A new bipolar precordial electrocardiographic lead configuration for specific evaluation of atrial depolarization in healthy dogs.

OBJECTIVE: The Lewis lead is an EGC configuration used to detect atrial activity and its relationship with ventricular activity. However, no equivalent configuration has been proposed in veterinary medicine. Therefore, this study explored new bipolar lead configurations to evaluate atrial depolarization and investigated their characteristics by comparing them with conventional leads. The authors hypothesized that a lead with a high absolute value of the P wave (|P|) and a high ratio of the P wave to the QRS complex (|P|/|QRS|) might be an appropriate configuration. ANIMALS: 6 laboratory Beagles were used. PROCEDURES: Electrocardiograms were recorded using bipolar limb leads (I, II, III, aVL, aVF, and aVR) and unipolar precordial leads (C2, C3, C4, C5, C6, M1, M2, M5, M6, 1st-R, CV6LL, and V10) in the standing position. The new bipolar leads were attached in the following configuration: the negative electrode was attached to M6, and the positive electrode was sequentially applied to M1 and M2. The leads were named M6M1 and M6M2. RESULTS: The waveforms obtained using the new bipolar leads M6M1 and M6M2 showed significantly higher |P|/|QRS| and |P| values than those obtained using conventional limb leads and precordial leads. CLINICAL RELEVANCE: The new leads achieved a specific enhancement of atrial activity conducted at a reduced ventricular amplitude and increased atrial amplitude, similar to the Lewis lead in human medicine. These findings suggest that M6M1 and M6M2 could be supplemental lead configurations to identify P waves without amplifying the QRS waves compared to conventional methods.

Involvement of neurokinin-1 receptors in the autonomic nervous system in colorectal distension-induced cardiovascular suppression in rats.

Situational syncope, which includes rectally mediated reflexes, is defined as syncope induced by a specific situation. Its pathogenesis generally involves disorders of the autonomic nervous system. However, the mechanisms and preventive strategies are not yet well understood. Therefore, we hypothesized that a tachykinin neurokinin-1 receptor might be involved in the autonomic nervous system, and that a neurokinin-1 receptor antagonist could mitigate reflex syncope. This study used a rat model in which the reflex was induced by afferent vagal stimulation with colorectal distension (CRD). In the study, the rats were divided into three groups: non-CRD, CRD, and CRD with a neurokinin-1 receptor antagonist. First, we examined the effect of fosaprepitant, a neurokinin-1 receptor antagonist, on the circulatory response in this model. We then determined the brain regions that showed increased numbers of c-Fos immunoreactive cells in the respective groups. Our results suggest that the colorectal distension procedure reduced blood pressure and that fosaprepitant lowered this response. In addition, the number of c-Fos immunoreactive cells was increased in the caudal ventrolateral medullary region with colorectal distension, and this number was decreased by the administration of fosaprepitant. In conclusion, fosaprepitant might be involved in the vagal reflex pathway and potentially suppress the circulatory response to colorectal distension.

Somatosensory evoked potentials of the tibial nerve during the surgical decompression of thoracolumbar intervertebral disk herniation in dogs.

This study aimed to identify the impact on spinal cord integrity and determine the electrophysiological safety level during surgery for thoracolumbar intervertebral disk herniation in dogs. A total of 52 dogs diagnosed with thoracolumbar intervertebral disk herniation were enrolled. The tibial nerve somatosensory evoked potential elicited on the scalp by stimulation of the tibial nerve was recorded before and during hemilaminectomy. Both the amplitude and latency of the somatosensory evoked potential were periodically registered, and the percentage changes from the pre-operative control values (amplitude rate and latency rate) were calculated. When the multifidus muscles were retracted after removal from the spinous processes and vertebrae, the somatosensory evoked potential amplitude rate decreased in all dogs, while the latency rate increased in 33 dogs examined. The amplitude rate remained unchanged during the halting procedure, loosening retraction, and hemilaminectomy. After removing the disc material from the spinal canal, the amplitude rate was increased. The somatosensory evoked potential latency increased when the multifidus muscles were retracted and shortened after multifidus muscles closure in four cases. The outcome of all cases showed improvement in clinical signs 7 days after operation. Spinal cord conduction is impaired by retraction of the multifidus muscles and improved by removal of disk materials. Maintaining intraoperative SEP amplitudes above 50% of control may help avoid additional spinal cord injury during surgery. Since we have no case that worsened after the surgery, however, further studies are necessary to confirm this proposal.

