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On the mechanisms of potentiation of local anesthetics by bicarbonate buffer: drug structure-activity studies on isolated peripheral nerve.
Anesth Analg
January 1993
Anesthesia Research Laboratories, Brigham and Women's Hospital, Boston, MA 02115.
Impulse inhibition by local anesthetics (LAs) is potentiated by extracellular solutions containing HCO3-. CO2 (BC), relative to the inhibition in BC-free solutions at the same pH. We studied the mechanistic basis of this potentiation by assaying compound action potential amplitudes in desheathed frog sciatic nerves with the sucrose-gap method.
View Article and Find Full Text PDFThe role of length of nerve exposed to local anesthetics in impulse blocking action.
Anesth Analg
May 1989
Department of Anesthesia, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
The quantitative relation between the concentration of local anesthetic (LA), the length of nerve exposed, and severity of conduction blockade was studied with use of a chamber where exposure length was varied as the concentration of lidocaine was held constant. Recordings of the compound action potential and of single axons established that small variations in the length of nerve exposed to LA strongly modulate conduction block even at exposure lengths in excess of 2 cm. Therefore, exposure length is a significant factor in determining blocking potency, and only at very high concentrations of LA, where voltage-dependent Na conductance is almost completely blocked, is the critical exposure length less than three nodes of Ranvier.
View Article and Find Full Text PDFThe protonation equilibrium and hydrophobic character of lidocaine were characterized by its pKa and the octanol:buffer partition coefficients of the charged (P+) and neutral (Po) drug species. These measurements were accomplished by ultraviolet spectrophotometry of pure lidocaine HCl solutions at different temperatures, ionic strengths, and buffer concentrations. Corroboration of the pKa determination by the potentiometric method and of the partition coefficients by gas chromatography validated the general application of the spectrophotometric technique.
View Article and Find Full Text PDFKinetics of nerve impulse blocking by protein cross-linking aldehydes. Apparent critical thermal points.
Biochim Biophys Acta
December 1981
The effect of formaldehyde, crotonaldehyde, butyraldehyde, glutaraldehyde and cinnamaldehyde on the compound action potential of frog sciatic nerve was studied in the temperature domain 20-35 degrees C at various aldehyde concentrations. All these reagents gradually decrease the amplitude of nerve action potential, up to the complete block, the order of effectiveness being: crotonaldehyde greater than cinnamaldehyde greater than butyraldehyde greater than formaldehyde greater than glutaraldehyde. The effect of cinnamaldehyde is almost completely reversible, while all others have irreversible action.
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