Journal of pharmacological and toxicological methods
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J Pharmacol Toxicol Methods · Mar 2004
Determination of interstitial rocuronium concentrations in the muscle tissue of anesthetized dogs by microdialysis.
The objective was to establish and validate a microdialysis technique for the quantification of interstitial concentrations of the neuromuscular blocker, rocuronium, in the muscle tissue of dogs under steady-state conditions. ⋯ Combined retrodialysis is a more reliable and accurate technique for quantitative assessment of rocuronium interstitial concentrations especially for lengthy anesthetic procedures. These findings have potential implications, as drug concentrations in the site of action would be more relevant for concentration-effect relation of muscle relaxants.
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The venous system contains about 70% of the blood volume, and approximately 75% of the venous volume is in the small veins and venules. Veins play an active role in the control of cardiac output (CO) and blood pressure. ⋯ In vivo methods used for the assessment of venous function in experimental animals and humans are as follows: the mean circulatory filling pressure (MCFP) method for the determination of body venous tone, constant CO reservoir technique for measuring vascular compliance and unstressed volume, plethysmography or blood-pool scintigraphy along with venous occlusion for measuring the volume and compliance of an organ, linear variable differential transformer (LVDT) technique for estimating the diameter of a human dorsal hand vein, intravascular ultrasound (IVUS) imaging technique to monitor the cross-sectional area of a large vein, and ultrasonic crystals to estimate the dimension of an organ. These methods are described and critically evaluated to disclose their validity, merits and limitations.
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J Pharmacol Toxicol Methods · Jan 2000
An in vivo method for the quantitative evaluation of local anesthetics.
We describe a mouse model for evaluation of skin anesthesia after infiltration of local anesthetic. The method involves subcutaneous injection of the anesthetic over the abdomen, and monitoring the vocalization response to electrical stimulus as a measure of analgesia. Prior to drug injection, the vocalization threshold was determined. ⋯ To further validate the model, we compared the duration of anesthesia between the 0.5% bupivacaine and a new long-acting liposomal formulation of 2% bupivacaine. The results showed that the new formulation significantly prolonged the duration of anesthesia (p<0.05). This simple and reliable method may facilitate research on the pharmacology of infiltration anesthesia and the development of new local anesthetics and/or formulations.
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J Pharmacol Toxicol Methods · Apr 1999
A method for normalizing drug responses to enhance reliability of parametric statistical tests.
Experimental constraints often require that pharmacologists study the effects of treatments upon responses elicited with a single concentration of agonist. The choice of statistical analysis, nonparametric or parametric, will depend upon whether or not the responses are normally distributed. ⋯ A simple transformation of responses, however, can restore normality. Researchers may find it beneficial to transform response data prior to performing t tests, analysis of variance or other parametric statistics in order to preserve the power and confidence level of the test.
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J Pharmacol Toxicol Methods · Apr 1999
A rat model of acute respiratory distress syndrome (ARDS) Part 2, influence of lavage volume, lavage repetition, and therapeutic treatment with rSP-C surfactant.
The influence of lavage volume, and lavage repetition with physiological saline solution (groups 1-3: 3x4, 4x4, 5x4, groups 7-9: 3x8, 5x8, 7x8, mL per animal) was studied in a rat lung lavage model of the acute respiratory distress syndrome (ARDS). Anesthetized and tracheotomized rats (12 rats/group) were pressure-controlled ventilated with 100% oxygen at a respiratory rate of 30 breaths/min, inspiration: expiration ratio of 1:2, peak inspiratory pressure of 28 cm H2O at positive end-expiratory pressure of 8 cm H2O during the whole experimental period. To investigate the influence of therapeutic treatment, a recombinant surfactant protein C (rSP-C) containing surfactant was used. Therefore, rats which received a lavage of 4x4 mL per animal (groups 4 to 6) or 7x8 mL per animal (groups 10-12) were treated intratracheally with surfactant doses of 12.5, 25, or 100 mg phospholipids (PL) per kg body weight (bw). In all groups, partial arterial oxygen pressures (PaO2, mm Hg) and partial arterial carbon dioxide pressures (PaCO2, mm Hg) were determined 30 min before, directly after, and 5, 30, 60, 90, 120, 150, 180, and 210 min after the last lavage. Additionally, animals were euthanized 210 min after the last lavage for semiquantitative histopathological grading of coded lung slides. Grading was performed with respect to the severity of hyaline membrane formation (HM), margination and infiltration of polymorphonuclear neutrophil leukocytes (PMNL) into the lung alveoli and interstitial and intraalveolar edema (E). The intrapulmonary distribution of intratracheally applied rSP-C was estimated in selected lung slides stained with polyclonal anti-rSP-C antibody and was compared to unlavaged control rats and unlavaged rats which received 100 mg/kg bw rSP-C. The repetitive lavage depleted the lung from its natural surfactant resources leading to a pathophysiological cascade similar to that of the acute respiratory distress syndrome. PaO2 levels and HM formation showed a lavage-induced decrease. Both changes were significantly dependent on the repetition and volume of the lavage; however, the parameters PMNL and E did not show such a dependence. Treatment with rSP-C surfactant significantly improved oxygenation and reduced HM-formation in a dose-dependent manner independent from the lavage volume. All doses of rSP-C surfactant showed no clear influence on the parameters PMNL and E independently from the lavage volume. In lavaged rat lungs (ARDS-model), the exogenously applied rSP-C was distributed homogeneously along the alveolar lining. Unlavaged rats that received a similar dose of rSP-C showed a marked inhomogeneous extracellular distribution, mainly associated with larger bronchi, while the type II pneumocytes were stained positively in unlavaged control and unlavaged rSP-C treated rats. ⋯ This model mimics very closely the wide spectrum of the clinical situation of human acute lung injury (ALI) because the variation of lavage volume and repetition lead to reproducible different severity grades and states of ALI. The significant reduction of pathognomic changes due to treatment with rSP-C surfactant showed that this is a useful model to estimate the influence of therapeutic concepts in ALI and ARDS.