Note: optimization of the numerical data analysis for conductivity percolation studies of drying moist porous systems.

A simplified data analysis protocol, for dielectric spectroscopy use to study conductivity percolation in dehydrating granular media is discussed. To enhance visibility of the protonic conductivity contribution to the dielectric loss spectrum, detrimental effects of either low-frequency dielectric relaxation or electrode polarization are removed. Use of the directly measurable monofrequency dielectric loss factor rather than estimated DC conductivity to parameterize the percolation transition substantially reduces the analysis work and time.

1H relaxation dispersion in solutions of nitroxide radicals: influence of electron spin relaxation.

The work presents a theory of nuclear ((1)H) spin-lattice relaxation dispersion for solutions of (15)N and (14)N radicals, including electron spin relaxation effects. The theory is a generalization of the approach presented by Kruk et al. [J. Chem. Phys. 137, 044512 (2012)]. The electron spin relaxation is attributed to the anisotropic part of the electron spin-nitrogen spin hyperfine interaction modulated by rotational dynamics of the paramagnetic molecule, and described by means of Redfield relaxation theory. The (1)H relaxation is caused by electron spin-proton spin dipole-dipole interactions which are modulated by relative translational motion of the solvent and solute molecules. The spectral density characterizing the translational dynamics is described by the force-free-hard-sphere model. The electronic relaxation influences the (1)H relaxation by contributing to the fluctuations of the inter-molecular dipolar interactions. The developed theory is tested against (1)H spin-lattice relaxation dispersion data for glycerol solutions of 4-oxo-TEMPO-d16-(15)N and 4-oxo-TEMPO-d16-(14)N covering the frequency range of 10 kHz-20 MHz. The studies are carried out as a function of temperature starting at 328 K and going down to 290 K. The theory gives a consistent overall interpretation of the experimental data for both (14)N and (15)N systems and explains the features of (1)H relaxation dispersion resulting from the electron spin relaxation.

Translational diffusion in paramagnetic liquids by 1H NMR relaxometry: nitroxide radicals in solution.

For nitroxide radicals in solution one can identify three frequency regimes in which (1)H spin-lattice relaxation rate of solvent molecules depend linearly on square root of the (1)H resonance frequency. Combining a recently developed theory of nuclear (proton) spin-lattice relaxation in solutions of nitroxide radicals [D. Kruk et al., J. Chem. Phys. 137, 044512 (2012)] with properties of the spectral density function associated with translational dynamics, relationships between the corresponding linear changes of the relaxation rate (for (14)N spin probes) and relative translational diffusion coefficient of the solvent and solute molecules have been derived (in analogy to (15)N spin probes [E. Belorizky et al., J. Phys. Chem. A 102, 3674 (1998)]). This method allows a simple and straightforward determination of diffusion coefficients in spin-labeled systems, by means of (1)H nuclear magnetic resonance (NMR) relaxometry. The approach has thoroughly been tested by applying to a large set of experimental data-(1)H spin-lattice relaxation dispersion results for solutions of different viscosity (decalin, glycerol, propylene glycol) of (14)N and (15)N spin probes. The experiments have been performed versus temperature (to cover a broad range of translational diffusion coefficients) using field cycling spectrometer which covers three decades in (1)H resonance frequency, 10 kHz-20 MHz. The limitations of NMR relaxometry caused by the time scale of the translational dynamics as well as electron spin relaxation have been discussed. It has been shown that for spin-labeled systems NMR relaxometry gives access to considerably faster diffusion processes than for diamagnetic systems.

ESR lineshape and 1H spin-lattice relaxation dispersion in propylene glycol solutions of nitroxide radicals--joint analysis.

