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Effect of buffer media composition on the solubility and effective permeability coefficient of ibuprofen.

The effect of perfusion medium composition on the two important biopharmaceutical parameters drug solubility and permeability was determined for ibuprofen. Eight commonly used buffers were examined. Equilibrium solubility, buffer capacity profiles and permeability coefficients, using the in situ rat gut perfusion model, were determined for each medium at 37 degrees C. The solubility of ibuprofen differed sixfold over the range of buffer systems studied. The differences in solubility were associated with different pHs of the buffers when saturated with drug and also the presence of micelles and divalent ions. The solubility of ibuprofen in FeSSIF was significantly higher than predicted from the pH due to micellisation, while that in Krebs was significantly lower due to ibuprofen-calcium salt formation. Buffer capacities varied over a 40-fold range. The pK(a) values of the buffer components were determined from the buffer capacity versus pH profiles and were in good agreement with the thermodynamic values when corrected for temperature and ionic strength. Smaller, but statistically significant differences in P(app) values for ibuprofen were also observed between some of the buffers. During perfusion, pHs of the perfusate samples gradually changed over time towards a median value of approximately 6.5. HBSS gave a P(app) approximately 50% greater than that observed in PBS 7.4. Physicochemical factors such as medium pH, buffer capacity and osmolarity should be considered when determining the P(app) values of ionisable compounds. Care needs to be exercised when comparing P(app) values from different laboratories as buffer composition can have a significant effect on both solubility and permeability of a drug, whose ionisation is substantially changed over the pH range of the buffers. Despite the high amount ionised, ibuprofen appears to be well absorbed and it can be classified as a highly permeable drug.

Animals↗

Importance of matrix:analyte ratio for buffer tolerance using 2,5-dihydroxybenzoic acid as a matrix in matrix-assisted laser desorption/ionization-Fourier transform mass spectrometry and matrix-assisted laser desorption/ionization-time of flight.

Many biological samples destined for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) contain buffers. The presence of these buffers often inhibits the ability to obtain spectra. Here, the results of a study of the effects of six different buffers on spectra of three representative small proteins are reported utilizing 2,5-dihydroxybenzoic acid as matrix. These proteins, bovine insulin, cytochrome c, and bovine albumin have masses from approximately 5000 to 66,000 Da. Three different sample preparation techniques were investigated: aerospray, dried-drop, and acetone redeposition. Both MALDI Fourier transform and time-of-flight mass spectrometry results show that buffer tolerance of MALDI-MS samples depends upon several factors, including the relative amount of the buffer in the MALDI matrix, as well as the identity of the specific buffer. Furthermore, the rate at which buffer tolerance decreases as buffer concentration is increased varies from buffer to buffer. The current results reveal that, at very high matrix:analyte ratios, buffer tolerance of MALDI is dramatically greater than concluded in previous literature reports.

Animals↗

Experimental design for the estimation of photophysical parameters of the two-state excited-state proton-exchange reaction in the presence of pH buffer.

The excited-state proton-exchange reaction of commonly used fluorescent pH probes at physiological pH becomes reversible upon addition of pH buffer. Using computer-generated fluorescence decay surfaces, we investigated under which experimental conditions (pH, buffer concentration, and excitation and emission wavelengths) the rate constants describing the excited-state processes (k(ij)) and the spectral parameters related to excitation ((~)b(1)) and emission ((~)c(1)) can be accurately and precisely estimated by global compartmental curve fitting. It was found that a minimum of three fluorescence decay traces should be collected for the pH probe in the presence of buffer. These three decays should be characterized by at least two different pH values and at least two different buffer concentrations. In addition to these three traces, a minimum of one trace corresponding to the pH probe without buffer has to be recorded. Furthermore, for the accurate estimation of k(ij), (~)b(1), and (~)c(1), at least two of these traces should be collected at the same pH and excitation and emission wavelengths. The experimental conditions should be chosen in such a way that decays with unambiguous biexponential character are obtained. For fluorescent pH probes with pK(a) approximately equal to 7 that are responsive in the near-neutral pH range, it is advisable to use buffers with pK(B)(a) values comparable to or higher than the pK(a) of the probe. Because the changes in the decay times are already apparent with a small quantity of buffer, there is no need to use excessively high buffer concentrations. From a practical point of view, the best experimental design is attained when one combines in a single fluorescence decay surface traces originating from samples characterized by different pH values at the same buffer concentration with traces characterized by different buffer concentrations at the same pH and decays of samples without buffer measured at several pH values.

