Fumonisin B(1) increases serum sphinganine concentration but does not alter serum sphingosine concentration or induce cardiovascular changes in milk-fed calves.

Fumonisin B(1) is the most toxic and commonly occurring form of a group of mycotoxins that alter sphingolipid biosynthesis and induce leukoencephalomalacia in horses and pulmonary edema in pigs. Purified fumonisin B(1) (1 mg/kg, iv, daily) increased serum sphinganine and sphingosine concentrations and decreased cardiovascular function in pigs within 5 days. We therefore examined whether the same dosage schedule of fumonisin B(1) produced a similar effect in calves. Ten milk-fed male Holstein calves were instrumented to obtain blood and cardiovascular measurements. Treated calves (n = 5) were administered purified fumonisin B(1) at 1 mg/kg, iv, daily for 7 days and controls (n = 5) were administered 10 ml 0.9% NaCl, iv, daily. Each calf was euthanized on day 7. In treated calves, serum sphinganine concentration increased from day 3 onward (day 7, 0.237 +/- 0.388 micromol/l; baseline, 0.010 +/- 0.007 micromol/l; mean +/- SD), whereas, serum sphingosine concentration was unchanged (day 7, 0.044 +/- 0.065 micromol/l; baseline, 0.021 +/- 0.025 micromol/l). Heart rate, cardiac output, stroke volume, mean arterial pressure, mean pulmonary artery pressure, pulmonary artery wedge pressure, central venous pressure, plasma volume, base-apex electrocardiogram, arterial Po(2), and systemic oxygen delivery were unchanged in treated and control calves. Fumonisin-treated calves developed metabolic acidosis (arterial blood pH, 7.27 +/- 0.11; base excess, -9.1 +/- 7.6 mEq/l), but all survived for 7 days. We conclude that calves are more resistant to fumonisin B(1) cardiovascular toxicity than pigs.

The oxytocic effect of xylazine on the canine uterus.

The effect of xylazine on intrauterine pressure was compared to that of prostaglandin and oxytocin in seven diestrual bitches. Microtipped pressure transducers were surgically implanted in the uteri of four bitches at 30 d diestrus and in three bitches at 60 d diestrus. Uterine contractile force was measured in the awake bitches on Day 1 and Day 2 following implantation. Uterine responses to intravenous prostaglandin (5 mug/kg), oxytocin (0.05 USP units/kg), and xylazine (0.22 mg/kg) were measured. In the 30-d diestrual bitches, prostaglandin and oxytocin increased intrauterine pressure to 67 and 69 mmHg, with the duration of action being 16 and 14 min, respectively. Xylazine increased intra-uterine pressure to 49 mmHg and had a duration of action of 8 min. All results were decreased but similar in the 60-d diestrual bitches. These findings indicate that xylazine, given intravenously, produces a transitory increase in intrauterine pressure in the diestrual bitch.

A technique for catheterisation of the coronary sinus in adult ponies (Equus caballus).

Long-term catheterisation of the coronary sinus using a specially designed catheter was accomplished in 6 ponies via a right lateral thoracotomy. The catheter comprised a 10 to 12 cm long stiff segment (Teflon) joined to a 100 cm length of pliable medical grade (vinyl) tubing. Catheters were kept functional up to 10 weeks postoperatively. Location of the catheter tip was verified by determining the oxygen tension of anaerobically withdrawn blood samples. Normal values of oxygen tension of the coronary sinus blood in ponies were similar to those reported for the dog, whereas oxygen content was significantly lower.

Hemodynamic effects of calcium gluconate administered to conscious horses.

Calcium gluconate was administered to conscious horses at 3 different rates (0.1, 0.2, and 0.4 mg/kg/min for 15 minutes each). Serum calcium concentrations and parameters of cardiovascular function were evaluated. All 3 calcium administration rates caused marked increases in both ionized and total calcium concentrations, cardiac index, stroke index, and cardiac contractility (dP/dtmax). Mean arterial pressure and right atrial pressure were unchanged; heart rate decreased markedly during calcium administration. Ionized calcium concentration remained between 54% and 57% of total calcium concentration throughout the study. We conclude that calcium gluconate can safely be administered to conscious horses at 0.1 to 0.4 mg/kg/min and that administration will result in improved cardiac function.

Performance and health of weanling bulls after butorphanol and xylazine administration at castration.

