Ralph C. Harvey

Alpha2 Agonists and Antagonists

This article discusses the use of the alpha 2 agonists in the dog and cat. A review of alpha 2 adrenoceptor activity is presented. The alpha 2 agonists xylazine and medetomidine are discussed. The physiological effects, clinical uses, and precautions and contradictions for each drug are presented. The use of the alpha 2 antagonists, yohimbine and atipamezole, are also discussed.

Mutagenesis at the ad-3A and ad-3B loci in haploid UV-sensitive strains of Neurospora crassa: V. Comparison of dose-response curves of single- and double-mutant strains with wild-type

The interactions of mutant alleles that individually confer radiation sensitivity in Neurospora crassa are being studied with regard to their effects on radiation-induced inactivation and forward-mutation induction at the ad-3 loci. This paper reports attempts to construct 3 double-mutant strains containing the following pair-wise combinations of repair-deficient mutants: upr-1,uvs-2; uvs-2,uvs-6; and uvs-3,uvs-6. The double-mutant strain with the 2 excision-repair-deficient mutants upr-1 and uvs-2 shows increased sensitivity to X-ray-induced mutagenesis and inactivation, relative to that shown by either of the parental single-mutant strains. This double mutant is no more sensitive than the parental single-mutant strains to either UV mutagenesis or inactivation. The combination of the uvs-2 and uvs-6 double-mutant strain is considerably more sensitive to both UV and X-ray inactivation than either the uvs-2 or uvs-6 strain, but it shows no greater sensitivity than the parental strains to ad-3 mutation induction by either agent. The combination of the uvs-3 and uvs-6 alleles is inviable. Tetrad analysis and microscopical examination of ascospores shows that ascospores of presumptive genotype uvs-3, uvs-6 do not grow beyond the formation of a few hyphal threads. The lethal and mutagenic effects of UV and X-irradiation in these double-mutant strains are interpreted in terms of the repair systems in Neurospora and other microorganisms.

Cardiopulmonary and Anesthetic Effects of Isoflurane and Propofol in Hispaniolan Amazon Parrots (Amazona ventralis)

Abstract The cardiopulmonary and anesthetic effects of isoflurane and propofol were determined in 10 healthy, adult Hispaniolan Amazon parrots (Amazona ventralis). Anesthesia was induced and maintained with isoflurane in oxygen for 30 minutes. Cardiopulmonary parameters including heart rate, respiratory rate, relative arterial oxygen hemoglobin saturation (SpO2), and esophageal temperature were recorded at 1, 2, 3, 4, 5, 10, 15, 20, 25, and 30 minutes. End-tidal CO2 (EtCO2) concentrations and inspired and expired end-tidal isoflurane concentrations were recorded continuously. Before the study continued, birds were allowed to recover from isoflurane anesthesia for at least 2 hours. In a second trial, anesthesia was induced by intravenous administration of propofol (5 mg/kg) and maintained for 30 minutes by constant rate infusion of propofol (1 mg/kg per min IV). No supplemental oxygen was provided. Cardiopulmonary parameters and EtCO2 concentrations were recorded as in the isoflurane trial. Induction times with propofol (51 ± 40 sec; mean ± SD) and isoflurane (58 ± 15 sec) were rapid and not significantly different. No significant changes in heart rates and SpO2 values over time were seen with isoflurane anesthesia, but the respiratory rate decreased significantly from 41 ± 17 breaths/min at 1 minute to 25 ± 15 breaths/min at 10 minutes following induction. A significant decrease in respiratory rate was noted only at 2 (26 ± 10 breaths/min) and 3 (29 ± 12 breaths/min) minutes following induction with propofol. A significant increase in EtCO2 concentrations was recorded at 3 (37% ± 4%) minutes and thereafter with propofol anesthesia. No significant change in heart rate was observed over time. The SpO2 values significantly decreased below 90% at 2 minutes after induction with propofol and remained significantly decreased for the remainder of the anesthetic event. No significant differences in partial pressure of oxygen (PaO2) values were observed over time. SpO2 values were significantly higher with isoflurane compared with propofol at any given time during anesthesia. No significant differences in EtCO2 concentrations and heart rates were observed between groups throughout the study. Propofol recovery times (15.4 ± 15.2 min) were prolonged when compared with isoflurane (4.6 ± 1.6 min), and 6 birds had agitated recoveries from propofol anesthesia. A constant rate infusion of propofol at 1 mg/kg per minute resulted in a light anesthesic plane in 8 Hispaniolan Amazon parrots (Amazona ventralis) and a surgical plane in 2 birds. Supplemental oxygen is recommended during propofol anesthesia. Propofol can be useful for brief, noninvasive procedures or as an induction agent to facilitate endotracheal intubation prior to inhalational anesthesia.