Electron Spin Resonance (ESR) spectroscopy and Nuclear Magnetic Relaxation Dispersion (NMRD) experiments are reported for propylene glycol solutions of the nitroxide radical: 4-oxo-TEMPO-d16 containing (15)N and (14)N isotopes. The NMRD experiments refer to (1)H spin-lattice relaxation measurements in a broad frequency range (10 kHz-20 MHz). A joint analysis of the ESR and NMRD data is performed. The ESR lineshapes give access to the nitrogen hyperfine tensor components and the rotational correlation time of the paramagnetic molecule. The NMRD data are interpreted in terms of the theory of paramagnetic relaxation enhancement in solutions of nitroxide radicals, recently presented by Kruk et al. [J. Chem. Phys. 138, 124506 (2013)]. The theory includes the effect of the electron spin relaxation on the (1)H relaxation of the solvent. The (1)H relaxation is caused by dipole-dipole interactions between the electron spin of the radical and the proton spins of the solvent molecules. These interactions are modulated by three dynamic processes: relative translational dynamics of the involved molecules, molecular rotation, and electron spin relaxation. The sensitivity to rotation originates from the non-central positions of the interacting spin in the molecules. The electronic relaxation is assumed to stem from the electron spin-nitrogen spin hyperfine coupling, modulated by rotation of the radical molecule. For the interpretation of the NMRD data, we use the nitrogen hyperfine coupling tensor obtained from ESR and fit the other relevant parameters. The consistency of the unified analysis of ESR and NMRD, evaluated by the agreement between the rotational correlation times obtained from ESR and NMRD, respectively, and the agreement of the translation diffusion coefficients with literature values obtained for pure propylene glycol, is demonstrated to be satisfactory.

1H relaxation dispersion in solutions of nitroxide radicals: effects of hyperfine interactions with 14N and 15N nuclei.

(1)H relaxation dispersion of decalin and glycerol solutions of nitroxide radicals, 4-oxo-TEMPO-d(16)-(15)N and 4-oxo-TEMPO-d(16)-(14)N was measured in the frequency range of 10 kHz-20 MHz (for (1)H) using STELAR Field Cycling spectrometer. The purpose of the studies is to reveal how the spin dynamics of the free electron of the nitroxide radical affects the proton spin relaxation of the solvent molecules, depending on dynamical properties of the solvent. Combining the results for both solvents, the range of translational diffusion coefficients, 10(-9)-10(-11) m(2)/s, was covered (these values refer to the relative diffusion of the solvent and solute molecules). The data were analyzed in terms of relaxation formulas including the isotropic part of the electron spin - nitrogen spin hyperfine coupling (for the case of (14)N and (15)N) and therefore valid for an arbitrary magnetic field. The influence of the hyperfine coupling on (1)H relaxation of solvent molecules depending on frequency and time-scale of the translational dynamics was discussed in detail. Special attention was given to the effect of isotope substitution ((14)N/(15)N). In parallel, the influence of rotational dynamics on the inter-molecular (radical - solvent) electron spin - proton spin dipole-dipole coupling (which is the relaxation mechanism of solvent protons) was investigated. The rotational dynamics is of importance as the interacting spins are not placed in the molecular centers. It was demonstrated that the role of the isotropic hyperfine coupling increases for slower dynamics, but it is of importance already in the fast motion range (10(-9)m(2)/s). The isotope effects is small, however clearly visible; the (1)H relaxation rate for the case of (15)N is larger (in the range of lower frequencies) than for (14)N. It was shown that when the diffusion coefficient decreases below 5 × 10(-11) m(2)/s electron spin relaxation becomes of importance and its role becomes progressively more significant when the dynamics slows done. As far as the influence of the rotational dynamics is concerned, it was show that this process is of importance not only in the range of higher frequencies (like for diamagnetic solutions) but also at low and intermediate frequencies.

Sensitivity of 2H NMR spectroscopy to motional models: proteins and highly viscous liquids as examples.

