Corr P B, Cain M E, Witkowski F X, Price D A, Sobel B E
Circ Res. 1979 Jun;44(6):822-32. doi: 10.1161/01.res.44.6.822.
We have recently detected accumulation of lysophosphoglycerides, catabolites of phospholipids, in ischemic myocardium early after coronary occlusion. In the present study we delineated effects of selected concentrations of albumin-bound lysophosphatidyl choline (LPC) comparable to those accompanying ischemia in vivo on action potentials of isolated canine Purkinje fibers. Lysophosphoglycerides induced concentration-dependent (0.75-3.0 mM) decreases in resting membrane potential, overshoot of phase 0, maximal velocity of upstroke (Vmax) of phase 0, and action potential duration. The highest concentrations (2.0-3.0 mM) induced fractionation of the action potential into several components, unresponsiveness to external stimulation, and enhanced automaticity at normal and reduced membrane potentials. LPC induced a rightward shift in the membrane response curve, a 40-fold prolongation of conduction time, and an increase in the ratio of effective refractory period to action potential duration such that the effective refractory period persisted beyond action potential duration, resulting in postrepolarization refractoriness. These electrophysiological alterations were entirely reversible after 70 minutes of perfusion without LPC, with the exception of a persistent depression in the Vmax of phase 0. Lysophosphatidyl ethanolamine (LPE) elicited alterations in action potentials indentical to those elicited by LPC. Furthermore, LPC (3.0 mM) induced comparable alterations in action potentials recorded from isolated rabbit papillary muscles. Since lysophospholipids accumulate early after myocardial ischemia, and since concentrations equivalent to those occurring in vivo induce electrophysiological alterations resembling those seen in ischemic myocardium in vivo, lysophosphoglycerides may be of major importance as biochemical mediators of malignant dysrhythmia induced by ischemia.
我们最近检测到，冠状动脉闭塞后早期，缺血心肌中磷脂的分解代谢产物溶血甘油磷脂有所蓄积。在本研究中，我们描绘了与体内缺血时相当的选定浓度的白蛋白结合溶血磷脂酰胆碱（LPC）对离体犬浦肯野纤维动作电位的影响。溶血甘油磷脂引起静息膜电位、0期超射、0期最大上升速度（Vmax）和动作电位持续时间呈浓度依赖性（0.75 - 3.0 mM）降低。最高浓度（2.0 - 3.0 mM）使动作电位分裂为几个成分，对外界刺激无反应，并在正常和降低的膜电位下增强自律性。LPC使膜反应曲线右移，传导时间延长40倍，有效不应期与动作电位持续时间的比值增加，导致有效不应期持续超过动作电位持续时间，从而产生复极化后不应期。在无LPC灌注70分钟后，除0期Vmax持续降低外，这些电生理改变完全可逆。溶血磷脂酰乙醇胺（LPE）引起的动作电位改变与LPC引起的相同。此外，LPC（3.0 mM）在离体兔乳头肌记录的动作电位中引起类似的改变。由于溶血磷脂在心肌缺血后早期蓄积，且体内出现的浓度可诱导出类似于体内缺血心肌所见的电生理改变，因此溶血甘油磷脂作为缺血诱导的恶性心律失常的生化介质可能具有重要意义。
