Original scientific paper
Differences in Cardiovascular Sensitivity to Propofol in a Chromosome Substitution Rat Model
Thomas A. Stekiel
Craig A. Weber
Stephen J. Contney
Željko J. Bošnjak
Abstract
Aim: Based on previous observations of strain-related alterations in sensitivity
to anesthetics, this study used a newly established genetic rat model
to identify differences in cardiovascular sensitivity to the commonly used, clinically relevant, anesthetic propofol and to correlate such differences with specific chromosomal substitutions.
Methods: Cardiovascular sensitivity to propofol was compared in groups of normotensive Dahl Salt Sensitive (SS) and Brown Norway (BN) inbred rats, as well as in a unique panel of consomic rats based on these SS and BN parentals. The consomics were produced by introgression of individual BN chromosomes into an otherwise unchanged SS genetic background. Cardiovascular sensitivity was assessed by measuring the infusion rate of propofol required to reduce mean arterial blood pressure by 50% and cause cardiovascular collapse in each parental and consomic
strain. Results: Significantly lower propofol infusion rates caused both a 50% reduction in mean arterial pressure and ultimate cardiovascular collapse in SS compared to BN. Substitution of BN chromosome 13, but not of any other BN chromosome, reversed the enhanced propofol sensitivity in SS rats to the level of BN rats.
Conclusions: Differential propofol sensitivity exhibited by SS and BN
rat strains is associated with chromosome 13. This is consistent with earlier findings and represents the first complete screening of all rat autosomes for their relationship to anesthetic sensitivity. Initial localization of this sensitivity reversal to chromosome 13 provides a basis upon which additional, more selective genetic screening studies can be applied. Such studies may serve to identify specific regions of the genome responsible for different physiological responses to various anesthetic agents.
Keywords
anesthetic propofol; chromosomal substitutions
Hrčak ID:
16440
URI
Publication date:
20.6.2007.
Visits: 1.160 *