Buffers↗

The influence of buffer species and strength on diltiazem HCl release from beads coated with the aqueous cationic polymer dispersions, Eudragit RS, RL 30D.

PURPOSE: Eudragit RL and RS 30D are pseudolatexes frequently used in the coating of solid dosage forms. They are based on cationic copolymers stabilized with quaternary ammonium groups (poly(ethylacrylate-methylmethacrylate-trimethylammonioethyl methacrylate chloride). A pH-independent drug release is expected because of the quaternary nature of the cationic groups. The objective was to explain a distinct "pH-dependent" drug release in various buffer media with coated diltiazem beads. METHODS: The diltiazem HCl release from and water uptake of Eudragit RS/RL-coated beads was determined in various buffers of different buffer species, pH or concentration. RESULTS: The drug release in the different buffer media was in the following order: pH 5.0 acetate > pH 3.5 formate > pH 7.4 phosphate buffer > 0.1M HCl). This "pH-dependent" drug release could be explained with an anion exchange process; the chloride counterions of the quaternary groups were exchanged with the anionic buffer species during the dissolution study. The water uptake of the coated beads correlated well with the drug release from the beads. Increasing the buffer strength (acetate buffer) first increased and then decreased the drug release, while increasing the ionic strength of different buffers with NaCl decreased the drug release and eliminated the observed buffer effects because of the excess of chloride ions. CONCLUSIONS: The anionic buffer species and not the pH had a significant effect on the hydration and hence on the drug release from beads coated with the cationic polymers, Eudragit RS and RL.

Acrylic Resins↗

Preformulation studies for an ultrashort-acting neuromuscular blocking agent GW280430A. I. Buffer and cosolvent effects on the solution stability.

GW280430A is an ultrashort-acting neuromuscular blocking agent targeted at muscle relaxation to facilitate surgical intubation. The objective of this work was to study the buffer and cosolvent effects on the solution stability of GW280430A. The buffer catalytic effect was examined in citrate, malate, tartrate, and glycine by measuring the rate of degradation of GW280430A (0.2 mg/mL) at constant pH (3), ionic strength (0.15 M), and various buffer concentrations (0.01-0.05 M). The temperature dependence of the buffer catalytic effect and the degradation of the GW280430A in cosolvent (ethanol, propylene glycol, polyethylene glycol 400, N,N-dimethylacetamide)/water mixtures were studied at 40, 50, and 60 degrees C. The loss of parent drug was monitored by reverse-phase high-performance liquid chromatography. The degradation of GW280430A followed first-order kinetics in all buffer solutions. Significant buffer-catalyzed hydrolysis of GW280430A was observed with citrate, tartrate, and malate buffers, but not in glycine-buffered solutions. The activation energies in all buffered drug solutions ranged from 70 to 80 kJ/mol and decreased with increasing buffer concentration. GW280430A degradation was primarily through ester hydrolysis and followed first-order kinetics in aqueous solutions. In cosolvent/water mixtures, new degradation products were observed, indicating a chemical reaction between GW280430A and cosolvents. The reaction activation energies in the cosolvent/water mixtures ranged from 75 to 85 kJ/mol, with the longest t(0.9) at 5 degrees C equal to approximately 12 months and at 25 degrees C equal to 36 days. Consideration should be given to the incorporation of glycine or a low concentration of citrate, malate, or tartrate buffer in the parenteral formulation development of GW280430A. Cosolvents prolonged the predicted t(0.9) for GW280430A in solution, but the enhancement was not significant enough to pursue a liquidformulation.

Buffers↗

Induction of polymerization of purified tubulin by sulfonate buffers. Marked differences between 4-morpholineethanesulfonate (Mes) and 1,4-piperazineethanesulfonate (Pipes).

