Persistence of external signs in Pacific herring Clupea pallasii Valenciennes with ichthyophoniasis.

The progression of external signs of Ichthyophonus infection in Pacific herring Clupea pallasii Valenciennes was highly variable and asynchronous after intraperitoneal injection with pure parasite preparations; however, external signs generally persisted through the end of the study (429 days post-exposure). Observed signs included papules, erosions and ulcers. The prevalence of external signs plateaued 35 days post-exposure and persisted in 73-79% of exposed individuals through the end of the first experiment (147 days post-exposure). Among a second group of infected herring, external signs completely resolved in only 10% of the fish after 429 days. The onset of mortality preceded the appearance of external signs. Histological examination of infected skin and skeletal muscle tissues indicated an apparent affinity of the parasite for host red muscle. Host responses consisted primarily of granulomatous inflammation, fibrosis and necrosis in the skeletal muscle and other tissues. The persistence and asynchrony of external signs and host response indicated that they were neither a precursor to host mortality nor did they provide reliable metrics for hindcasting on the date of exposure. However, the long-term persistence of clinical signs in Pacific herring may be useful in ascertaining the population-level impacts of ichthyophoniasis in regularly observed populations.

Infecting Pacific Herring with Ichthyophonus sp. in the Laboratory.

The protistan parasite Ichthyophonus sp. occurs in coastal populations of Pacific Herring Clupea pallasii throughout the northeast Pacific region, but the route(s) by which these planktivorous fish become infected is unknown. Several methods for establishing Ichthyophonus infections in laboratory challenges were examined. Infections were most effectively established after intraperitoneal (IP) injections with suspended parasite isolates from culture or after repeated feedings with infected fish tissues. Among groups that were offered the infected tissues, infection prevalence was greater after multiple feedings (65%) than after a single feeding (5%). Additionally, among groups that were exposed to parasite suspensions prepared from culture isolates, infection prevalence was greater after exposure by IP injection (74%) than after exposure via gastric intubation (12%); the flushing of parasite suspensions over the gills did not lead to infections in any of the experimental fish. Although the consumption of infected fish tissues is unlikely to be the primary route of Ichthyophonus sp. transmission in wild populations of Pacific Herring, this route may contribute to abnormally high infection prevalence in areas where juveniles have access to infected offal.

The acute antihyperalgesic action of nonsteroidal, anti-inflammatory drugs and release of spinal prostaglandin E2 is mediated by the inhibition of constitutive spinal cyclooxygenase-2 (COX-2) but not COX-1.

Western blots show the constitutive expression of COX-1 and COX-2 in the rat spinal dorsal and ventral horns and in the dorsal root ganglia. Using selective inhibitors of cyclooxygenase (COX) isozymes, we show that in rats with chronic indwelling intrathecal catheters the acute thermal hyperalgesia evoked by the spinal delivery of substance P (SP; 20 nmol) or NMDA (2 nmol) and the thermal hyperalgesia induced by the injection of carrageenan into the paw are suppressed by intrathecal and systemic COX-2 inhibitors. The intrathecal effects are dose-dependent and stereospecific. In contrast, a COX-1 inhibitor given systemically, but not spinally, reduced carrageenan-evoked thermal hyperalgesia but had no effect by any route with spinal SP hyperalgesia. Using intrathecal loop dialysis catheters, we showed that intrathecal SP would enhance the release of prostaglandin E(2) (PGE(2)). This intrathecally evoked release of spinal PGE(2) was diminished by systemic delivery of nonspecific COX and COX-2-selective inhibitors, but not a COX-1-selective inhibitor. Given at systemic doses that block SP- and carrageenan-evoked hyperalgesia, COX-2, but not COX-1, inhibitors reduced spinal SP-evoked PGE(2) release. Thus, constitutive spinal COX-2, but not COX-1, is an important contributor to the acute antihyperalgesic effects of spinal as well as systemic COX-2 inhibitors.

Maturational changes in the thermal nociceptive responses of developing rats.