Repeated-Dose Pharmacodynamics of Pimobendan in Healthy Cats.

The aims of this study were to investigate the effects of repeated and multiple-dose pimobendan on cardiac systolic function and the correlations between changes in cardiac systolic function and plasma concentrations of pimobendan and O-desmethylpimobendan (ODMP). Five clinically healthy cats were subjected to four different medication protocols for 14 days, with a washout period of at least 1 month between each protocol. The protocols were pimobendan 0.5 mg/kg q12h (high dosage [HD] group); pimobendan 0.25 mg/kg q12h (standard dosage [SD] group); pimobendan 0.125 mg/kg q12h (low dosage group); and Biofermin R, one tablet q12h (placebo group). Echocardiography and measurement of plasma concentrations of pimobendan and ODMP were performed prior to medication administration (baseline) and 20, 40, 60, 120, 240, 360, and 480 min after administration, and the correlation between the changes in cardiac systolic function and plasma concentration of pimobendan, ODMP, or the sum of both were examined. The cardiac systolic function increased in the HD and SD groups, and there were significant correlations between the lateral peak systolic myocardial velocity (S') changes and plasma pimobendan, plasma ODMP, and the sum of both. Repeated doses of pimobendan in healthy cats increased cardiac systolic function, and there were significant correlations between cardiac function and plasma concentrations of pimobendan and ODMP. The results of this study highlight the effectiveness of a higher dose of pimobendan.

Recurrence analysis of intraoperative acridine orange-photodynamic therapy for dogs with intranasal tumors.

Intraoperative acridine orange-photodynamic therapy (AO-PDT) and cribriform plate irradiation are used to treat canine intranasal tumors. The purpose of this study was to evaluate the effects of AO-PDT on intranasal tumors and the recurrence rate of tumors after this treatment. Treatments with AO-PDT were performed on 38 dogs through a narrow window of the dorsal nasal cavity. The median progression-free interval was 12 mo and recurrence was detected in 21 dogs. Based on computed tomography, recurrence in 16 dogs was biased to the following areas: lateral (n = 10), medial (n = 2), ventral (n = 0), rostral (n = 0), and caudal (n = 8). Side effects were mild and included subcutaneous emphysema and rhinitis. The median survival time was 24 mo. Although AO-PDT with cribriform irradiation is an effective treatment for intranasal tumors, AO-PDT techniques should be improved to treat the nasal cavity more uniformly and thoroughly.

Analyse de récurrence de la thérapie photodynamique peropératoire à l'acridine orange pour des chiens atteints de tumeurs intranasales. La thérapie photodynamique peropératoire à l'acridine orange (AO-PDT) et l'irradiation de la plaque cribriforme sont utilisées pour traiter les tumeurs intranasales canines. Le but de cette étude était d'évaluer les effets de l'AO-PDT sur les tumeurs intranasales et le taux de récidive des tumeurs après ce traitement. Des traitements avec AO-PDT ont été effectués sur 38 chiens à travers une fenêtre étroite de la cavité nasale dorsale. L'intervalle médian sans progression était de 12 mois et une récidive a été détectée chez 21 chiens. Sur la base de la tomodensitométrie, la récidive chez 16 chiens était biaisée dans les zones suivantes : latérale (n = 10), médiale (n = 2), ventrale (n = 0), rostrale (n = 0) et caudale (n = 8). Les effets secondaires étaient légers et comprenaient l'emphysème sous-cutané et la rhinite. La durée médiane de survie était de 24 mois. Bien que l'AO-PDT avec irradiation de la plaque cribriforme soit un traitement efficace pour les tumeurs intranasales, les techniques d'AO-PDT devraient être améliorées pour traiter la cavité nasale de manière plus uniforme et plus complète.(Traduit par Dr Serge Messier).

Safety of alternate-day treatment with TS-1TM (tegafur/gimeracil/oteracil) in tumor-bearing dogs: a pilot study.

