title: Predicting cardiotoxicity propensity of the novel iodinated contrast medium GE-145: Ventricular fibrillation during left coronary arteriography in pigs.
abstract: BACKGROUND
  Severe side effects caused by iodinated radiographic contrast media (CM) are rare, but can occur in high risk patients and during percutaneous coronary intervention. To minimize this risk a new nonionic CM with low inherent osmolality has been designed, giving room for a relatively high concentration of favorable electrolytes in the isotonic formulation.
  
  
  OBJECTIVE
  To test a new radiographic CM (GE-145) in a pig model of cardiotoxicity by comparing its ventricular fibrillation (VF) propensity and hemodynamic effects to that of iodixanol.
  
  
  METHODS
  Test agents were injected into the left anterior descending coronary artery (LAD) of pigs through an inflated balloon catheter (injection volume 25 ml, injection rate 0.4 ml/s, maximum injection time 62.5 s). Series 1: GE-145 (338 mg I/ml) + 45 mM NaCl and iodixanol (321 mg I/ml) + 19 mM NaCl were injected in five pigs. Series 2: GE-145 (320 mg I/ml) + 45 mM NaCl + 0.1, 0.3, or 0.7 mM CaCl₂ and iodixanol (320 mg I/ml) + 19 mM NaCl + 0.3 mM CaC₂ (Visipaque) were injected in six pigs.
  
  
  RESULTS
  Iodixanol + NaCl caused VF in 6 of 13 injections (46%) after 60.3±7.5 s (mean ± SD). GE-145 + NaCl did not cause any VF in 13 injections (0%) (P<0.05). Iodixanol + 19 mM NaCl + 0.3 mM CaCl₂ caused VF in 9 of 9 injections (100%) after 61±4 s. GE-145 + 45 mM NaCl + 0.1, 0.3, or 0.7 mM CaCl₂ did not cause any VF during or after 9 injections of each agent (0%) (P<0.05). The least hemodynamic effects were seen with GE-145 + 45 mM NaCl + 0.7 mM CaCl₂.
  
  
  CONCLUSIONS
  In this model of direct administration of CM into the LAD of anesthetized pigs, the tested GE-145 formulations had a significantly lower propensity to induce VF than iodixanol with electrolytes. Favorable hemodynamic properties of GE-145 can be achieved by optimizing concentrations of sodium and calcium.
authors.affiliation: Dept. of Clinical Sciences/Medical Radiology, Lund Univeristy, Lund, Sweden.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Chai
authors.forename: Henrik
authors.initials: H
authors.lastname: Rasmussen
authors.forename: Morten
authors.initials: M
authors.lastname: Eriksen
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Hvoslef
authors.forename: Paul
authors.initials: P
authors.lastname: Evans
authors.forename: Ben B
authors.initials: BB
authors.lastname: Newton
authors.forename: Signe
authors.initials: S
authors.lastname: Videm
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage / Q000633:toxicity*; D017023:Coronary Angiography; D004562:Electrocardiography; D005559:Formamides / Q000008:administration & dosage / Q000633:toxicity*; D006439:Hemodynamics / Q000187:drug effects; D018709:Statistics, Nonparametric; D013552:Swine; D014283:Triiodobenzoic Acids / Q000008:administration & dosage / Q000633:toxicity*; D014693:Ventricular Fibrillation / Q000139:chemically induced*
chemical_list: C553686:5-(formyl-(3-(formyl-(3,5-bis (2,3-dihydroxypropylcarbamoyl)-2,4,6-triiodophenyl) amino)-2-hydroxypropyl)amino)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide; D003287:Contrast Media; D005559:Formamides; D014283:Triiodobenzoic Acids; C044834:iodixanol