Horner S M, Murphy C F, Coen B, Dick D J, Lab M J
Department of Physiology, Charing Cross and Westminster Medical School, Hammersmith, London, UK.
Cardiovasc Res. 1996 Jul;32(1):148-57.
Increased sympathetic stimulation is known to be arrhythmogenic. Likewise increased loading of the myocardium can directly generate arrhythmias. The interaction between the two on the electrophysiology of the myocardium has not been investigated before. We investigated the effect of dobutamine infusion on the shortening of the monophasic action potential duration secondary to increased loading. This was investigated during steady-state pacing and during an alteration in beat-to-beat interval in the form of a restitution curve.
Pigs were anaesthetised and their hearts exposed. Monophasic action potentials and segment lengths were recorded from the anterior surface of the left ventricle. The loading of the ventricle was increased by transiently occluding the aorta. Steady-state pacing and a restitution curve were performed. Recordings were taken before and during dobutamine infusion.
At steady state, increased loading of the heart shortened the monophasic action potential duration by a mean (+/- s.e.m.) of 4.0 (+/- 0.5) ms (P < 0.001). During dobutamine infusion this shortening of the monophasic action potential increased. Shortening of the action potential duration increased with the dose of dobutamine up to 10 micrograms/kg/min after which a plateau was reached. By comparison to control, dobutamine depressed the electrical restitution curve at short test pulse intervals did not significantly alter the plateau. Increased loading elevated the initial section of the electrical restitution curve at short test pulse intervals and depressed the plateau in both the control recordings and those taken during dobutamine infusion. Increased loading increased the amplitude of the supernormal phase of the electrical restitution curve in control recordings and those taken during dobutamine infusion. Sympathetic stimulation by dobutamine during the steady state potentiates the effect of mechanoelectric feedback on the myocardium. The effect on the restitution curve varies with test pulse interval. At short test pulse intervals the effect of sympathetic stimulation dominates with only minor antagonistic modification by increased loading. However, at longer test pulse intervals the effect of mechanoelectric feedback is equal to that of sympathetic stimulation and is synergistic with it.
The mechanically induced changes we describe in the normal pig heart in situ are relatively small. However, they are in the right direction to possibly contribute to arrhythmia under pathological conditions where mechanical as well as electrophysiological inhomogeneity is prominent.
已知交感神经刺激增强具有致心律失常作用。同样，心肌负荷增加也可直接引发心律失常。此前尚未研究二者在心肌电生理方面的相互作用。我们研究了多巴酚丁胺输注对因负荷增加导致的单相动作电位时程缩短的影响。在稳态起搏期间以及以恢复曲线形式改变逐搏间期时对此进行了研究。
对猪进行麻醉并显露其心脏。从左心室前表面记录单相动作电位和节段长度。通过短暂阻断主动脉增加心室负荷。进行稳态起搏和恢复曲线实验。在多巴酚丁胺输注前及输注期间进行记录。
在稳态时，心脏负荷增加使单相动作电位时程平均（±标准误）缩短4.0（±0.5）毫秒（P<0.001）。在多巴酚丁胺输注期间，单相动作电位的这种缩短有所增加。动作电位时程的缩短随多巴酚丁胺剂量增加，直至10微克/千克/分钟时达到平台期。与对照组相比，多巴酚丁胺在短测试脉冲间期压低电恢复曲线，而对平台期无显著影响。负荷增加在短测试脉冲间期抬高电恢复曲线的起始段，并在对照组记录以及多巴酚丁胺输注期间的记录中压低平台期。负荷增加使对照组记录以及多巴酚丁胺输注期间的记录中的电恢复曲线超常期幅度增大。稳态时多巴酚丁胺引起的交感神经刺激增强了机电反馈对心肌的作用。对恢复曲线的影响随测试脉冲间期而变化。在短测试脉冲间期，交感神经刺激的作用占主导，负荷增加仅有轻微的拮抗作用。然而，在较长测试脉冲间期，机电反馈的作用与交感神经刺激的作用相当且二者具有协同作用。
我们在正常猪原位心脏中描述的机械性诱导变化相对较小。然而，在机械及电生理不均一性突出的病理状态下，它们朝着可能导致心律失常的正确方向发展。
