Effects of equinatoxin II from Actinin equina (L.) on isolated rat heart: The role of direct cardiotoxic effects in equinatoxin II lethality

Equinatoxin II is a lethal basic protein isolated from the sea anemone Acti nia equina (L.) with LD50 in mice 35 mu g/kg. The putative cause of death i s cardiorespiratory arrest, but the mechanism of cardiotoxicity is poorly u nderstood. It is not clear whether the toxin injected intravenously into an experimental animal reaches the heart in a concentration sufficient to cau se direct effects on the heart. Therefore experiments were performed on rat s and on isolated rat hearts in order to investigate the possible direct ca rdiotoxic effects of the toxin. For this reason the hearts were perfused wi th different concentrations of the toxin and with the effluent from the lun gs collected during perfusion of the lungs with equinatoxin II. The results revealed the clear dose-dependent, direct cardiotoxic effects of the toxin and of the effluent from the lungs on Langendorff's heart preparations. Th e threshold concentration of equinatoxin II causing a drop in the perfusion rate, decreased left ventricular pressure, arrhythmia and increased LDH re lease, was found to be around 0.1 to 1 nM. With 10 nM equinatoxin II the le ft ventricular pressure dropped to 14 +/- 11% of the control, and the coron ary flow to 9 +/- 3%. These effects were followed by arrhythmia and cardiac arrest. The concentration of equinatoxin recovered from the lungs after th e perfusion with 100 nM equinatoxin II ranged between 0.8 and 5 nM. The res ults indicate that direct cardiotoxic effects of equinatoxin II play an imp ortant role in the lethal effects of the toxin. (C) 1998 Elsevier Science L td. All rights reserved.