title: Preliminary assessment of cardiac short term safety and efficacy of manganese chloride for cardiovascular magnetic resonance in humans.
abstract: BACKGROUND
  Manganese based agents are intracellular and accumulate inside myocytes allowing for different imaging strategies compared to gadolinium contrasts. While previous agents release manganese very slowly in the circulation, MnCl2 allows for rapid Mn2+ uptake in myocytes, creating a memory effect that can be potentially explored. Data on animal models are very encouraging but the safety and efficacy of this approach in humans has not yet been investigated. Therefore, our objectives were to study the safety and efficacy of a rapid infusion of manganese chloride (MnCl2) for cardiovascular magnetic resonance (CMR) in humans.
  
  
  METHODS
  Fifteen healthy volunteers underwent a CMR scan on a 1.5 T scanner. Before the infusion, cardiac function was calculated and images of a short axis mid-ventricular slice were obtained using a 2D and 3D gradient-echo inversion recovery (GRE-IR) sequence, a phase-sensitive IR sequence and a single breath-hold segmented IR prepared steady-state precession acquisition for T1 calculations. MnCl2 was infused over three minutes at a total dose of 5 μMol/kg. Immediately after the infusion, and at 15 and 30 minutes later, new images were obtained and cardiac function re-evaluated.
  
  
  RESULTS
  There was a significant decrease in T1 values compared to baseline, sustained up to 30 minutes after the MnCl2 infusion (pre,839 ± 281 ms; 0 min, 684 ± 99; 15 min, 714 ± 168; 30 min, 706 ± 172, P = 0.003). The 2D and 3D GRE-IR sequence showed the greatest increase in signal-to-noise ratio compared to the other sequences (baseline 6.6 ± 4.2 and 9.7 ± 5.3; 0 min, 11.3 ± 4.1 and 15.0 ± 8.7; 15 min, 10.8 ± 4.0 and 16.9 ± 10.2; 30 min, 10.6 ± 5.2 and 16.5 ± 8.3, P < 0.001 for both). There was a slight increase in systolic pressure and heart rate after three and four minutes of the infusion with normalization of these parameters thereafter. Patients showed good tolerance to MnCl2 with no major adverse events, despite all reporting transient facial flush.
  
  
  CONCLUSIONS
  In the short term, MnCl2 appears safe for human use. It effectively decreases myocardium T1, maintaining this effect for a relatively long period of time and allowing for the development of new imaging strategies in CMR, especially in ischemia research.
authors.affiliation: Department of Internal Medicine, University of Campinas, Unicamp, Campinas, Brazil. jlaraf@fcm.unicamp.br
authors.forename: Juliano L
authors.initials: JL
authors.lastname: Fernandes
authors.forename: Pippa
authors.initials: P
authors.lastname: Storey
authors.forename: Jose Alvaro
authors.initials: JA
authors.lastname: da Silva
authors.forename: Gabriel S
authors.initials: GS
authors.lastname: de Figueiredo
authors.forename: Jose M
authors.initials: JM
authors.lastname: Kalaf
authors.forename: Otavio R
authors.initials: OR
authors.lastname: Coelho
mesh_terms: D000328:Adult; D001794:Blood Pressure; D001938:Brazil; D002712:Chlorides / Q000008:administration & dosage / Q000009:adverse effects; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology*; D006339:Heart Rate; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007262:Infusions, Intravenous; D019028:Magnetic Resonance Imaging, Cine / Q000009:adverse effects / Q000379:methods*; D008297:Male; D017895:Manganese Compounds / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment; D013318:Stroke Volume; D013997:Time Factors; D016277:Ventricular Function, Left
chemical_list: D002712:Chlorides; D003287:Contrast Media; D017895:Manganese Compounds; C025340:manganese chloride