Tegafur is a prodrug of fluoropyrimidine 5-fluorouracil (5-FU), while TS-1TM is an oral fixed-dose combination of three active drugs, tegafur, gimeracil, and oteracil. This pilot study evaluated the safety of tegafur/gimeracil/oteracil in the treatment of cancers in dogs. Tegafur/gimeracil/oteracil was administered orally at a mean dose of 1.1 mg/kg twice daily on alternate days, Monday-Wednesday-Friday, every week to 11 dogs with tumors. Partial response and stable disease were observed in one dog each, whereas six exhibited progressive disease. Three dogs were not assessed. Adverse events, the most serious being grade 2, were noted in seven dogs. Adverse events were acceptable, and the drug was effective in some dogs. Therefore, tegafur/gimeracil/oteracil may be useful for treating malignant solid tumors in canines.

Displacement of center of mass in dogs in response to foot sensory stimulation.

OBJECTIVE: Evaluate center of mass (CoM) displacement values during four-limb and three-limb standing with limb suspension in dogs before and after applying sensory stimulation to a forelimb or hindlimb. STUDY DESIGN: Experimental study. ANIMALS: Six clinically normal beagles. METHODS: A four force-plate apparatus was built to assess static weight distribution. Dogs stood on the device with one limb in contact with each force plate. We created a plastic device to induce sensory stimulation so that lameness could not be detected visually when stimulating the paw. Experimenters confirmed the degree of lameness by walking before and after measurement. Body-weight shifts were induced via suspension of each limb and transient sensory stimulation to the right forelimb or left hindlimb. CoMs of five postures were compared, with and without transient sensory stimulation. RESULTS: The four-limb CoM was located cranial to the center of the X- and Y-axis coordinates (X: -0.82 ± 9.12, Y: 61.00 ± 5.82). During three-limb standing with suspension of either forelimb, CoM shifted backward toward the contralateral side compared to four-limb standing. During hindlimb suspension, CoM shifted to the contralateral side. With right forelimb sensory stimulation, there were large CoM changes for both four-limb and three-limb standing (X: -34.53 ± 9.09, Y: 52.21 ± 6.88). CoM changes were small with left hindlimb sensory stimulation (X: 6.47 ± 13.86, Y: 69.41 ± 5.55). CONCLUSION: CoMs during four-limb and three-limb standing were influenced by sensory stimulation of a forelimb and, to a lesser extent, of a hindlimb. CLINICAL SIGNIFICANCE: Static evaluation of CoM may aid clinicians in the diagnosis and recovery of forelimb lameness.

Serum concentration and safety of intravenous drip versus subcutaneous administration of carboplatin in dogs.

Carboplatin is used to treat certain cancers in dogs and cats and is routinely administered via intravenous drip (IVD). Subcutaneous (SC) administration has also been described. However, the toxicity, serum concentrations, and area under blood concentration-time curves (AUCs) of SC carboplatin are unknown. This study aimed to compare serum carboplatin concentrations in dogs after SC and IVD and to monitor any adverse events. In this crossover study, five dogs received SC or IV carboplatin (300 mg/m2). After a minimum of 3 weeks, each dog received the other treatment. No gross skin toxicity or abnormal clinical signs were observed in any of the dogs. Blood test abnormalities were detected in most dogs. Decreased neutrophil and platelet counts, and increased C-reactive protein (CRP) levels were found. There was no significant difference in the neutropenia, thrombocytopenia, and CRP scores between the groups. Systemic toxicities of SC carboplatin were comparable to those of IVD carboplatin. The time to maximum carboplatin concentration after SC was longer than that after IVD (P<0.001). SC carboplatin remained in the serum longer than IVD carboplatin (P=0.008). The AUC of SC was less than that of IVD (P=0.002). The AUC and time taken to reach the maximum concentration of SC carboplatin were lower than those of IVD carboplatin. This study suggests that SC carboplatin may be an efficacious option for the treatment of tumors in dogs, particularly where IVD administration is challenging.

F-wave parameters for the tibial nerve in Miniature Dachshunds with and without naturally acquired thoracolumbar intervertebral disk herniation.

