased blood lactate concentrations. The anion gap in dogs with endotoxic shock was positively (r = 0.77) and significantly correlated with the blood lactate concentration. Therefore, the blood lactate concentration of a dog in endotoxic shock may be estimated by use of the equation: lactate = 0.27 (anion gap) - 1.46. Confidence limits for this estimation were calculated. Dogs with endotoxic shock developed a lactic acidosis and hyperchloremic metabolic acidosis, with hyperventilation.     

Hemodynamic characteristics of vasopressin in dogs with severe hemorrhagic shock

The effect of vasopressin was compared with that of the established vasopressor epinephrine in experimentally induced hemorrhagic shock. After rapid crystalloid resuscitation in a ratio of three volumes of 0.9% saline to one volume of blood (3:1 crystalloid resuscitation), six dogs were given 0.4 IU/kg vasopressin and another six dogs were given 0.1 mg/kg epinephrine. Five dogs in the control group were given fluid resuscitation in the same manner as above without administration of any drugs. Administration of vasopressin increased diastolic arterial pressure (DAP) from 45.0 +/- 4.9 to 91.2 +/- 9.6 mmHg within 5 min, compared with epinephrine from 46 +/- 4.0 to 51.8 +/- 7.7, and control from 47.3 +/- 7.5 to 46.3 +/- 7.3. Systolic arterial pressure (SAP) did not increase significantly following vasopressin compared with epinephrine and control group. Results of DAP and systemic vascular resistance index (SVRI) suggested that vasopressin administration was vasoconstrictive after fluid resuscitation in decompensatory hemorrhagic shock in dogs, whereas epinephrine did not compared with control. In addition, epinephrine did not affect the cardiac index (CI) and SVRI, while a significant decrease in CI and increase in SVRI were observed in vasopressin group. The pressor effect of epinephrine in the vascular system was abrupt and only lasted a short period of time (within 5 min), while that of vasopressin was steady and lasted for more than 1 hr, especially regard to in DAP. When compared with epinephrine, vasopressin can be a more effective and safer choice in patients with severe hemorrhagic shock.     

Determination of optimal dose of arginine vasopressin in hemorrhagic shock in dogs

The hemodynamic effects of vasopressin of high/low doses on dogs were investigated using experimentally induced hemorrhagic shock model. Experimental groups were categorized according to administered doses of vasopressin (0.1, 0.4 and 1.6 IU/kg) and hemodynamic parameters were measured before and after the graded-dose administration of vasopressin. Administration of high- and middle-dose vasopressin (0.4 and 1.6 IU/kg) showed superior increase in blood pressure and systemic vascular resistance, compared with those of low-dose one (0.1 IU/kg). Results of systolic arterial pressure and mean arterial pressure in 1.6 IU/kg-administered group revealed lower efficacy than that in 0.4 IU/kg group in spite of administration of higher dose. This study demonstrates that 0.4 IU/kg of vasopressin can be used as the most effective dose for improving hemodynamic condition in the decompensatory phase of hemorrhagic shock in dogs.     

Comparison of heartworm extract-induced shock and endotoxin-induced shock in dogs by determination of serum tumor necrosis factor concentrations

OBJECTIVE: To compare the mechanisms of heartworm (HW) extract-induced shock and endotoxin-induced shock in dogs by determination of serum tumor necrosis factor (TNF) concentrations. ANIMALS: 11 mixed-breed dogs (7 without and 4 with HW infections). PROCEDURE: Eight dogs were treated with 2 ml of HW extract IV, and 3 dogs were given endotoxin (Escherichia coli lipopolysaccharide [LPS]) at 40 or 400 microg/kg of body weight, IV. Changes in clinical and hematologic findings and serum TNF concentrations were examined from before treatment to 120 minutes after treatment in dogs given HW extract or from before treatment to 180 minutes after treatment in dogs given LPS. Tumor necrosis factor concentration was determined by cytotoxic assay, using WEHI-164 murine sarcoma cells, and plasma endotoxin concentration was determined in 2 dogs treated with HW extract, using the endotoxin-specific chromogenic test. RESULTS: Eight dogs developed shock 3 to 16 minutes after HW extract treatment. Rectal temperature did not change during examination. Serum TNF concentration was detected at a low concentration only 60 and 120 minutes after HW extract treatment, and plasma endotoxin was not detected during examination. In dogs treated with LPS, rectal temperature increased to > 40 C in 2 of 3 dogs, and serum TNF concentration began to increase 30 minutes after LPS treatment, reaching a maximum concentration by 60 minutes. CONCLUSIONS: The cause and mechanism of HW extract-induced shock may be different from those of endotoxin-induced shock, because TNF, which was a pivotal mediator in endotoxin-induced shock, increased minimally in serum of dogs treated with HW extract.     

