Effects of plasma aldosterone concentration and treatment with eplerenone on the survival of cats with chronic kidney disease.

This study investigated the plasma aldosterone concentration (PAC) in cats with chronic kidney disease (CKD) and retrospectively evaluated the survival of cats with high PAC. Furthermore, this study prospectively examined eplerenone's effect on survival time in CKD cats with high PAC. The PAC was measured retrospectively in blood samples obtained from 156 client-owned cats that visited a veterinary hospital. The cats were designated into 2 groups: clinically healthy (n = 101) and those with CKD (n = 55). The PAC was measured by solid-phase radioimmunoassay; median (minimum-maximum) PAC in healthy cats was 97 pg/mL (range: 10 to 416 pg/mL) and the upper limit (95th percentile) was 243 pg/mL. In the CKD group, PAC [126 pg/mL (range: 10 to 981 pg/mL)] was higher (P < 0.01) than in the clinically healthy group. In cats with CKD, the survival time of those with high PAC (n = 16) (> 243 pg/mL) was shorter (P = 0.019) than that of those (n = 39) with normal PAC. Administering an aldosterone antagonist, eplerenone, at 2.5 to 5 mg/kg body weight prolonged survival (P = 0.005) in CKD cats with high PAC (n = 8). In conclusion, PAC could be a prognostic marker of CKD in cats and eplerenone may prolong survival in cats with CKD and a high PAC.

Effets de la concentration plasmatique d'aldostérone et du traitement à l'éplérénone sur la survie des chats atteints d'insuffisance rénale chronique. Cette étude a examiné la concentration plasmatique d'aldostérone (PAC) chez les chats atteints d'insuffisance rénale chronique (IRC) et a évalué rétrospectivement la survie des chats ayant une PAC élevée. De plus, cette étude a examiné de manière prospective l'effet de l'éplérénone sur le temps de survie chez les chats IRC avec une PAC élevée. La PAC a été mesurée rétrospectivement dans des échantillons de sang prélevés sur 156 chats appartenant à des clients ayant visité un hôpital vétérinaire. Les chats ont été répartis en 2 groupes : cliniquement sains (n = 101) et ceux atteints d'IRC (n = 55). La PAC a été mesurée par radio-immunodosage en phase solide; la PAC médiane (minimale-maximale) chez les chats sains était de 97 pg/mL (plage : 10 à 416 pg/mL) et la limite supérieure (95e centile) était de 243 pg/mL. Dans le groupe IRC, la PAC [126 pg/mL (plage : 10 à 981 pg/mL)] était plus élevée (P < 0,01) que dans le groupe cliniquement sain. Chez les chats atteints d'IRC, le temps de survie de ceux avec une PAC élevée (n = 16) (> 243 pg/mL) était plus court (P = 0,019) que celui de ceux (n = 39) avec une PAC normale. L'administration d'un antagoniste de l'aldostérone, l'éplérénone, à raison de 2,5 à 5 mg/kg de poids corporel a prolongé la survie (P = 0,005) chez les chats atteints d'IRC avec une PAC élevée (n = 8). En conclusion, la PAC pourrait être un marqueur pronostique de l'IRC chez le chat et l'éplérénone pourrait prolonger la survie des chats atteints d'IRC et d'une PAC élevée.(Traduit par Dr Serge Messier).

Effects of constant rate infusions of dexmedetomidine, remifentanil and their combination on minimum alveolar concentration of sevoflurane in dogs.