A total of 268 crossbred, 6- to 9-mo-old, bull calves (214 +/- 19 kg) were used in two separate 27-d experiments to assess the effects of butorphanol and xylazine administration (BXA) on the subsequent performance and health of beef calves. In each experiment, calves were randomly allotted to four treatment groups: 1) castration with BXA, 2) castration without BXA, 3) no castration with BXA, and 4) no castration without BXA. There were two replicates within each experiment. The intravenous administration of .07 mg/kg of butorphanol and .02 mg/kg of xylazine occurred 90 s before tail hold and castration procedures. Calves were placed in a squeeze chute and manually restrained by tail elevation. In Exp. 2, the cattle also were scored for chute activity (on a 1 to 5 scale with 5 being the most active). Cattle were weighed at the beginning and end of the experiment, feed intake was recorded daily, and cattle were monitored daily for respiratory disease. There were no castration x BXA interactions (P greater than .51). Castration reduced (P less than .01) daily gain and gain/feed and tended (P = .13) to reduce feed intake. The administration of BXA had no effect (P greater than .05) on gain or gain/feed but did tend (P = .13) to reduce feed intake. No differences (P greater than .45) were observed in morbidity or mortality due to either BXA or castration. Castration and BXA increased (P less than .01) blood cortisol levels on d 3, whereas control animals had reduced cortisol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations in epinephrine-induced arrhythmogenesis after xylazine and subsequent yohimbine administration in isoflurane-anesthetized dogs.

Effects of xylazine (1.1 mg/kg of body weight, IV bolus, plus 1.1 mg/kg/h infusion) and subsequent yohimbine (0.125 mg/kg, IV bolus) administration on the arrhythmogenic dose of epinephrine (ADE) in isoflurane (1.8% end-tidal)-anesthetized dogs were evaluated. The ADE was defined as the total dose of epinephrine that induced greater than or equal to 4 premature ventricular contractions within 15 seconds during a 3-minute infusion period or within 1 minute after the end of infusion. Total ADE values during isoflurane anesthesia, after xylazine administration, and after yohimbine injection were 36.6 +/- 8.45 micrograms/kg, 24.1 +/- 6.10 micrograms/kg, and 45.7 +/- 6.19 micrograms/kg, respectively. Intravenous xylazine administration significantly (P less than 0.05) increased blood pressure and decreased heart rate, whereas yohimbine administration induced a significant (P less than 0.05) decrease in blood pressure. induced a significant (P less than 0.05) decrease in blood pressure. After yohimbine administration, the ADE significantly (P less than 0.05) increased above that after isoflurane plus xylazine administration. After yohimbine administration, blood pressure measured immediately before epinephrine-induced arrhythmia was significantly (P less than 0.05) less than the value recorded during isoflurane plus xylazine anesthesia. Heart rate was unchanged among treatments immediately before epinephrine-induced arrhythmia. Seemingly, yohimbine possessed a protective action against catecholamine-induced arrhythmias in dogs anesthetized with isoflurane and xylazine.

Anesthetic potency of nitrous oxide in young swine (Sus scrofa).

Determination of nitrous oxide (N2O) potency was accomplished by extrapolation using the concepts of minimum alveolar concentration (MAC) and additivity among inhalation anesthetics. Halothane and isoflurane anesthetic requirement (alveolar concentration) necessary to achieve MAC in 9 pigs decreased with each successive increase in the percentage of inspired N2O (25%, 50%, 75%). Halothane and isoflurane MAC was determined to be 0.94 +/- 0.03 and 1.75 +/- 0.01 volumes percent, respectively. Halothane and isoflurane requirements decreased to 0.74 +/- 0.02, 0.66 +/- 0.02, and 0.58 +/- 0.02; and to 1.56 +/- 0.02, 1.38 +/- 0.02, and 1.08 +/- 0.03 volumes percent with 25%, 50%, and 75% N2O, respectively. The line of best fit derived from regression analysis of the combined data (isoflurane and halothane MAC values) had a correlation coefficient of 0.987 and an X intercept equivalent to 195% N2O. The potency of N2O in pigs was similar to that of other domesticated mammals and reduced halothane and isoflurane anesthetic requirements by approximately 50% of the reduction observed in human beings.

Halothane-catecholamine arrhythmias in swine (Sus scrofa).

