Influence of Severity of Myocardial Injury on Distribution of Macromolecules: Extravascular Versus Intravascular Gadolinium-Based Magnetic Resonance Contrast Agents

Objectives. This study sought to 1) compare the distribution of extravascular (573 Da) and intravascular (92 kDa) magnetic resonance (MR) contrast agents in reperfused infarcted myocardium, and 2) investigate the effect of injury severity on these distribution patterns. Background. Myocardial distribution of low and high molecular weight contrast agents depends on vascular permeability, diffusive/convective transport within the interstitium and accessibility of the intracellular compartment (cellular integrity). Methods. To vary the severity of myocardial injury, 72 rats were subjected to 20, 30, 45 or 75 min (n = 18, respectively) of coronary artery occlusion. After 2 h of reflow, the animals received either 0.05 mmol/kg of gadolinium-diethylenetriaminepentaacetic acid-bismethylamide (Gd-DTPA-BMA) (n = 24), (Gd-DTPA)30-albumin (n = 24) or saline (control group, n = 24). Three minutes after injection, the hearts were excised and imaged (spin-echo imaging parameters: repetition time 300 ms, echo time 8 ms, 2-tesl system), followed by triphenyltetrazolium chloride staining for infarct detection and sizing. Results. Histomorphometric and MR infarct size (expressed as percent of slice surface) correlated well: r = 0.96 for Gd-DTPA-BMA; r = 0.95 for (Gd-DTPA)30-albumin. On Gd-DTPA-BMA–enhanced images, reperfused myocardial infarctions were homogeneously enhanced. The ratio of signal intensity of infarcted/normal myocardium increased with increasing duration of ischemi (overall p < 0.0001, analysis of variance [ANOVA]), indicating an increase in the distribution volume of Gd-DTPA-BM in postischemic myocardium. On (Gd-DTPA)30-albumin–enhanced images, reperfused infarctions consisted of bright border zone and less enhanced central core. The extent of the core increased with increasing duration of ischemi (overall p value < 0.0001, ANOVA). Conclusions. At 2 h of reperfusion, the distribution of MR contrast agents in postischemic myocardium is 1) specific for extravascular and intravascular agents, and 2) modulated by the duration of ischemia.