OBJECTIVE: To evaluate the effects of constant rate infusions (CRIs) of dexmedetomidine and remifentanil alone and their combination on minimum alveolar concentration (MAC) of sevoflurane in dogs. STUDY DESIGN: Randomized crossover experimental study. ANIMALS: A total of six (three males, three females) healthy, adult neutered Beagle dogs weighing 12.6 ± 1.4 kg. METHODS: Anesthesia was induced with sevoflurane in oxygen until endotracheal intubation was possible and anesthesia maintained with sevoflurane using positive-pressure ventilation. Each dog was anesthetized five times and was administered each of the following treatments: saline (1 mL kg-1 hour-1) or dexmedetomidine at 0.1, 0.5, 1.0 or 5.0 µg kg-1 loading dose intravenously over 10 minutes followed by CRI at 0.1, 0.5, 1.0 or 5.0 µg kg-1 hour-1, respectively. Following 60 minutes of CRI, sevoflurane MAC was determined in duplicate using an electrical stimulus (50 V, 50 Hz, 10 ms). Then, CRI of successively increasing doses of remifentanil (0.15, 0.60 and 2.40 µg kg-1 minute-1) was added to each treatment. MAC was also determined after 30 minutes equilibration at each remifentanil dose. Isobolographic analysis determined interaction from the predicted doses required for a 50% MAC reduction (ED50) with remifentanil, dexmedetomidine and remifentanil combined with dexmedetomidine, with the exception of dexmedetomidine 5.0 µg kg-1 hour-1, obtained using log-linear regression analysis. RESULTS: The sevoflurane MAC decreased dose-dependently with increasing infusion rates of dexmedetomidine and remifentanil. Remifentanil ED50 values were lower when combined with dexmedetomidine than those obtained during saline-remifentanil. Synergistic interactions between dexmedetomidine and remifentanil for MAC reduction occurred with dexmedetomidine at 0.5 and 1.0 µg kg-1 hour-1. CONCLUSIONS AND CLINICAL RELEVANCE: Combined CRIs of dexmedetomidine and remifentanil synergistically resulted in sevoflurane MAC reduction. The combination of dexmedetomidine and remifentanil effectively reduced the requirement of sevoflurane during anesthesia in dogs.

Nicardipine constant rate infusion alleviates the cardiovascular effects of dexmedetomidine infusions without affecting the minimal alveolar concentration in sevoflurane-anesthetized dogs.

Two randomized crossover trials evaluated the effects of nicardipine constant rate infusion (CRI) on 1) the anesthetic potency of sevoflurane and 2) the ability to attenuate dexmedetomidine-induced cardiovascular depression in anesthetized dogs. First, six healthy Beagle dogs weighing 11.7 ± 0.9 kg were allocated to one of three treatments that administered a CRI of carrier (saline) or dexmedetomidine 0.5 or 3.0 µg/kg/h following a loading dose. The minimum alveolar concentration (MAC) of sevoflurane was determined utilizing electric stimuli before and after the loading dose of nicardipine (20 µg/kg intravenously for 10 min), followed by CRI at 40 µg/kg/h with 60 min of equilibration. Subsequently, cardiovascular and blood gas variables were evaluated in another trial under sevoflurane anesthesia at the individual 1.5 MAC. After baseline measurements, the dogs were assigned to two treatments (dexmedetomidine CRI at 0.5 or 3.0 µg/kg/h following a loading dose) with sevoflurane doses adjusted to 1.5 times of MAC equivalent, and the measurements were repeated every 15 min for 120 min. After 60 min, nicardipine CRI at 40 µg/kg/h with a loading dose was added to the dexmedetomidine CRI. Dexmedetomidine infusions significantly decreased the sevoflurane MAC but nicardipine did not significantly alter the MAC either with or without dexmedetomidine CRI in dogs. Dexmedetomidine dose-dependently decreased the cardiac index and increased the systemic vascular resistance index; these effects were fully counteracted by concomitant nicardipine CRI. Nicardipine CRI can be useful for controlling the cardiovascular depression elicited by dexmedetomidine in anesthetized dogs without affecting the anesthetic potency of sevoflurane.

Effects of imidazoline and non-imidazoline α-adrenergic agents on rabbit platelet aggregation.

BACKGROUND/AIMS: Imidazoline α2-adrenergic agents exert complex effects on mammalian platelet aggregation. Although non-adrenergic, imidazoline (I) receptors have been revealed in human platelets, there is limited information about imidazoline's action on platelet aggregation. This study aimed to investigate aggregatory and anti-aggregatory effects of various imidazoline or non-imidazoline α-adrenergic agents on rabbit platelets. METHODS: Aggregatory responses of agents on rabbit platelets were examined by turbidimetric method. Radioligand binding assay to platelet I1 and I2 receptors was performed using [(3)H]-clonidine and [(3)H]-idazoxan, respectively. RESULTS: Aggregation was not induced by α-adrenoceptor agonists alone. Adrenaline and noradrenaline produced dose-dependent potentiation of ADP- or collagen-induced aggregation. Imidazoline adrenoceptor agonists clonidine and p-aminoclonidine also potentiated ADP-induced platelet aggregation. The α2-adrenoceptor antagonists and/or certain imidazoline adrenergic agents inhibited adrenaline-potentiated aggregation in a dose-dependent manner, whereas α1-adrenoceptor antagonists and non-imidazoline α-adrenergic agents were either ineffective or less effective in inhibiting adrenaline-potentiated aggregation. Rabbit platelets did not have I1 receptors, but had I2 receptors, indicating that adrenaline-potentiated platelet aggregation was inhibited by idazoxan, but not by imidazoline compounds clonidine and oxymetazoline. CONCLUSIONS/IMPLICATIONS: These results demonstrated that α2-adrenoceptor-blocking agents and/or imidazoline α-adrenergic agents effectively inhibit adrenaline-potentiated platelet aggregation. It is proposed that imidazoline structure in part plays a role in the inhibition of adrenaline-potentiated aggregation.

