Biomedical subjects

R H van den Hoogen

Publications and source records attributed to R H van den Hoogen.

8 recordsLinked to original sources

PubMed1988

Respiratory effects of epidural and subcutaneous morphine, meperidine, fentanyl and sufentanil in the rat.

This study compared the respiratory effects of subcutaneous and epidural morphine, meperidine, fentanyl, and sufentanil in rats breathing air or 8% CO2 in air. A whole body plethysmographic technique was used to measure minute volumes of breathing. The ED50s of subcutaneously injected morphine, meperidine, fentanyl, and sufentanil in depressing the minute volume response to 8% CO2 in air were 2300 micrograms/kg, 8800 micrograms/kg, 20 micrograms/kg, and 2.3 micrograms/kg, respectively. These doses were nearly the same as the subcutaneous ED50s of these compounds in producing analgesia, found in an earlier study. Roughly equianalgesic doses of the four opiates after epidural injection, however, failed to cause any detectable respiratory effect. Fourfold greater doses increased significantly the incidence of low minute volumes with fentanyl and sufentanil, but soon after epidural injection, i.e., at the time that analgesia was produced. None of the epidurally injected opiates had a significant delayed effect on respiration. However, one of the seven rats treated epidurally with the higher dose of morphine developed depression of the minute volume response to 8% CO2 in air as late as 7 hours after the injection. We conclude that epidural injection, in contrast to subcutaneous injection, of analgesic doses of morphine, meperidine, fentanyl, and sufentanil produces no significant respiratory effects.

Animals↗

PubMed1987

Epidural and subcutaneous morphine, meperidine (pethidine), fentanyl and sufentanil in the rat: analgesia and other in vivo pharmacologic effects.

The experiments examined the characteristics of analgesia produced by different doses of morphine, meperidine (pethidine), fentanyl, and sufentanil after epidural and subcutaneous injection in rats. The specificity of the analgesia was also determined; other in vivo pharmacologic activities (i.e., blockade of pinna and cornea reflexes and production of skeletal muscle rigidity) were monitored as pharmacologic indices of opiate drug activity in the brain. After subcutaneous injection, the opiates produced dose-dependent analgesia, blocked the pinna and cornea reflexes, and induced muscle rigidity. After epidural injection, all four compounds produced dose-dependent analgesia and had greater potency, earlier onset, shorter duration, and greater specificity of analgesic action than was the case after subcutaneous injection. Specificity is defined here as the ratio of the ED50 dose that blocked the pinna reflex to the ED50 dose that produced analgesia. The gains in potency and specificity, but not the gains in onset time and the losses in duration of analgesia, differed considerably among the compounds that were examined. The subcutaneous-to-epidural potency ratio related in a linear manner with the lipid-to-water partition coefficient. The gain in specificity also appeared to be related to lipid solubility. The microgram X kg-1 doses at which the opiates produced analgesia in rats correlate well with the potency of these compounds in producing analgesia after epidural injection in humans. The rat epidural preparation reflected the doses, onset, and specificity, but not the duration, of analgesia produced by epidural opiates in humans.

Analgesia↗

PubMed1986

Epidural and intravenous sufentanil in the rat: analgesia, opiate receptor binding, and drug concentrations in plasma and brain.

Doses of sufentanil (i.e., 0.01, 0.04, 0.16, 0.63, 2.5, 10, and 40 micrograms/rat) were injected either into the lumbar epidural space or intravenously in rats weighing +/- 250 g, and in vivo pharmacologic activities (i.e., prolongation of latency to tail withdrawal in response to noxious heat, blockade of cornea and pinna reflexes, increase of skeletal muscle tone), ex vivo mu-opiate receptor binding (i.e., displacement of specific 3H-sufentanil binding in thalamus, striatum, hippocampus, cortex, mamillary body-medulla oblongata segment, medulla oblongata, and in cervical, thoracic, and lumbar spinal cord), and drug concentrations in plasma, brain, cortex, and cerebellum, were determined. An ED50 dose of intravenous sufentanil of 0.075 micrograms/rat produced analgesia. CNS-mediated in vivo side effects (i.e., blockade of pinna and cornea reflexes, muscle rigidity) were apparent at 6-28 times higher doses. Epidural sufentanil also produced analgesia at an ED50 dose of 0.08 micrograms/rat, but CNS-mediated side effects occurred only at 35 to 76 times higher doses. This greater in vivo selectivity of epidural sufentanil in producing analgesia was consistent with ex vivo binding data that showed that in most areas of brain, but not in spinal cord, more mu-opiate binding occurs with intravenous than with epidural sufentanil. The two routes nonetheless differed by no more than a factor of approximately two in producing detectable levels of sufentanil both in plasma and in brain tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗

PubMed1986

Respiratory effects of morphine in awake unrestrained rats.

