Barrington P L, Yang C C, Rosenberg P
Life Sci. 1984 Aug 27;35(9):987-95. doi: 10.1016/0024-3205(84)90665-9.
N. nigricollis phospholipase A2 (200 micrograms) has marked cardiotoxic actions on the perfused rat heart including the induction of arrhythmias, increases in ventricular thresholds, conduction and resting tension, and decreases in contractile tension. In contrast, perfusion with lysophosphatidyl choline and oleic acid, in concentrations comparable to those estimated to be formed during N. nigricollis treatment, has little effect on cardiac function. The less toxic N. n. atra phospholipase A2 also has little effect on cardiac function even though it causes approximately the same low percentage of phospholipid hydrolysis as produced by N. nigricollis phospholipase A2. Perfusion with albumin did not alter the phospholipase A2 induced changes in cardiac function. Lysophosphatidyl choline in concentrations higher than expected to be formed during N. nigricollis phospholipase A2 treatment, increased conduction time to a greater extent than ventricular threshold whereas the reverse was true for phospholipase A2. We conclude that the cardiotoxic effects of N. nigricollis phospholipase A2 are not due to the accumulation of phospholipid hydrolytic products, and on the basis of prior studies with chemically modified phospholipase A2 enzymes we suggest that N. nigricollis phospholipase A2 has a direct, non-enzymatic, cardiotoxic action.
黑颈眼镜蛇磷脂酶A2（200微克）对灌注的大鼠心脏具有明显的心脏毒性作用，包括诱发心律失常、提高心室阈值、增加传导和静息张力以及降低收缩张力。相比之下，用溶血磷脂酰胆碱和油酸进行灌注，其浓度与黑颈眼镜蛇治疗过程中估计形成的浓度相当，但对心脏功能几乎没有影响。毒性较小的中华眼镜蛇磷脂酶A2对心脏功能也几乎没有影响，尽管它引起的磷脂水解百分比与黑颈眼镜蛇磷脂酶A2产生的大致相同。用白蛋白灌注并没有改变磷脂酶A2引起的心脏功能变化。浓度高于黑颈眼镜蛇磷脂酶A2治疗过程中预期形成浓度的溶血磷脂酰胆碱，对传导时间的增加幅度大于心室阈值，而磷脂酶A2的情况则相反。我们得出结论，黑颈眼镜蛇磷脂酶A2的心脏毒性作用并非由于磷脂水解产物的积累，并且基于之前对化学修饰的磷脂酶A2酶的研究，我们认为黑颈眼镜蛇磷脂酶A2具有直接的、非酶促的心脏毒性作用。