Effects of naloxone in treating hemorrhagic shock in dogs with maintained baroreceptor responsiveness

The efficacy of treating hemorrhagic shock with naloxone in conjunction with fluids, compared with fluid therapy alone, was studied. Previously instrumented dogs were anesthetized with 0.04 mg of fentanyl/kg + 2.2 mg of droperidol/kg and pentobarbital sodium (to effect). Blood was withdrawn from each animal to achieve and maintain a mean arterial blood pressure of 40 to 50 mm of Hg for the first 2 hours of the experiment (t = 0 to 120 minutes). At t = 120 minutes, IV fluid administration was begun (all dogs) and continued for 1 hour (lactated Ringer's solution at a dosage of 70 ml/kg/hr). Hypothermia was corrected. Control dogs were given no other treatment. Dogs in the naloxone plus fluids group were given an IV bolus of naloxone (1 mg/kg) at t = 120 minutes and 1 mg of naloxone/kg/hr in the fluids from t = 120 to t = 180 minutes. Treatment (either naloxone plus fluids or fluids alone) was stopped at t = 180 minutes, and measuring of response was continued for an additional hour (posttherapeutic period). Significant differences were not seen in mean arterial pressures, left ventricular peak systolic pressures, dP/dt max, time constant T (a measure of left ventricular elasticity), and mean pulmonary arterial pressures between the dogs given naloxone and fluid therapy and those given fluid therapy alone. All dogs in both groups survived the procedure.     

Developing a predictive model for spinal shock in dogs with spinal cord injury

BackgroundReduced pelvic limb reflexes in dogs with spinal cord injury typically suggests a lesion of the L4‐S3 spinal cord segments. However, pelvic limb reflexes might also be reduced in dogs with a T3‐L3 myelopathy and concurrent spinal shock.Hypothesis/ObjectivesWe hypothesized that statistical models could be used to identify clinical variables associated with spinal shock in dogs with spinal cord injuries.AnimalsCohort of 59 dogs with T3‐L3 myelopathies and spinal shock and 13 dogs with L4‐S3 myelopathies.MethodsData used for this study were prospectively entered by partner institutions into the International Canine Spinal Cord Injury observational registry between October 2016 and July 2019. Univariable logistic regression analyses were performed to assess the association between independent variables and the presence of spinal shock. Independent variables were selected for inclusion in a multivariable logistic regression model if they had a significant effect (P ≤ .1) on the odds of spinal shock in univariable logistic regression.ResultsThe final multivariable model included the natural log of weight (kg), the natural log of duration of clinical signs (hours), severity (paresis vs paraplegia), and pelvic limb tone (normal vs decreased/absent). The odds of spinal shock decreased with increasing weight (odds ratio [OR] = 0.28, P = .09; confidence interval [CI] 0.07‐1.2), increasing duration (OR = 0.44, P = .02; CI 0.21‐0.9), decreased pelvic limb tone (OR = 0.04, P = .003; CI 0.01‐0.36), and increased in the presence of paraplegia (OR = 7.87, P = .04; CI 1.1‐56.62).Conclusions and Clinical ImportanceA formula, as developed by the present study and after external validation, could be useful for assisting clinicians in determining the likelihood of spinal shock in various clinical scenarios and aid in diagnostic planning.     

