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Ionic mechanisms mediating the differential effects of methohexital and thiopental on action potential duration in guinea pig and rabbit isolated ventricular myocytes.
Anesthesiology. 1999 Jan; 90(1):156-64.A

Abstract

BACKGROUND

Commonly used barbiturate anesthetics may significantly influence cardiac electrophysiologic characteristics. The authors evaluated thiopental (a thiobarbiturate) and methohexital (an oxybarbiturate), two compounds with similar physicochemical properties but different structures, to determine whether they have distinct effects on the major ionic currents that determine action potential duration (APD) in ventricular myocytes.

METHODS

The effects of thiopental and methohexital (50 microM) on APD at 50% (APD50) and 90% (APD90) repolarization were studied in guinea pig and rabbit single ventricular myocytes using the patch-clamp technique in a whole-cell configuration. The ionic mechanisms underlying the APD changes were evaluated by measuring the anesthetics' effects on the L-type calcium inward current, the inward rectifier potassium current, and the delayed rectifier potassium current in guinea pig cells and on the transient outward potassium current in rabbit cells.

RESULTS

Thiopental and methohexital caused opposite effects on APD. Whereas thiopental prolonged APD50 and APD90 in guinea pig and rabbit ventricular myocytes, methohexital shortened them. Thiopental markedly depressed both the inward and outward components of the inward rectifier potassium current, whereas methohexital caused minimal inhibition of the inward component and no change in the outward component. The delayed rectifier potassium current was inhibited by thiopental but significantly potentiated by methohexital. Neither thiopental nor methohexital significantly affected the transient outward potassium current or the L-type calcium inward current.

CONCLUSIONS

Despite their similar lipid solubilities, molecular weights, and pKa values, thiopental increased and methohexital decreased the APD in ventricular myocytes by predominantly inhibiting the inward rectifier potassium current and the delayed rectifier potassium current and by increasing the delayed rectifier potassium current, respectively. These characteristics suggest distinct structure-specific actions of barbiturates on the function of myocardial ionic channels.

Authors+Show Affiliations

Department of Anesthesiology, University of Florida, Gainesville 32610-0254, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9915324

Citation

Martynyuk, A E., et al. "Ionic Mechanisms Mediating the Differential Effects of Methohexital and Thiopental On Action Potential Duration in Guinea Pig and Rabbit Isolated Ventricular Myocytes." Anesthesiology, vol. 90, no. 1, 1999, pp. 156-64.
Martynyuk AE, Morey TE, Raatikainen MJ, et al. Ionic mechanisms mediating the differential effects of methohexital and thiopental on action potential duration in guinea pig and rabbit isolated ventricular myocytes. Anesthesiology. 1999;90(1):156-64.
Martynyuk, A. E., Morey, T. E., Raatikainen, M. J., Seubert, C. N., & Dennis, D. M. (1999). Ionic mechanisms mediating the differential effects of methohexital and thiopental on action potential duration in guinea pig and rabbit isolated ventricular myocytes. Anesthesiology, 90(1), 156-64.
Martynyuk AE, et al. Ionic Mechanisms Mediating the Differential Effects of Methohexital and Thiopental On Action Potential Duration in Guinea Pig and Rabbit Isolated Ventricular Myocytes. Anesthesiology. 1999;90(1):156-64. PubMed PMID: 9915324.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ionic mechanisms mediating the differential effects of methohexital and thiopental on action potential duration in guinea pig and rabbit isolated ventricular myocytes. AU - Martynyuk,A E, AU - Morey,T E, AU - Raatikainen,M J, AU - Seubert,C N, AU - Dennis,D M, PY - 1999/1/23/pubmed PY - 1999/1/23/medline PY - 1999/1/23/entrez SP - 156 EP - 64 JF - Anesthesiology JO - Anesthesiology VL - 90 IS - 1 N2 - BACKGROUND: Commonly used barbiturate anesthetics may significantly influence cardiac electrophysiologic characteristics. The authors evaluated thiopental (a thiobarbiturate) and methohexital (an oxybarbiturate), two compounds with similar physicochemical properties but different structures, to determine whether they have distinct effects on the major ionic currents that determine action potential duration (APD) in ventricular myocytes. METHODS: The effects of thiopental and methohexital (50 microM) on APD at 50% (APD50) and 90% (APD90) repolarization were studied in guinea pig and rabbit single ventricular myocytes using the patch-clamp technique in a whole-cell configuration. The ionic mechanisms underlying the APD changes were evaluated by measuring the anesthetics' effects on the L-type calcium inward current, the inward rectifier potassium current, and the delayed rectifier potassium current in guinea pig cells and on the transient outward potassium current in rabbit cells. RESULTS: Thiopental and methohexital caused opposite effects on APD. Whereas thiopental prolonged APD50 and APD90 in guinea pig and rabbit ventricular myocytes, methohexital shortened them. Thiopental markedly depressed both the inward and outward components of the inward rectifier potassium current, whereas methohexital caused minimal inhibition of the inward component and no change in the outward component. The delayed rectifier potassium current was inhibited by thiopental but significantly potentiated by methohexital. Neither thiopental nor methohexital significantly affected the transient outward potassium current or the L-type calcium inward current. CONCLUSIONS: Despite their similar lipid solubilities, molecular weights, and pKa values, thiopental increased and methohexital decreased the APD in ventricular myocytes by predominantly inhibiting the inward rectifier potassium current and the delayed rectifier potassium current and by increasing the delayed rectifier potassium current, respectively. These characteristics suggest distinct structure-specific actions of barbiturates on the function of myocardial ionic channels. SN - 0003-3022 UR - https://www.unboundmedicine.com/medline/citation/9915324/Ionic_mechanisms_mediating_the_differential_effects_of_methohexital_and_thiopental_on_action_potential_duration_in_guinea_pig_and_rabbit_isolated_ventricular_myocytes_ L2 - https://pubs.asahq.org/anesthesiology/article-lookup/doi/10.1097/00000542-199901000-00021 DB - PRIME DP - Unbound Medicine ER -