OBJECTIVE: To determine values of F-wave parameters for the tibial nerve in clinically normal Miniature Dachshunds and those with thoracolumbar intervertebral disk herniation (IVDH). ANIMALS: 53 Miniature Dachshunds (10 clinically normal and 43 with various clinical grades of thoracolumbar IVDH). PROCEDURES: F-waves were elicited in the interosseous muscles of 1 hind limb in each dog by stimulation of the tibial nerve. F-wave parameters were measured for 32 stimuli/dog, and mean values were calculated. Linear regression was performed to assess correlations between F-wave parameters and clinical severity of IVDH. RESULTS: For clinically normal dogs, mean ± SD values of shortest F-wave latency, mean F-wave conduction velocity, mean F-wave duration, and ratio of the mean F-wave amplitude to M response amplitude were 8.6 ± 0.6 milliseconds, 83.7 ± 6.1 m/s, 6.6 ± 1.5 milliseconds, and 9.8 ± 8.5%, respectively. F-wave persistence was 100%. Mean F-wave duration was positively correlated with clinical grade of IVDH. Linear regression yielded the following regression equation: F-wave duration (milliseconds) = 6.0 + 2.7 × IVDH grade. One dog with grade 2 IVDH had a mean F-wave duration shorter than that of all 5 dogs with grade 1 IVDH; 1 dog with grade 3 IVDH had a longer duration than that of all 10 dogs with grade 4 IVDH. CONCLUSIONS AND CLINICAL RELEVANCE: Mean F-wave duration was correlated with the severity of inhibitory motor tract dysfunction in the spinal cord of dogs. F-wave examination may be useful for objective functional evaluation of upper motor neurons in the spinal cord.

Intraoperative acridine orange photodynamic therapy and cribriform electron-beam irradiation for canine intranasal carcinomas: 14 cases.

Canine intranasal carcinomas are almost always malignant. Surgery alone often results in rapid tumor regrowth. Radiotherapy is the treatment of choice for dogs with intranasal tumors. Here, we retrospectively assessed treatment of intranasal carcinoma by marginal tumor resection followed by intraoperative acridine orange (AO) photodynamic therapy (PDT) and cribriform plate electron-beam intraoperative radiotherapy (IORT). Fourteen canine cases were assessed, 12 of which had stage I tumors, one with stage III, and one with stage IV. Recurrence was detected in 8, with a median recurrence from the time of treatment of 6 months (range: 3 to 16 months). The median progression-free survival time and overall survival time after treatment were 13 and 22 months, respectively. Adverse events were mild. Marginal tumor resection followed by intraoperative AO-PDT and cribriform plate electron-beam IORT may increase the tumor control time in dogs with marginally resectable intranasal malignant tumors beyond that incurred by surgery alone.

Thérapie photodynamique peropératoire à l'acridine orange et irradiation par faisceau électrique pour carcinome intranasal canin : 14 cas. Un carcinome intranasal canin est presque toujours malin. Une simple opération chirurgicale résulte souvent dans la rapide réapparition de la tumeur. Dans cet article, nous discutons d'un traitement d'un carcinome intranasal par résection marginale de la tumeur effectué simultanément à une thérapie photodynamique (TPD) peropératoire à l'acridine orange (AO) et une radiothérapie peropératoire (RPO) par faisceau électrique des lames criblées. L'étude a porté sur quatorze cas chez le chien dont 12 tumeurs étaient classées au stade I, une au stade III et une au stade IV. Huit des cas étaient des cas de récidive selon une moyenne de 6 mois depuis la période du traitement (plage de 3 à 16 mois). Le temps de survie moyen à l'état stabilisé et le temps de survie général après traitement étaient respectivement de 13 et 22 mois. Les incidents thérapeutiques sont moindres (cinq cas d'emphysème sous-cutané et quatre cas de rhinite). La résection marginale de la tumeur conduite simultanément avec une TPD-AO peropératoire et une RPO par faisceau électrique des lames criblées semble permettre une plus longue phase de maîtrise des tumeurs chez le chien porteur d'une tumeur intranasale maligne à résection marginales possible par rapport aux résultats obtenus par simple intervention chirurgicale.(Traduit par les auteurs).

