LOSS OF CARDIAC MAGNESIUM IN EXPERIMENTAL HEART-FAILURE PROLONGS AND DESTABILIZES REPOLARIZATION IN DOGS

Objectives. We sought to determine whether heart failure results in lo ss of cardiac magnesium sufficient to alter cellular electrophysiology , Background. Free magnesium has numerous intracellular roles affectin g metabolism, excitability and RNA synthesis. Total cardiac magnesium content is reduced in heart failure, but it is unclear whether magnesi um loss is primary or iatrogenic. Furthermore, it is unknown whether f ree magnesium levels are affected or whether a change in free magnesiu m 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 a nd loaded with Mag-Indo-1 to measure free magnesium ([Mg2+](i)); myocy tes from eight normal dogs served as controls, To test whether changes in [Mg2+](i) in this range could alter cellular repolarization, curre nt-clamped myocytes were dialyzed with 0.5 or 1.0 mmol/liter MgCl2. Re sults. 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), Ti me to 90% repolarization was significantly shorter in cells dialyzed w ith 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 fai lure; p < 0.05 for each). Conclusions. Experimental heart failure resu lts in both tissue and cardiac magnesium loss in the absence of drug t herapy. Free cardiac magnesium is significantly reduced, possibly cont ributing to abnormal repolarization in heart failure. (C) 1998 by the American College of Cardiology.