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.

Purpose: 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.

Material and 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 CaCl₂ (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.

Conclusion: 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.

Key words::

• Heart
• cardiac
• blood
• experimental investigations
• arteries

Acknowledgements

The expert technical assistance from Gerd Torgersen, Eva Gustavsson, and Arshad F. Mohammed is gratefully acknowledged. This work was sponsored by GE Healthcare.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.