In an effort to better understand the role of vasodilators in the management of pulmonary hypertension associated with chronic heartworm disease (HWD), pulmonary hemodynamic measurements were obtained from 7 experimentally infected, anesthetized dogs before and after hydralazine administration (mean dose, 1.96 mg/kg of body weight). Five dogs were maintained on room air, while 2 were maintained on 100% oxygen during the hydralazine study. The hemodynamic effect of hydralazine in dogs with HWD was evaluated, using heart rate, cardiac index, mean pulmonary artery pressure, mean arterial pressure, total pulmonary resistance, total systemic resistance, total systemic resistance/total pulmonary resistance, left ventricular dP/dt(max), left ventricular end diastolic pressure, and left and right ventricular double products ([mean arterial pressure X heart rate] and [mean pulmonary artery pressure X heart rate], respectively). Responders were defined as those in which total pulmonary resistance decreased greater than or equal to 20% without an increase in mean pulmonary arterial pressure and in which heart rate increase was less than or equal to 10%. Comparison was also made between maximal hemodynamic effect of hydralazine with that after 100% oxygen administration for 15 minutes to previously normoxemic dogs (n = 5). Significance was determined if P < 0.05, using the paired t-test. Hydralazine induced significant reductions in mean pulmonary and systemic arterial pressures and total pulmonary resistance, with no significant change in heart rate, cardiac index, total systemic resistance, left ventricular dP/dt(max), left ventricular end diastolic pressure, or right and left ventricular double products. Four (57%) of the 7 dogs studied were considered responders. Pretreatment cardiac index, mean pulmonary artery pressure, and total pulmonary resistance did not allow differentiation of responders from nonresponders. However, pretreatment right ventricular end diastolic pressure was significantly less in responders than in nonresponders. Two dogs sustained hypotension after hydralazine administration, but no dogs had significant tachycardia. In dogs with experimentally induced HWD, treatment with hydralazine had significantly greater effect on cardiac index and mean pulmonary and systemic arterial pressures and resistance than did administration of 100% oxygen. These data indicate that further study of vasodilators for treatment of HWD-induced pulmonary hypertension may be warranted.

Effects of low-flow ischemia and reperfusion of the large colon on systemic and colonic hemodynamic and metabolic variables were determined in horses. Twenty-four adult horses were randomly allocated to 3 groups: sham-operated (n = 6), 6 hours of ischemia (n = 9), and 3 hours of ischemia and 3 hours of reperfusion (n = 9). Low-flow ischemia was induced in groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline. Heart rate, arterial blood pressures, cardiac index, pulmonary artery pressure, right atrial pressure, and colonic blood flow were monitored. Arterial, mixed-venous, and colonic venous blood gas and oximetry analyses; PCV; and blood lactate and pyruvate and plasma total protein concentrations were measured. Data were recorded, and blood samples were collected at baseline and at 30-minute intervals for 6 hours; additionally, data were collected at 185, 190, and 195 minutes (corresponding to 5, 10, and 15 minutes of reperfusion in group-3 horses). There were no differences among groups at baseline or across time for any systemic hemodynamic or metabolic variable. Colonic blood flow did not change across time in group-1 horses. Colonic blood flow significantly (P < 0.05) decreased to 20% of baseline at induction of ischemia in horses of groups 2 and 3 and remained significantly decreased throughout the ischemic period in horses of groups 2 (6 hours) and 3 (3 hours). Colonic blood flow significantly (P < 0.05) increased above baseline by 5 minutes of reperfusion in group-3 horses. Colonic oxygen delivery and oxygen consumption, and colonic venous pH, PO2, percentage saturation of hemoglobin, and oxygen content were significantly (P < 0.05) decreased within 30 minutes after induction of ischemia in horses of groups 2 and 3; colonic venous PCO2, colonic oxygen extraction ratio, and lactate and pyruvate concentrations were significantly (P < 0.05) increased by 30 minutes of ischemia. These alterations continued throughout ischemia, but within 5 minutes of reperfusion in group-3 horses, these variables either returned to baseline (pH, PCO2, lactate, pyruvate), significantly (P < 0.05) increased above baseline (PO2, oxygen content, % saturation of hemoglobin), or significantly (P < 0.05) decreased below baseline (colonic oxygen extraction ratio). Colonic oxygen consumption remained decreased during reperfusion in group-3 horses. Colonic mucosal ischemia-reperfusion injury observed in this model of ischemia was associated with local colonic hemodynamic and metabolic alterations in the presence of systemic hemodynamic and metabolic stability. Reactive hyperemia was observed at restoration of colonic blood flow in group-3 horses and persisted during reperfusion. Colonic venous metabolic alterations were corrected at reperfusion, indicating adaptation of the colon to the return of blood flow and oxygen delivery with resultant decrease in anaerobic metabolism. The early alterations in these variables may simply represent a washout of metabolic by-products.

