Search PubMed⌕ Search

Biomedical subjects

B Akerman

Publications and source records attributed to B Akerman.

At least 37 records · Page 2Linked to original sources
PubMed1988

Effects of macromolecular adjuvants on the duration of prilocaine. Experimental studies on the effect of variations of viscosity and sodium content and of inclusion of adrenaline.

Sodium hyaluronate (HA) and dextran (Dx) of different molecular weights and concentrations were used as adjuvants to prilocaine for studies of the duration of infraorbital nerve block in the rat (IONB) and spinal anaesthesia in the mouse (SA). A positive relation was found between duration of block on the one hand and the concentration as well as the molecular weight of the adjuvant on the other. A direct relation was found between the duration of block and the viscosity of the anaesthetic solution. Low-sodium-content solutions of plain prilocaine caused a markedly prolonged duration of the most profound degrees of IONB as compared to medium- or high-sodium-content solutions, while no differences between the solutions were found for the weakest intensity of IONB studied or for SA. Solutions of low-sodium-content containing prilocaine and HA were associated with significant prolongations of IONB and SA as compared to corresponding solutions of medium- or high-sodium content. Inclusion of adrenaline, 5 micrograms/ml, in solutions containing prilocaine and Dx significantly prolonged the duration of the most profound degrees of IONB and of SA. By contrast, the inclusion of adrenaline in solutions containing prilocaine and HA did not prolong the duration of IONB or SA. It is concluded that modulations of the viscosity of local anaesthetic solutions by the addition of macromolecular compounds strongly affect the duration of peripheral and central nerve blocks in experimental animals. A further prolongation is accomplished by reducing the sodium content of the solutions and, in the case of Dx-containing solutions, by inclusion of adrenaline in the anaesthetic solution. The possible mechanisms of these actions are discussed.

Adjuvants, Anesthesia↗
PubMed1988

Primary evaluation of the local anaesthetic properties of the amino amide agent ropivacaine (LEA 103).

The local anaesthestic properties of 1-propyl-2',6'-pipecoloxylidide, a congener of mepivacaine and bupivacaine, and its enantiomers were compared in animals. The (S)-enantiomer (ropivacaine, LEA 103) produced a longer duration of sciatic nerve block and infiltration anaesthesia than the racemate and the (R)-form. Ropivacaine and bupivacaine were equally potent in terms of block of evoked action potential in vitro and minimum effective concentration in vivo. Ropivacaine 0.25-1.0% was distinctly longer acting than bupivacaine on infiltration, equally effective in sciatic and brachial plexus block and somewhat shorter lasting in epidural and spinal blockade. There were tendencies towards a greater benefit from the addition of adrenaline with ropivacaine in epidural anaesthesia and a shorter latency to block in some of the tests. Ropivacaine seems less vasodilative than bupivacaine and capable of producing some vasoconstriction over a wider range of low concentrations, which may explain its longer duration of intradermal anaesthesia. The somewhat shorter duration of central blockade of ropivacaine is probably a result of lesser lipid solubility. Ropivacaine was less toxic (i.v. and s.c. LD50-values) than bupivacaine but more toxic than lidocaine, and produced only weak local irritation. Due to a combination of interesting local anaesthetic properties and relative safety including cardiotoxic potential, we consider ropivacaine a candidate for further studies.

Amides↗
PubMed1988

Local anesthetics potentiate spinal morphine antinociception.

Some investigators have postulated a synergistic analgesic effect of local anesthetic agents and opiates when given intrathecally or epidurally, but little objective evidence has been presented to quantitate such an effect. A study was therefore undertaken to compare in mice the antinociceptive effects of intrathecal injections of mixtures of morphine with bupivacaine or lidocaine with the effects of these agents when administered alone. The antinociceptive effects (tail-flick and hotp-late tests) of morphine (0.1-1.6 micrograms) with either bupivacaine, 25 micrograms, or lidocaine, 200 micrograms, were significantly greater than the effects of morphine or the local anesthetics when administered alone. When morphine was administered with the local anesthetics, the intensity and the duration of antinociception were greater, although the time courses of the effects resembled that of morphine administered alone. An enhanced effect was also observed when combinations of local anesthetics and low doses of morphine were used that by themselves had no or little effect. The addition of morphine did not affect the motor block produced by the local anesthetics. The results indicate a potentiating effect of local anesthetics on spinal morphine antinociception, a finding that may have important clinical implications.

