Cardiotoxic effects of Naja nigricollis venom phospholipase A2 are not due to phospholipid hydrolytic products.

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.