Effects of ropivacaine combined with morphine at 0.15 and 0.2 mg kg(-1) in bitches undergoing epidural anesthesia.

PURPOSE: To investigate cardiorespiratory effects and serum concentration of ropivacaine combined with morphine at different doses. METHODS: Sixteen healthy adult female dogs weighting 9.8 ± 4.1 kg were included in the study. Twenty minutes after being premedicated with acepromazine and midazolam, the animals were randomly assigned to receive an epidural injection according to each group: RM0.15 = ropivacaine + morphine (0.15 mg kg(-1)) and RM0.2 = ropivacaine + morphine (0.2 mg kg(-1)). Variables recorded consisted of: heart rate and cardiac rhythm, respiratory rate, oxyhemoglobin saturation, inspired oxygen fraction, end-tidal carbon dioxide tension, systolic, mean and diastolic arterial pressures, serum cortisol, plasma ropivacaine and morphine. RESULTS: SAP, MAP and DAP were significantly increased at TPR in RM0.15 but returned to normal values at the end of the procedure. Arterial pH was decreased in T30 and TESu in both groups and also returned to acceptable ranges at TR. Both PaO2 and PaCO2 were increased along the duration period of the epidural blockade (T30 and TESu) and returned to acceptable values at TR. Serum cortisol was lower at TB, T30 and TR when compared to TESu. CONCLUSION: The procedures were performed safely and minimal changes in cardiovascular and respiratory variables.

Effects of ropivacaine combined with morphine at 0.15 and 0.2 mg kg-1 in bitches undergoing epidural anesthesia

PURPOSE: To investigate cardiorespiratory effects and serum concentration of ropivacaine combined with morphine at different doses. METHODS: Sixteen healthy adult female dogs weighting 9.8±4.1 kg were included in the study. Twenty minutes after being premedicated with acepromazine and midazolam, the animals were randomly assigned to receive an epidural injection according to each group: RM0.15 = ropivacaine + morphine (0.15 mg kg-1) and RM0.2 = ropivacaine + morphine (0.2 mg kg-1). Variables recorded consisted of: heart rate and cardiac rhythm, respiratory rate, oxyhemoglobin saturation, inspired oxygen fraction, end-tidal carbon dioxide tension, systolic, mean and diastolic arterial pressures, serum cortisol, plasma ropivacaine and morphine. RESULTS: SAP, MAP and DAP were significantly increased at TPR in RM0.15 but returned to normal values at the end of the procedure. Arterial pH was decreased in T30 and TESu in both groups and also returned to acceptable ranges at TR. Both PaO2 and PaCO2 were increased along the duration period of the epidural blockade (T30 and TESu) and returned to acceptable values at TR. Serum cortisol was lower at TB, T30 and TR when compared to TESu. CONCLUSION: The procedures were performed safely and minimal changes in cardiovascular and respiratory variables. .

Bispectral index in calves anesthetized with xylazine, midazolam, ketamine, isoflurane and subjected to continuous rate infusion of lidocaine.

PURPOSE: To assess the bispectral index (BIS) and recovery in calves anesthetized with xylazine, midazolam, ketamine and isoflurane and subjected to CRI of lidocaine. METHODS: Xilazine was administered followed by ketamine and midazolam, orotracheal intubation and maintenance on isoflurane using mechanical ventilation. Lidocaine (2 mg kg(-1) bolus) or saline (0.9%) was administered i.v. followed by a CRI (100 µg kg(-1) minute(-1)) of lidocaine (L) or saline (C). Were recorded BIS, heart rate (HR), mean arterial pressure (MAP) and rectal temperature (RT) before administration of premedication (TB) and 15 minutes after (TX), before administering lidocaine (T0) and 20, 40, 60 and 80 minutes after the start of the CRI . Time do sternal recumbency (SRE) and standing (ST) and plasma lidocaine concentration also evaluated. RESULTS: In both treatments BIS decreased significantly at all times compared to TB. TX was higher than the subsequent times. HR decreased from baseline at all times and decreased from T40 in L compared to C. SRE was higher in L compared to C. CONCLUSIONS: Bispectral index values were consistent with the degree of hypnosis of the animals. Lidocaine did not potentiate isoflurane anesthesia assessed by BIS in unstimulated calves anesthetized with constant E´Iso. Lidocaine increased the time to sternal recumbency.