Therapeutic effect of low-dose imatinib on pulmonary arterial hypertension in dogs.

This was a pilot study to determine the effectiveness of low-dose imatinib therapy for hemodynamic disturbances, including pulmonary arterial hypertension (PAH), and clinical manifestations caused by chronic heart failure in dogs. Six client-owned dogs with PAH were administered imatinib mesylate orally, 3 mg/kg body weight q24h, for 30 d. Physical examination, blood biochemical tests, radiography, and Doppler echocardiography were performed prior to imatinib administration and again 30 days after administration. Clinical scores were significantly reduced after imatinib treatment. Systolic pulmonary arterial pressure, heart rate, maximum tricuspid regurgitation velocity, left atrium/aorta ratio, right and left ventricular Tei indexes, early diastolic transmitral flow wave/mitral annulus velocity ratio, and plasma atrial natriuretic peptide concentration decreased significantly after therapy. Diastolic blood pressure, stroke volume, cardiac output, and left ventricular fractional shortening increased significantly after therapy. These results indicate that low-dose imatinib therapy was effective for heart failure in dogs with PAH.

Effet thérapeutique de faibles doses d'imatinib sur l'hypertension artérielle pulmonaire chez les chiens. Cette étude pilote visait à déterminer l'efficacité d'une thérapie à l'aide de faibles doses d'imatinib pour les perturbations hémodynamiques incluant l'hypertension artérielle pulmonaire (HAP) et les manifestations cliniques causées par une insuffisance cardiaque chronique chez les chiens. On a administré le mésylate d'imatinib oralement, 3 mg/kg de poids corporel, q24h, pendant 30 jours, à six chiens atteints de HAP appartenant à des clients. Un examen physique, des tests sanguins biochimiques, une radiographie et une échographie par Doppler ont été réalisés avant l'administration d'imatinib, puis de nouveau 30 jours après l'administration. Les cotes cliniques ont été significativement réduites après le traitement à l'imatinib. La pression artérielle pulmonaire systolique, la fréquence cardiaque, la vélocité de régurgitation tricuspidienne maximale, le rapport oreillette gauche/aorte, les index Tei ventriculaires gauche et droit, le rapport de vélocité diastolique précoce du débit transmitral/annulus mitral et la concentration de peptides natriurétiques du plasma atrial ont baissé significativement après la thérapie. La pression artérielle diastolique, le volume d'éjection systolique, le débit cardiaque et le raccourcissement fractionnel ventriculaire gauche ont augmenté significativement après la thérapie. Ces résultats indiquent que le traitement à faibles doses d'imatinib a été efficace pour l'insuffisance cardiaque chez les chiens atteints de HAP.(Traduit par Isabelle Vallières).

A randomized clinical trial on effects of alfaxalone combined with medetomidine and midazolam in preventing stress-related neurohormonal and metabolic responses of isoflurane-anesthetized cats undergoing surgery.