Although it is known that the QT interval is dependent on the preceding RR interval, QT interval does not vary during respiratory sinus arrhythmia, despite a wide variation in heart rate. To assess the rate of change of the QT interval following an abrupt increase or decrease in heart rate, QT intervals were measured from ECG of healthy, anesthetized, thoracotomized dogs in which a junctional rhythm had been induced by destroying the sinoatrial node. Atria were paced at 800- or 600-millisecond cycle durations until a steady state was reached, and then the cycle duration was changed suddenly to a new cycle duration (600 or 800 milliseconds, respectively). The time and number of heart beats required until the QT interval achieved a value of 63% (1 time constant) of the new steady state were calculated. Time constants for change in QT interval vs the number of beats following the change were 2.8 (SD = 1.3 s) seconds when heart rate was accelerated and 4.7 (SD = 2.1 s) seconds when heart rate was slowed. Differences were not statistically significant. The time constants for change in QT interval duration vs duration after the sudden change in heart rate were 1.7 (SD = 0.8 s) seconds when heart rate was accelerated and 3.7 (SD = 1.7 s) seconds when heart rate was slowed. These time constants differed significantly (P < 0.01). Response of QT interval, therefore, depended on the number of heart beats following sudden change in heart rate, but not time, except as time determined the number of heart beats. The QT interval did not change until 3 to 5 beats after the heart rate was suddenly changed. This number of beats would be more than that which would occur in 1 respiratory cycle in dogs; therefore, QT interval memory would prohibit changes in QT intervals that occur during respiratory sinus arrhythmia.

Medetomidine, an investigational drug indicated for clinical use as a short-term chemical restraint in dogs, was evaluated for its cardiopulmonary effects, in 10 naturally heartworm-infected (HW+) and 10 noninfected (HW-) Beagles. The drug was randomly administered IV (30 microgram/kg of body weight) and IM (40 microgram/kg) in single injections to all dogs. Heart rate, respiratory rate, ECG, blood gas tensions, blood pH, central venous and arterial pressures were measured at 0, 15, 30, 60, 90, 120, and 180 minutes. Medetomidine induced an immediate significant (P less than or equal to 0.001) increase in mean arterial blood pressure followed by decreased blood pressure that remained below normal throughout the study in both groups, irrespective of route of administration. Medetomidine increased central venous pressure, over time, for both groups and both routes of administration. Heart and respiratory rates were significantly (P less than or equal 0.001) decreased after medetomidine administration and remained reduced for the duration of the study in all dogs. The ECG variables were not significantly different between groups or between routes of administration. The HW+ dogs tended to have higher mean PaO2 than did HW- dogs at several postinjection determination times, particularly when the drug was administered IM. The PaO2 decreased during the first 30 minutes in both groups and tended to increase gradually thereafter. The pH decreased over time for both groups and both routes. A significant (P less than or equal to 0.05) decrease in pH was seen in the HW- dogs, compared with HW+ dogs at each measuring time for both routes. The PaCO2 did not significantly change for groups or routes. In general, bradycardia was the predominant cardiovascular effect seen after medetomidine administration in all dogs, irrespective of route. Lowering of blood pressure and heart rate (after a transient blood pressure increase) was synchronized with sedation in these dogs. The overall clinical response with regard to cardiopulmonary effects in HW+ dogs was similar to that in HW- dogs.

