多沙唑嗪对映体对大鼠离体心脏心肌活力的作用

Effect of doxazosin enantiomers on mechanical performance of isolated heart muscle of rats

目的观察多沙唑嗪(Dox)对映体对大鼠离体心房肌和心室肌功能的作用。方法制备大鼠离体左心房、右心房和右心室肌条标本。左右心房均分别累积给予Dox对映体3,10和30μmol·L-1。右心室非累积给予Dox对映体3,10和30μmol·L-1。测定心率和心肌收缩力。结果右旋Dox(R-Dox)3～10μmol·L-1,使28%的右心房(含窦房结)发生停搏反应,消旋Dox(rac-Dox)3～10μmol·L-1使7%的右心房(含窦房结)发生停博反应,左旋Dox(S-Dox)3～10μmol·L-1未诱发右心房(含窦房结)停搏反应。R-Dox3～30μmol·L-1随浓度增加,减慢大鼠离体右心房心率作用有增强趋势。rac-Dox 10和30μmol·L-1显著减慢大鼠离体右心房心率(P<0.01)。S-Dox 3～30μmol·L-1对大鼠离体右心房心率无影响。S-Dox 3～30μmol·L-1增强大鼠离体左心房心肌收缩。相反,R-Dox 3～30μmol·L-1浓度依赖性地抑制左心房心肌收缩(P<0.01)。rac-Dox 3～30μmol·L-1亦浓度依赖性地抑制左心房心肌收缩。S-Dox 3～30μmol·L-1对大鼠右心室肌收缩力无显著影响。R-Dox和rac-Dox 3～30μmol·L-1浓度依赖性地抑制右心室肌收缩(P<0.01)。结论 rac-Dox 3～10μmol·L-1可诱发大鼠离体心脏停搏,并显著抑制大鼠心室肌的收缩;rac-Dox对心脏的作用与R-Dox有关;同浓度的S-Dox对大鼠离体右心房心率无影响,对大鼠心室肌的收缩无作用。

OBJECTIVE To observe effect of doxazosin enantiomers on functions of rats′ isolated atrium and ventricle.METHODS The isolated right atrium,left atrium and right ventricle strip of rats were prepared.Doxazosin enantiomers 3,10 and 30 μmol·L-1 were cumulatively applied to isolated atrium preparation of rats but were non-cumulatively applied to isolated right ventricle preparation of rats.Effects of doxazosin enantiomers on the contractile force and heart rate were observed.RESULTS S-Dox 3-10 μmol·L-1 did not induce cardiac arrest,while R-Dox and rac-Dox induced cardiac arrest by 28% and 7%,respectively.S-Dox 3-30 μmol·L-1 did not affect the heart rate of the isolated right atrium of rats,while R-Dox and rac-Dox decreased the heart rate.S-Dox 3-30 μmol·L-1 concentration-dependently increased the contractile force of isolated left atrium.R-Dox and rac-Dox at the same concentration decreased the contractile force of the isolated left atrium in a concentration-dependent manner.CONCLUSION rac-Dox 3-10 μmol·L-1 induces cardiac arrest and its heart toxicity is related to R-Dox.S-Dox at the same concentration does not induce cardiac arrest.S-Dox 3-30 μmol·L-1 has no effect on the contractile force of the isolated right ventricle strip,while R-Dox and rac-Dox concentration-dependently decrease the contractile force of the isolated right ventricle strip.There is difference between the action mechanism of R-Dox and S-Dox in isolated heart muscle of rats.