In order to study to what extent mechanisms of molecular motion can be unambiguously revealed by (2)H NMR spectroscopy, (2)H spectra for proteins (chicken villin protein headpiece HP36, selectively methyl-deuterated at leucine-69, C(δ) D(3)) and binary systems of high viscosity (benzene-d(6) in tricresyl phosphate) have been carefully analyzed as illustrative examples (the spectra are taken from the literature). In the first case, a model of restricted diffusion mediated by jumps between rotameric orientations has been tested against jump- and free diffusion models which describe rotational motion combined with jump dynamics. It has been found that the set of (2)H spectra of methyl-deuterated at leucine-69 chicken villin protein headpiece HP36 can be consistently explained by different motional models as well as by a gaussian distribution of correlation times assuming isotropic rotation (simple brownian diffusion model). The last finding shows that when the possible distribution of correlation times is not very broad one might not be able to distinguish between heterogeneous and homogenous (but more complex) dynamics by analyzing (2)H lineshapes. For benzene-d(6) in tricresyl phosphate, the dynamics is heterogeneous and it has been demonstrated that a gaussian distribution of correlation times reproduces well the experimental lineshapes, while for a Cole-Davidson distribution the agreement is somewhat worse. For inquires into the sensitivity of quadrupolar NMR spectral analysis (by "quadrupolar NMR spectroscopy we understand NMR spectroscopy of nuclei possessing quadrupole moment), the recently presented theoretical approach [Kruk et al., J. Chem. Phys. 135, 224511 (2011)] has been used as it allows simulating quadrupolar spectra for arbitrary motional conditions by employing the stochastic Liouville equation.

1H NMR relaxation in glycerol solutions of nitroxide radicals: effects of translational and rotational dynamics.

(1)H spin-lattice relaxation rates in glycerol solutions of selected nitroxide radicals at temperatures between 200 K and 400 K were measured at 15 MHz and 25 MHz. The frequency and temperature conditions were chosen in such a way that the relaxation rates go through their maximum values and are affected by neither the electron spin relaxation nor the electron-nitrogen nucleus hyperfine coupling, so that the focus could be put on the mechanisms of motion. By comparison with (1)H spin-lattice relaxation results for pure glycerol, it has been demonstrated that the inter-molecular electron spin-proton spin dipole-dipole interactions are affected not only by relative translational motion of the solvent and solute molecules, but also by their rotational dynamics as the interacting spins are displaced from the molecular centers; the eccentricity effects are usually not taken into account. The (1)H relaxation data have been decomposed into translational and rotational contributions and their relative importance as a function of frequency and temperature discussed in detail. It has been demonstrated that neglecting the rotational effects on the inter-molecular interactions leads to non-realistic conclusions regarding the translational dynamics of the paramagnetic molecules.

Nuclear quadrupole resonance lineshape analysis for different motional models: stochastic Liouville approach.

A general theory of lineshapes in nuclear quadrupole resonance (NQR), based on the stochastic Liouville equation, is presented. The description is valid for arbitrary motional conditions (particularly beyond the valid range of perturbation approaches) and interaction strengths. It can be applied to the computation of NQR spectra for any spin quantum number and for any applied magnetic field. The treatment presented here is an adaptation of the "Swedish slow motion theory," [T. Nilsson and J. Kowalewski, J. Magn. Reson. 146, 345 (2000)] originally formulated for paramagnetic systems, to NQR spectral analysis. The description is formulated for simple (Brownian) diffusion, free diffusion, and jump diffusion models. The two latter models account for molecular cooperativity effects in dense systems (such as liquids of high viscosity or molecular glasses). The sensitivity of NQR slow motion spectra to the mechanism of the motional processes modulating the nuclear quadrupole interaction is discussed.

Electron spin resonance in studies of membranes and proteins.

We provide a review of current electron spin resonance (ESR) techniques for studying basic molecular mechanisms in membranes and proteins by using nitroxide spin labels. In particular, nitroxide spin label studies with high-field/high-frequency ESR and two-dimensional Fourier transform ESR enable one to accurately determine distances in biomolecules, unravel the details of the complex dynamics in proteins, characterize the dynamic structure of membrane domains, and discriminate between bulk lipids and boundary lipids that coat transmembrane peptides or proteins; these studies can also provide time resolution to studies of functional dynamics of proteins. We illustrate these capabilities with recent examples.

Propofol sedation produces dose-dependent suppression of lidocaine-induced seizures in rats.

