Identification and description of separate mechanisms for two components of renografin cardiotoxicity.

SLUMMARY Both hemodynamic and electrocardiographic effects of Renografin-76 (diatrizoate meglumine) were studied in intact, anesthetized dogs. The left coronary artery in nine dogs was injected with equal amounts of Renografin-76, an equiosmolar dextrose solution (1690 mOsm/1) and a solution of the same electrolytic content (190 mEq/l sodium). Renografin and the dextrose solution produced significant sinus slowing, axis shift and prolongation of PR, QRS and QT intervals. On the other hand, Renografin and the electrolytic solution caused arterial hypotension, elevation of the left ventricular end-diastolic pressure and depression of left ventricular dP/dt. The dextrose solution did not impair left ventricular hemodynamic performance while the only electrocardiographic effect of the electrolytic solution was QT lengthening. None of the effects of any solution were modified by atrial pacing, and thus were independent of bradycardia. Four other dogs underwent left coronary arterial injections of 1) Renografin-76, 2) Renografin-76 with 40 mEq/l Ca+ +, 3) the previously used electrolytic solution, 4) the electrolytic solution with 40 mEq/l Ca+ , and 5) a saline solution with 190 mEq/l Na+. The addition of Ca-+ ameliorated but did not prevent the hemodynamic effects of the electrolytic solution. When added to Renografin, however, slight elevation of systemic blood pressure and marked increase in dP/dt were seen. We conclude that hyperosmolarity is responsible for the deleterious electrocardiographic effects of Renografin, while hypocalcemia induced by calcium-chelating agents is at least partly responsible for hemodynamic depression. The creation of a new contrast agent with more physiologic osmolaritv and electrolytic composition would be preferable to attempts at altering currently available media.