The arrhythmogenic dose of epinephrine (ADE) was determined in 6 pigs during steady-state anesthesia (1.5% halothane in O2) and steady-state anesthesia plus xylazine (1.1 mg X kg-1 X hr-1; IV infusion) and after either prazosin (alpha 1) or metoprolol (beta 1) adrenergic blockade during halothane-xylazine (H-X) anesthesia. A constant infusion (1, 2, 3, 5, and 10 micrograms X kg-1 X min-1) of freshly mixed epinephrine (100 micrograms X ml-1 in saline solution) was used to determine ADE. The ADE was defined as the total dose of epinephrine which produced 4 or more continuous or intermittent, premature, ventricular contractions within a 15-s period. The mean epinephrine total dose values during 1.5% halothane anesthesia, H-X anesthesia alone, or H-X anesthesia after either prazosin (0.1 mg X kg-1) or metoprolol (0.5 mg X kg-1) adrenergic blockade were 3.60 +/- 0.844, 2.68 +/- 0.402, 11.85 +/- 3.804, and 5.17 +/- 0.587 micrograms X kg-1, respectively. Xylazine administration did not significantly decrease ADE, although mean arterial pressure significantly increased. Prazosin administration significantly increased ADE and was associated with an increased heart rate and a decreased mean arterial pressure. We conclude that alpha 1-blockade with prazosin is more protective to epinephrine-induced arrhythmias in H-X-anesthetized pigs than is beta 1-blockade with metoprolol.

Cardiopulmonary responses of swine to intravenous infusion of guaifenesin, ketamine, and xylazine.

Swine were anesthetized with a 5% solution of dextrose in water containing 50 mg of guaifenesin, 1 mg of ketamine, and 1 mg of xylazine X ml-1 (G-K-X) infused IV at a rate of 2.2 ml X kg-1 X hr-1. Mean arterial blood pressure and systemic vascular resistance were significantly increased from base-line values throughout the 2 hours of G-K-X infusion. Cardiac index decreased significantly initially, but returned to near base line at 30 minutes. Fifteen minutes after G-K-X infusion was discontinued, cardiac index was not significantly different from base line. Heart rate decreased significantly from base line 90 minutes after infusion of G-K-X began and remained so throughout the study. However, the mean heart rate remained within the acceptable range for swine. Rate-pressure product was not significantly altered. The PaCO2 decreased, and arterial pH increased significantly from base line, supporting our clinical impression that pigs breathe well when anesthetized with G-K-X. We conclude that G-K-X is a satisfactory combination of drugs for induction and maintenance of surgical anesthesia in healthy swine for a period of 2 hours.

Alterations in the arrhythmogenic dose of epinephrine after adrenergic receptor blockade with prazosin, metoprolol, or yohimbine in halothane-xylazine-anesthetized dogs.

Recent evidence has linked alpha-receptor and beta-receptor activations with ventricular arrhythmia genesis. In order to assess the relative contribution of specific adrenoceptors (alpha 1, alpha 2, beta 1) on ventricular arrhythmogenic activity during xylazine (1.1 mg X kg-1 X hr-1)-halothane (1.35%) anesthesia, the arrhythmogenic dose of epinephrine (ADE) was repeatedly determined before and after prazosin (alpha 1 antagonist; 0.1 mg X kg-1), metoprolol (beta 1 antagonist; 0.5 mg X kg-1), and yohimbine (alpha 2 antagonist; 0.125 mg X kg-1) administration in 6 dogs. The ADE was expressed as infusion rate and total dose. The ADE was defined as the dose which produced 4 or more intermittent premature ventricular contractions within 15 s during a 3-minute infusion period or within 1 minute from end of infusion. Control ADE was 2.69 +/- 0.372 (micrograms X kg-1 X min-1) and 4.17 +/- 0.544 (micrograms X kg X -1) for infusion rate and total dose, respectively. The ADE significantly increased after prazosin (P less than 0.005), metoprolol (P less than 0.005), and yohimbine (P less than 0.05) administration. The ADE values increased to 5.42 +/- 1.22 (rate) and 8.10 +/- 1.95 (dose) after alpha 2 blockade, but were significantly less than the alpha 1 and beta 1 blockade ADE values. In conclusion, although both alpha- and beta-adrenoceptor blockade depressed ventricular arrhythmia genesis in xylazine-halothane-anesthetized dogs, alpha 2 blockade, which was achieved with the recommended dose of yohimbine for reversal of anesthetic-induced CNS depression, was not as protective as alpha 1 (prazosin) or beta 1 (metoprolol) blockade.