OBJECTIVE: To evaluate the effects of IM and IV administration of alfaxalone alone and in combination with medetomidine, midazolam, or both on key stress-related neurohormonal and metabolic changes in isoflurane-anesthetized cats undergoing ovariohysterectomy or castration. ANIMALS: 72 client-owned mixed-breed cats undergoing ovariohysterectomy or castration between October 4, 2018, and January 10, 2020. PROCEDURES: For each type of surgery, cats were assigned to 1 of 6 premedication protocols groups, with 6 cats/group: physiologic saline (0.9% NaCl) solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IV); physiologic saline solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IM); medetomidine (50 µg/kg, IM) and alfaxalone (5 mg/kg, IV); medetomidine (50 µg/kg, IM) and alfaxalone (5 mg/kg, IM); midazolam (0.5 mg/kg, IM), medetomidine (50 µg/kg, IM), and alfaxalone (5 mg/kg, IV); or midazolam (0.5 mg/kg, IM), medetomidine (50 µg/kg, IM), and alfaxalone (5 mg/kg, IM). Venous blood was taken before pretreatment, pre- and postoperatively during anesthesia with isoflurane and oxygen, and during early and complete recovery. RESULTS: Compared with baseline concentrations, plasma adrenaline and noradrenaline concentrations decreased during anesthesia in cats premedicated with alfaxalone alone and in combination with medetomidine. The combination of medetomidine, midazolam, and alfaxalone prevented an excessive increase in catecholamines during anesthesia and surgery in cats. Postoperative plasma cortisol concentration after ovariohysterectomy was lower for cats premedicated with the combination of medetomidine and alfaxalone or the combination of medetomidine, midazolam, and alfaxalone, compared with cats premedicated with alfaxalone alone. Cats treated with combinations that included medetomidine and midazolam had hyperglycemia during anesthesia. Cats treated with medetomidine or medetomidine and midazolam in combination with alfaxalone, compared with alfaxalone alone, had lower concentrations of nonesterified fatty acids during anesthesia. Behavioral recovery scores were lower (better) for cats that received medetomidine in addition to alfaxalone, compared with alfaxalone alone. CLINICAL RELEVANCE: Results indicated that pretreatments with medetomidine and alfaxalone or with medetomidine, midazolam, and alfaxalone were useful for preventing stress-related hormonal and metabolic responses, other than hyperglycemia, during isoflurane anesthesia and surgery in cats.

Reversal effects of atipamezole, flumazenil, and 4-aminopyridine on bradycardia and increases in blood pressures induced by medetomidine, midazolam, and ketamine in isoflurane-anesthetized cats.

OBJECTIVE: To investigate the effects of a fixed dose of atipamezole (AT), flumazenil (FL), and 4-aminopyridine (AP), both alone and in combination, on changes in arterial blood pressure and heart rate induced by medetomidine (ME), midazolam (MI), and ketamine (KE) under isoflurane anesthesia with controlled ventilation in healthy cats. DESIGN: Prospective experimental study. SETTING: University animal research facility. ANIMALS: Healthy adult mixed-breed cats were used for 8 investigation groups (6 cats per group), with ≥2 weeks between interventions. INTERVENTIONS: Cats were anesthetized with an end-tidal isoflurane concentration of 2% under controlled ventilation. A catheter was inserted into the right or left femoral artery for arterial pressure monitoring and blood gas sampling, and ECG electrodes were placed. Upon completed preparations, cats were administered a mixture of ME (0.05 mg/kg) and MI (0.5 mg/kg), followed 10 minutes later by intramuscular KE (10 mg/kg). Twenty minutes after KE injection, the cats received IV injection with either a physiological saline solution at 0.1 mL/kg (control), or 1 of 7 variations of experimental drugs, alone or in combination: AT (0.2 mg/kg), FL (0.1 mg/kg), AP (0.5 mg/kg), AT+FL, FL+AP, AT+AP, and AT+FL+AP. Arterial blood pressure and heart rate were continuously measured over 120 minutes after administration of potential antagonists. MEASUREMENTS AND MAIN RESULTS: ME+MI+KE induced an increase in blood pressure and bradycardia. Potential antagonists alone or in combination did not significantly alter the bradycardia. FL, AP alone, and FL+AP did not significantly alter the changes in blood pressures induced by ME+MI+KE. Meanwhile, administration of AT alone or in combination reversed the increase in blood pressure induced by ME+MI+KE but transiently caused excessive hypotension. CONCLUSION: These results revealed that AT alone or in combination is effective for antagonizing hypertension induced by ME+MI+KE; however, attention should be paid to temporary hypotension in cats anesthetized with isoflurane.

A sero-survey of subtype H3 influenza A virus infection in dogs and cats in Japan.

A sero-epidemiological survey of human and equine H3 influenza A virus infections in dogs and cats using the hemagglutination inhibition (HI) and neuraminidase inhibition (NI) tests was conducted. Serum samples were collected from 582 dogs and 237 cats in Japan during the periods 2002-2008 and 1997-2008, respectively. Although no HI antibodies against equine H3 virus were detected, 9 (3.8%) from cats and 12 (2.1%) from dogs were HI-positive against human H3 virus. Only one serum each from dogs and cats was NI-positive against N2 virus. These findings suggest that although equine H3 influenza virus infections have not been prevalent in companion animals, human H3N2 influenza A virus infections have occurred in dogs and cats in recent years in Japan.

Effect of Pravastatin as an Adjunctive Therapeutic for Mitral Insufficiency with Hyperlipidemia in a Dog.