Interactions of both purified tubulin and microtubule protein (tubulin plus associated proteins) with two commonly used sulfonate buffers were examined. 1,4-Piperazineethanesulfonate (Pipes) and 4-morpholineethanesulfonate (Mes) at high concentrations induce the polymerization of purified tubulin in reactions requiring only buffer, tubulin and GTP. While both reactions were temperature-dependent, cold-reversible and inhibited by GDP, colchicine or Ca2+, there were significant differences between them. Substantially lower tubulin and buffer concentrations were required for Pipes-induced polymerization; and turbidity was much more intense in the Pipes-induced than in the Mes-induced reaction at the same protein concentration. Electron microscopy demonstrated that for the most part typical smooth-walled microtubules were formed in Mes, while aberrant forms were the predominant structures formed in Pipes. When the polymerization of microtubule protein was examined as a function of buffer concentration, biphasic patterns were observed with both Pipes and Mes: polymerization occurred at both low and high, but not intermediate, buffer concentrations. The turbidity observed at high concentrations of Pipes greatly exceeded that at low concentrations. With Mes, equivalent turbidity developed at both high and low buffer concentrations. Although associated proteins copolymerized with tubulin at low buffer concentrations, they were excluded from the polymerized material at high buffer concentrations. Pipes and Mes were compared to sodium phosphate, Tris/HCl and imidazole/HCl buffers at 0.1 M in several polymerization systems using both purified tubulin and microtubule protein. The sulfonate buffers were invariably associated with more vigorous reactions than the other buffers.

Alkanesulfonates↗

Pain perception after subcutaneous injections of media containing different buffers.

Several hormones are administered by daily subcutaneous injections. Pain caused by subcutaneous injection is an unpleasant condition, which can limit patient compliance. The objective of the present study was to evaluate the perception of pain by subcutaneous injection of two different and commercially available solutions for dispensing recombinant human growth hormone. The solutions are characterised by pH, conservation, and buffer. Isotonic saline was used as reference solution. Fifty-four healthy volunteers (mean age (+/-S.E.M.): 35.5+/-1.1 years) were recruited to the double-blind, randomised study. All injections were performed pairwise (right and left thigh) in one day by the same experienced nurse. Perception of pain was evaluated by the volunteers immediately after injection and 2 min. after injection into the thigh of three formulations, which differed with respect to pH and buffers (histidine, citrate and saline, respectively). Significantly more participants (38/54) found than the citrate buffer caused more pain than the histidine buffer immediately after injection (P=0.002). Histidine buffer did not cause more pain than saline (P=0.996). After 2 min., there was no difference between the histidine and the citrate buffer (P=1.00), nor between the histidine buffer and saline (P=1.00). In summary, the solution-containing citrate as buffer caused more pain after subcutaneous injection than the solution with histidine as buffer. Considering patient compliance, it seems advisable to employ histidine-buffered solution rather than citrate-buffered solution for dispensing recombinant human growth hormone by daily subcutaneous injections.

Adult↗

Comparison of alternative buffers for use with a new live oral cholera vaccine, Peru-15, in outpatient volunteers.

During development of Peru-15, a new live oral vaccine for cholera, the role of buffer needed to be evaluated. Generally, oral bacterial vaccines are acid labile and need to be administered by using a formulation which protects them from gastric acid. We compared three different buffers for use with Peru-15, including a standard bicarbonate-ascorbic acid buffer, Alka-Seltzer, and a new electrolyte-rice buffer, CeraVacx. Saline served as the control. Thirty-nine healthy adult volunteers received Peru-15 (10(8) CFU) with one of the three buffers or saline in a double-masked study. The volunteers were monitored for symptoms for 7 days after the dose, serum was tested for antibody responses by vibriocidal antibody and immunoglobulin G antitoxin enzyme-linked immunosorbent assays, and stool samples were tested for excretion of the vaccine strain. Side effects were minimal in all groups. All 30 volunteers who took Peru-15 with a buffer showed significant rises in vibriocidal antibody titer. The magnitude of the rises was higher in the CeraVacx group than in the other two buffer groups. Four of nine volunteers who took the vaccine with saline also showed increased titers, but they were lower than those in any of the three buffer groups. Excretion of the vaccine strain was similar in the buffer groups, but excretion was not associated with the magnitude of the vibriocidal responses. Excretion of Peru-15 was not detected in the saline group. We conclude that buffer does amplify the serological response to Peru-15 and that CeraVacx may provide benefits not provided by other buffers.

Administration, Oral↗

Cardiac electrophysiological variables in blood-perfused and buffer-perfused, isolated, working rabbit heart.