Ivermectin plasma concentrations in collies sensitive to ivermectin-induced toxicosis.

Five Collies sensitive to toxic effects of ivermectin and 7 nonsensitive Collies were given 100 micrograms of ivermectin/kg of body weight, PO. Blood samples were collected from each dog before treatment; at posttreatment hours 1, 2, 3.5, 5, and 8; and at posttreatment days 1, 2, 4, 7, 14, and 21. Each sample was assayed for ivermectin concentration, and statistical analyses were performed on the resulting plasma concentration data to determine differences in absorption and clearance of drugs between the 2 groups. Variables measured were area under the curve (using the trapezoidal rule), peak plasma concentration, and the time to peak concentration. Differences between sensitive and nonsensitive Collies for variables analyzed were not significant (P greater than 0.05).

Assessment of toxicosis induced by high-dose administration of milbemycin oxime in collies.

Fifteen Collies, previously having mild reactions to ivermectin challenge (120 micrograms/kg of body weight; 20 times the recommended dosage level), were studied to evaluate the effects of milbemycin oxime administration at 5 and 10 mg/kg (10 and 20 times the manufacturer's recommended dosage). Five replicates, comprising 3 dogs each, were formed on the basis of body weight. Within replicates, each dog was randomly allocated to treatment with 5 or 10 mg of milbemycin/kg or served as a untreated control. Dogs were examined repeatedly for signs of toxicosis for 4 days after treatment and daily thereafter. Two of 5 dogs treated at 5 mg/kg (10x) developed signs of mild depression on the day of treatment, but were normal 24 hours after treatment. All 5 dogs treated at 10 mg/kg (20x) developed signs of mild depression and ataxia by 6 hours. Signs persisted for 24 hours in 3 dogs. Two of these dogs also had mydriasis, whereas 3 salivated excessively. All dogs recovered completely by day 2 after treatment. The results of this study demonstrated that Collies sensitive to the effects of 120 micrograms of ivermectin (20x)/kg show similar sensitivity to the effects of milbemycin oxine administered at 10 mg/kg (20x). We conclude that ivermectin and milbemycin commercial formulations have similar margins of safety and that milbemycin toxicosis appears to be dose-dependent in Collies with a demonstrated sensitivity to ivermectin.

Safety of moxidectin in avermectin-sensitive collies.

OBJECTIVE: To evaluate the safety of moxidectin administration at doses of 30, 60, and 90 microg/kg of body weight (10, 20, and 30 times the manufacturer's recommended dose) in avermectin-sensitive Collies. ANIMALS: 24 Collies. PROCEDURE: Collies with mild to severe reactions to ivermectin challenge (120 mg/kg; 20 times the recommended dose for heartworm prevention) were used. Six replicates of 4 dogs each were formed on the basis of body weight and severity of reaction to ivermectin test dose. Within replicates, each dog was randomly allocated to treatment with oral administration of 30, 60, or 90 microg of moxidectin/kg or was given a comparable volume of placebo tablet formulation. Dogs were observed hourly for the first 8 hours and twice daily thereafter for 1 month for signs of toxicosis. RESULTS: Signs of toxicosis were not observed in any control group dog throughout the treatment observation period. Likewise, signs of toxicosis were not observed in any dog receiving moxidectin at 30, 60, or 90 microg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: The moxidectin formulation used in the study reported here appears to have a wider margin of safety than ivermectin or milbemycin in avermectin-sensitive Collies.

Organ blood flow and distribution of cardiac output in hypocapnic ketamine-anesthetized swine.

