Effects of sodium nitroprusside on hemodialysis-induced platelet activation.
BACKGROUND
Hemodialysis (HD) is associated with increased platelet activation as reflected by enhanced P-selectin expression on platelets and by increased formation of heterotypic platelet-leukocyte aggregates. Both may play a pathophysiologic role in HD-associated platelet dysfunction or the propagation of atherosclerosis. As nitric oxide (NO) is a potent inhibitor of platelet activation, we were interested in whether HD-induced platelet activation could be blunted by a NO donor.


METHODS
After a pilot study in 12 patients to gain an estimate for the sample size, the main trial was conducted as a randomized, double-blind, placebo-controlled, two-way, cross-over study. Twelve patients received an infusion of sodium nitroprusside (1 microgram/kg/min for over 15 min) or placebo into the inlet port of the HD device.


RESULTS
Platelet activation increased within five minutes after start of HD (P < 0.05). Infusion of sodium nitroprusside neither decreased platelet activation (P-selectin + platelets) nor affected the number of platelet-leukocyte aggregates (CD41+ neutrophils) as measured by flow cytometry.


CONCLUSIONS
Although NO may have inhibitory effects on platelet activation in vivo, our results confirm recent findings showing that NO donors were ineffective in preventing platelet activation by extracorporeal circulation during cardiopulmonary bypass or plateletpheresis. Thus, NO donors do not appear to be ideal candidate drugs to inhibit HD-associated platelet activation.
Jilma
B
B
Department of Clinical Pharmacology-TARGET, Vienna University Hospital School of Medicine, Austria. Bernd.Jilma@univie.ac.at
Hergovich
N
N
Stohlawetz
P
P
Stummvoll
G
G
Albinni
S
S
Simak
S
S
Schmaldienst
S
S
Pohanka
E
E
Eichler
H G
HG
Kapiotis
S
S
D000328:Adult; D000368:Aged; D001772:Blood Cell Count / Q000187:drug effects; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology; D002449:Cell Aggregation / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005240:Feasibility Studies; D006801:Humans; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D009599:Nitroprusside / Q000627:therapeutic use*; D019007:P-Selectin / Q000097:blood; D010865:Pilot Projects; D015539:Platelet Activation / Q000187:drug effects*; D006435:Renal Dialysis; D017211:Treatment Failure