Bispectral index in calves anesthetized with xylazine, midazolam, ketamine, isoflurane and subjected to continuous rate infusion of lidocaine

PURPOSE: To assess the bispectral index (BIS) and recovery in calves anesthetized with xylazine, midazolam, ketamine and isoflurane and subjected to CRI of lidocaine. METHODS: Xilazine was administered followed by ketamine and midazolam, orotracheal intubation and maintenance on isoflurane using mechanical ventilation. Lidocaine (2 mg kg-1 bolus) or saline (0.9%) was administered IV followed by a CRI (100 µg kg-1 minute-1) of lidocaine (L) or saline (C). Were recorded BIS, heart rate (HR), mean arterial pressure (MAP) and rectal temperature (RT) before administration of premedication (TB) and 15 minutes after (TX), before administering lidocaine (T0) and 20, 40, 60 and 80 minutes after the start of the CRI . Time do sternal recumbency (SRE) and standing (ST) and plasma lidocaine concentration also evaluated. RESULTS: In both treatments BIS decreased significantly at all times compared to TB. TX was higher than the subsequent times. HR decreased from baseline at all times and decreased from T40 in L compared to C. SRE was higher in L compared to C. CONCLUSIONS: Bispectral index values were consistent with the degree of hypnosis of the animals. Lidocaine did not potentiate isoflurane anesthesia assessed by BIS in unstimulated calves anesthetized with constant E´Iso. Lidocaine increased the time to sternal recumbency. .

Propylthiouracil quantification in human plasma by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry: application in a bioequivalence study.

UNLABELLED: A rapid, sensitive and specific method for quantifying propylthiouracil in human plasma using methylthiouracil as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by liquid-liquid extraction using an organic solvent (ethyl acetate). The extracts were analyzed by high performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS) in negative mode (ES-). Chromatography was performed using a Phenomenex Gemini C18 5µm analytical column (4.6mm×150mm i.d.) and a mobile phase consisting of methanol/water/acetonitrile (40/40/20, v/v/v)+0.1% of formic acid. For propylthiouracil and I.S., the optimized parameters of the declustering potential, collision energy and collision exit potential were -60 (V), -26 (eV) and -5 (V), respectively. The method had a chromatographic run time of 2.5min and a linear calibration curve over the range 20-5000ng/mL. The limit of quantification was 20ng/mL. The stability tests indicated no significant degradation. This HPLC-MS/MS procedure was used to assess the bioequivalence of two propylthiouracil 100mg tablet formulations in healthy volunteers of both sexes in fasted and fed state. The geometric mean and 90% confidence interval CI of Test/Reference percent ratios were, without and with food, respectively: 109.28% (103.63-115.25%) and 115.60% (109.03-122.58%) for Cmax, 103.31% (100.74-105.96%) and 103.40% (101.03-105.84) for AUClast. CONCLUSION: This method offers advantages over those previously reported, in terms of both a simple liquid-liquid extraction without clean-up procedures, as well as a faster run time (2.5min). The LOQ of 20ng/mL is well suited for pharmacokinetic studies. The assay performance results indicate that the method is precise and accurate enough for the routine determination of the propylthiouracil in human plasma. The test formulation with and without food was bioequivalent to reference formulation. Food administration increased the Tmax and decreased the bioavailability (Cmax and AUC).

Role of a novel tetrodotoxin-resistant sodium channel in the nitrergic relaxation of corpus cavernosum from the South American rattlesnake Crotalus durissus terrificus.

INTRODUCTION: Coitus in snakes may last up to 28 hours; however, the mechanisms involved are unknown. AIM: To evaluate the relevance of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-phosphodiesterase type 5 (PDE5) system in snake corpus cavernosum reactivity. METHODS: Hemipenes were removed from anesthetized South American rattlesnakes (Crotalus durissus terrificus) and studied by light and scanning electronic microscopy. Isolated Crotalus corpora cavernosa (CCC) were dissected from the non-spiny region of the hemipenises, and tissue reactivity was assessed in organ baths. MAIN OUTCOME MEASURES: Cumulative concentration-response curves were constructed for acetylcholine (ACh), sodium nitroprusside (SNP), 5-cyclopropyl-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4-ylamine (BAY 41-2272), and tadalafil in CCC precontracted with phenylephrine. Relaxation induced by electrical field stimulation (EFS) was also done in the absence and presence of N(ω) nitro-L-arginine methyl ester (L-NAME; 100 µM), 1H-[1, 2, 4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 µM) and tetrodotoxin (TTX; 1 µM). RESULTS: The hemipenes consisted of two functionally concentric corpora cavernosa, one of them containing radiating bundles of smooth muscle fibers (confirmed by α-actin immunostaining). Endothelial and neural nitric oxide synthases were present in the endothelium and neural structures, respectively; whereas soluble guanylate cyclase and PDE5 were expressed in trabecular smooth muscle. ACh and SNP relaxed isolated CCC, with the relaxations being markedly reduced by L-NAME and ODQ, respectively. BAY 41-2272 and tadalafil caused sustained relaxations with potency (pEC(50) ) values of 5.84 ± 0.17 and 5.10 ± 0.08 (N=3-4), respectively. In precontracted CCC, EFS caused frequency-dependent relaxations that lasted three times longer than those in mammalian CC. Although these relaxations were almost abolished by either L-NAME or ODQ, they were unaffected by TTX. In contrast, EFS-induced relaxations in marmoset CC were abolished by TTX. CONCLUSIONS: Rattlesnake CC relaxation is mediated by the NO-cGMP-PDE5 pathway in a manner similar to mammals. The novel TTX-resistant Na channel identified here may be responsible for the slow response of smooth muscle following nerve stimulation and could explain the extraordinary duration of snake coitus.