Assessment of Cardiac Toxicity of Manganese Chloride for Cardiovascular Magnetic Resonance

Elodie Lamonzie; Fanny Vaillant; Emma Abell; Sabine Charron; Dounia El Hamrani; Bruno Quesson; Fabien Brette

doi:10.3389/fphys.2022.952043

Assessment of Cardiac Toxicity of Manganese Chloride for Cardiovascular Magnetic Resonance

Front Physiol. 2022 Jul 7:13:952043. doi: 10.3389/fphys.2022.952043. eCollection 2022.

Authors

Elodie Lamonzie^{1

2}, Fanny Vaillant^{1

2}, Emma Abell^{1

2}, Sabine Charron¹, Dounia El Hamrani^{1

2}, Bruno Quesson^{1

2}, Fabien Brette^{1

2}

Affiliations

¹ Univ, Bordeaux, CRCTB, Inserm, Bordeaux, France.
² IHU Liryc, Electrophysiology and Heart Modeling Institute, Bordeaux, France.

Abstract

MRI is widely used in cardiology to characterize the structure and function of the heart. Currently, gadolinium-based contrast agents are widely used to improve sensitivity and specificity of diagnostic images. Recently, Manganese, a calcium analogue, has emerged as a complementary contrast agent with the potential to reveal remaining viable cells within altered tissue. Imaging applications may be limited by substantial toxicity of manganese. Indeed, cardiac safety of manganese is not yet comprehensively assessed. In this study we investigated the effect of MnCl₂ (1-100 µM) on cardiac function. Hemodynamic function was determined ex vivo using an isolated working rat heart preparation. HL-1 cardiac myocytes were used to investigate cell viability (calcein AM) and calcium cycling (Cal-520 a.m.). Rat ventricular cardiomyocytes were dissociated by enzymatic digestion. Action potentials and calcium currents were recorded using the patch clamp technique. MRI experiments were performed at 1.5T on formalin-fixed rat hearts, previously perfused with MnCl₂. MnCl₂ perfusion from 1 up to 100 µM in isolated working hearts did not alter left ventricular hemodynamic parameters. Contractility and relaxation index were not altered up to 50 µM MnCl₂. In HL-1 cardiac myocytes, incubation with increasing concentrations of MnCl₂ did not impact cell viability. The amplitude of the calcium transients were significantly reduced at 50 and 100 µM MnCl₂. In freshly isolated ventricular myocytes, action potential duration at 20, 50 and 90% of repolarization were not modified up to 10 µM of MnCl₂. L-type calcium current amplitude was significantly decreased by 50 and 100 µM of MnCl₂. MRI on heart perfused with 25 and 100 µM of MnCl₂ showed a dose dependent decrease in the T1 relaxation time. In conclusion, our results show that low concentrations of MnCl₂ (up to 25 µM) can be used as a contrast agent in MRI, without significant impact on cardiac hemodynamic or electrophysiology parameters.

Keywords: MRI; calcium; cardiac function; electrophysiology; manganese; toxicity.