Direct effects of colchicine on myocardial function - Studies in hypertrophied and failing spontaneously hypertensive rats
Direct effects of colchicine on myocardial function - Studies in hypertrophied and failing spontaneously hypertensive rats
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DOI：
10.1161/01.hyp.33.1.60
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发表时间：
1999-01-01
期刊：
影响因子：
8.3
通讯作者：
Bing, OHL
中科院分区：
文献类型：
--
作者：
Cicogna, AC;Robinson, KG;Bing, OHL
衰老型自发性高血压大鼠（SHR）是一种观察到慢性稳定型左心室肥厚向显性心力衰竭转变的模型。虽然SHR引起心肌肥厚和衰竭的机制已被研究，但没有一个能完全解释心肌收缩异常。心肌细胞骨架被认为是心肌功能障碍的可能原因。如果微管的增加导致功能障碍，那么秋水仙碱对心肌微管的破坏应该会促进心脏功能的改善。我们研究了18- 24月龄伴有心力衰竭的SHR （SHR- f, n=6）、年龄匹配的无心力衰竭SHR （SHR- nf, n=6）和年龄匹配的正常血压Wistar-Kyoto大鼠（WKY, n=5）的离体左心室乳头肌的主动和被动特性。对秋水仙碱（10（-5）、10（-4）、10(-3)mol/L）加入前和加入后90分钟的力学参数进行分析。在基线状态下，WKY组乳头肌产生的主动张力（AT）高于shl - nf组和shl - f组(WKY 5.69+/-1.47 g/mm(2)[平均值+/-SD]， shl - nf 3.41+/-1.05, shl - f 2.87+/-0.26；SHR-NF和shr - fp
The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm(2) [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P