To evaluate the myocardial metabolic effects of a new nonionic contrast agent, iopamidol, a randomized, double-blind study was performed comparing iopamidol with sodium meglumine diatrizoate (Renografin-76) in 23 patients with ischemic heart disease. Coronary sinus and arterial metabolic samples were obtained prior to and during the 20-minute period following the contrast left ventriculogram. Ten patients received iopamidol and 13 received Renografin-76. The chemical lactate extraction in the iopamidol group was 13 +/- 9% prior to left ventriculography and 17 +/- 12% following the contrast injection (p less than 0.005). In the Renografin-76 group, the lactate extraction was 23 +/- 13% and decreased significantly to 12 +/- 24% following the ventriculogram (p less than 0.01). In a subset of these patients (n = 10), [1-(14)C] lactate was infused as a tracer to quantitate the amount of lactate released by the myocardium. [1-(14)C] lactate analysis demonstrated that the fall in lactate extraction ratio following Renografin-76 was due to an increase in myocardial lactate release. In the Renografin-76 group there was a 53 +/- 37% increase in lactate release at 10 minutes after contrast agent injection (p less than 0.005), while in the iopamidol patients there was no significant change in lactate release following contrast ventriculography. The increase in lactate release in the Renografin-76 group suggests that myocardial ischemia is induced with this ionic contrast agent. In comparison, the nonionic contrast agent is less toxic to the myocardium and is not associated with the biochemical changes of cellular ischemia.