Anesthesia, Endotracheal↗
PubMed1987

Characterization of interaction between DNA and 4',6-diamidino-2-phenylindole by optical spectroscopy.

We have examined the interaction between 4',6-diamidino-2-phenylindole (DAPI) and DNA using flow linear dichroism (LD), circular dichroism (CD), and fluorescence techniques. We show the presence of two spectroscopically distinct binding sites at low binding ratios with saturation values of 0.025 and 0.17, respectively. In both sites DAPI is bound with its long axis approximately parallel to the grooves of the DNA helix. Resolution of CD spectra shows that an exciton component is present at higher binding ratios, which we attribute to the interaction of two accidentally close-lying DAPI molecules. We also find evidence that DAPI, at least in the high-affinity site, binds preferentially to AT-rich regions. From the spectroscopic results, supported by structural considerations, we can completely exclude that DAPI is bound to DNA by intercalation. Binding geometries and site densities are consistent with a location of DAPI in the grooves of DNA, with the high-affinity site most probably in the minor groove.

Circular Dichroism↗
PubMed1985

Effects of adjuvants to local anaesthetics on their duration. I. Studies of dextrans of widely varying molecular weight and adrenaline in rat infraorbital nerve block.

Local anaesthetics of the amide type were studied in a modified rat infraorbital nerve block model, with which it was possible to determine varying degrees of sensory block. Of the agents investigated, 0.5% bupivacaine tended to give a longer duration of block than 2% prilocaine or 2% lidocaine, while 0.5% etidocaine had the shortest duration. The duration of prilocaine was prolonged by addition of adrenaline, 5 micrograms/ml, more than that of the other agents. Addition of dextrans of Mw 40-110 X 10(3) did not cause any prolongation of block induced by bupivacaine. When mixed with dextrans over a wide range of Mw (40-4900 X 10(3), prilocaine exhibited significant prolongations of its action by up to 200%. The extent of prolongation was dependent on the degree of block, the concentration of dextrans in the local anaesthetic solution, and the Mw of the dextran although in a less uniform way. An increase in the relative viscosity of the solutions might be a factor of importance for the prolonging effect of addition of dextran to local anaesthetics. Since a formulation providing analgesia of a long duration would be of clinical value, further studies on combinations of the comparatively low-toxicity agent prilocaine and macromolecular substances are of interest.

Anesthetics, Local↗
PubMed1985

Effects of adjuvants to local anaesthetics on their duration. II. Studies of some substituted dextrans and other macromolecules in rat infraorbital nerve block.

The effects of adding various macromolecular substances to 2% prilocaine on duration of rat infraorbital nerve block were investigated. The tested substances consisted of dextrans with lipophilic or charged substituents as well as other neutral or highly charged macromolecules. Most of the adjuvants caused significant prolongations of sensory block. For substituted dextrans the duration of sensory block degree 3 amounted to between 120% (3% capryldextran II) and 350% (3% carboxymethyldextran) in comparison to prilocaine plain. The corresponding values for hydroxypropylstarch (3%) alginic acid (0.5%), beta-cyclodextrin (1.5%) and hyaluronic acid (0.25%) were about 170%, 285% and 380%, respectively. The results suggest that the increased duration of local analgesia by prilocaine is related to increased viscosity of the solution produced by the macromolecular compounds. The mechanism seems to be of a physical character, and hyaluronic acid seems to be worthy of further studies.

Alginates↗
PubMed1985

Effects of adjuvants to local anaesthetics on their duration. III. Experimental studies of hyaluronic acid.