Effects of crystalloid buffer and blood-buffer perfusates on cardiac electrophysiological parameters were compared in four groups of isolated, working rabbit hearts. Hearts were perfused with Krebs-Henseleit buffer or blood plus Krebs-Henseleit buffer (10% hematocrit) over a range of left ventricular afterload (30-100 cmH2O) and cardiac outputs (30-180 ml/min). Left ventricular monophasic action potential duration (APD) was significantly shorter at low afterload and high cardiac output in buffer-perfused (114 +/- 35 ms) compared with blood-perfused hearts (177 +/- 23 ms, P < 0.001). APD shortened in blood-perfused hearts after an increase in afterload to 100 cmH2O (P < 0.05), and APD was similar in blood-perfused (151 +/- 19 ms) compared with buffer-perfused hearts (142 +/- 24 ms, P = NS). Ventricular effective refractory period (VERP) was significantly shorter at low afterload in buffer-perfused (154 +/- 32 ms) compared with blood-perfused hearts (227 +/- 17 ms, P < 0.001). VERP shortened in blood-perfused hearts after an increase in afterload to 100 cmH2O (P < 0.05) and was similar in blood-perfused (166 +/- 26 ms) compared with buffer-perfused hearts (151 +/- 37 ms, P = NS). Determination of VERP was associated with induction of ventricular fibrillation in 10 of 15 buffer-perfused hearts, whereas ventricular fibrillation was not observed in blood-perfused hearts (P < 0.001). Thus significant differences in ventricular repolarization and cardiac hemodynamics are observed in working rabbit hearts perfused with a blood-buffer perfusate compared with a crystalloid buffer. Blood-perfused working hearts are electrophysiologically more stable.

Animals↗

In vitro buffering capacity changes of seven commodities under controlled moisture and heating conditions.

Effects of adding 0 or .25 g of water/g of feed and heating for 0, 20, or 40 h at 100 degrees C on buffering capacity of beet pulp, almond hulls, alfalfa hay, oat hay, wheat bran, oat bran, and barley were determined in vitro. Feeds were examined for ash, N, NDF, ADF, acid detergent lignin, total buffering capacity (pH 4 to 9), and physiological buffering capacity (pH 5.5 to 7). Minerals were measured at 0 g of water/g of feed, 0 h of heat and at .25 g of water/g of feed, 40 h of heat; differences were negligible. Total buffering capacity was high for alfalfa, oat hay, and almond hulls; low for barley and oat bran; and intermediate for beet pulp and wheat bran. Physiological buffering capacity was consistently lower than total buffering capacity, but differences varied among and within feeds. Moisture had little effect on buffering capacity, NDF, ADF, or lignin. Time of heating had a significant effect on buffering capacity, NDF, ADF, and lignin but not on N or ash. Heating increased buffering capacity in most cases. Lignin was a poorer predictor of buffering capacity than total ash across feeds but a better predictor within feed across treatments. Large errors could occur when using total ash to predict buffering capacity for feeds subjected to heat.

Animal Feed↗

Combined effects of buffer and adrenergic agents on postresuscitation myocardial function.

Although buffer agents alone have failed to improve the success of resuscitation, we now examine the widely held concept that it is the combined effect of alkaline buffer and adrenergic agents that improves outcomes of cardiopulmonary resuscitation. In the present report, the effects of both CO(2)-consuming and CO(2)-generating buffer agents in combination with adrenergic vasopressor drugs were investigated. Ventricular fibrillation was electrically induced in Sprague-Dawley rats weighing between 450 and 550 g. Precordial compression and mechanical ventilation were initiated after 8 min of untreated ventricular fibrillation. Animals were then randomized to receive bolus injections of either inorganic sodium bicarbonate buffer, organic tromethamine buffer, or saline placebo. The beta(1) adrenergic effects of epinephrine were blocked with esmolol. The vasopressor amine was injected 2 min after injection of the buffer agent. Electrical defibrillation was attempted at the end of 8 min of precordial compression. In 15 additional animals, the sequence of administration of the adrenergic vasopressor and buffer agents was reversed such that the adrenergic vasopressor was injected before the buffer agents. All animals were restored to spontaneous circulation. Both bicarbonate and tromethamine significantly decreased coronary perfusion pressure from 26 to 15 mm Hg and reduced the magnitude of the vasopressor effect of the adrenergic vasopressor. When the vasopressor preceded the buffer, declines in coronary perfusion pressure after administration of buffer agents were prevented. In each instance, however, greater impairment of postresuscitation myocardial function and decreased postresuscitation survival were observed after treatment with buffer agents.

