川芎嗪对心室快速起搏心力衰竭实验犬心房颤动及心房纤维化的影响

目的:观察川芎嗪(tetra methyl pyrazine,TMP)对心室快速起搏致充血性心力衰竭(congestive heart failure,CHF)实验犬心房颤动及心房纤维化的影响。方法:选择健康成年杂种犬21只,随机分为正常对照组、CHF模型组和TMP治疗组。采用右心室快速起搏建立实验犬CHF模型。Burst刺激诱发心房颤动(atrial fibrillation,AF)。超声心动图仪检测实验犬左心室射血分数(left ventricular ejection fraction,LVEF)。Mallory’s三色法染色检测心房组织纤维化程度。采用放射免疫法测定血浆血管紧张素Ⅱ和醛固酮的浓度,测定血清Ⅲ型前胶原氨基末端肽(amino-terminal peptide of typeⅢ procollagen,PⅢNP)、层粘连蛋白(laminin,LN)和透明质酸(hyaluronic acid,HA)的水平。结果:CHF模型组LVEF较正常对照组明显下降(P<0.01);AF发生率、持续性AF发生率及AF持续时间较正常对照组均明显增加(P<0.01);左右心房纤维化程度较正常对照组亦有明显增加(P<0.01);AF持续时间与左心房纤维化程度呈密切正相关(r=0.84,P=0.018);血浆血管紧张素Ⅱ、醛固酮以及血清PⅢNP、HA水平较正常对照组均有明显升高(P<0.05,P<0.01);LN比较则无统计学差异;血浆血管紧张素Ⅱ水平与醛固酮水平呈密切正相关(r=0.759,P=0.048)。TMP治疗组LVEF较CHF模型组有明显改善(P<0.05);持续性AF发生率较CHF模型组有明显降低(P<0.05);左右心房纤维化程度较CHF模型组有明显减轻(P<0.01)。结论:TMP可减轻CHF时心房纤维化的程度,这可能是其减少CHF时AF发生率及持续时间的机制之一。

Effects of tetramethylpyrazine on fibrosis of atrial tissue and atrial fibrillation in a canine model of congestive heart failure induced by ventricular tachypacing

OBJECTIVE: To explore the effects of tetramethylpyrazine (TMP) on fibrosis of atrial tissue and atrial fibrillation in a canine model of congestive heart failure (CHF) induced by ventricular tachypacing. METHODS: Twenty-one healthy mongrel dogs were randomly divided into three groups, which were normal control group, untreated group and TMP-treated group. Atrial fibrillation (AF) was induced by burst of atrial pacing, after the canine model of CHF was established. The atrial tissues were sampled and stained with Mallory's trichromic stains, then the fibrosis in the atrial tissues was analyzed. The left ventricular ejection fraction (LVEF) was evaluated by echocardiography. The levels of angiotensin II (AngII), aldosterone (ALD), amino-terminal peptide of type III procollagen (PIIINP)ìlaminin (LN) and hyaluronic acid (HA) in peripheral blood were examined by radioimmunoassay. RESULTS: The LVEF was significantly decreased in the untreated group as compared with that in the normal control group (P<0.01), while the frequencies of AF and sustaining AF were significantly increased and the AF duration was obviously prolonged in the untreated group as compared with those in the normal control group (P<0.01). The fibrosis degree in the left or right atrial tissue in the untreated group was more serious than that in the normal control group (P<0.01). The AF duration was positively correlated with the fibrosis degree in the left atrial tissue (r=0.84, P=0.018). The levels of AngII, ALD, PIIINP and HA in peripheral blood were significantly higher in the untreated group than those in the normal control group (P<0.05 or P<0.01). The level of AngII was positively correlated with the level of ALD in peripheral blood (r=0.759, P=0.048). The LVEF and the frequency of sustaining AF were both significantly improved in the TMP-treated group as compared with those in the untreated group (P<0.05). The fibrosis in the left or right atrial tissue in the untreated group was more serious than that in the untreated group (P<0.01). The levels of AngII and PIIINP in peripheral blood were also markedly higher in the TMP-treated group than those in the untreated group (P=0.05, P=0.01). CONCLUSION: Tetramethylpyrazine has the effect of reducing the fibrosis degree of atrial tissue in dogs with CHF, and this efficacy may be related to the mechanism of decreasing the frequency of AF and shortening the AF duration.