The effects of addition of hyaluronic acid (sodium hyaluronate, Healon) to different local anaesthetics of the amide type on the duration of sensory or motor blocks following various regional anaesthetic procedures were studied in animal experiments. In the rat infra-orbital nerve block model, the addition of 0.1-0.5% hyaluronic acid (HA) to 2% prilocaine increased the duration of sensory block of varying degrees in a dose-dependent way by up to 500% of values obtained with plain prilocaine. The duration of degree 5 blocks produced by 0.5% etidocaine and 0.5% bupivacaine was also significantly prolonged when 0.4% HA was included to 206% and 282% of control, respectively, while blocks induced by 2% lidocaine were prolonged to 123% of control. The duration of motor block following spinal anaesthesia in the mouse was prolonged in a dose-dependent way when HA was added to prilocaine, bupivacaine and etidocaine. For solutions containing 0.4% HA, prolongations to 254%, 166% and 134% of control, respectively, were obtained. A concomitant increase of latency to onset of block and failure rate occurred with increasing concentrations of HA. The duration of corneal anaesthesia in the rabbit increased by 57% and 44% when 0.3% HA was added to prilocaine and bupivacaine, respectively. The duration of infiltration anaesthesia was not affected by the addition of HA to the local anaesthetic solutions. Addition of HA had no effect on the onset, depth and duration of prilocaine-induced block of the nervous transmission in vitro. The duration of infra-orbital nerve block and spinal anaesthesia shows a significant relation to the relative viscosity of the local anaesthetic solution.

Anesthetics, Local↗
PubMed1984

Influence of hyaluronidase upon local infiltration anaesthesia by lidocaine. An experimental study in the guinea-pig.

A study was made in the guinea-pig to examine how the mucolytic enzyme hyaluronidase influenced the spread and duration of subcutaneously injected lidocaine with and without adrenaline. Addition of hyaluronidase 200 IU/ml to lidocaine 5 mg/ml plain solution diminished the spread of the analgesic efficacy but did not affect the duration of action. Addition of hyaluronidase 200 IU/ml to lidocaine 5 mg/ml containing adrenaline 5 micrograms/ml gave a significantly larger area of analgesia compared to the solution without the enzyme but slightly shortened the duration of action. The solution containing both adrenaline and hyaluronidase approximately doubled the distance necessary for satisfactory analgesia between two subcutaneous sites of administration, a finding that may have clinical implications.

Anesthesia, Local↗
PubMed1979

Penetration enhancers and other factors governing percutaneous local anaesthesia with lidocaine.

The percutaneous penetration of the local anaestetic lidocaine was investigated in the guinea-pig. Three different types of composition were employed: lidocaine hydrochloride in aqueous solution, lidocaine base in an aqueous alcoholic solvent mixture and lidocaine base in aqueous solutions of dipolar aprotic solvents. The latter solvents included simple tertiary aliphatic amides, amides related to dimethylacetamide, some cyclic amides as well as a number of miscellaneous compounds. The degree of dermal anaesthesia was noted in each case. In addition, the uptake and distribution of lidocaine in the skin and its absorption into the blood were studied using tritium-labelled drug. The results show that the percutaneous penetration of lidocaine is dependent on the concentration of the agent, the time of epicutaneous application of the composition, whether the agent was used as salt or free base, and the nature of the solvent medium. Lidocaine base in aqueous dimethylacetamide was most effective in producing percutaneous local anaesthesia.

Amides↗
PubMed1979

Effect of different types of anaesthesia including percutaneous local anaesthesia on survival of experimental skin flaps.

Local anaesthesia by epicutaneous application of the ketocaine solution A2358 gave survival of experimental skin flaps in the guinea pig which corresponded on average to 71% of the total flap. The survival after pentobarbitone anaesthesia, general anaesthesia with ether, and infiltration of prilocaine without and with adrenalin varied between 41 and 53%. The difference in effect between percutaneous anaesthesia with A2358 and the other procedures was statistically significant (p less than 0.001). Epicutaneous application of A2358 followed by one of the other forms of anaesthesia gave a flap survival that did not differ from that following local anaesthesia with A2358 alone, except when followed by injection of prilocaine with adrenalin. The improved survival after epicutaneously applied A2358 is probably attributable to an effect on the peripheral vascular bed resulting in increasing blood supply and nutrition. It may be possible that A2358, for example, could be used in man as a complement to other forms of anaesthesia to provide enhanced tissue survival in skin flaps.

Anesthesia, General↗