Loss of cardiac magnesium in experimental heart failure prolongs and destabilizes repolarization in dogs.

Abstract

OBJECTIVES:

We sought to determine whether heart failure results in loss of cardiac magnesium sufficient to alter cellular electrophysiology.

BACKGROUND:

Free magnesium has numerous intracellular roles affecting metabolism, excitability and RNA synthesis. Total cardiac magnesium content is reduced in heart failure, but it is unclear whether magnesium loss is primary or iatrogenic. Furthermore, it is unknown whether free magnesium levels are affected or whether a change in free magnesium would alter cellular electrophysiology.

METHODS:

Eight mongrel dogs underwent demand ventricular pacing (VVI) at 250 beats/min for 3 weeks to induce heart failure. Sublingual epithelial magnesium was measured before pacing and at death. Left ventricular myocytes were isolated and loaded with Mag-Indo-1 to measure free magnesium ([Mg2+]i); myocytes from eight normal dogs served as controls. To test whether changes in [Mg2+]i in this range could alter cellular repolarization, current-clamped myocytes were dialyzed with 0.5 or 1.0 mmol/liter MgCl2.

RESULTS:

Mean sublingual epithelial magnesium fell significantly in the paced animals, from 36.9 +/- 0.5 to 33.9 +/- 0.7 mEq/liter (p < 0.01). Mean cardiac [Mg2+]i was significantly lower in the dogs with heart failure--0.49 +/- 0.06 versus 1.06 +/- 0.15 mmol/liter (p < 0.003). Time to 90% repolarization was significantly shorter in cells dialyzed with 1.0 mmol/liter compared with 0.5 mmol/liter MgCl2 in myocytes from normal dogs or dogs with heart failure (596 +/- 34 vs. 760 +/- 58 ms in normal dogs and 586 +/- 29 vs. 838 +/- 98 ms in dogs with heart failure; p < 0.05 for each).

CONCLUSIONS:

Experimental heart failure results in both tissue and cardiac magnesium loss in the absence of drug therapy. Free cardiac magnesium is significantly reduced, possibly contributing to abnormal repolarization in heart failure.

• Authors: M C Haigney, S Wei, S Kääb, E Griffiths, R Berger, R Tunin, D Kass, W G Fisher, B Silver, H Silverman
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 31 Issue 3 Pg. 701-6 (Mar 01 1998) ISSN: 0735-1097 [Print] United States
• PMID: 9502656 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Magnesium

Topics

• Action Potentials
• Animals
• Disease Models, Animal
• Dogs
• Electrophysiology
• Heart Conduction System
• Heart Failure (metabolism, physiopathology)
• Magnesium (metabolism)
• Myocardium (cytology, metabolism)