Electroacupuncture improves neuronal function by stimulation of ascending peripheral nerve conduction in rats with spinal cord injury.

OBJECTIVE: To establish a method of transient sciatic nerve blockade and to examine the involvement of the ascending peripheral nerve pathway in the therapeutic effect of electroacupuncture at Zusanli (ST 36) in rats with spinal cord injury (SCI). METHODS: We examined the transient effect of daily lidocaine administration into the posteromedial part of the greater trochanter on sciatic nerve function using electrophysiological examination and histopathology of the sciatic nerve. Rats were divided into three groups: an SCI group (SCI without treatment), an SCI with electroacupuncture treatment (SCI-EA) group, and an SCI with nerve block and electroacupuncture (SCI-NB-EA) group (nerve block was achieved by lidocaine administration to transiently block the ascending peripheral nerve pathway). Behavioral tests and electrophysiological examinations were performed to evaluate recovery of neurological function. RESULTS: Sciatic nerve conduction was normal immediately before daily lidocaine administration. Histopathological analysis also indicated normal sciatic nerve, confirming that lidocaine nerve blockade was suitable and reversible for transiently eliminating nerve transmission. Neurological function in the SCI-EA group was superior to that in the SCI group, while no differences were found between the SCI and SCI-NB-EA groups. CONCLUSION: Electroacupuncture treatment can promote recovery of neurological function. Facilitation of nerve conduction may play an important role in this recovery.

Effects of three infusion fluids with different sodium chloride contents on steady-state serum concentrations of bromide in dogs.

Potassium bromide overdose (bromism) in the management of canine epilepsy has been known. However, a protocol to reduce bromide concentrations rapidly has not been previously established. The effects of three infusion fluids with different chloride contents on the steady-state serum concentrations of bromide in beagles were determined. After stabilization of the serum bromide concentrations, seven dogs were infused with saline (Na+ 154 mmol/L; Cl- 154 mmol/L), lactated Ringer's (Na+ 131 mmol/L; Cl- 110 mmol/L), or maintenance solutions (Na+ 35 mmol/L; Cl- 35 mmol/L) at a rate of 2 or 10 ml kg-1  hr-1 for 5 hr. Serum and urine were collected hourly, and the bromide concentrations were measured. When saline and lactated Ringer's solutions were infused at a rate of 10 ml kg-1  hr-1 for 5 hr, serum bromide concentrations were decreased by 14.24% and urine bromide concentrations by 17.63%, respectively. Of all compositions of infusion fluids, only sodium and chloride contents were associated with the decreased serum concentrations and the increased renal clearance of bromide. In summary, saline and lactated Ringer's solutions reduced serum bromide concentrations in a sodium chloride-dependent manner in dogs were found when infused at 10 ml kg-1  hr-1 for 5 hr.

Safety and efficacy of intravenous administration for tranexamic acid-induced emesis in dogs with accidental ingestion of foreign substances.

A prospective observational study was performed in canine clinical medicine to evaluate the emetic action and adverse effects of tranexamic acid. Veterinarians treated 137 dogs with a single dose of tranexamic acid (50 mg/kg, IV) after accidental ingestion of foreign substances. If needed, a second (median, 50 mg/kg; range, 20-50 mg/kg, IV) or third dose (median, 50 mg/kg; range, 25-50 mg/kg, IV) was administered. Tranexamic acid induced emesis in 116 of 137 (84.7%) dogs. Median time to onset of emesis was 116.5 sec (range, 26-370 sec), median duration of emesis was 151.5 sec (range, 30-780 sec), and median number of emesis episodes was 2 (range, 1-8). Second and third administrations of tranexamic acid induced emesis in 64.7 and 66.7% of dogs, respectively. In total, IV administration of tranexamic acid successfully induced emesis in 129 of 137 (94.2%) dogs. Adverse effects included a tonic-clonic convulsion and hemostatic disorder in two different dogs, both of which recovered after receiving medical care. Tranexamic acid induced emesis in most dogs following a single-dose. When a single dose was not sufficient, an additional dosage effectively induced emesis. Overall, adverse effects were considered low and self-limiting.

