title: Magnesium--a profibrillatory or antifibrillatory drug depending on plasma concentration, heart rate and myocardial perfusion.
abstract: BACKGROUND
  The opinions on the efficacy of magnesium as an antiarrhythmic drug vary considerably. The action of magnesium on vulnerability to fibrillation was therefore investigated in anaesthetized, open-chest pigs under different conditions as regards plasma concentration, heart rate and myocardial perfusion.
  
  
  METHODS
  Vulnerability to fibrillation was assessed by electrical fibrillation threshold (EFT), measured with 100-ms duration diastolic impulses. These stimuli were delivered to the heart normally perfused, at a usual (90 and 120 beats/min) or accelerated (180 beats/min) rate. Vulnerability to fibrillation was also assessed at the high rate (180 beats/min) in the heart made ischaemic by complete occlusion of the left anterior descending coronary artery near its origin. EFT was then measured at the end of occlusion periods which were of increasing duration (30, 60, 90, 120 s). Monophasic action potential (MAP) duration, intraventricular conduction time, left ventricular dP/dt max (LVdP/dt max) and mean blood pressure were concurrently measured.
  
  
  RESULTS
  In the absence of ischaemia, 5 mumol.kg-1.min-1 magnesium i.v. infusion, which raised plasma concentration to 1.78 +/- 0.14 mmol/L, lowered EFT, measured at the rate of 116 beats/min, from 14.0 +/- 1.1 to 6.8 +/- 1.0 mA (P < 0.001), without significant variation of the other parameters. Administered as previously or in a markedly higher dose (400 mumol.kg-1 loading dose and 10 mumol.kg-1.min-1 infusion) which raised plasma concentration up to 4.84 +/- 0.52 mmol/L, magnesium significantly influenced neither EFT nor MAP duration, reduced by the high rate (180 beats/min) to 6.2-6.7 mA and 212-220 ms respectively. Under the same conditions, at the same 180 beats/min rate, ischaemia brings about a fall of EFT, from 6.9 down to nearly 0 mA, with occurrence of fibrillation, in approximately 120 s. Magnesium failed to slow this fall and to delay the onset of fibrillation. In contrast, within the minutes following the end of occlusion, magnesium increased EFT to a great extent (from 7.1 +/- 0.4 to 13.5 +/- 0.7 mA, P < 0.001), with a significant prolongation of MAP duration (212 +/- 6 to 234 +/- 8 ms, P < 0.01).
  
  
  CONCLUSIONS
  Magnesium may develop profibrillatory or antifibrillatory effects depending on plasma concentration, heart rate and myocardial perfusion.
authors.affiliation: Department of Cardiology, Saint Joseph-Saint Luc Hospital, Lyon, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Aupetit
authors.forename: M
authors.initials: M
authors.lastname: Freysz
authors.forename: G
authors.initials: G
authors.lastname: Faucon
authors.forename: J
authors.initials: J
authors.lastname: Loufoua-Moundanga
authors.forename: H
authors.initials: H
authors.lastname: Coquelin
authors.forename: Q
authors.initials: Q
authors.lastname: Timour
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate; D008274:Magnesium / Q000097:blood / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D013552:Swine; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000889:Anti-Arrhythmia Agents; D008274:Magnesium