This report describes a systematic analysis of opiate drug effects on ventilation and its components tidal volume and frequency in intact, awake and unrestrained rats. A whole-body plethysmographic method was used to measure these parameters of respiration while animals breathed air or various concentrations of CO2 in air. Subcutaneous doses of morphine lower than 40 mg/kg exerted little or no apparent effect in rats breathing air; in rats breathing 4 to 8% of CO2 these doses of morphine also failed to depress any of the ventilatory parameters below the level of saline controls breathing air. Doses (0.16 to 160 mg/kg) of morphine blunted the frequency response to CO2 in a biphasic manner. The effects of morphine on tidal volume consisted of a slight increase at 0.16 and 0.63 mg/kg, a dose-dependent decrease at 2.5 to 40 mg/kg and a paradoxical rise at 160 mg/kg. These complex effects of morphine on tidal volume and frequency resulted in a simple sigmoid depression of minute volume. The slope of this sigmoid dose-response curve varied with the inspirate; it increased as the concentration of CO2 was higher. Naloxone antagonized the frequency depression produced by 40 mg/kg of morphine in a dose-dependent manner at doses ranging from 0.01 to 0.16 mg/kg, but frequency decreased again at 0.63 mg/kg. The effects of naloxone on the tidal volume depression consisted of a paradoxical further decrease at 0.01 mg/kg, a dose-dependent antagonism of depression at 0.04 to 0.16 mg/kg and a stimulation above the normal control level at 0.63 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1983

Time course of the ventilatory response to adjuvant arthritis in the rat.

The present study determined the time course of the ventilatory response to adjuvant arthritis in the rat. It was found that the minute ventilation of arthritic rats reliably exceeded that of control animals during a period of about 4 weeks. The ventilatory response had its onset during the 2nd week after inoculation of Mycobacterium butyricum in the tail base, peaked on day 21, and was statistically reliable up to the 35th day. A smaller difference persisted throughout the further six weeks of the study, which covered 77 days in all. The changes in minute ventilation appeared to be closely time-locked with the changes in body weight and paw diameter which are characteristic of rats with adjuvant arthritis. The peak minute ventilation of individual animals also correlated in a significant manner with changes in weight and in paw diameter. The data are consistent with an earlier attempt to characterize the time course of the chronic pain which is presumably associated with adjuvant arthritis in the rat; minute ventilation is discussed as a possible measure of this putative pain.

Animals↗

PubMed1983

Ventilatory response to adjuvant arthritis in the rat.

This study examined ventilation in rats with arthritis induced by Mycobacterium butyricum. It was found that, 19 days after inoculation, the minute ventilation of arthritic rats breathing air was about two-fold higher than that of control animals. This increase resulted from an increase both in respiratory frequency and in tidal volume. Air-CO2 mixtures continued to stimulate ventilation in arthritic rats, and the minute ventilation of these animals on breathing 5 or 7% CO2 exceeded that of controls. The results are consistent with the hypothesis that arthritic rats hyperventilate and contribute to the validation of adjuvant arthritis as an animal model of chronic pain.

Animals↗

PubMed1981

Long term catheterization of the lumbar epidural space in rats.

This note describes a simple technique for the administration of drug solutions into the lumbar epidural space of the unanesthetized and freely moving rat. A poly-ethylene (PE-10) catheter is inserted into the epidural space through a hole in the third lumbar vertebra, and subcutaneously tunneled towards the neck region. The implantation procedure is well-tolerated, and repeated saline injections over a prolonged period of time were found not to exert any deleterious effect on the animals' apparent health or gross behavior. The viability of the technique is demonstrated in an experiment on the effect of injection volume on the analgesic action of epidurally administered fentanyl.

Analgesia↗

PubMed1981

Systemic hyperthermia by the immersion bath method.

Several methods to administer systemic hyperthermia (41.8-42.0 degrees C) as an oncologic procedure have been described in the literature. We have developed a method to induce and maintain a body temperature of 42.0 degrees C (rectal) using a high-flow water immersion bath. This method was tested in a small series of sheep and proved to be applicable. In a preliminary clinical series of 10 treatment sessions advantages compared to the described other methods were noted. After a short induction period, accurate temperature control can be maintained. During the procedure the patient can be observed and handled, while buoyancy in water is an asset. Short term clinical were favourable.

Body Temperature↗