Hemodynamic alterations in dogs with shock induced by intravenous injection of heartworm extract

To elucidate one way of the shock mechanisms, the hemodynamic alterations were examined in 7 dogs with heartworm (HW) extract-induced shock. The first alteration observed after injection of HW extract was a decrease in right ventricular end-diastolic pressure (RVEDP). After that, left ventricular (LV) end-diastolic pressure, LV systolic pressure, and LV dp/dt fell significantly, followed by a decrease in the cardiac output of all dogs to below the detectable level (1.00 l/min). Since RVEDP depends on blood flow into the right ventricle, the decrease in RVEDP means a reduction in venous return. Therefore, this study showed that the first trigger of a decrease in blood pressure in HW extract-induced shock is the reduction in venous return.     

Detection of anti-Babesia gibsoni heat shock protein 70 antibody and anti-canine heat shock protein 70 antibody in sera from Babesia gibsoni-infected dogs

Antibodies that recognized either Babesia gibsoni or canine red blood cell (RBC) 70-kilodalton (kDa) protein were detected in serum from acutely and chronically B. gibsoni-infected. In those sera, antibodies that reacted with recombinant B. gibsoni and canine heat shock protein 70 (rBgHsp70 and rcHsp70) were detected; therefore, B. gibsoni and canine RBC 70-kDa proteins seemed to be BgHsp70 and cHsp70, respectively. In infected dogs, the amounts of these antibodies increased after infection. Interestingly, polyclonal antibody raised against rBgHsp70 in two rabbits reacted not only with rBgHsp70 but also with rcHsp70 and native cHsp70 from canine RBCs. Because BgHsp70 showed high homology with cHsp70 (70.8%), anti-rBgHsp70 antibody might cross-react with cHsp70. Additionally, the localizations of both BgHsp70 and cHsp70 were observed by indirect fluorescence assay. As a result, cHsp70 was not found on the membrane surface of erythrocytes, suggesting that erythrocytes would not be targets of anti-cHsp70 antibody. Meanwhile, only exoerythrocytic parasites were stained by anti-rBgHsp70 antibody. This result showed that BgHsp70 would be expressed on the surface of parasites during the exoerythrocytic stage. These results indicated that BgHsp70 was a highly immunogenic protein in canine B. gibsoni infection, and that exoerythrocytic parasites might be targets of anti-BgHsp70 antibody.     

Evaluation of shock waveform configuration on the defibrillation capacity of implantable cardioverter defibrillators in dogs

BackgroundImplantable cardioverter defibrillators (ICD) are programmed to detect ventricular arrhythmias and terminate them by delivering an electrical shock. A defibrillation threshold (DFT) at least 10 J below the maximum device output is recommended for successful therapy. Shock waveform configuration is a programmable parameter used to achieve a low DFT. It is hypothesized that a fixed-pulse configuration results in lower defibrillation energy requirements than a fixed-tilt configuration.Animals10 mongrel dogs.Materials and methodsICD generator and transvenous lead were surgically implanted. Defibrillation threshold was determined using a protocol guided by the upper limit of vulnerability. Fixed-pulse and fixed-tilt (50%/50%) waveform configurations were tested in a random order. Plasma cardiac troponin I (cTnI) was measured for signs of myocardial injury.ResultsThe experiment was completed in 9 dogs. Overall mean DFT value was 424 ± 88 V (9.2 ± 3.9 J). Mean differences among voltage, energy and impedance at the DFT for fixed-pulse (422 ± 97 V, 9.1 ± 4.2 J, 62.6 ± 13.8 Ω) and fixed-tilt (426 ± 83 V, 9.3 ± 3.8 J, 62.8 ± 18.5 Ω) configurations were not statistically significant (All P > 0.21). Cardiac TnI concentration changed from 0.03 ng/mL (95% CI: 0.02–0.04) at baseline to 0.11 ng/mL (95 CI: 0.08–0.16) after DFT was obtained with the first waveform configuration and 0.19 ng/mL (95% CI: 0.13–0.28) at the end of the study period. There were no significant changes in heart rate, end-tidal CO2 and blood pressure over time (all P > 0.09).ConclusionThe tested ICD device and lead placement reliably produced acceptable DFT values, based on a 10-J safety margin below the maximum device output. A benefit of fixed-pulse configuration could not be demonstrated over the standard fixed-tilt waveform. Signs of acute myocardial damage from repeated high-voltage shocks and episodes of ventricular fibrillation seemed of limited clinical significance.