Pravastatin (PS) has been found to increase left ventricle (LV) expansion capacity and decrease LV constriction and left atrial pressure in healthy dogs. To date, there are no available reports on the effects of PS in dogs with hypercholesterolemia with chronic heart failure (CHF). This case report demonstrates a successful long-term treatment plan using PS in a dog suffering from mitral insufficiency with hyperlipidemia. A 12-year-old, castrated male Chihuahua dog had mitral insufficiency with hyperlipidemia. The dog presented with symptoms of chronic coughing. PS was orally administered (1 mg/kg, SID) in addition to general treatment for mitral insufficiency. The follow-up period was 375 days. PS administration decreased the heart rate (HR), vertebral heart size (VHS), and N-terminal probrain natriuretic peptide (NT-proBNP) concentration of the dog. In addition, PS administration also improved chronic cardiac failure induced by mitral insufficiency and hyperlipidemia. This report suggests that PS can be useful as an adjunctive therapeutic for dogs with hypercholesterolemia with mitral insufficiency.

Effects of pretreatment with medetomidine, midazolam, ketamine, and their combinations on stress-related hormonal and metabolic responses in isoflurane-anesthetized cats undergoing surgery.

OBJECTIVE: The purpose of this study was to compare the effects of pretreatment with medetomidine (Me), midazolam (Mi), and ketamine (Ke) on stress-related neurohormonal and metabolic responses in isoflurane-anesthetized cats undergoing ovariohysterectomy and castration. MATERIALS AND METHODS: We prospectively recruited 112 client-owned healthy mixed-breed cats. In both surgeries, we divided the cats into seven groups (eight cats per group): non-treatment (control), Me (50 µg/kg), Mi (0.5 mg/kg), Ke (5 mg/kg), Me + Mi, Me + Ke and Me + Mi + Ke administered intramuscularly. After pretreatments, we maintained anesthesia with isoflurane and oxygen. Venous blood was taken before pretreatment, pre- and post-operatively during anesthesia, and at early- and complete-recovery. RESULTS: Both plasma adrenaline and noradrenaline were reduced during anesthesia in all groups. Plasma cortisol increased during anesthesia and at early recovery in non-Me-treated groups, whereas it decreased in Me-treated groups in both surgeries. Plasma insulin and non-esterified fatty acid (NEFA) decreased, and glucose increased during anesthesia in all groups, but hyperglycemia and decrease in NEFA were greater in Me-treated groups. CONCLUSIONS: In isoflurane-anesthetized cats undergoing surgeries, premedication with Me alone and in combination is useful for reducing the perioperative stress-related increase in cortisol and catecholamines except for hyperglycemia.

Cardiovascular and renal effects of constant rate infusions of remifentanil, dexmedetomidine and their combination in dogs anesthetized with sevoflurane.

We evaluated changes in cardiovascular and renal functions as well as arginine vasopressin (AVP) secretion, with remifentanil and dexmedetomidine administration alone or in combination in sevoflurane-anesthetized dogs. Six healthy adult Beagle dogs received one of the following four treatments in a randomized crossover study: saline (C), remifentanil alone at successively increasing doses (R; 0.15, 0.60, and 2.40 µg/kg/min), dexmedetomidine alone (D; 0.5 µg/kg intravenously for initial 10 min followed by a constant rate infusion at 0.5 µg/kg/hr), and a combination of remifentanil and dexmedetomidine at the above-mentioned doses (RD). Sevoflurane doses were adjusted to 1.5 times of minimum alveolar concentration (MAC) equivalent according to MAC-sparing effects with remifentanil and dexmedetomidine as previously reported. Cardiovascular measurements, renal function data, and plasma AVP concentrations were determined before and every 60 min until 180 min after drug administration as per each treatment. In the R, D and RD, heart rate significantly decreased and mean arterial pressure significantly increased from baseline or with C. Cardiac index significantly decreased and systemic vascular resistance index increased with D and RD. Oxygen extraction ratio, renal blood flow, and glomerular filtration rate were not affected. The plasma AVP concentrations significantly decreased in D and RD, but increased in R. Only in D, the natriuresis was elicited. The combination of remifentanil and dexmedetomidine in sevoflurane-anesthetized dogs was acceptable in terms of the hemodynamics, oxygenation, and renal function. Remifentanil may interfere with dexmedetomidine-induced diuresis and inhibition of AVP secretion.

Mydriasis associated with local dysfunction of parasympathetic nerves in two dogs.

