Biomedical subjects

R C Wilson

Publications and source records attributed to R C Wilson.

At least 109 records · Page 6Linked to original sources

PubMed1986

Prompt arousal from fentanyl-droperidol-pentobarbital anesthesia in dogs: a preliminary study.

Groups of fentanyl-droperidol-pentobarbital-anesthetized dogs (n = 6 dogs/group) were given IV saline solution (control group), graded doses of naloxone (0.01, 0.1, 1.0, 10.0 mg/kg) or fixed doses of 4-aminopyridine (0.5 mg/kg), yohimbine (0.4 mg/kg), or doxapram (5.0 mg/kg) alone or in combination with a fixed dose of naloxone (1.0 mg/kg). The purpose was to determine which drug or drug combination would produce arousal most quickly without producing obvious undesirable side effects. Control group mean arousal time, mean walk time and mean duration of postarousal sedation were 66.1 minutes, 112.4 minutes and 5.6 hours, respectively. Naloxone (1.0 mg/kg) decreased mean arousal time to 10.8 minutes without significantly decreasing mean walk time or mean duration of postarousal sedation. The combination of naloxone + doxapram decreased mean arousal time and mean walk time to 1.0 minute and 57.1 minutes, respectively, without decreasing mean duration of postarousal sedation. In all groups, emergence from anesthesia was smooth. Relapses or undesirable side effects were not observed. Naloxone + doxapram is superior to naloxone alone for arousal of fentanyl-droperidol-pentobarbital-anesthetized dogs.

4-Aminopyridine↗

PubMed1986

Pharmacokinetics of minocycline hydrochloride in clinically normal and hypoproteinemic sheep.

Eight adult sheep were given 2.2 mg of minocycline hydrochloride/kg of body weight IV before and after blood was collected to induce hypoproteinemia. The blood collection produced a significant (P less than 0.01) reduction in PCV, hemoglobin, and total serum protein values. Pharmacokinetic evaluation of the serum drug concentration vs time data was performed, using a noncompartmental model based on statistical moment theory. Pharmacokinetic values obtained from the sheep with normal serum protein were 5.94 +/- 1.78 ml/kg/min for clearance, 1.32 +/- 0.16 L/kg for the steady-state volume of distribution, and 3.89 +/- 0.80 hours for mean residence time. Significant differences were not found in these values obtained from the sheep when they were hypoproteinemic. The effective half-life, reported as the harmonic mean, increased from 2.57 hours in sheep before blood collection to 2.91 hours in sheep when they were hypoproteinemic. The 2.2 mg of minocycline/kg administered once or twice daily would not be expected to produce adequate serum concentrations for most susceptible microorganisms. Some evidence that minocycline disposition may follow zero-order kinetics is presented.

Animals↗

PubMed1986

Thiacetarsamide in dogs: disposition kinetics and correlations with selected indocyanine green kinetic values.

The pharmacokinetic values of thiacetarsamide (2.2 mg/kg) were determined in 6 healthy dogs after IV injection. A semilogarithmic plot of serum concentration vs time indicated that the 2-compartment open model best described thiacetarsamide disposition. A least-squares log linear regression microcomputer program was used to calculate the pharmacokinetic values. The mean elimination-phase half-life and clearance rate were 43 minutes and 200 ml/kg/min, respectively. Wide ranges in values were seen for the half-life (20.5 to 83.4 minutes) and the clearance rate (80.0 to 350.0 ml/kg/min). Before thiacetarsamide was given to the dogs, indocyanine green (ICG), an anionic dye that is eliminated almost entirely by hepatobiliary excretion, was administered IV at a dosage of 0.5 mg/kg of body weight. The half-life of ICG was 7.4 minutes, and the clearance rate was 8.43 ml/kg/min. There was a significant (P less than 0.01) correlation between the half-lives of thiacetarsamide and ICG, but not between the clearance rates. The variations in ICG half-lives and clearance rates were less than those seen for thiacetarsamide.

Animals↗

PubMed1985

Electrophysiological manifestation of luteinizing hormone-releasing hormone pulse generator activity in the rhesus monkey: influence of alpha-adrenergic and dopaminergic blocking agents.

