Control of cardiac contractility in the rat working heart-brainstem preparation
Control of cardiac contractility in the rat working heart-brainstem preparation
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DOI：
10.1113/expphysiol.2009.048710
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发表时间：
2010-01-01
影响因子：
2.7
通讯作者：
Paton, Julian F. R.
中科院分区：
文献类型：
--
作者：
Nalivaiko, Eugene;Antunes, Vagner R.;Paton, Julian F. R.
关于大鼠心肌功能的神经控制已有大量知识。针对这一问题的大多数研究要么是在全身麻醉下进行，要么是在体外离体心脏上进行。我们的主要目的是在一种保留功能性脑干且无麻醉的制备标本中，对大鼠心脏收缩性的控制机制进行详细的定量描述。此外，虽然迷走神经介导的负性变力作用是一种众所周知的现象，但目前尚无其在大鼠中存在的直接证据；我们对此进行了探寻。为此，在大鼠动脉灌注的工作心脏 - 脑干制备标本中，我们测量了左心室压（LVP）并计算了它的一阶导数（LVdP/dt）。我们有以下新的发现。（i）扎替雷定（心脏钠通道起搏器电流阻滞剂）导致心动过缓，同时伴有LVP和LVdP/dt的升高；后一种效应是通过一种频率依赖性机制产生的。（ii）我们证实，在大鼠中，力 - 频率关系（收缩性对心率的依赖性）在低心率范围内是正相关的，在生理心率水平是负相关且呈线性的，并给出了其定量描述。（iii）体循环压力升高导致收缩性增强，迷走神经阻滞或中枢神经系统破坏并未改变这种变力效应，这表明它是由心脏内在机制介导的。（iv）在非起搏制备标本中，迷走神经刺激导致LVdP/dt和LVP发生复杂的多相变化；在起搏过程中，它导致LVdP/dt缓慢下降，而阿托品可阻止这种下降。我们得出结论，大鼠心脏心室收缩性的控制不仅在其负性频率依赖性方面，而且在主动脉压力对LVdP/dt的强大影响方面，都不同于其他哺乳动物。在自主神经控制层面，我们新发现的迷走神经介导的负性变力效应，增加了关于心室心肌副交感神经支配的存在及其功能重要性的大量数据。
A great deal of knowledge exists regarding neural control of myocardial function in the rat. Most of the studies addressing this issue were conducted either under general anaesthesia or in isolated hearts in vitro. Our principal aim was to provide a detailed quantitative description of mechanisms controlling cardiac contractility in the rat, in an anaesthetic-free preparation with a preserved functional brainstem. Furthermore, while vagally mediated negative inotropy is a well-known phenomenon, at present there is no direct evidence for its presence in the rat; we searched for such evidence. To this end, in the arterially perfused working heart-brainstem preparation of the rat, we measured left ventricular pressure (LVP) and computed its first derivative (LVdP/dt). We made the following new observations. (i) Zatebradine (cardiac sodium pacemaker current blocker) caused a bradycardia associated with increases in LVP and LVdP/dt; the latter effect was via a frequency-dependent mechanism. (ii) We confirmed that in the rat, the force-frequency relationship (dependence of contractility on heart rate) is positive over a low range of heart rates, and negative and linear at physiological levels of heart rate, and provided its quantitative description. (iii) The increase in systemic pressure caused a rise in contractility, and vagal blockade or destruction of the central nervous system did not alter this inotropic effect, suggesting that it was mediated by intrinsic cardiac mechanisms. (iv) Vagal stimulation caused complex polyphasic changes in LVdP/dt and LVP in unpaced preparations; during pacing, it caused slowly developing falls in LVdP/dt that could be prevented by atropine. We conclude that control of ventricular contractility in the rat heart differs from that in other mammals not only by its negative frequency dependence, but also in the potent influence of aortic pressure on LVdP/dt. At the level of autonomic neural control, our newly found, vagally mediated negative inotropic effect adds to the accumulating body of data regarding both the presence and the functional importance of parasympathetic innervation of the ventricular myocardium.