A Chronic Sheep Preparation for the Study of Drug Pharmacokinetics in Spinal and Ventricular CSF

We describe a sheep preparation utilizing chronic vascular and subarachnoid catheterization and ventriculocisternal perfusion. This preparation allows simultaneous, atraumatic sampling of plasma and CSF after drug administration by the intravenous, intracerebroventricular, or lumbar intrathecal (i.t.) routes in an unanesthesized animal. This sheep preparation provides a convenient means of studying the CSF distribution of exogenous and/or endogenous substances. During intravenous infusion at a rate of 2.2 micrograms/kg/min, morphine appears in cisternal CSF within 15 min. The steady-state plasma concentration and CSF flux (or appearance rate) of morphine was 0.037 and 0.009 micrograms/min, respectively. At steady state, 0.008% of the administered dose appears in CSF/min. The coadministration of morphine, methadone, and [14C]sucrose into the fifth lumbar subarachnoid space is associated with the simultaneous appearance of morphine and [14C]sucrose, but not methadone, in cisternal CSF. The ratio of [14C]sucrose to morphine increased by nearly sevenfold in cisternal CSF, indicating clearance of morphine relative to [14C]sucrose as the compounds ascend in the CSF axis. The simultaneous appearance of morphine and [14C]sucrose in cisternal CSF after lumbar subarachnoid administration indicates that morphine, like sucrose, is distributed within the CSF by bulk flow. This sheep preparation can be used to provide the quantitative data necessary for the development of pharmacokinetic-pharmacodynamic models that relate plasma and CSF concentrations of opiates to their pharmacological effects. These studies will help to provide the pharmacological rationale for the administration of opiates by novel routes for pain management in man.

Precautions when Using Mask Induction

There are few techniques as frequently employed in veterinary anesthesia that are more dependent on good clinical judgment, technical skill, and finesse than mask induction. The technique can be extremely valuable in selected patients.

Determination of Propofol Using High Performance Liquid Chromatography in Whole Blood with Fluorescence Detection

High-performance liquid chromatography method for the determination of propofol has been developed and validated. Following a liquid extraction using ethyl acetate and hexane, samples were separated by reverse-phase high-performance liquid chromatography on an XBridge C(18) column and quantified using fluorescence detection at an excitation of 276 nm and an emission of 310 nm. The mobile phase was a mixture of water (pH 4.0) and acetonitrile, with a flow rate of 1.5 mL/min. The standard curve ranged from 5-2000 ng/mL. Intra- and inter-assay variability for propofol was less than 10%, and the average recovery was greater than 95%. This assay is suitable for use in pharmacokinetic studies.

Anesthesia and Analgesia in Dogs, Cats, and Ferrets

Publisher Summary Customizing anesthetic techniques to be used for each research model or protocol is possible through the application of this information from the accumulation of clinical experience with dogs, cats, and ferrets as domestic pets. The state or condition referred to as anesthesia, or particularly general anesthesia, includes the component conditions of unconsciousness, amnesia, lack of sensation to potentially noxious stimuli, and muscle relaxation. The characteristics of each of these constituent components of general anesthesia are affected by the choice of anesthetics and anesthetic techniques. Anesthetic protocols should include consideration of sedation; pharmacological restraint (occasionally appropriate as an alternative to general anesthesia); induction and maintenance of general anesthesia; perioperative physiological management or support; anesthetic monitoring and plans for responding to anticipated physiological changes; and, in chronic studies, the recovery from anesthesia and postoperative care. The safety that often has been associated with inhalant, as opposed to injectable anesthetics, is largely due to the provision of supplemental oxygen as the carrier gas for the volatile anesthetics. Endotracheal intubation and administration of supplementary oxygen can easily be incorporated into injectable anesthetic techniques and can add substantial safety. If anesthesia is deep enough to allow for placement of an endotracheal tube, then the animal is no longer able to protect its airway from the aspiration of regurgitated or foreign material. Although not all anesthetized animals will require supplementary oxygen administration, most animals should be considered for this level of support during anesthesia and surgery.

MANAGEMENT OF GERIATRIC PATIENTS : A COMMON OCCURRENCE

The anesthetic and perioperative care of geriatric animals requires increased vigilance and support. The margin of acceptable physiological variation is probably more narrow than in younger patients. Underlying disease, which is often subclinical, influences metabolism and recovery from anesthetics and also predisposes the patients to adverse outcome. Limited respiratory and cardiovascular reserve diminishes the ability of many older patients to meet the challenges of anesthesia and surgery or other stressful medical procedures. The psychological, as well as physiological, stress of hospitalization is increased in many geriatric patients.

High-performance liquid chromatographic determination of intrathecally administered [d-Ala2-d-Leu5]-enkephalin concentrations in canine cerebrospinal fluid

A rapid and useful method for high-performance liquid chromatographic analysis of exogenous [D-Ala2-D-Leu5]-enkephalin (DADLE) in cerebrospinal fluid (CSF) is described. CSF (0.5 ml) samples were filtered using a 0.22-micron Co-Star filter. Chromatography was performed on a mu Bondapak C18 column using a mobile phase of A, 0.05 M sodium phosphate (monobasic, pH 6.0) and B, 60% acetonitrile in 0.05 M sodium phosphate (pH 6.0) with a flow-rate of 1 ml/min. Absorbance at 210 nm was measured. The procedure produced a linear curve for the concentration range 1-10 micrograms/ml. The development of the assay produced rapid, repeatable and accurate results for CSF analysis of DADLE at concentrations achieved with therapeutic administration of the peptide. This method could also be used in the future for analysis of compounds like DADLE.