Some find developmental differences in rodent thermal nociceptive responses and others do not. To address these inconsistencies, the escape latencies of immature (5-to 25-day-old) and adult (3-to 4-month-old) albino rats were recorded following tail exposure to different intensities of radiant heat (650-W halogen lamp placed 10-30 mm from the tail) or conductive heat 35-50 degrees C water). Developmental differences in tail flick latencies were not observed in immature rats when the lamp was closest to the tail (although adult latencies were longer than 5-and 15-day-old responses) When radiant heat intensity was reduced, 5-day-old rats had shorter escape latencies than 15-, 25-, and 90-day-old animals. Age differences persisted in the latencies of immature animals even when the test aperture was varied to compensate for maturational changes in tail width (whereas adult responses no longer differed from those of 5-and 15-day-old rats). Developmental differences were eliminated when the tail skin was blackened so as to normalize the absorption of radiant heat across age. Similar age-and intensity-dependent differences were observed in rats exposed to conductive heat: Five-and 10-day-old pups had shorter escape responses than older rats when tails were immersed in intermediate (40 or 45 degrees C) but not lower (35 degree C) or higher (50 degrees C) temperature water. Blackening the tails did not change conductive heat escape latencies. No sex differences were found at any age or stimulus intensity with either type of heat. Higher intensities of thermal stimuli applied to the tail are required to elicit escape responses in older rats compared to younger ones, but the use of relatively intense thermal test stimuli can mask age-dependent differences in nociception. Some of the inconsistent results reported previously about maturational changes in thermal nociception may be due to intensity differences in the noxious test stimuli used. Maturational differences in the radiant absorption properties of the tail seem to account for most of the age-related changes in rodent responses to radiant heat, but the mechanism(s) which subserve developmental differences in conductive heat nociception need to be elucidated.

Interactions between nicardipine and enflurane, isoflurane, and sevoflurane.

PURPOSE: During nicardipine induced hypotension, different inhalational anaesthetics may have different effects on haemodynamic variables, sympathetic function and drug metabolism. Therefore, the haemodynamic effects and pharmacokinetics of nicardipine were studied in the presence of the three inhalation anaesthetics enflurane, isoflurane and sevoflurane. METHODS: Thirty patients scheduled for neurosurgery were randomly assigned to one of three anaesthetic techniques: enflurane, isoflurane or sevoflurane. Nicardipine (0.017 mg.kg-1) was administered during stable anaesthesia and the following measurements made for 30 min: blood pressure, heart rate, and plasma concentration of norepinephrine, epinephrine and nicardipine. RESULTS: With sevoflurane, plasma concentrations of nicardipine, five minutes after administration, (39.8 +/- 3.5 ng.ml-1, mean +/- SEM) were higher (P < 0.05) than in the other two groups (28.3 +/- 2.9 ng.ml-1, 32.6 +/- 4.3 ng.ml-1, enflurane and isoflurane, respectively). With isoflurane, the approximated half-life of nicardipine (14 +/- 4 min) was shorter and clearance (2.1 +/- 0.3 l.min-1) more rapid. Peak heart rates were similar in all groups but elevated rates continued longer with isoflurane (> 30 min). Nicardipine-induced reduction in blood pressure was greater with sevoflurane but low pressures persisted for longer with isoflurane. Plasma catecholamine concentrations increased with isoflurane and enflurane, but not with sevoflurane: considerably higher epinephrine concentrations were seen with isoflurane. CONCLUSION: This study showed that the action of nicardipine is modified by different inhalational anaesthetic agents. Nicardipine has a prolonged duration of action in the presence of isoflurane and produces greater initial hypotension with sevoflurane.

Gaseous homeostasis and the circle system. Factors influencing anaesthetic gas exchange.

A mathematical model of a subject breathing from a circle system has been used to follow the course of anaesthetic uptake during the simulated administration of 60% nitrous oxide, 2% halothane and 2% methoxyflurane, under non-rebreathing conditions and with fresh gas flows to the circle system of between 8 and 0.25 litre min-1. Compared with the non-rebreathing state, the use of a circle system reduced the initial rate of increase of alveolar towards fresh gas anaesthetic concentration, and the rate of increase in body anaesthetic content. The degree of reduction became more marked as fresh gas flow was reduced, and as agents of increasing blood solubility were used. These effects of a circle system were influenced by the volume of the circle system and the composition of gas initially present within the system. When the circle system was in use there were increases in the magnitude of both the concentration effect and the second gas effect which were related to the magnitude of fresh gas flow. The use of a circle system augmented the effects of changes in cardiac output and reduced the effects of changes in ventilation on the alveolar concentrations of the anaesthetic. These influences of a circle system were also dependent on the magnitude of fresh gas flow. The degree of augmentation of the effects of cardiac output decreased with increasing blood solubility of the agent in use, whilst the limitation of the effects of ventilation was greatest with the agent of highest blood solubility. Both under non-rebreathing conditions and with the circle system in use, the effects of cardiac output and ventilation were greater with 2% nitrous oxide than with 60% nitrous oxide, and were also greater when gases were given separately than when administered in combination.

Gaseous homeostasis and the circle system. Validation of a model.

The performance of a model of a subject breathing from a circle system has been examined in relation to nitrogen and helium. The ability of the model to maintain a nitrogen steady-state breathing air, the attainment of a new steady-state after perturbation of an existing nitrogen equilibrium, the washout of nitrogen from the subject model on breathing oxygen, and the estimation of functional residual capacity using a rebreathing method with helium as an indicator have been assessed. The predictable and accurate performance of the model in these studies, together with its ability to reproduce the results of a number of previously published studies in man, suggest that the model can be used to predict the behaviour of circle systems when used with inhaled anaesthetic agents.