In clinical practice, photophobia resulting from persistent mydriasis may be associated with dysfunction of ocular parasympathetic nerves or primary iris lesions. We encountered a 5-year-old Miniature Dachshund and a 7-year-old Shih Tzu with mydriasis, abnormal pupillary light reflexes, and photophobia. Except for sustained mydriasis and photophobia, no abnormalities were detected on general physical examination or ocular examination of either dog. We performed pharmacological examinations using 0.1% and 2% pilocarpine to evaluate and diagnose parasympathetic denervation of the affected pupillary sphincter muscles. On the basis of the results, we diagnosed a pupillary abnormality due to parasympathetic dysfunction and not to overt primary iris lesions. The test revealed that neuroanatomic localization of the lesion was postciliary ganglionic in the first dog.

Effects of imidazoline and nonimidazoline α-adrenoceptor agonists and antagonists, including xylazine, medetomidine, dexmedetomidine, yohimbine, and atipamezole, on aggregation of feline platelets.

OBJECTIVE: To examine the effects of imidazoline and nonimidazoline α-adrenergic agents on aggregation of feline platelets. SAMPLE: Blood samples from 12 healthy adult cats. PROCEDURES: In 7 experiments, the effects of 23 imidazoline and nonimidazoline α-adrenoceptor agonists or antagonists on aggregation and antiaggregation of feline platelets were determined via a turbidimetric method. Collagen and ADP were used to initiate aggregation. RESULTS: Platelet aggregation was not induced by α-adrenoceptor agonists alone. Adrenaline and noradrenaline induced a dose-dependent potentiation of ADP- or collagen-induced aggregation. Oxymetazoline and xylometazoline also induced a small potentiation of ADP-stimulated aggregation, but other α-adrenoceptor agonists did not induce potentiation. The α2-adrenoceptor antagonists and certain imidazoline α-adrenergic agents including phentolamine, yohimbine, atipamezole, clonidine, medetomidine, and dexmedetomidine inhibited adrenaline-potentiated aggregation induced by ADP or collagen in a dose-dependent manner. The imidazoline compound antazoline inhibited adrenaline-potentiated aggregation in a dose-dependent manner. Conversely, α1-adrenoceptor antagonists and nonimidazoline α-adrenergic agents including xylazine and prazosin were ineffective or less effective for inhibiting adrenaline-potentiated aggregation. Moxonidine also was ineffective for inhibiting adrenaline-potentiated aggregation induced by collagen. Medetomidine and xylazine did not reverse the inhibitory effect of atipamezole and yohimbine on adrenaline-potentiated aggregation. CONCLUSIONS AND CLINICAL RELEVANCE: Adrenaline-potentiated aggregation of feline platelets may be mediated by α2-adrenoceptors, whereas imidazoline agents may inhibit in vitro platelet aggregation via imidazoline receptors. Imidazoline α-adrenergic agents may have clinical use for conditions in which there is platelet reactivity to adrenaline. Xylazine, medetomidine, and dexmedetomidine may be used clinically in cats with minimal concerns for adverse effects on platelet function.

Effects of Eplerenone on Blood Pressure and Echocardiographic and Serum Biochemical Variables in Five Healthy Dogs: A Pilot Study.

Eplerenone (EP), an aldosterone antagonist, is reported to produce renal and cardiac protective effects in noncanine species. However, there are no detailed reports available on cardiovascular effects of EP in dogs. This study aimed to determine effect of EP on echocardiographic parameters, blood pressures, and biochemical variables in healthy dogs. Five healthy Beagle dogs were randomly divided and repeatedly used in each of 3 dose groups, receiving 2.5, 5, or 10 mg/kg BW EP orally q24 h for 4 wks. Serum biochemical test, blood pressure, and Doppler echocardiography measurements were performed before EP administration and at 1, 2, and 4 weeks after EP administration. Treatment with EP reduced mean blood pressure in a dose-dependent manner and significantly (but in a dose-independent manner) decreased left atrium/aorta ratio, early diastolic transmitral flow, early diastolic transmitral flow/late diastolic transmitral flow, peak velocity of early diastolic transmitral flow/peak velocity of early diastolic mitral annular motion, left ventricle and right ventricle Tei indices, stroke volume, cardiac output, and mid systole myocardial velocity gradient 1 to 4 weeks after administration. Deceleration time of early diastolic transmitral flow significantly increased after EP administration. No significant changes were observed in serum biochemical variables. The results indicated that EP might reduce preload, thereby decreasing left atrial size. In addition, reduction of left ventricular stiffness may have theoretically taken place but this could not be tested using the present study design. It is suggested that EP administration within the dose range used in this study is safe for administration to healthy dogs. Further studies are needed to explore both safety and efficacy, as well as to seek a recommended dose range of EP treatment in client-owned dogs with heart disease.

