Alfentanil's analgesic, respiratory, and cardiovascular actions in relation to dose and plasma concentration in unanesthetized dogs.

Relationships between plasma concentrations of alfentanil and its analgesic, respiratory, and cardiovascular effects were determined in dogs. To avoid drug interaction, trained, unanesthetized, spontaneously breathing dogs were used. After a control period in the awake state, alfentanil was injected in increasing amounts (10, 20, 80, 160, and 320 micrograms/kg) at 5-min intervals to a total dose of 590 micrograms/kg administered over 20 min. The effects were observed on pain responses (heart rate and blood pressure changes and somatic reactions to tail clamping), respiration (respiratory rate, oxygen consumption [VO2], blood gas tensions) and circulation (heart rate and blood pressure). The plasma concentration-effect curves, derived by relating the changes in multiple variables from the awake state to the corresponding plasma concentrations (range 8-5079 ng/ml), plateaued at and around 200 ng/ml during the injection period but were displaced in parallel to two-fold higher concentrations during recovery, which resembles acute tolerance. At maximally effective analgesic concentrations, which precipitated profound cardiorespiratory slowing with conspicuous hypoxemia, the VO2 of 4.4 +/- 0.3 ml X kg-1 X min-1 corresponded with the calculated metabolic rate but increased to 6.3 +/- 1.6 ml X kg-1 during recovery. The analgesic action of alfentanil, which cannot be separated from its depressant cardiorespiratory effects and maximally effective analgesic concentrations (between 200 and 400 ng/ml), apparently does not jeopardize the adequacy of tissue oxygenation in dogs.

Fentanyl's analgesic, respiratory, and cardiovascular actions in relation to dose and plasma concentration in unanesthetized dogs.

Relationships between plasma concentrations of fentanyl and is analgesic, respiratory and cardiovascular effects were determined in unanesthetized dogs. To avoid drug interactions the authors used trained unanesthetized spontaneously breathing dogs. After a control period in the awake state, fentanyl was injected in increasing amounts (2.5, 5, 20, 40, and 100 micrograms/kg) at 5-min intervals to a cumulative dose of 167.5 micrograms/kg administered over 20 min and its effects studied on pain responses (heart and blood pressure changes and somatic responses to tail clamping), respiration (respiratory rate, oxygen consumption, blood gas tensions), and circulation (heart rate and blood pressure). Plasma concentration/effect curves were derived by relating the changes in variables from the awake state to the corresponding plasma concentration (range 2-453 ng/ml). Maximum effects occurred at plasma concentrations at and around 30 ng/ml. Oxygen consumption decreased only slightly and remained well above the basal metabolic rate. Cardiac output, heart rate, respiratory rate, and arterial oxygen tension were almost halved during the full action of fentanyl. In dogs, fentanyl's analgesic action cannot be separated from its respiratory and cardiovascular effects. All receptor-mediated effects are maximal at the same plasma concentration, a phenomenon suggesting saturation of the opiate receptors.

Effect of hexachlorobenzene (HCB) on photosynthetic oxygen evolution and respiration of Chlorella pyrenoidosa.

In experiments with Chlorella pyrenoidosa it was shown that an exposure of these cells to HCB at a dose level of 0.1, 1.0, and 5.0 ppm caused an inhibition of photosynthetic oxygen evolution of 33.3, 42, and 51%, respectively. Respiration, however, was inhibited only slightly, if at all.

Effect of hexachlorobenzene and acetone on algal growth: physiology and ultrastructure.

The effect of hexachlorobenzene (HCB) and acetone on growth and ultrastructure of the freshwater alga Chlorella pyrenoidosa was studied. The algal cells were grown for 76 h under continuous light in 10 ppm HCB with 0.33% acetone or in 0.33% acetone alone; the control cells were grown in nutrient solution only. As was deduced from determinations of dry matter, carbohydrates, chlorophyll content and total nitrogen, 0.33% acetone in nutrient solution slightly decreased the growth of the cells without having any influence on their ultrastructure while 3.33% acetone affected the ultrastructure of the cells severely. An incubation of Chlorella with 10 ppm HCB in nutrient sultion containing 0.33% acetone led to a drastic decrease of all growth parameters studied, total nitrogen and chlorophyll content being affected most strongly. These latter observations were in accord with the changes in ultrastructure showing damage to the cell membranes, disintegrated cytoplasm and sometimes even break down of cell organells leaving only starch grains, the pyrenoid and some endomembranes. In addition to these cells with severe lesions, quite normal cells were found.

Effect of hexachlorobenzene (HCB) on growth of Tetrahymena pyriformis.

Tetrahymena pyriformis Wh 14 was incubated with HCB (0.001 - 0.5 ppm) in Erlenmeyer flasks under continuous stirring at 30degreesC for 10 days in an incubator. HCB decreased growth as deduced from measurements of dry weight, carbohydrates, and total nitrogen. Total nitrogen and carbohydrates are decreased drastically while dry matter is reduced only by a factor of two. The excretion of a compound into the nutrient solution which yields a colour with modified Ehrlich reagent like porphobilinogen is very strongly increased by HCB. All effects observed were very well correlated with the concentration of this compound applied.

Effect of hexachlorobenzene on some growth parameters of Chlorella pyrenoidosa.

Chlorella pyrenoidosa was incubated with HCB (0.001-10.0 ppm) in a "light-thermostat" at 30 degrees C for 46 h with continuous light (4000 Lux) and aeration. HCB decreased growth as deduced from measurements of chlorophyll content, dry matter, carbohydrate content, and total nitrogen. Incubation with HCB for three months in Erlenmeyer-flasks resulted in an increase of chlorophyll over control value in cultures receiving 0.1 and 1.0 ppm HCB. After transfer of the cultures from Erlenmeyer-flasks to growth conditions of a "light-thermostat", growth of the algae was greatly enhanced by all HCB concentrations studied; a concentration of 0.1 ppm being most effective.