Weil J, Eschenhagen T, Hirt S, Magnussen O, Mittmann C, Remmers U, Scholz H
Abteilung Allgemeine Pharmakologie, Universitäts Krankenhaus Eppendorf, Germany.
Cardiovasc Res. 1998 Feb;37(2):541-8. doi: 10.1016/s0008-6363(97)00227-7.
The goal of the present study was to examine the ability of failing myocardium to respond to enhanced preload with an increase in force development.
The effect of various preload conditions (2.5-15 mN) on force development was studied in right ventricular trabeculae carneae from explanted human failing hearts with ischemic cardiomyopathy (ICM, n = 5, 42 preparations) or idiopathic dilated cardiomyopathy (DCM, n = 9, 77 preparations). To determine the severity of cardiac impairment we measured the positive inotropic effect of beta-adrenoceptor stimulation and calcium (ISO/Ca2+ ratio) and the expression of atrial natriuretic peptide (ANP) mRNA in all hearts.
(1) Force of contraction increased with stepwise augmentation of preload (length at 2.5 mN preload to length of maximal force development) from 3.7 +/- 0.5 (ICM) and 2.7 +/- 0.4 (DCM) to 8.3 +/- 0.9 and 6.5 +/- 0.8 mN/mm2, respectively (p < 0.05). (2) The ISO/Ca2+ ratio was 0.40 +/- 0.04 (ICM) and 0.35 +/- 0.03 (DCM), respectively. (3) ANP mRNA was expressed in all preparations, albeit at greatly varying levels (ICM 22.5 +/- 6.1 and DCM 18.7 +/- 4.7 normalized arbitrary units). (4) Contraction experiments performed in left ventricular tissue (n = 3, 32 preparations) essentially confirmed the results.
The Frank-Starling mechanism is preserved in terminally failing human hearts irrespective of the underlying etiology. We found no relation between the severity of cardiac impairment as assessed by either ANP expression or the ISO/Ca2+ ratio and the ability of failing human myocardium to respond to enhanced preload with an increase in force development.
本研究的目的是检测衰竭心肌在增加前负荷时产生力量增加的反应能力。
研究了不同前负荷条件（2.5 - 15 mN）对取自患有缺血性心肌病（ICM，n = 5，42个标本）或特发性扩张型心肌病（DCM，n = 9，77个标本）的 explanted 人衰竭心脏的右心室乳头肌力量产生的影响。为了确定心脏损伤的严重程度，我们测量了所有心脏中β - 肾上腺素能受体刺激和钙的正性肌力作用（ISO/Ca2+ 比值）以及心房利钠肽（ANP）mRNA 的表达。
（1）随着前负荷（2.5 mN 前负荷时的长度至最大力量产生时的长度）逐步增加，收缩力从 3.7±0.5（ICM）和 2.7±0.4（DCM）分别增加到 8.3±0.9 和 6.5±0.8 mN/mm2（p < 0.05）。（2）ISO/Ca2+ 比值分别为 0.40±0.04（ICM）和 0.35±0.03（DCM）。（3）所有标本中均表达了 ANP mRNA，尽管水平差异很大（ICM 为 22.5±6.1，DCM 为 18.7±4.7 标准化任意单位）。（4）在左心室组织（n = 3，32 个标本）中进行的收缩实验基本证实了结果。
无论潜在病因如何，Frank - Starling 机制在终末期衰竭的人心脏中得以保留。我们发现，通过 ANP 表达或 ISO/Ca2+ 比值评估的心脏损伤严重程度与衰竭的人心肌对增加前负荷产生力量增加的反应能力之间没有关系。