UNLABELLED: The association of propofol with excitatory motor activity, such as myoclonic jerking and opisthotonus, in humans and in animals suggests that it may aggravate clinical seizure activity in some circumstances, although evidence suggests that under other circumstances, propofol inhibits seizure activity. In the current study, we assessed the effect of sedating doses of propofol on lidocaine-induced seizure activity in spontaneously breathing rats receiving no other anesthetics. Adult Sprague-Dawley male rats, 300-400 g, were divided into a control group and three experimental groups representing three graded levels of propofol sedation. The control rats then received a lidocaine infusion at the rate of 150 mg x kg(-1) x h(-1), resulting in a slow, progressive increase in systemic lidocaine concentrations. At the onset of electroencephalographic (EEG) seizure activity, arterial lidocaine concentrations were obtained. The treated rats received propofol according to three different dose schedules: Dose 1 = 10 mg x kg(-1) x h(-1) after a 2.5-mg/kg bolus; Dose 2 = 20 mg x kg(-1) x h(-1) after a 5-mg/kg bolus; Dose 3 = 40 mg x kg(-1) x h(-1) after a 10-mg/kg bolus. After 30 min, a steady level of sedation, dependent on the dose of propofol, was achieved. The lidocaine infusion was then started, and systemic lidocaine levels were obtained at the onset of EEG seizure activity. The lidocaine was continued until the onset of death by cardiac arrest. Plasma lidocaine was measured by gas chromatography. Analysis of variance and Dunnett's t-test were used for comparisons with the control values. Continuous propofol sedation increased the seizure dose of lidocaine from 37.7 +/- 3.5 mg/kg (mean +/- SEM) to 52.5 +/- 2.6 mg/kg (Dose 1, P < 0.05) and 67.9 +/- 8.6 mg/kg (Dose 2, P < 0.05), and completely abolished lidocaine seizures at Dose 3. The lethal dose of lidocaine, 89.4 +/- 10.5 mg/kg control versus 108.7 +/- 10.3 mg/kg (Dose 1), 98.3 +/- 10.1 mg/kg (Dose 2), and 93.5 +/- 10.4 mg/kg (Dose 3) did not differ among groups. The lidocaine levels at seizure threshold were increased in the propofol-treated rats: 16.9 +/- 0.5 microg/mL control versus 19.2 +/- 0.7 microg/mL (Dose 1, P = not significant) and 23.7 +/- 1.8 microg/mL (Dose 2, P < 0.05). Continuous propofol sedation in spontaneously breathing rats receiving no other anesthetics exerts a protective effect against lidocaine-induced seizures in a monotonic, dose-dependent fashion. The cardiac arrest dose of lidocaine is unaffected by propofol under these conditions. IMPLICATIONS: The i.v. anesthetic drug propofol, given to rats to produce sedation, was found to suppress seizure activity caused by overdosage of the local anesthetic lidocaine.

Nitric oxide synthase inhibitors, 7-nitro indazole and nitroG-L-arginine methyl ester, dose dependently reduce the threshold for isoflurane anesthesia.