Adrenergic beta-Agonists↗

Free flow cell electrophoresis using zwitterionic buffer.

Studies of a zwitterionic buffer formulated for cell electrophoresis were done using the McDonnell-Douglas Continuous Flow Electrophoresis System. Standard buffers were analyzed for their stability in the electrical field and the results showed that both buffers tested were inherently unstable. Further, titration studies showed that the standards buffers buffered poorly at the pH employed for electrophoresis. The zwitterionic buffer buffered well at its nominal pH and was shown to be stable in the electrical field. Comparative studies of the buffer with standard cell separation buffers using formalin fixed rabbit and goose red blood cells showed that the zwitterionic buffer gave better resolution of the fixed cells. Studies with viable hybridoma cells showed that buffer Q supported cell viability equal to Hank's Balanced Salt Solution and that hybridoma cells in different stages of the growth cycle demonstrated reproducible differences in electrophoretic mobility.

Animals↗

Endothelium-dependent relaxations in rabbit aorta are depressed in artificial buffered solutions.

Contractile and relaxant responses of rabbit aortae in artificial buffered (Tris and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) solutions were compared with those in bicarbonate-buffered solution. EC50 values for responses to KCl in aortae equilibrated in Tris and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid were slightly less than those in bicarbonate; maximum contractions did not differ. There were no significant differences in contractile responses to prostaglandin Fa alpha or histamine in the three buffered solutions. In aortae precontracted with prostaglandin F2 alpha, both acetylcholine and the calcium ionophore, A23187, elicited much less relaxation in artificial buffered solutions than in bicarbonate-buffered solutions. Maximum relaxations to nitroprusside or D600 did not differ among the three solutions. Relaxant responses to isoproterenol were also depressed in artificial buffered solutions. Endothelial damage eliminated relaxant responses to acetylcholine and A23187, as well as the difference in responsiveness to KCl and isoproterenol noted in artificial buffered compared with bicarbonate-buffered solutions. Within the same solution, endothelial damage alone did not alter the responsiveness to KCl or histamine. Total and La -resistant Ca++ binding was similar in all three buffered solutions. Thus, contractile responses are not depressed in Tris- or N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered solutions, whereas endothelium-dependent relaxations are attenuated in similar solutions. Overall, the results imply that, in artificial buffered solutions, the production and/or release of an endothelium derived relaxing factor is attenuated or that its action on aortic smooth muscle is, in some manner, functionally antagonized.

Animals↗

The effects of hepes buffer on clotting tests, assay of factors V and VIII and on the hydrolysis of esters by thrombin and thrombokinase.

Shorter clotting times were found in the presence of 50 mM Hepes (N-2-hydroxyethylpiperazine-N1-2-ethanesulfonic acid) buffer than of 50mM Imidazole buffer in one-stage assays of factors V and VIII, in modified APTT and PT tests and in tests of the clotting of human plasma by purified human thrombin. All tests were performed at ionic strength 0.155 in the presence of either Hepes. NaOH or Imidazole. HCl buffer, pH 7.4 at 37 degrees. The faster clotting in the presence of Hepes buffer, therefore, is probably due, at least in part, to acceleration by Hepes of thrombin's enzymatic action on fibrinogen and/or of the polymerization of the fibrin monomers. Hepes may also have effects of other blood clotting reactions. Rates of hydrolysis of TAME or BAME (p-toluenesulfonyl- or benzoyl-L-arginine methyl ester) at pH 7.4 37 degrees by purified human bovine thrombin were essentially the same in 200 mM Hepes as in 250 mM Tris. HCl buffer (rates in Hepes. NaOH or Hepes. KOH buffers were compared with those in Tris. HCl plus NaCl for KCl). However, with purified bovine thrombokinase, rates of TAME hydrolysis in Hepes buffer were accelerated and rates of BAME hydrolysis slightly inhibited. Hepes, therefore, reacts with thrombokinase but whether this accelerates (or inhibits) the rate of converting prothrombin to thrombin remains to be determined. In addition, Hepes has an inhibitory effect on clotting since increasing the concentration of Hepes from 50 mM to 200 mM inhibits clotting in the PT, APTT and bovine thrombin-human plasma tests. Hepes buffer is being added to some plasmas and to some reagents used in clotting tests. It is, therefore, important to realize that its concentration must be monitored closely or erroneous results may be obtained in clotting tests and assays of clotting factors. The clotting times were the same in the presence of 50 mM Tris. HCl as in Imidazole. HCl buffers in APTT tests at three ionic strengths but they differed slightly in plasma-thrombin tests. Depending upon the ionic strength, 17 mM Barbital Sodium. HCl buffer inhibited APTT tests but accelerated plasma-thrombin tests. All the buffers tested, therefore, have individual effects on the clotting tests.

