The use of tri-iodinated water-soluble organic molecules as radiographic contrast material for visualization of coronary arteries during x-ray examination is a commonly used procedure despite the significant incidence of major side effects. Extensive research concerning the origen of contrast material toxicity has revealed several important areas of concern but has failed to result in toxicity free preparations. Side effects include arrhythmias (1), ventricular fibrillation (2), and the loss of myocardial contractility (3). Investigations into the causes of these side effects have centered on changes in osmolarity (4), lack of oxigen delivery (5), PH (6), and electrolyte composition. Many of these investigations have led to reductions in toxicity, yet significant toxicity remains - the origin of which is still uncertain. The overall goal of the research proposed in this application is to test the hypothesis that, while there are multiple factors responsible for toxicity, transient changes in electrolyte composition of the extracellular compartment induced by selective arterial contrast administration are the major determinants of toxicity. Such changes in the extracellular concentration of electrolytes leads to alteration of intracellular electrolyte composition. This, in turn, leads to alterations of myocardial function and metabolism. It is our further goal to use the results of our studies to design contrast materials with minimal toxicity. In order to accomplish these goals, new and developing techniques of Na-23 and P-31 nuclear magnetic resonance to study intracellular sodium concentrations, intracellular PH and intracellular high-energy phosphate concentrations in isolated perfused working rat hearts will be used during and following administration of contrast materials of a variety of compositions.