Plasma concentration of immunoreactive atrial natriuretic peptide (ir-ANP) was investigated in 83 Cavalier King Charles Spaniels with variable severity of mitral regurgitation caused by chronic valvular disease (CVD). Severity of mitral incompetence was assessed by echocardiography. Significant differences in plasma concentrations of ir-ANP were not found between clinically normal dogs (New York Heart Association functional class O), dogs with only cardiac murmur (class I), and dogs with echocardiographic evidence of slight to moderate left atrial and ventricular dilatation (class II). Dogs with severe left atrial and ventricular dilatation and clinical signs of congestion (classes III and IV) were found to have significantly (P < 0.001) increased plasma concentration of ir-ANP. Overall, moderate degree of association was found between plasma concentration of ir-ANP and left atrial and left ventricular diameters (Pearson's r = 0.65, 0.60, respectively, P < 0.001), as well as heart rate (r = 0.47, P < 0.01). However, left atrial enlargement as found to have the predominant effect on plasma ir-ANP concentration. It is concluded that the plasma concentration of ir-ANP did not become markedly increased before decompensation of chronic mitral regurgitation associated with severe enlargement of the left atrium and ventricle in Cavalier King Charles Spaniels.

Polymyxin B and an antiserum against an Re mutant Salmonella typhimurium were evaluated for protective effect in an equine model of endotoxemia. Six 3- to 5-month-old foals were given endotoxin (0.25 micrograms/kg of body weight) IV after no pretreatment, or pretreatment with polymyxin B (6,000 U/kg, IV) or S typhimurium antiserum (1.5 ml/kg, IV). When given without pretreatment, endotoxin caused transient recumbency and increases in rectal temperature, and heart and respiratory rates. In addition, leukopenia and increases in circulating tumor necrosis factor (TNF) and interleukin 6 (IL-6) activities were detected. Compared with results obtained when endotoxin was given alone, pretreatment with polymyxin B resulted in significantly (P < 0.05) lower maximal plasma TNF and IL-6 activities, and significantly lower rectal temperature and respiratory rate. In contrast, compared with effects of endotoxin given without pretreatment, use of antiserum was associated with significantly (P < 0.05) higher respiratory rate, maximal plasma IL-6 activity, and total TNF response (as determined by areas under curves of plasma TNF vs time). These results indicate that polymyxin B may have potential as a treatment for equine endotoxemia. Salmonella typhimurium antiserum had no positive effect in this model, and, under certain conditions, may exacerbate the actions of endotoxin.

Dexmedetomidine (Dex), an alpha 2-receptor agonist, is the pharmacologically active d-isomer of medetomidine, a compound used as a sedative in veterinary medicine. Isoflurane anesthetic requirement (minimum alveolar concentration; MAC), rectal temperature, and cardiorespiratory variables were studied in chronically instrumented Yucatan miniature swine during DEX (20 micrograms/kg of body weight)-induced changes in body temperature. All studies were performed at room temperature of 22 C. The DEX was given as a 2-minute infusion into the left atrium. Each pig was studied twice. For protocol 1, the core temperature of the pigs was maintained at (mean +/- SD) 38.2 +/- 0.5 C by use of a thermostatically controlled water blanket and a heating lamp. For protocol 2, the core temperature was not externally manipulated and it decreased from 38.2 +/- 0.4 C to 32.2 +/- 1.2 C during the more than 3 hours of the protocol. Control isoflurane MAC was 1.66 +/- 0.2% and was 1.74 +/- 0.3% for protocols 1 and 2, respectively; DEX decreased MAC by 34 and 44%, respectively. For protocol 1, reduction in MAC after DEX administration returned by 50 and 80% at 84 and 138 minutes, respectively. If rectal temperature was not maintained (eg, allowed to decrease), MAC was reduced by 57% at the same time as the return to 80% in the swine with maintained body temperature. Respiratory rate and minute ventilation were significantly higher in swine with maintained temperature. The PaCO2 was lower and, accordingly, pH was higher in these swine. Blood pressure and heart rate were not affected by temperature changes.