Characteristic increases in neuronal electrical activity associated with the initiation of each LH pulse were recorded from ovariectomized rhesus monkeys bearing multiple chronic electrodes in the medial basal hypothalamus. These electrophysiological manifestations of hypothalamic LHRH pulse generator activity were inhibited by the alpha-adrenergic blocker phentolamine or the alpha 1-adrenoceptor blockers phenoxybenzamine and prazosin. At the dosages used, the effects of single injections of these drugs ranged from a reduction in the frequency of LHRH pulse generator activity to its complete arrest. This was faithfully reflected in the pattern of pulsatile LH discharges. The dopaminergic blocking agent metaclopramide similarly reduced the frequency of the pulse generator or arrested its activity altogether. The alpha 2-adrenoceptor blocker yohimbine had no demonstrable effect on hypothalamic electrical activity at the doses studied. These findings support the view of a central action of alpha 1-adrenergic and dopaminergic blockade on LHRH pulse generator activity and the concept that central adrenergic and dopaminergic inputs can modulate the frequency of the LHRH pulse generator.

Adrenergic alpha-Antagonists↗

PubMed1985

Reversal of thiopental-induced anesthesia by 4-aminopyridine, yohimbine, and doxapram in dogs pretreated with xylazine or acepromazine.

Groups of atropinized dogs (6 dogs/group) were sedated, using xylazine HCl (2.2 mg/kg of body weight, IM) or acepromazine maleate (0.25 mg/kg, IM), and were anesthetized to loss of pedal reflexes, using thiopental, IV. The dogs were given 1 of the following test antagonists, IV: saline solution (2 ml; control group), 4-aminopyridine (4-AP; 0.5 mg/kg), yohimbine (0.4 mg/kg), doxapram (5.0 mg/kg), or dual combinations of the latter 3 substances in the same doses as used for each agent. In xylazine-treated dogs, the mean dosage of thiopental required to induce anesthesia was 4.8 mg/kg. Control mean arousal time (MAT) and walk time (MWT) were 37.1 minutes and 53.8 minutes, respectively. These values were decreased to less than 2 minutes and less than 3 minutes, respectively, by yohimbine, 4-AP + yohimbine, and doxapram + yohimbine. With doxapram and with 4-AP + doxapram, MAT was less than 2 minutes and MWT was less than 8 minutes. In acepromazine-treated dogs, the mean dosage of thiopental required for anesthesia was 15.0 mg/kg. Control MAT and MWT were 20.7 minutes and 36.5 minutes, respectively. These values were decreased to 8.1 minutes and 18.1 minutes, respectively, by doxapram, and to 3.5 minutes and 19.9 minutes, respectively, by doxapram + yohimbine. Doxapram, 4-AP + doxapram, and doxapram + yohimbine caused periodic extensor rigidity before and during arousal. This rigidity was accompanied by opisthotonos in 2 dogs of the doxapram + yohimbine group and may have been mild tonic seizures.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗

PubMed1985

Compartmental and noncompartmental pharmacokinetic analyses of minocycline hydrochloride in the dog.

Six adult dogs were given 5 mg of minocycline hydrochloride/kg of body weight IV. Pharmacokinetic evaluation of the serum drug concentration versus time data was performed, using the 2-compartment open model, the 3-compartment open model, and a noncompartmental model involving use of the statistical moment theory. All pharmacokinetic values except clearance were model independent. Minocycline half-life ranged between 6.48 and 7.24 hours; volume of distribution at steady state, between 1.859 +/- 0.368 and 2.001 +/- 0.468 L/kg; and clearance, between 3.195 +/- 0.618 and 3.424 +/- 0.684 ml/min/kg. These data are similar to those reported for oxytetracycline and indicate that the frequency of administration of the 2 tetracyclines should be the same. Three of the 6 dogs developed an adverse response to the IV injection of minocycline. Dog 1 developed urticaria and had initial serum drug concentrations of approximately 2 times the mean concentrations for the other dogs; values were not included in the pharmacokinetic analysis. Two other dogs had transient signs indicating cardiovascular depression or hypotension; their data were included. Due to the frequency of the unexpected reactions found in this study, it was concluded that dogs should not be given minocycline rapidly IV.