BACKGROUND: Nitric oxide (NO), a recognized cell messenger for activating soluble guanylate cyclase, is produced by the enzyme NO synthase in a wide variety of tissues, including vascular endothelium and the central nervous system. The authors previously reported the possible involvement of the NO pathway in the anesthetic state by showing that a specific NO synthase inhibitor, nitroG-L-arginine methyl ester (L-NAME), dose dependently and reversibly decreases the minimum alveolar concentration (MAC) for halothane anesthesia. The availability of a structurally distinct inhibitor selective for the neuronal isoform of NO synthase, 7-nitro indazole (7-NI), allowed for the possibility of dissociating the central nervous system effects of neuronal NO synthase inhibition from the cardiovascular effects of endothelial NO synthase inhibition. METHODS: The effect of two structurally distinct inhibitors of NO synthase, L-NAME and 7-NI, on the MAC of isoflurane was investigated in Sprague-Dawley rats while concurrently monitoring the animals' arterial blood pressure and heart rate. L-NAME (1 to 30 mg/kg given intravenously, dissolved in 0.9% saline) and 7-NI (20 to 1,000 mg/kg given intraperitoneally, dissolved in arachis oil) were administered after determining control MAC and 30 min before determining MAC in the presence of NO synthase inhibitor. RESULTS: L-NAME and 7-NI caused a dose-dependent decrease from isoflurane control MAC (maximal effect: 35.5 +/- 2.5% and 43.0 +/- 1.7%, respectively) with a ceiling effect observed for both NO synthase inhibitors (above 10 mg/kg and 120 mg/kg, respectively). L-NAME administration significantly increased systolic and diastolic blood pressures (maximal effect: 39.9 +/- 2.2% and 64.3 +/- 4.0%, respectively), which were not accompanied by any changes in heart rate. 7-NI administration resulted in no changes in blood pressure and a small but clinically insignificant decrease in heart rate. CONCLUSIONS: Inhibition of the NO synthase pathway decreased the MAC for isoflurane, which suggests that inhibition of the NO pathway decreases the level of consciousness and augments sedation, analgesia, and anesthesia. The MAC reduction by two structurally distinct NO synthase inhibitors supports that this is a specific effect on NO synthase. Furthermore, the action of the neuronal NO synthase inhibitor 7-NI supports an effect selective for neuronal NO synthase and also avoids the hypertensive response of generalized NO synthase inhibitors.

250-GHz electron spin resonance studies of polarity gradients along the aliphatic chains in phospholipid membranes.

Rigid-limit 250-GHz electron spin resonance (FIR-ESR) spectra have been studied for a series of phosphatidylcholine spin labels (n-PC, where n = 5, 7, 10, 12, 16) in pure lipid dispersions of dipalmitoylphosphatidylcholine (DPPC) and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), as well as dispersions of DPPC containing the peptide gramicidin A (GA) in a 1:1 molar ratio. The enhanced g-tensor resolution of 250-GHz ESR for these spin labels permitted a careful study of the nitroxide g-tensor as a function of spin probe location and membrane composition. In particular, as the spin label is displaced from the polar head group, Azz decreases and gxx increases as they assume values typical of a nonpolar environment, appropriate for the hydrophobic alkyl chains in the case of pure lipid dispersions. The field shifts of spectral features due to changes in gxx are an order of magnitude larger than those from changes in Azz. The magnetic tensor parameters measured in the presence of GA were characteristic of a polar environment and showed only a very weak dependence of Azz and gxx on label position. These results demonstrate the significant influence of GA on the local polarity along the lipid molecule, and may reflect increased penetration of water into the alkyl chain region of the lipid in the presence of GA. The spectra from the pure lipid dispersions also exhibit a broad background signal that is most significant for 7-, 10-, and 12-PC, and is more pronounced in DPPC than in POPC. It is attributed to spin probe aggregation yielding spin exchange narrowing. The addition of GA to DPPC essentially suppressed the broad background signal observed in pure DPPC dispersions.

Nitric oxide synthase inhibitor dose-dependently and reversibly reduces the threshold for halothane anesthesia. A role for nitric oxide in mediating consciousness?

Nitric oxide is a newly recognized cell messenger for the activation of soluble guanylate cyclase and is produced from L-arginine by the enzyme nitric oxide synthase in a wide variety of tissues, including vascular endothelium and brain. Inhalational anesthetics inhibit nitric oxide production from vascular endothelium and also decrease resting cyclic guanosine monophosphate content in multiple brain regions. Halothane has been shown to depress neurotransmission by L-glutamate and N-methyl-D-aspartate. These amino acid neurotransmitters are known to increase neuronal cyclic guanosine monophosphate content by stimulation of nitric oxide production. To investigate the possible involvement of the L-arginine-to-nitric oxide pathway in the anesthetic state, the effect of a specific nitric oxide synthase inhibitor, nitroG-L-arginine methyl ester, on the minimum alveolar concentration (MAC) for halothane anesthesia was determined in Sprague-Dawley rats. Bolus injection of nitroG-L-arginine methyl ester at 0, 1, 5, 10, 20, and 30 mg/kg resulted in a dose-dependent reduction in MAC for halothane of 0 +/- 0, 2.3 +/- 0.4, 21.5 +/- 3.9, 30.5 +/- 2.4, 51.0 +/- 7.8, and 26.0 +/- 2.8%, respectively. NitroG-L-arginine methyl ester had no effect on MAC for halothane. Bolus infusion of L-arginine 300 mg/kg after MAC reduction by nitroG-L-arginine methyl ester 10 mg/kg resulted in an immediate and complete reversal of the MAC reduction. No reversal was observed after infusion of D-arginine 300 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)