Antagonistic effects of atipamezole and yohimbine on xylazine-induced diuresis in healthy dogs.

The aim of this study was to investigate and compare the antagonistic effects of atipamezole and yohimbine on xylazine-induced diuresis in healthy dogs. Five healthy male beagles were assigned to each of the 8 treatment groups in a randomized design at 1-week intervals in the same dog. One group was not medicated. The dogs in the other groups received 2 mg/kg xylazine intramuscularly (IM) and a treatment of saline (control), 50, 100 or 300 microg/kg of each atipamezole or yohimbine IM 0.5 hr later. Urine and blood samples were collected 11 times over the course of 24 hr. Urine volume, pH, specific gravity and creatinine values; osmolality, electrolyte and arginine vasopressin (AVP) values in both urine and plasma; and plasma atrial natriuretic peptide (ANP) concentration were measured. Both atipamezole and yohimbine antagonized xylazine-induced diuresis. The reversal effect of yohimbine was more potent, but not dose-dependent at the tested doses, in contrast with atipamezole. Both atipamezole and yohimbine exhibited similar potency in reversing the decreases in urine specific gravity, osmolality, creatinine, sodium and chloride concentrations and the increase in the plasma potassium concentration induced by xylazine. Both also inhibited xylazine-induced diuresis without significantly altering the hormonal profile in the dogs. A higher dose of atipamezole tended to increase the plasma ANP concentration. This may not be due only to actions mediated by alpha(2)-adrenoceptors. Both drugs can be used as antagonistic agents against xylazine-induced diuresis in healthy dogs.

A case of persistent Müllerian duct syndrome with sertoli cell tumor and hydrometra in a dog.

A 10-year-old Miniature Schnauzer with bilateral cryptorchidism and male external genitalia was referred with a history of abdominal enlargement. Upon exploratory laparotomy, two tumors and a connecting structure similar to fluid-filled uterus were recognized. After cytological and bacterial examinations of the fluid and histological examination, this dog was diagnosed with bilateral Sertoli cell tumor with hydrometra. The karyotype of this dog was 78, XY and the sry gene was detected positive by PCR. We diagnosed this dog as a case of persistent Müllerian duct syndrome (PMDS), which is male pseudohermaphroditism. This is the first report regarding the incidence of PMDS in Miniature Schnauzers in Japan, and it suggests the involvement of a gene carrier.

Differential diagnosis of hepatic tumor-like lesions in dog by using dynamic CT scanning.

Dynamic liver CT scanning is used to observe the hemodynamics of hepatic tumor-like lesions by taking images sequentially after administration of contrast media. In this study in dogs, we compared the hemodynamic patterns of hepatocellular carcinoma (HCC), one of the malignant tumors, and nodular hyperplasia (NH), a benign tumor that is more common in older dogs. Thirty-six dogs with HCC and 40 dogs with NH, which were histopathologically diagnosed at Taniura Animal Hospital, were used as subjects. Dynamic CT scanning was performed and the data of each scanning phase were collected. Dilated blood vessels, septum formation, and capsule formation were noted in the tumors from 25, 17, and 25 animals with HCC, respectively. In the arterial phase, high density and low contrast were noted in 8 and 23 dogs, respectively. Low density was noted in 34 dogs in the equilibrium phase. In contrast, no dilated blood vessels, septum formation, or capsule formation was noted in the dogs with NH. High density, low contrast, and low density were noted in 8, 9, and 23 dogs, respectively, in the arterial phase. In the equilibrium phase, the enhancement level was equal to the surrounding liver tissues in all animals. The CT values of HCC in the plain, the arterial phase, portal venous phase and equilibrium phase after the administration of contrast media, were significantly (p < 0.05 to 0.001) lower than those of the surrounding liver tissues. In the arterial phase, the percent incidence of low density was significantly less in HCC than NH, while that of low contrast was significantly greater (p < 0.001) in HCC than NH. Dynamic CT scanning identified differences between the hemodynamics and internal structures of HCC and NH in dogs. Dynamic liver CT scanning can therefore be considered a useful technique in the differential diagnosis of hepatic tumor-like lesions in dogs.

Effects of masitinib compared with tadalafil for the treatment of monocrotaline-induced pulmonary arterial hypertension in rats.