Organ blood flow and distribution of cardiac output (CO) were determined in 9 awake (control) and ketamine-anesthesized swine (4 mg/kg bolus followed by continuous infusion of 0.3 mg/kg/min, IV), using 15 micron diameter radionuclide-labeled microspheres. Absolute values of blood flow (per 100 g basis) were determined for various organs and peripheral tissues. Internal organs of the swine, which constituted 8.25 +/- 0.79% of the total body mass, received 55.83 +/- 5.13% of the CO. The fraction of CO received by brain, heart, kidneys, liver (via hepatic artery), and gastrointestinal tract was 1.10%, 2.67%, 19.84%, 11.81%, and 16.84%, respectively. During ketamine anesthesia, the fraction of CO perfusing the kidneys and liver (hepatic artery) increased from control and values for brain, heart, and splanchnic organs remained unchanged. Blood flow (per unit weight) of brain, cardiac, and splanchnic organs decreased; kidney and skeletal muscle blood flow was unaltered; and hepatic arterial blood flow increased from the awake (control) values. The hyperdynamic state often associated with ketamine anesthesia was not evident in these pigs during intermittent positive-pressure ventilation resulting in hypocapnia.

Hemodynamic response of calves to tiletamine-zolazepam-xylazine anesthesia.

Six healthy Holstein calves were anesthesized with isoflurane in O2 and instrumented for hemodynamic studies. A saphenous artery was catheterized for measurement of blood pressure and withdrawal of blood for determination of the partial pressure of carbon dioxide (PaCO2), oxygen (PaO2), and arterial pH (pHa). Respiration was controlled throughout the study. The ECG and EEG were monitored continuously. A thermodilution catheter was passed via the right jugular vein into the pulmonary artery for determination of cardiac output and measurement of central venous pressure, pulmonary arterial pressure, and pulmonary capillary wedge pressure. Baseline values (time 0) were recorded following recovery from isoflurane. Tiletamine-zolazepam (4 mg/kg)-xylazine (0.1 mg/kg) were administered IV immediately after recording baseline values. Values were again recorded at 5, 10, 20, 30, 40, 50, and 60 minutes after injection. Changes in left ventricular stroke work index, PaCO2, and pHa were insignificant. Arterial blood pressure and systemic vascular resistance increased above baseline at 5 minutes and then gradually decreased below baseline at 40 minutes, demonstrating a biphasic response. Values for pulmonary capillary wedge pressure, pulmonary arterial pressure, central venous pressure, and PaO2 were increased above baseline from 5 to 60 minutes. Stroke volume, stroke index, and right ventricular stroke work index were increased from 20 or 30 minutes to 60 minutes. Pulmonary vascular resistance increased at 10 minutes, returned to baseline at 20 minutes, and was increased again at 60 minutes. Heart rate, cardiac output, cardiac index, and rate pressure product were decreased at 5 minutes, and with the exception of cardiac output, remained so for 60 minutes. Cardiac output returned to the baseline value at 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of nifedipine on xylazine-induced acute pressor response in halothane-anesthetized dogs.

Effects and interaction of nifedipine (Ca channel blocker) and xylazine (mixed alpha agonist) during halothane anesthesia were examined in 6 dogs. After achievement of steady-state halothane (1.35%) anesthesia, blood pressure (BP) and heart rate (HR) were recorded in these dogs during 3-minute saline or nifedipine (20 micrograms/kg) infusion periods. Seven minutes after the end of saline or nifedipine infusion, xylazine (1.1 mg/kg of body weight) was infused over a 2-minute period. After saline pretreatment, xylazine administration increased diastolic BP (33.67 +/- 3.91 mm of Hg) and decreased HR. Nifedipine infusion induced a transient reduction in BP, accompanied by a more persistent increase in HR. Compared with saline pretreatment, nifedipine pretreatment significantly decreased the acute increase in diastolic BP (33.67 +/- 3.91 vs 14.00 +/- 2.94 mm of Hg) which occurred during xylazine injection. After saline and nifedipine infusions, xylazine administration decreased HR 30 +/- 15.02 and 36.5 +/- 10.36 beats/min, respectively. A pronounced sinus arrhythmia and/or 2nd-degree atrioventricular block developed in all dogs during xylazine injection after saline infusion. Arrhythmias were not observed in the dogs after nifedipine infusion. Nifedipine's Ca blocking action depressed xylazine-induced acute vasoconstriction and concomitant increase in diastolic BP. Because alpha 2-, but not alpha 1-adrenoceptor-mediated vasoconstriction is Ca-dependent, these results indicate that a portion of the acute pressor response induced by IV xylazine in halothane-anesthetized dogs may be alpha 2-mediated. Seemingly, nifedipine-induced hypotension and damping of xylazine-induced increases in BP attenuated xylazine's actions on cardiac rate and rhythm.

