Respiratory reflexes in response to upper-airway administration of sevoflurane and isoflurane in anesthetized, spontaneously breathing dogs

OBJECTIVE: To evaluate the respiratory effects occurring during administration of sevoflurane or isoflurane to the upper airway in dogs. STUDY DESIGN: A prospective, randomized study. ANIMALS: Twelve healthy adult beagles (6 males, 6 females). METHODS: At least 2 weeks after undergoing permanent tracheostomy, dogs were premedicated with acepromazine-buprenorphine, and anesthesia was induced with thiopental and maintained with alpha-chloralose. The upper airway was functionally isolated so that the inhalant could be administered to the upper airway while dogs were breathing 100% O2 via the tracheostomy. Respiratory reflexes in response to the administration of sevoflurane or isoflurane at concentrations of 1.2, 1.8, and 2.4 times the minimal alveolar concentration (MAC) (administered in 100% O2 at a flow rate of 5 L/min) were recorded. Reflexes in response to administration of each anesthetic were also recorded following upper-airway administration of lidocaine. RESULTS: Respiratory reflexes elicited by upper-airway administration of each anesthetic were characterized by a dose-dependent increase in expiration time, with a resultant decrease in respiratory minute ventilation and increase in end-tidal PCO2. The magnitude of these responses was greater with isoflurane than with sevoflurane at 1.8 and 2.4 MAC. These reflexes were abolished after lidocaine nebulization into the upper airway. CONCLUSION: Isoflurane induces greater reflex inhibition of breathing than does sevoflurane when the anesthetic is inhaled into the upper airway at concentrations used for mask induction.     

Effect of age on myocardial function assessed by two-dimensional speckle-tracking echocardiography in healthy beagle dogs

ObjectivesThe objective of this study was to evaluate the effect of age on myocardial function assessed by two-dimensional speckle-tracking echocardiography (2D-STE) in healthy dogs.AnimalsThirty-two healthy Beagles were used.MethodsMyocardial function was assessed in each dog by using 2D-STE, and the results were compared between young and old dogs.ResultsThe myocardial deformations in systole, besides the apical rotation rate, were not significantly different between young and old dogs. In contrast, the early diastolic circumferential strain rate, basal rotation rate, and torsion rate were significantly lower in old dogs than in young dogs (P = 0.03, P = 0.033, and P = 0.015, respectively). Late diastolic longitudinal and radial strain rates were significantly higher in old dogs than in young dogs (P = 0.002 and P = 0.018, respectively).ConclusionsYoung and old dogs showed similar systolic myocardial deformations, but significant differences in the values of some diastolic deformation variables were found between young and old dogs, highlighting the need for using age-matched control subjects in studies of diastolic function.     

The posterior nasal nerve plays an important role on cardiopulmonary reflexes to nasal application of capsaicin, distilled water and l-menthol in anesthetized dogs

The sensory innervation of the cardiopulmonary reflexes to nasal application of capsaicin (CAPS), distilled water (DW) and l-menthol (LM) was studied in anesthetized dogs breathing through tracheostomy. A marked cardiopulmonary reflex was observed by CAPS and DW into the nasal cavity, while a prolongation of expiration was induced by LM. All these reflexes were significantly decreased by bilateral section of the posterior nasal nerve (PNN) and completely abolished by topical nasal anesthesia with lidocaine. Responses of the whole nerve activity of the PNN to these substances corresponded to the magnitude of the reflexes. These results indicate that PNN afferents play an important role on the reflex elicitation of the noxious, water and cold stimuli from the nasal cavity.     

Relationship between retinoic acid receptor alpha gene expression and growth-inhibitory effect of all-trans retinoic acid on canine tumor cells

Retinoids show antitumor effects on human acute promyelocytic leukemia and other tumors via retinoid receptors. In dogs, the role of retinoid receptors in inhibiting tumor development remains unclear. To evaluate the correlation between the degree of expression of retinoic acid receptor alpha (RARalpha) mRNA and the antiproliferative effects of all-trans retinoic acid (ATRA) treatments, expression analysis of RARalpha mRNA and cell growth inhibition assay were performed on 17 established canine tumor cell lines, including 6 mammary gland tumor (MGT) cell lines, 3 osteosarcoma cell lines, 5 melanoma cell lines, and 3 mast cell tumor (MCT) cell lines. Among the cell lines investigated, all 3 MCT cell lines showed high expression of RARalpha, and the most effective cell growth inhibition was observed in ATRA-treated MCT cell lines. However, remarkable antiproliferative effects of ATRA treatments were not observed on other tumor cell lines with moderate or low RARalpha mRNA expression. As a result of the relationship between RARalpha mRNA expression and ATRA treatment with regression analysis, statistically significant correlation was suggested. Furthermore, real-time quantitative polymerase chain reaction analysis of RARalpha was performed on MCT tissue samples of dogs with spontaneous disease, and 5 of 9 tissues showed high expression. These results suggest that ATRA may be an effective antitumor agent for MCT in dogs, and that prior measurement of expression of RARalpha mRNA may be a good indicator of the effectiveness of ATRA treatment.     