Animals↗

Field-based evaluation tool for riparian buffer zones in agricultural catchments.

Riparian buffer zones can improve water quality and enhance habitat, but a comprehensive yet rapid method that can assist the resource manager in assessing the effectiveness of buffers is not available. The aim of this paper is to describe and illustrate the use of a newly developed field-based evaluation tool for riparian buffer zones in agricultural catchments. The Buffer Zone Inventory and Evaluation Form (BZIEF) incorporates criteria-based scoring systems developed from literature review, subsequent peer-review, and then a pilot field study. Use of the BZIEF is demonstrated by comparing buffer zones in three catchments established for water quality and habitat improvement under the Water Fringe Option agrienvironment scheme in England in order to assess whether the buffers were likely to provide environmental enhancement. Results among the three catchments were generally similar; buffer zones scored highly for their abundant vegetation cover, lack of erosion, stream habitat quality, and sufficient width. Furthermore, previous grassland or arable land use did not substantially affect buffer zone ratings. However, the BZIEF indicated that inappropriate soil characteristics in one catchment were likely to constrain buffer zone effectiveness for improving water quality. In another catchment, poor riparian vegetation diversity and structure may yield ineffective habitat enhancement, according to the BZIEF. It was concluded that the BZIEF might be a useful tool for buffer zone comparison and monitoring, even though more work is needed to test and validate the method. For example, the BZIEF could be used to target appropriate locations for buffer zones and is flexible, so could be adapted for different policies, objectives and regions.

Agriculture↗

Impacts of rotational grazing and riparian buffers on physicochemical and biological characteristicsof southeastern Minnesota, USA, streams.

We assessed the relationship between riparian management and stream quality along five southeastern Minnesota streams in 1995 and 1996. Specifically, we examined the effect of rotationally and continuously grazed pastures and different types of riparian buffer strips on water chemistry, physical habitat, benthic macroinvertebrates, and fish as indicators of stream quality. We collected data at 17 sites under different combinations of grazing and riparian management, using a longitudinal design on three streams and a paired watershed design on two others. Continuous and rotational grazing were compared along one longitudinal study stream and at the paired watershed. Riparian buffer management, fenced trees (wood buffer), fenced grass, and unfenced rotationally grazed areas were the focus along the two remaining longitudinal streams. Principal components analysis (PCA) of water chemistry, physical habitat, and biotic data indicated a local management effect. The ordinations separated continuous grazing from sites with rotational grazing and sites with wood buffers from those with grass buffers or rotationally grazed areas. Fecal coliform and turbidity were consistently higher at continuously grazed than rotationally grazed sites. Percent fines in the streambed were significantly higher at sites with wood buffers than grass and rotationally grazed areas, and canopy cover was similar at sites with wood and grass buffers. Benthic macroinvertebrate metrics were significant but were not consistent across grazing and riparian buffer management types. Fish density and abundance were related to riparian buffer type, rather than grazing practices. Our study has potentially important implications for stream restoration programs in the midwestern United States. Our comparisons suggest further consideration and study of a combination of grass and wood riparian buffer strips as midwestern stream management options, rather than universally installing wood buffers in every instance. RID="" ID="" The Unit is jointly sponsored by the US Geological Survey, Biological Resources Division; the Minnesota Department of Natural Resources; the University of Minnesota; and the Wildlife Management Institute.

Journal Article↗

[The vascular smooth muscle of great arteries: local control site of arterial buffering function?].