Ketorolac does not decrease the MAC of halothane or depress ventilation in rats.

To determine the effects of intravenous (IV) ketorolac on anesthesia and the mechanisms involved, we evaluated its effects on minimum alveolar anesthetic concentration (MAC) and ventilation in halothane-anesthetized rats. Ketorolac in clinical (0.2 and 2 mg/kg) and large (20 and 40 mg/kg) IV doses did not affect the MAC of halothane (0.82% +/- 0.02%). Resting end-tidal CO2 tension (5.1% +/- 0.1%) and the slope of the CO2 response curves (70 +/- 6 mL.min-1.%-1) were also unaffected by IV ketorolac. The mean arterial blood pressure did not significantly change after ketorolac in doses of 0.2, 2, or 20 mg/kg but decreased significantly (P less than 0.05) after 40 mg/kg (placebo 99 +/- 8 mm Hg; ketorolac 87 +/- 6 mm Hg). This study demonstrates that MAC, ventilation, and mean arterial blood pressure are unaffected by clinical doses of IV ketorolac. Furthermore, the lack of effect on MAC and ventilation from larger doses suggests that ketorolac does not have mechanisms of action in the central nervous system.

Thiopental reduces halothane MAC in rats.

The anesthetic contribution of specific plasma concentrations of thiopental has not been previously defined in laboratory animals. The plasma thiopental concentrations needed to reduce the anesthetic requirement for halothane by fractions of the minimum alveolar anesthetic concentration (MAC) were assessed in the rat. After steady-state thiopental plasma concentrations were established with a constant infusion, the tail-clamp technique was used to determine control MAC and the MAC of halothane with increasing concentrations of thiopental. We observed progressive reductions in halothane MAC. This required logarithmic increases in thiopental concentration rather than linear ones. A nonlinear reduction in anesthetic requirement was noted with an approximate 50% reduction in MAC at a thiopental plasma concentration of 7.4 micrograms/mL and an approximate 90% reduction at 32 micrograms/mL. Thiopental appears to provide essentially complete anesthesia in the rat model with a logarithmic contribution of increasing plasma concentrations.

Dynamics of phosphatidylcholine-cholesterol mixed model membranes in the liquid crystalline state.

The effects of cholesterol on the dynamics of cholestane spin probe (CSL) in various phosphatidylcholine-cholesterol mixed model membranes are examined. The lateral diffusion, D of CSL in DMPC/POPC/cholesterol ternary mixtures, is measured utilizing an improved dynamic imaging electron spin resonance method. It shows a factor of two decrease at 10 mol % and 25 degrees C, whereas it shows only a 40% decrease at 50 mol % and 50 degrees C. A comparison with results in POPC/cholesterol mixtures, which show a stronger effect of cholesterol on D, indicates that acyl chain unsaturation leads to stronger self association of cholesterol in PC model membranes. An S2CSL dependence of the activation energy for D, has been confirmed for the DMPC/POPC/cholesterol mixtures. Here SCSL is the order parameter for CSL. A similar correlation of R perpendicular, the perpendicular component of the rotational diffusion coefficient, with SCSL, which is true for all three mixtures (DMPC/cholesterol, POPC/cholesterol, and DMPC/POPC/cholesterol) we have studied, is also found. These are associated with the effects of enhanced local ordering on the free volume needed for translation and reorientation. Such correlations of dynamic properties D and R perpendicular with the thermodynamic quantity S, as well as the consistent interpretations of the effect of acyl chain unsaturation on the dynamics in terms of the activity coefficients, strongly emphasize the interrelation between the dynamic structure and the thermodynamics of the PC/cholesterol mixtures.

