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.


OBJECTIVE
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.
Averbukh
Zhan
Z
Nephrology Division, Assaf Harofeh Medical Center, Affiliated to Sackler Medical School, Tel Aviv University, Zerifin, Israel. averbukhzh@asaf.health.gov.il
Berman
Sylvia
S
Efrati
Shai
S
Manevits
Elena
E
Rosenberg
Rosa
R
Malcev
Ela
E
Galperin
Elena
E
Weissgarten
Joshua
J
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D002118:Calcium / Q000378:metabolism*; D017315:Cilazapril / Q000008:administration & dosage*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000008:administration & dosage*; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D013777:Tetrazoles; D017315:Cilazapril; D000068756:Valsartan; D014633:Valine; D008274:Magnesium; D002118:Calcium