Targeting vascular remodeling in pulmonary arterial hypertension (PAH) remains a challenge given the lack of potent anti-remodeling abilities of the therapeutic drugs. Although sildenafil has been shown to ameliorate cardiopulmonary remodeling, that of tadalafil is questionable. Masitinib, a tyrosine kinase inhibitor appears safer and more potent than imatinib for treatment of malignancies, but its efficacy on PAH is unknown. Therefore, we investigated the anti-remodeling properties of masitinib (5, 15, 50 mg/kg) and tadalafil (5, 10 mg/kg) using a monocrotaline-induced rat model of PAH. The 14-day treatment with masitinib (15, 50 mg/kg) resulted in significantly decreased right ventricular (RV) systolic pressure (RVSP) and hypertrophy (RVH), and pulmonary vascular remodeling, whereas tadalafil showed weaker anti-remodeling properties. Besides, masitinib significantly blocked the mitogen-associated protein kinase (MAPK) pathway, and reduced phosphodiesterase (PDE)-5 mRNA expression in the lungs. By contrast, tadalafil did not significantly inhibit the MAPK pathway. Further, the 28-day treatment extension revealed that masitinib-treated rats (15 mg/kg) had significantly lower RVSP, and higher heart rate and serum cyclic guanosine monophosphate (cGMP) level, whereas those treated with tadalafil (10 mg/kg) showed insignificantly lower RVSP and higher cGMP level. Moreover, the RVH indices, heart rates, body weight gains, and survival rates of rats in both groups were comparable. Collectively, these results suggest that the treatment with a low-dose masitinib was non-inferior than tadalafil. A lower dose of masitinib may represent a novel approach to target both the cardiopulmonary remodeling and the dysregulated vasoconstriction in PAH.

Assessment of urinary pharmacokinetic and pharmacodynamic profiles of faropenem against extended-spectrum ß-lactamase-producing Escherichia coli with canine ex vivo modelling: a pilot study.

This study was carried out to investigate the urinary pharmacokinetics and pharmacodynamics of faropenem administered orally at 5 mg kg-1 in six healthy dogs to assess the efficacy of the drug for canine urinary tract infections (UTIs) with extended-spectrum ß-lactamase (ESBL)-producing bacteria. Six strains of ESBL-producing Escherichia coli (ESBL-EC) with the following faropenem minimum inhibitory concentrations (MICs) were used: 1 µg ml-1 (n=2), 2 µg ml-1 (n=2), 4 µg ml-1 (n=1) and 16 µg ml-1 (n=1). Urine samples were obtained every 4 h for the first 12 h after administration to measure urinary drug concentration and urinary bactericidal titres (UBTs). Both the urine concentration of faropenem and the UBTs for all tested strains peaked at 0-4 h after administration, and decreased markedly at 8-12 h. The mean urinary concentration of faropenem at 8-12 h (23±5.2 µg ml-1) exceeded the MIC of 1 µg ml-1 by fourfold, which is required to inhibit the growth of 90  % of ESBL-EC. These findings indicate that faropenem administered twice daily at a dose of 5 mg kg-1 is acceptable for the treatment of most dogs with ESBL-EC-related UTIs.

In vitro evaluation of the growth inhibitory activities of 15 drugs against Babesia gibsoni (Aomori strain).

The in vitro growth inhibitory activities of 15 drugs against Babesia gibsoni were evaluated following establishment of a continuous culture isolate (Aomori isolate). The culture was successfully continued in an RPMI-1640 medium supplemented with 20% normal canine serum or fetal bovine serum in a humidified atmosphere containing 5% CO2 and 5% O2 at 37 degrees C. We used this isolate to evaluate the growth inhibitory effect of naphthoquinone (atovaquone), aromatic diamidine (diminazene and pentamidine), artemisinin compounds (artesunate and dihydroartemisinin), an iron chelator (deferoxamine), quinoline-containing compounds (quinine and chloroquine), macrolide antibiotics (azithromycin), lyncomycin antibiotics (clindamycin), tetracycline antibiotics (doxycycline and minocycline), imidazole antifungals (clotrimazole and ketoconazole), and a nitroimidazole antiprotozoal (metronidazole). Atovaquone and aromatic diamidine showed the highest activity; they were followed by artesunate compounds with nanomole levels of IC50. Metronidazole did not exhibit activity against the parasite. Other drugs exhibited intermediate in vitro activities with micromole levels of IC50. This is the first report to screen drug activities against B. gibsoni in vitro. The results of our study may support further in vitro drug evaluation for the establishment of therapeutic strategies against canine B. gibsoni infections.