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[急性心肌梗死后心力衰竭患者ACE基因多态性、左心室结构功能状态及ACE抑制剂培哚普利的作用]

[Polymorphism of the ACE gene, structural-functional state of the left ventricle in patients with post-infarction cardiac failure and effects of the ACE-inhibitor Perindopril].

作者信息

Tereshchenko S N, Demidova I V, Kobalava Zh D, Moiseev V S

出版信息

Ter Arkh. 2002;74(4):56-8.

Abstract

AIM

To evaluate relationships between structural-functional state of the left ventricle (LV) and genotype of angiotensin converting enzyme (ACE) gene in patients with postinfarction chronic cardiac failure (CCF) and effects of ACE inhibitor perindopril on hemodynamics depending on ACE gene polymorphism.

MATERIAL AND METHODS

In 52 patients with CCF (functional class III-IV by NYHA criteria) who had survived macrofocal myocardial infarction we studied ACE gene using thermostable DNA-polymerase Taq. Isolation of genome DNA from human venous blood was made by phenolchloroform extraction with the use of chelate polymer Chelex-100. Polymerase chain reaction was conducted on amplificator PHC-2 or PolyChain II. LV contractile function was studied on echocardiograph "Toshiba SSH-160A (Japan). Echocardiography was performed before intake of perindopril, in the end of titration phase, on therapy month 6 and 12.

RESULTS

Genotype II of ACE gene was detected in 11(21.1%) patients, ID genotype--in 20(38.5%), DD genotype--in 21(40.4%). Patients with ACE gene genotype II and ID have no differences by parameters of central hemodynamics. They were divided into two groups: group 1--patients with genotypes II and ID of ACE gene, group 2--patients with genotype DD. End diastolic volume (EDV), end systolic volume (ESV), index of LV myocardial mass were significantly less in group 1 than in group 2 (by 45.7, 81.6 and 31.2%, respectively). In group 1 ejection fraction (EF) and %delta S were higher by 35.3 and 35.7%, respectively. The hemodynamic effect of perindopril was higher in group 2. A month therapy resulted in a 8.7 and 14.8% reduction in group 2 EDV and ESV, respectively (p < 0.05). This entailed an increase in EF and %delta S by 18.3% (p < 0.05) and 19.8% (p < 0.05). Later, perindopril retained influence on central hemodynamics. Diastolic function to the end of therapy in both groups differed insignificantly.

CONCLUSION

In CCF patients functional class III-IV with the history of myocardial infarction, structural-functional LV parameters depend on genotype of ACE gene. Perindopril is most effective in DD-genotype of ACE gene.

摘要

目的

评估心肌梗死后慢性心力衰竭(CCF)患者左心室(LV)的结构功能状态与血管紧张素转换酶(ACE)基因基因型之间的关系,以及依那普利对血流动力学的影响(取决于ACE基因多态性)。

材料与方法

对52例CCF患者(根据纽约心脏协会标准为III-IV级功能分级)进行研究,这些患者均为大面积心肌梗死幸存者。使用热稳定DNA聚合酶Taq研究ACE基因。采用螯合聚合物Chelex-100通过酚氯仿提取法从人静脉血中分离基因组DNA。在PHC-2或PolyChain II扩增仪上进行聚合酶链反应。使用“东芝SSH-160A(日本)”超声心动图仪研究LV收缩功能。在服用依那普利前、滴定阶段结束时、治疗第6个月和第12个月进行超声心动图检查。

结果

11例(21.1%)患者检测到ACE基因的II型基因型,20例(38.5%)为ID基因型,21例(40.4%)为DD基因型。ACE基因II型和ID型基因型患者的中心血流动力学参数无差异。将他们分为两组:第1组为ACE基因II型和ID型基因型患者,第2组为DD型基因型患者。第1组的舒张末期容积(EDV)、收缩末期容积(ESV)、LV心肌质量指数明显低于第2组(分别低45.7%、81.6%和31.2%)。第1组的射血分数(EF)和%delta S分别高35.3%和35.7%。依那普利对第2组的血流动力学作用更高。治疗1个月后,第2组的EDV和ESV分别降低8.7%和14.8%(p<0.05)。这导致EF和%delta S分别增加18.3%(p<0.05)和19.8%(p<0.05)。之后,依那普利对中心血流动力学仍有影响。两组治疗结束时的舒张功能无显著差异。

结论

在有心肌梗死病史的III-IV级功能分级的CCF患者中,LV的结构功能参数取决于ACE基因的基因型。依那普利对ACE基因DD基因型最为有效。

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