INTRODUCTION AND OBJECTIVES: To characterize the viscoelastic properties of the aorta and pulmonary arteries and the effects of vascular smooth muscle activation on arterial buffering function. MATERIAL AND METHOD: Aortic and pulmonary artery pressure and diameter were measured in six anesthetized sheep under baseline conditions, and during arterial hypertension induced by mechanical vascular occlusion (passive), and i.v. phenylephrine (active). Arterial wall elasticity and viscosity were calculated, and buffering function was characterized: a) locally as the viscosity/elasticity ratio, and b) globally for each circuit, as the time-constant of ventricular relaxation. RESULTS: Viscoelasticity was higher in the aorta than in the pulmonary artery (p < 0.05), however, parietal buffering function was similar in both. Global buffering function was highest in the systemic circuit (p < 0.05). During passive hypertension, elasticity was significantly increased with no change in viscosity; this led to a significant reduction in local buffering function, and in global buffering function in each circuit. During active hypertension, viscosity increased (p < 0.05), while local and global buffering functions returned to baseline values. CONCLUSIONS: The viscosity/elasticity ratio was higher in the aorta than in the pulmonary artery, and arterial wall buffering function was similar in both vessels. Systemic global buffering function was higher than pulmonary circuit buffering function. Elasticity depends on intravascular pressure, whereas viscosity is a marker of the degree of smooth muscle activation. Smooth muscle activation may benefit the cardiovascular system by maintaining local and global buffering functions.

Animals↗

Comparison of effects of lidocaine hydrochloride, buffered lidocaine, diphenhydramine, and normal saline after intradermal injection.

STUDY OBJECTIVE: To evaluate pain and the spread of analgesia when local anesthetics are given as an intradermal injection into the dorsal aspect of the hand. DESIGN: Randomized, double-blinded, placebo-controlled study. SETTING: University medical center. PATIENTS: 40 consenting adult volunteers. INTERVENTIONS: Volunteers were randomly assigned to receive a 0.25-mL injection of either lidocaine hydrochloride (1%), buffered lidocaine, diphenhydramine (1%), or placebo (0.9% sodium chloride solution) into the dorsal aspect of both hands. MEASUREMENTS: The volunteers used a visual analog scale to compare the pain of needle insertion and solution injection. Then at 1, 2, 5, 10, 20, and 30 minutes after intradermal injection, the extent of the analgesic area was marked on a strip of tape placed horizontally across the hand. Then at 32 minutes after intradermal injection, the extent of the analgesic area was marked on a strip of tape placed vertically across the hand. The volunteers were called each day and asked the duration of their numbness or hyperesthesia until their hands were no longer numb or sore. MAIN RESULTS: Buffered lidocaine during intradermal infiltration was found to be significantly (p < 0.05) less painful than either lidocaine hydrochloride or diphenhydramine and equivalent to placebo. Diphenhydramine and lidocaine hydrochloride during intradermal infiltration induced significantly (p < 0.05) more pain than buffered lidocaine or placebo. Lidocaine hydrochloride displayed a significantly (p < 0.05) larger diameter of analgesia than placebo by 1 minute after the injection, buffered lidocaine by 2 minutes after injection, and diphenhydramine by 5 minutes after injection. By 20 minutes after injection, diphenhydramine diameter of analgesia was significantly (p < 0.05) larger than placebo but significantly less than buffered lidocaine. By 30 minutes after injection, diphenhydramine diameter of analgesia was equivalent to placebo whereas buffered lidocaine and lidocaine diameters were still significantly (p < 0.05) larger than placebo. Diphenhydramine injection resulted in numbness that lasted significantly (p < 0.05) longer than other study solutions whereas buffered lidocaine and lidocaine injections resulted in numbness that lasted significantly longer than placebo. Diphenhydramine injection resulted in hyperesthesia that lasted for 2 or more days in 12 of the volunteers. CONCLUSION: There is a reduction of infiltration pain using buffered lidocaine as opposed to lidocaine and diphenhydramine. Although lidocaine injection resulted in a slightly faster spread of analgesic diameter, buffered lidocaine was equivalent to lidocaine from minute 2 until minute 30. Therefore, to obtain optimal anesthetic conditions, we recommend that buffered lidocaine be given 2 minutes before performing catheterization, whereas diphenhydramine should be given 5 minutes before catheterization, but only when buffered lidocaine cannot be used.

Adult↗