Pharmacokinetics of fentanyl after single intravenous injection and constant rate infusion in dogs

OBJECTIVE: To determine the plasma concentration and define the pharmacokinetic characteristics of fentanyl (10 microg kg(-1)) administered as a single intravenous (IV) injection followed by: (a) no further drug; or (b) a constant rate infusion (CRI) of fentanyl 10 microg kg(-1) hour(-1) lasting 1, 3 or 4 hours in dogs. Animals Fourteen healthy adult beagles (seven males and seven females). EXPERIMENTAL DESIGN: Randomized cross-over design. MATERIALS AND METHODS: Dogs were randomly assigned to four treatment groups. Drugs were administered to each dog in a randomized cross-over design with at least a 14-day washout interval between experiments. All dogs received an IV loading dose of fentanyl (10 microg kg(-1)). One group received no further fentanyl. In others, the loading dose was followed by a CRI of fentanyl (10 microg kg(-1) hour(-1)) for 1, 3 or 4 hours. Blood samples were collected and plasma fentanyl concentrations determined using high-performance liquid chromatography-mass spectrometry. Plasma pharmacokinetic estimates were obtained by plotting plasma concentrations versus time data and by fitting the change in concentration to a pharmacokinetic model, using a purpose-built program written by the Graduate School of Pharmaceutical Sciences (Kyoto University) in Visual Basic (VBA) on Excel (Microsoft Corporation). RESULTS: Plasma fentanyl concentration decreased rapidly after single IV injection: the plasma concentration-time curve best fitted a two-compartment model. Pharmacokinetic variables for IV injection were characterized by a short distribution half-time (t1/2alpha was 4.5 minutes), a relatively long elimination half time (t1/2beta was 45.7 minutes), a large volume of distribution (approximately 5 L kg(-1)) and high total body clearance (77.9 mL minute(-1) kg(-1)). Stable plasma fentanyl levels were obtained in all CRI groups although pharmacokinetic variables were influenced by the duration of administration. CONCLUSIONS AND CLINICAL RELEVANCE: While this study clarified the pharmacokinetic features of rapid IV fentanyl injection and CRI in dogs, the plasma concentration achieving analgesia was not and so further research is needed. Further studies on the effects of other sedatives and/or anaesthetics on fentanyl's disposition are also required as the drug is commonly used with other agents.     

Evaluation of the thermal property of bovine intramuscular adipose tissue using differential scanning calorimetry

The thermal property of bovine intramuscular adipose tissue (IAT) was evaluated using differential scanning calorimetry (DSC) and compared with the melting point temperature (MP) of the fat extract of IAT, which was measured using the slip point method. The beef samples were classified according to the beef marbling score (BMS). Beef with a high BMS contained less protein than that with middle or low BMS. Beef with a high BMS contained significantly more fat than that with a low BMS (P < 0.05). The endothermic point temperature (EP) of IAT, measured by DSC, was significantly higher than the MP of IAT fat (P < 0.05). The EP showed no significant difference among the three marbling grade groups. Although the MP was correlated with the monounsaturated fatty acids (MUFA) content of IAT (R² = 0.505), there was no correlation between the EP and the MUFA (R² = 0.040). However, the EP of IAT treated with collagenase was relatively highly correlated with the MP (R² = 0.655). Thus, these results suggested that DSC analysis would give us the practical thermal information regarding the melt‐in the‐mouth of beef such as the gelatinization of collagen, along with the melting of fat in IAT.     

Retinoid receptors and the induction of apoptosis in canine osteosarcoma cells

Retinoids, all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9-cis-RA), induced morphological changes and apoptosis-like cell death characterized by cell shrinkage, chromatin condensation and nuclear disintegration in three canine osteosarcoma cells, OOS, HOS and POS, at a concentration of 10(-5) M. Both retinoid receptors, RARs and RXRs, were identified in these cells. 9-cis-RA bound to both the RXRs and the RARs, whereas ATRA bound to only the RARs in these cells. Those results indicate that the induction of apoptosis in canine osteosarcoma cells may be mediated by the specific control of RARs and RXRs.     

Effects of perineural capsaicin treatment on cardiopulmonary reflexes elicited by laryngeal instillations of capsaicin and distilled water in sevoflurane-anesthetized dogs

The aim of this study was to determine the effect of perineural capsaicin (CAPS) treatment on cardiopulmonary reflexes elicited by topical laryngeal instillation of CAPS and distilled water (DW) in sevoflurane-anesthetized dogs. Cardiopulmonary reflexes elicited by CAPS (10 microg/ml, 10 ml) were attenuated by perineural CAPS treatment to the superior laryngeal nerves (SLNs) (P<0.05), whereas those by DW (10 ml) remained unaffected (P>0.05). The reflex responses to DW that remained even after the perineural CAPS treatment were eliminated by laryngeal anesthesia with lidocaine. These results suggest that cardiopulmonary reflexes from the laryngeal mucosa elicited by CAPS instillation can be blocked by perineural CAPS treatment to the SLNs, which may result from inhibition of the laryngeal CAPS-sensitive C-fiber afferents.