Blockade of renin-angiotensin system reduces QT dispersion and improves intracellular Ca/Mg status in hemodialysis patients.

BACKGROUND: Electrolyte impairments are common in hemodialysis (HD) patients. Consequently, QT dispersion (QTd) is prolonged, correlating with high intracellular magnesium. In patients with cardiac disorders, renin-angiotensin system (RAS) inhibition reduces QTd. AIM: To compare the effects of ACE inhibition or AT-1 blockade on QTd duration and intracellular magnesium (Mg)/calcium (Ca) in peripheral blood mononuclear cells (PBMC) from chronic HD patients. METHODS: 24 HD patients received cilazapril for 8 weeks and, following a 2-week withdrawal, were switched to valsartan for additional 8 weeks. QTd measurements and PBMC isolation were performed at the beginning and the end of each period. Total intracellular Ca and Mg were assessed by atomic spectrometer, and cytosolic free Ca2+ by fluorocytometer. RESULTS: Both treatments significantly decreased QTd, demonstrating similar reduction magnitudes. In both groups, PBMC exhibited basally low cytosolic Ca2+ and undisturbed high transmembrane Ca2+ influx following phytohemagglutinin stimulation. Total intracellular Ca was increased, while Mg was reduced, following either treatment. The total intracellular Ca/Mg ratio inversely correlated with QTd duration. CONCLUSIONS: (1) RAS inhibition reduces prolonged QTd in HD patients. (2) In PBMC from ordinarily Ca-depleted HD patients, RAS suppression brings about elevation of total intracellular Ca. (3) RAS blockade decreases high intracellular Mg in PBMC from HD patients. Consequently, the Ca/Mg ratio increases, inversely correlating with QTd reduction.

Cell-associated magnesium and QT dispersion in hemodialysis patients.

BACKGROUND: Impaired magnesium (Mg) homeostasis has been implicated in a variety of cardiovascular disturbances, including ventricular arrhythmias and changes in the interval between the onset of wave Q to the end of wave T (QT interval) on electrocardiogram. Cardiac arrhythmias are common in patients on hemodialysis therapy. METHODS: We investigated the relationship between QT interval corrected for heart rate (QTc) dispersion and Mg content in peripheral blood mononuclear cells (PBMC) of chronic hemodialysis patients treated with high-dose calcium carbonate providing Mg in excess (group I; n = 18) or low-dose calcium carbonate and smaller Mg load (group II; n = 13). RESULTS: Mean Mg content in PBMC of group I patients (27.9 +/- 4.2 [SD] micromol/L/mg protein) was significantly greater than in group II patients (10.4 +/- 4.1 micromol/L/mg protein; P < 0.05) and greater in both groups than in healthy control subjects (2.75 +/- 0.6 micromol/L/mg protein; P < 0.05). Mean QTc dispersion was significantly longer (74.6 +/- 21.4 milliseconds) in group I than group II (37.8 +/- 13.1 milliseconds; P < 0.02) and longer in both groups than in controls (27.3 +/- 9.6 milliseconds; P < 0.05). After dialysis, in both groups of patients, cell-associated Mg (c-a Mg) levels and QTc dispersion were significantly greater (P < 0.05) than before dialysis started. One week after stopping calcium carbonate treatment, group 1 patients showed significant reductions in predialytic c-a Mg levels (to 19.5 +/- 9.8 micromol/L/mg protein; P < 0.05) and QTc dispersions (to 48.9 +/- 23.7 milliseconds; P < 0.05). Plasma Mg and other electrolyte concentrations prior to and during hemodialysis did not correlate with QTc dispersion. CONCLUSION: Prolongation of QTc dispersion in patients on chronic hemodialysis therapy could be, at least in part, a consequence of increased concentrations of c-a Mg resulting from excess daily Mg intake.