Venous access devices connected to jugular vein catheters were implanted SC in 2 groups of 6 White Carneau pigeons (Columba livia). Total parenteral nutrition (TPN), or a control solution (lactated Ringer's solution) was infused as a bolus 4 times daily. Physiologic, hematologic, and biochemical variables were monitored over 5 days. Complications in the TPN-treated pigeons included 8.7% weight loss during the 5-day trial, hyperglycemia for up to 90 minutes after infusion, and glucosuria after infusion. Control pigeons lost 1.3% of their body weight and did not become hyperglycemic or glucosuric after infusion. Hematocrit in both groups of pigeons decreased to a value slightly below published reference values for pigeons. Five pigeons developed venous thrombosis in the proximal part of the cranial vena cava. Results indicated that intermittent administration of TPN is possible in birds; however, further research is required to develop better techniques for administration of TPN solutions. Additionally, it is important to determine, more specifically, the caloric and nutrient requirements of pigeons under stress and receiving TPN.

A specific, sensitive, reverse-phase high-performance liquid chromatographic assay for acepromazine, with analytic sensitivity as low as 5 ng/ml of plasma, and electrochemical detection with an oxidation potential of 0.7 V, was used to study the pharmacokinetics of acepromazine given at a dosage of 0.15 mg/kg of body weight in horses. The relation between effect and pharmacokinetics of the drug was examined. The effects studied included those on blood pressure, pulse, PCV, measures of respiration function, and sedation. Intravenously administered doses led to a biphasic concentration decay pattern with an alpha-phase distribution half-life of < 3 minutes. The beta-phase half-life was in the range of 50 to 150 minutes. The CNS effects peaked at 20 minutes after administration, and the hemodynamic effects peaked at 100 minutes. In all horses, the most sensitive variable was the PCV, which decreased by up to 20% (P < 0.0001). Systolic, diastolic, and mean blood pressures decreased (P < 0.0001); heart rate was unchanged (P > 0.05). Neither blood gas tensions nor blood pH changed noticeably (P > 0.05). In all horses studied, acepromazine had a significant (P < 0.0001) sedative effect, as observed by posture and alertness. None of the observed pharmacodynamic effects correlated well with plasma acepromazine concentration. These effects persisted beyond the time of detectable acepromazine concentration, indicating that they might be caused by active metabolites, or that their timing could result from complex pharmacokinetic compartment influences.

We characterized the clinicopathologic manifestations of experimentally induced endotoxin-induced mastitis. Responses to hypertonic fluid therapy also were assessed. Eight cows received 1 mg of endotoxin by in infusion in the left forequarter. Four hours after endotoxin administration, cows received 0.9% NaCl, 5 ml/kg of body weight (n = 4) or 7.5% NaCl, 5 ml/kg (n = 4) IV. Endotoxin-infused cows had expanded plasma volume, hyponatremia, transient hyperchloremia and hypophosphatemia, increased serum glucose concentration, and decreased serum activities of liver- and muscle-specific enzymes. Calculated plasma volume increased at 6 hours in cows receiving hypertonic NaCl, and at 12, 24, and 48 hours after endotoxin infusion in both groups. Concurrent observations of decreased serum protein concentration, erythrocyte count, and hematocrit supported observations of increased plasma volume. Relative plasma volume was greater in cows receiving hypertonic NaCl (124.3%) than in cows receiving isotonic NaCl (106.6%) at 6 hours after endotoxin infusion. Cattle receiving hypertonic NaCl had increased voluntary water intake after IV fluid administration. Increased water consumption was not accompanied by increased body weight, indicating probable occurrence of offsetting body water loss. Serum sodium concentration in cows receiving hypertonic NaCl was increased 2 hours after fluid administration, but the magnitude of the change was minimal (< 4 mmol/L) and transient, indicating rapid equilibration with either interstitial or intracellular spaces. Serum sodium concentration was decreased in cows receiving isotonic NaCl at 12, 24, and 48 hours after endotoxin administration, compared with concentration prior to endotoxin administration, indicating selective loss of sodium.