Blockade of Renin-Angiotensin System Reduces QT Dispersion and Improves Intracellular Ca/Mg Status in Hemodialysis Patients

Abstract

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.

Losartan and QT Dispersion in Hypertensive Patients on Maintenance Hemodialysis

“…The changes in QTcd were positively correlated with changes in the serum levels of lipoperoxidation and with changes in diastolic BP. Moreover, RAS inhibitors by the way that change cell membrane electrolyte gradient may decrease QTd [17]. Averbukh et al [17] Original QTd and QTcd in our small dialysis cohort could be due to differences in the study population and methodology or the shorter study duration for structural changes in the heart.…”

“…Moreover, RAS inhibitors by the way that change cell membrane electrolyte gradient may decrease QTd [17]. Averbukh et al [17] Original QTd and QTcd in our small dialysis cohort could be due to differences in the study population and methodology or the shorter study duration for structural changes in the heart. Therefore, a direct comparison of other studies with our preliminary investigation was difficult.…”

“…It is possible that losartan may be acting directly or indirectly as an antiarrhythmic agent [16]. Very few studies have investigated effect of ARB on QTd in HD patients [17]. Therefore, we analyzed the effect of losartan on QTd in hypertensive HD patients.…”

Briefly noted

“…QT dispersion (QTd, the difference between the longest and shortest QT intervals on ECG) is an independent risk fact for cardiovascular mortality . QTd was examined in 24 chronic hemodialysis patients without cardiovascular disease before and after two 8‐week treatment periods, first with an ACE inhibitor (cilazapril) and then an ARB (valsartan) (7). Both ACE inhibitor treatment (mean QTd—before: 81 milliseconds, during: 46 milliseconds) and ARB treatment (70 milliseconds, 50 milliseconds) substantially reduced QTd.…”