First-pass entry of nonionic contrast agent into the myocardial extravascular space: Effects on radiographic estimates of transit time and blood volume

Background. Almost all x-ray-based techniques intended to assess regional myocardial perfusion from myocardial concentration-time curves following the administration of soluble contrast agents assume that these agents behave as intravascular indicators and can therefore provide measurements of intravascular transit time and intramyocardial blood volume. Methods and Results. We tested this assumption by comparing a conventional nonionic contrast agent (ioversol) to a particulate emulsion (ethiodol) that remained in the vascular space in closed-chest dogs during pharmacological vasodilation. Using fast computed tomography (CT), pairs of myocardial CT intensity-time curves were obtained following sequential bolus aortic administration of the two contrast agents. The emulsion (particle size <3 μm) was almost completely washed out of the myocardial region of interest within a few seconds, as would be anticipated for a vascular indicator. At the onset of recirculation, CT intensity for ethiodol fell to 5±1% (SEM) of peak values in normally perfused areas and to 10±4% of peak values in an area in which flow had been reduced by 50% by a chronically implanted coronary artery occluder (p=NS). In comparison, the diffusible nonionic contrast agent ioversol showed substantial intramyocardial retention at the onset of recirculation. At the time of recirculation, CT intensities for ioversol averaged 36±2% of peak values in normally perfused nonstenotic areas and 54±4% of peak values in stenotic areas (p<0.01). Using residue function analysis for a diffusible indicator, first-pass extractions of the conventional nonionic agent averaged 33±2% in normally perfused areas and 50±3% in stenotic areas (p<0.01). Because of the significant first-pass myocardial retention of ioversol, both mean myocardial appearance time and intramyocardial blood volume were consistently overestimated. Conclusions. Soluble radiographic contrast agents, like other small molecules, enter the interstitial space to a degree, which is important because it affects estimates of myocardial perfusion based on transit time and intramyocardial blood volume. Indicator dilution models intended to quantify myocardial perfusion with conventional radiographic contrast agents need to account for this extravascular exchange.