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Contrast materials may alter coronary blood flow (CBF) by a direct vasodilating action or indirectly by changing determinants of myocardial oxygen requirements (MVO2). The current study compared the vasodilatory actions of ionic (Renografin 76®, R76) and nonionic contrast materials (iohexol and metrizamide) after direct injection into the coronary and femoral circulation of anesthetized dogs. R76 did not cause a significantly greater increase in CBF compared with the nonionic materials in spite of causing significantly greater increases in osmolality of blood in the coronary sinus. Concomitant with the peak increase in CBF, the ionic materials caused sharp decrease in peak left ventricular (LV) systolic pressure and dp/dt, while the nonionic materials increased these major determinants of MVO2. In contradistinction to the effects on CBF, ionic contrast material caused substantially and significantly greater increase in femoral blood flow, compared with the nonionic materials. In conclusion, these studies infer that the increase in CBF with contrast materials involves both indirect vascular and metabolic actions, while the increase in FBF is due to a direct vascular action.