Pharmacodynamics of alacepril in healthy cats.

Objectives The aims of this study were to investigate the pharmacodynamics of alacepril and to determine the appropriate dose for clinical usage in cats. Methods Six experimental cats were used. Each cat received alacepril orally at a single dose of 1 mg/kg, 2 mg/kg and 3 mg/kg. Blood samples were collected before administration and at 2, 4, 6, 8, 12, 24, 36, 48 and 72 h after administration to measure serum angiotensin converting enzyme (ACE) activity. Systolic blood pressure was also measured at the same time point. Results Dose-dependent inhibition of ACE activity was observed. Doses of 2 mg/kg and 3 mg/kg alacepril were considered to effectively inhibit ACE activity. There were no significant differences in systolic blood pressue among groups at any time point. Conclusions and relevance Alacepril 2-3 mg/kg q24h may be an appropriate dosage for clinical use in cats.

Antibodies reacting to carbonic anhydrase isozymes (I and II) and albumin in sera from dogs.

IgGs to carbonic anhydrase isozymes (CA-I and CA-II) and albumin were identified in dog serum. IgG titers were determined in the sera of asymptomatic dogs, and in dogs with atopic dermatitis, diarrhea and/or vomiting, diabetes and/or pancreatitis, kidney disease, hepatic disease, and thyroid gland disease, using ELISA. Low titres of IgG-reactive CA-I, CA-II, BSA, and CSA were found in the sera of healthy beagles. Compared with healthy beagles, there was a significant difference in the titers of antibodies against CA-I in asymptomatic dogs, dogs with diabetes and/or pancreatitis, or thyroid gland disease, or hepatic disease. Compared with healthy beagles, there was a significant difference in the antibody titer of anti-CA-II IgG in asymptomatic dogs and in those with hepatic disease. There was a significant difference in the antibody titer of anti-BSA IgG between healthy beagles and dogs with hepatic disease.

Swing time ratio, a new parameter of gait disturbance, for the evaluation of the severity of neuropathic pain in a rat model of partial sciatic nerve ligation.

INTRODUCTION: Dynamic weight bearing tests are used to evaluate the chronic pain severity in animal models of nociceptive pain (such as osteoarthritis); however, common tests frequently fail to collect the characteristics of neuropathic pain such as allodynia, because surgical intervention which is sometimes required to establish the models causes both nociceptive and neuropathic pain. METHODS: In this study, we used rats with partial sciatic nerve ligation (PSL) as the neuropathic and chronic pain model. To assess the severity of pain by gait disturbance, we applied automatic analysis on walking function using the GAIT® system. The system employs a novel index of abnormal step cycles, the swing time ratio (STR), of laboratory animals. Data were compared to those obtained with conventional tests, including a von Frey test and a hot plate test. Finally, we analyzed recovery of walking function after single or repeated administration of pregabalin. RESULTS: By using rats with PSL, we confirmed that results obtained by the GAIT® system were comparable to those obtained by both von Frey tests and hot plate tests. Single administration of pregabalin transiently improved STR, on the other hand, repeated pregabalin treatment showed lasting STR recovery. DISCUSSION: STR is sensitive to claudication of rats with PSL, providing a new scale to evaluate neuropathic pain in addition to conventional tests. Moreover, STR analysis enables us to evaluate walking function of animal models after neuropathic injury, which is quite important to judge the effectiveness of new treatments and analgesics.

Combination of Cilostazol and L-Carnitine Improves Walking Performance in Peripheral Arterial Disease Model Rats.

Cilostazol and L-carnitine have been used as a first-line drug and supplement, respectively, in patients with peripheral arterial disease with intermittent claudication. In this study, the effect of the combination of cilostazol and L-carnitine has been investigated in rats with unilateral hindlimb ischemia. For 28 days, cilostazol and L-carnitine were administrated separately or as a combination. The distance walked before gait disturbance developed was measured using a treadmill for 5 days a week. The capillary density of the ischemic hindlimb was evaluated by immunohistochemical staining at days 7, 14, 21, and 28. Angiogenic gene expression was measured by real-time RT-PCR at days 7 and 28. The greatest increase in the distance was observed in the combination therapy group when compared to the other groups. The capillary density in the adductor muscles of rats treated with cilostazol alone and combination therapy increased at day 28. Angiopoietin-2/Angiopoietin-1 expression ratios were higher, suggesting the promotion of angiogenesis, with cilostazol alone and combination therapy at day 7. This is the first study to show functional improvement of the hind limb following combination therapy with cilostazol and L-carnitine in experimental animals. This study also revealed that cilostazol promotes angiogenesis, and L-carnitine additively contributes to functional improvement via a non-angiogenic mechanism.

