title: Influence of severity of myocardial injury on distribution of macromolecules: extravascular versus intravascular gadolinium-based magnetic resonance contrast agents.
abstract: OBJECTIVE
  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-tesla 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 ischemia (overall p < 0.0001, analysis of variance [ANOVA]), indicating an increase in the distribution volume of Gd-DTPA-BMA in postischemic myocardium. On (Gd-DTPA)30-albumin-enhanced images, reperfused infarctions consisted of a bright border zone and a less enhanced central core. The extent of the core increased with increasing duration of ischemia (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.
authors.affiliation: Department of Radiology, University of California at San Francisco 94143-0628, USA.
authors.forename: J
authors.initials: J
authors.lastname: Schwitter
authors.forename: M
authors.initials: M
authors.lastname: Saeed
authors.forename: M F
authors.initials: MF
authors.lastname: Wendland
authors.forename: N
authors.initials: N
authors.lastname: Derugin
authors.forename: E
authors.initials: E
authors.lastname: Canet
authors.forename: R C
authors.initials: RC
authors.lastname: Brasch
authors.forename: C B
authors.initials: CB
authors.lastname: Higgins
mesh_terms: D000418:Albumins / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D019786:Gadolinium DTPA / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging; D008970:Molecular Weight; D009203:Myocardial Infarction / Q000145:classification* / Q000473:pathology* / Q000628:therapy; D015425:Myocardial Reperfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D014018:Tissue Distribution
chemical_list: D000418:Albumins; D003287:Contrast Media; C058946:albumin-(gadolinium-DTPA); C064925:gadodiamide; D019786:Gadolinium DTPA