In vitro diffusion of lidocaine across endotracheal tube cuffs.

Smooth emergence from general endotracheal anesthesia is frequently complicated by coughing induced by stimulation from an endotracheal tube. Lidocaine and other local anesthetics have been shown to anesthetize important rapidly adpating stretch receptors in the dog trachea. With the aim of providing a reservoir for continuous lidocaine release to adjacent tracheal tissue, we examined the ability of clinically used concentrations of lidocaine to diffuse across a commonly used endotracheal tube cuff. Cuffs were filled with either 2% or 4% lidocaine and placed in a 200 mL bath with samples drawn at time intervals up to 360 minutes. Samples were then analyzed for lidocaine concentration. Another set of endotracheal tube cuffs were prefilled for one or 2.5 hours with 2% or 4% lidocaine, emptied, and then refilled with 2% lidocaine. They were then bathed and sampled as above. Cuffs exposed to 4% lidocaine during the prefilling or the diffusion stages resulted in significantly higher concentrations of lidocaine in the baths throughout the time course of the experiment, although all groups demonstrated a rise in the concentration of lidocaine in the baths with time. The highest concentration obtained was 17.49 +/- 2.03 micrograms/mL after 360 minutes. We conclude lidocaine diffuses across endotracheal tube cuffs in a fashion that may enable the cuff to serve a potentially useful role as a reservoir for local anesthetic. This in turn appears to have the potential to smooth emergence from general endotracheal anesthesia in those patients in whom tracheal stimulation may be a complicating factor.

Vascular effects of 2-chloroprocaine and sodium metabisulfite on isolated rat aortic rings.

Neurologic deficits have followed the intrathecal injection of 2-chloroprocaine 3% (10(-1) M) with sodium metabisulfite 0.2% (10(-2) M) as a preservative. This study evaluated the effects of varying concentrations of 2-chloroprocaine and sodium metabisulfite, as well as the combination of the two, on the vascular reactivity of isolated rings of rat thoracic aorta. Isolated Sprague-Dawley rat thoracic aortic rings were prepared and connected to force transducers for measurement of isometric tension. The tension produced by log-arithmically increasing concentrations of 2-chloroprocaine, sodium metabisulfite, and their paired combination was measured. Sodium metabisulfite concentrations below 0.2% (10(-2) M) caused a maximum of 40% vasoconstriction compared to control followed by vasodilation with a maximum of 80% at 10(-2) M (the concentration in the former clinical preparation). 2-chloroprocaine alone produced a progressive relaxation at 10(-3) M or higher concentration with a maximum of 130%. The effects of the mixture of sodium metabisulfite and 2-chloroprocaine were identical to the effects produced by 2-chloroprocaine alone. The relaxation effects of 2-chloroprocaine dominate the vasoconstricting effects of sodium metabisulfite when the two drugs are combined.

Enhancement of anesthetic effect of halothane by spiradoline, a selective kappa-agonist.

Reduction in the anesthetic requirement of halothane by narcotics has been studied extensively in humans and animals. Problems of respiratory depression, cardiovascular depression, muscle rigidity, and abuse potential make narcotics less than ideal as supplements to general anesthesia with inhalational agents. Spiradoline, a clinical candidate, is a highly potent and selective kappa-agonist. As such it was considered important to study the effects of spiradoline on the minimum anesthetic concentration (MAC) of halothane required to block responses to noxious stimulation. The results of these experiments in rats showed a dose and plasma concentration-dependent reduction in halothane MAC over a wide range of subcutaneous doses of spiradoline (0.03 to 300 mg/kg). A maximum MAC reduction of 70% was obtained. Plasma levels of spiradoline (6 to 1800 ng/ml) were linearly related to dose. Measurement of blood pressure, heart rate, and PCO2 determined over the course of each experiment showed minor variations which would be acceptable if observed in a clinical setting. It is concluded that spiradoline has promise as an anesthetic supplement.