Gaseous homeostasis and the circle system. Description of a model.

A model has been constructed of a subject breathing from a circle system. The subject model is based on the circulation-time model of anaesthetic uptake described by Mapleson. This is a multi-compartmental model of body tissues in which gas exchange in each compartment is calculated at each heart beat. The lung compartment of Mapleson's model has been modified to allow for an unlimited number of gases to be present in the inspired gas mixture. The circle system model assumes total absorption of all expired carbon dioxide and full mixing of all gases within the system. The volume of gas in the system and its composition is calculated for each respiratory cycle. The subject model can be considered as being either attached to a non-rebreathing system, when inspired gas composition is under the control of the operator, or attached to the circle system, when the operator has control of fresh gas flow and composition. The model has been realized as a computer program written in Pascal.

Alveolar gas relationships during use of the circle system with carbon dioxide absorption.

Expressions have been derived to show the dependence of alveolar oxygen and anaesthetic concentration on fresh gas flow to a circle system, the composition of fresh gas, ventilation and gas uptake. The form of these expressions is influenced by the degree of mixing of fresh and expired gases within the circle system. These expressions assume an equilibrium state within the circle system and the rate at which equilibrium will be approached has been quantified in terms of the time-constants of change of composition of gas within the system. Time-constants approach infinity as fresh gas flow approaches values which just satisfy gas uptake. Whilst simplifying assumptions made in the derivation of the various alveolar gas equations limits their accuracy, the expression can serve as a guide to the likely behaviour of circle systems under any given conditions of use.

Factors affecting carbon dioxide homeostasis during controlled ventilation with circle systems.

An experimental lung model was used, with controlled ventilation, to determine the effect of different circle arrangements and varying ventilatory frequencies on the efficiency of carbon dioxide removal from a circle system without carbon dioxide absorption. Greater efficiency was found when fresh gas entered the system between the unidirectional inspiratory valve and the subject that when the fresh gas inlet was on the ventilator side of this valve. At any fresh gas flow and minute volume, efficiency was greater at low respiratory frequencies. Good correlations existed between carbon dioxide concentration in the model lung, fresh gas flow and minute ventilation when respiratory frequency was constant. Paradoxical results were obtained when minute volume was varied by changes in frequency at a constant tidal volume. The major cause of the various differences in performance has been ascribed to variations in the degree of mixing of fresh and expired gas within the system.

Inhibition of neuronal uptake of noradrenaline in the isolated perfused rat heart by pancuronium and its homologues, Org. 6368, Org. 7268 and NC 45.

The cardiovascular effects of pancuronium may be caused partly by an interaction of this drug with the sympathetic nervous system. We examined one possible mechanism of interaction, the effect on the re-uptake processes for noradrenaline. Pancuronium and its closely related steroidal homologues, Org. 6368, Org. 7268 and NC 45, were studied at a high concentration (500 mumol litre-1) for inhibition of the uptake of tritiated noradrenaline into neuronal sites (Uptake1) and extraneuronal sites (Uptake2) in the isolated perfused rat heart. All drugs tested caused almost total inhibition of Uptake1. The bis-quaternary steroids pancuronium and Org. 6368 were selective for Uptake1 inhibition, the mono-quaternary steriods Org. 7268 and NC45 also produced significant inhibition of Uptake2. Uptake1 inhibition was investigated in detail using lesser concentrations of the compounds. All four steroids were found to cause a concentration-dependent inhibition of Uptake1. It seems likely, therefore, that inhibition of neuronal uptake of noradrenaline plays a significant role in the aetiology of the chronotropic actions of pancuronium in the rat.

Spontaneous ventilation with the Bain anaesthetic system.

Measurements of ventilation and of inspired gas composition were made while volunteers breathed a non-anaesthetic gas through a Bain anaesthetic system. It was found that rebreathing occurred when the fresh gas flow was between two-and-a-half and three times the minute volume. Fresh gas flows at least three times the minute volume appear to be necessary to prevent rebreathing when using this system.

An assessment of the TM3 gas differentiator.

The TM3 Gas differentiator, a simple device introduced to differentiate between nitrous oxide and oxygen, was found to be capable of positively distinguishing between these gases when only they were known to be present. The differentiator gave nearly equal responses to nitrous oxide and carbon dioxide. Cyclopropane, halothane, methoxyflurane, trichloroethylene and nitrogen all produced smaller responses on the differentiator's built-in meter. This apparatus has proved in use to be a practicable and simple method of checking the composition of gases emerging from pipelines.