Cardiopulmonary effects of an intravenous infusion of guaifenesin, ketamine, and xylazine in dogs.

A 5% solution of dextrose in water containing 50 mg of guaifenesin, 0.25 mg of xylazine, and 1 mg of ketamine/ml was infused IV at the rate of 2.2 ml X kg-1 X hour-1 in dogs. Heart rate, systemic vascular resistance, mean arterial blood pressure, rate-pressure product, and arterial oxygen tension were not altered significantly from baseline values during 2 hours of anesthesia. Cardiac index was significantly (P less than 0.05) decreased from base-line values. Hypoventilation resulted in increased arterial carbon dioxide tension and decreased arterial pH. After the dogs were given glycopyrrolate, cardiac index returned to base line, and heart rate, mean arterial pressure, and rate-pressure product were significantly greater (P less than 0.05) than base-line values.

Clinical observations in collies given ivermectin orally.

An oral liquid form of ivermectin was administered to 14 purebred Collies (12 rough coated, 2 smooth coated). All Collies were given ivermectin at dosages of 100 and then 200 micrograms/kg of body weight. Three of the dogs developed mild clinical signs of toxicosis (salivation, vomiting, confusion, ataxia, and tremors) with the 100 micrograms/kg dosage. After the 200 micrograms/kg dosage, 7 dogs (including 1 smooth-coated Collie) developed severe toxicosis (seizure-like activity, recumbency, nonresponsiveness, and coma). Because dogs that developed severe toxicosis were not retreated, only the 7 remaining dogs were given ivermectin at 600 micrograms/kg. Severe toxic signs were not observed in the dogs given the 600 micrograms/kg dosage, and only 1 of these 7 dogs developed severe toxicosis when given ivermectin at 2,500 micrograms/kg. Dogs that developed severe toxicosis were given supportive care while in the comatose state. All dogs recovered completely. The results indicated that Collies (including the smooth-coated Collies) have a wide range of sensitivity to ivermectin-induced toxicosis.

Cardiopulmonary effects of continuous intravenous infusion of guaifenesin, ketamine, and xylazine in ponies.

Eight ponies were anesthetized with a solution containing 50 mg of guaifenesin, 1 mg of ketamine, and 0.5 mg of xylazine X ml-1 of 5% dextrose in water. Anesthesia was induced by IV injection (1.1 ml X kg-1), followed by continuous IV infusion at 2.75 ml X kg-1 X hr-1. Heart rate, rate-pressure product, mean pulmonary artery pressure, and standard bicarbonate were not significantly changed throughout the study. Systolic, diastolic, and mean arterial pressures and left ventricular stroke work index were significantly decreased at 5 and 15 minutes after a bolus of the anesthetic solution was injected. Systolic blood pressure returned to within the base-line range at 30 minutes, but diastolic and mean arterial pressures were significantly decreased throughout the study. Cardiac index and arterial pH were decreased at 5 minutes only. Systemic vascular resistance was significantly decreased 60 minutes after bolus injection was given. Hypoventilation, as indicated by increased PaCO2, occurred 5 minutes after bolus injection was given.

Hypotension and cutaneous reactions associated with intravenous administration of etoposide in the dog.

A study was undertaken to determine the pressor and toxic effects of etoposide, an antineoplastic agent, when administered IV in 0.9% sodium chloride solution (0.4 mg of etoposide/ml) over a 30-minute period to dogs at a dosage of 40 mg/m2 of body surface. On day 1, 6 adult German Shorthaired Pointers were anesthetized with halothane, and blood pressures were measured via a femoral artery catheter before, during, and after the etoposide was administered. Systolic, diastolic, and mean blood pressures of each dog decreased [corrected] significantly (P less than 0.01) within 30 minutes after initiation of etoposide infusion. On day 3, when the dogs were not anesthetized, etoposide was again administered to each dog, using the same dosage. Each dog developed a moderate to severe cutaneous reaction characterized by moderate to severe pruritus, urticaria, and swelling of the head and extremities that began during the second infusion of etoposide. These same cutaneous reactions were seen on day 30, when etoposide was administered to 3 of the previously treated dogs and 2 previously untreated Beagles. We concluded that the administration of the commercial preparation of etoposide is likely to cause a significant reduction in blood pressure of anesthetized dogs, and that the drug is likely to induce a moderate to severe cutaneous reaction when administered to unanesthetized dogs.