Animals↗

PubMed1984

Central electrophysiologic correlates of pulsatile luteinizing hormone secretion in the rhesus monkey.

Characteristic increases in neuronal activity coincident with the pulsatile release of luteinizing hormone from the pituitary gland have been recorded from electrodes chronically implanted in the medial basal hypothalamus of the rhesus monkey. This electrophysiologic manifestation of the hypothalamic 'pulse generator' which governs the secretion of hypothalamic luteinizing hormone releasing hormone provides, for the first time, direct access to the central component of the neuroendocrine control system which regulates reproductive processes in this higher primate.

Anesthesia↗

PubMed1984

Influence of endotoxin-induced fever on the pharmacokinetics of gentamicin in ewes.

The pharmacokinetics of gentamicin (3 mg/kg of body weight) were evaluated in 6 adult ewes before and after fever was induced with Escherichia coli endotoxin (1 micrograms/kg). In the ewes with normal rectal temperature, significant (P less than 0.05) increases in rectal temperature occurred before gentamicin injection and during the first 2 hours. Other mild clinical signs of fever also were present. In the same ewes with endotoxin-induced fever, statistically (P less than 0.05) increased gentamicin concentrations occurred at 15 and 40 minutes and at 6 hours after injection of gentamicin. Changes were not observed in the apparent volume of distribution calculated by the area method, the volume of distribution at steady state, the overall biological half-life, or body clearance. Significant (P less than 0.05) reductions occurred in the zero time intercept for distribution, the distribution rate constant, the concentration in plasma at time of injection, the volume of the peripheral compartment, and the first order transfer rate constants; only the volume of the central compartment was increased. Total amounts of gentamicin were increased in the central compartment and decreased in the peripheral or tissue compartment.

Animals↗

PubMed1984

Antagonism of xylazine sedation in steers by doxapram and 4-aminopyridine.

Five groups of 6 fasted crossbred steers were injected IM with standard dosages of xylazine hydrochloride (0.3 to 0.5 mg/kg). At maximal sedation, the steers were injected IV with the antagonists' doxapram (1.0 mg/kg), doxapram + yohimbine (0.125 mg of yohimbine/kg), doxapram + 4-aminopyridine (4-AP; 0.3 mg of 4-AP/kg), or 4-AP + yohimbine. One group was given 1.0 ml of saline solution IV instead of antagonists. Doxapram, doxapram + yohimbine, doxapram + 4-AP, and 4-AP + yohimbine decreased mean standing time (time from antagonist injection until animal could stand unaided) to 17.0, 4.3, 3.3, and 4.5 minutes, respectively--significantly (P less than 0.05) down from a control value of 49.8 minutes. Mean total recovery time (time from xylazine injection until animal resumed eating) was decreased to 78 minutes by doxapram and 81.6 minutes by doxapram + 4-AP--significantly (P less than 0.05) down from the control value of 142.9 minutes. Respiratory character was improved (depth of respiration was increased) only by doxapram + 4-AP. Relapses to recumbency and marked sedation were not seen in steers given doxapram + 4-AP or the saline solution. One steer given doxapram, 2 given doxapram + yohimbine, and 1 given 4-AP + yohimbine relapsed to recumbency and sedation. Recovery was relatively smooth in steers given doxapram + 4-AP or 4-AP + yohimbine. Animals given doxapram or doxapram + yohimbine had difficult recoveries.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗

PubMed1984

Pharmacokinetics of 4-aminopyridine in cattle.

Concentrations of 4-aminopyridine hydrochloride in plasma of cattle were measured over an 8-hour period following a bolus IV injection (0.3 mg/kg). The drug was assayed by a gas-liquid chromatographic method using a nitrogen-phosphorus detector. Plasma 4-aminopyridine hydrochloride vs time data best fit a 2-compartment pharmacokinetic model. Distribution half-life was 12.08 minutes; elimination half-life, 128.96 minutes; volume of the central compartment, 1.48 L/kg; volume of distribution based on total area, 3.07 L/kg; volume of distribution at steady state, 2.75 L/kg; and body clearance, 16.57 ml/min/kg.

4-Aminopyridine↗

PubMed1984