Tugging force: A new objective index for evaluating acute changes in neuromuscular function in mice.

INTRODUCTION: Many agents, including muscle relaxants, influence neuromuscular function. Although in vitro and in situ measurement systems of skeletal muscular contractility have been developed and in use for years, no convenient device and parameter are available to examine the time course of the acute effects of such agents on neuromuscular function in conscious mice. METHODS: We created a two-compartment device consisting of a transparent, wide, acrylic chamber with a foot shock grid, and an attached, opaque narrow tunnel to measure neuromuscular performance. A mouse placed into the wide chamber, quickly enters the narrow tunnel. We attached a string to the tail of the mouse to measure the developed tugging force when the mouse entered the narrow tunnel. RESULTS: After administering the muscle relaxants suxamethonium, vecuronium, and pancuronium, the peak tugging force decreased maximally at 3 or 5 min after administration, and recovered within 20 min. These responses to the muscle relaxants were dose-dependent. DISCUSSION: Tugging force is an objective and reproducible parameter for examining the time course of an acute change in neuromuscular function.

Efficacy and safety of tranexamic acid as an emetic in dogs.

OBJECTIVE: To determine dose dependency of tranexamic acid-induced emesis and the time course of the antifibrinolytic potency of tranexamic acid in dogs. ANIMALS: 10 Beagles. PROCEDURES: In a dose-escalating experiment, ascending doses of tranexamic acid (10, 20, and 30 mg/kg, IV) were administered at 5-minute intervals until vomiting was observed. In a separate single-dose experiment, ascending doses of tranexamic acid (20, 30, 40, and 50 mg/kg, IV) were administered at 1-week intervals until vomiting was observed. Time to onset of vomiting and number of vomiting episodes were measured in both experiments. In a coagulation experiment, a single 50 mg/kg bolus of tranexamic acid was administered, and blood was obtained 1 hour before and 20 minutes, 3 hours, and 24 hours after administration. Antifibrinolytic potency of tranexamic acid was evaluated by use of a modified rotational thromboelastography method. RESULTS: Tranexamic acid induced vomiting in a dose-dependent manner. Vomiting frequency was ≤ 2 episodes, and vomiting concluded ≤ 250 seconds after administration. Antifibrinolytic potency of tranexamic acid was significantly higher at 20 minutes following administration, but not different by 24 hours, when compared with the potency measured before administration. No adverse effects were observed in any experiment. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of tranexamic acid induced emesis in a dose-dependent manner. The antifibrinolytic potency of tranexamic acid decreased in a time-dependent manner and was resolved ≤ 24 hours after administration. Further studies are warranted to investigate the emetic and other adverse effects of tranexamic acid in dogs of various breeds and ages.

Urinary carbonic anhydrase VI as a biomarker for kidney disease in pigs.

This study investigated whether carbonic anhydrase (CA)-VI has utility as a biomarker in swine kidney disease. Serum chemistry, histopathology, immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA) analyses were performed. In the kidney of normal healthy pigs, CA-VI was localized in the epithelial cells of the renal distal straight tubules. CA-VI levels were 16 ± 35 ng/g wet tissue and 50 ± 66 ng/mL in normal pig kidney and urine, respectively, and 136 ± 173 ng/mL in the urine of pigs with kidney disease. CA-VI urinary concentration was not correlated with urinary urea nitrogen (UUN), urinary creatinine (Cre), or urinary albumin levels in pigs with kidney disease. However, UUN and Cre levels were positively correlated in the urine of pigs with kidney disease. These data suggest that urinary CA-VI may represent a biomarker for kidney disease in pigs, particularly for disorders affecting distal straight tubules.