The Journal of Thoracic and Cardiovascular Surgery, Vol 96, 535-541, Copyright © 1988 by The American Association for Thoracic Surgery and The Western Thoracic Surgical Association
Temporary inhibition of platelet function with iloprost (ZK36374) preserves canine platelets during extracorporeal membrane oxygenation
ED Cottrell, JR Kappa, N Stenach, CA Fisher, GP Tuszynski, HI Switalska and VP Addonizio
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104.
Contact between blood and artificial surfaces results in extensive
quantitative and qualitative alterations in platelet function. We evaluated
the efficacy of a brief infusion of iloprost (ZK36374), a stable analog of
prostacyclin, in preventing these platelet changes during extracorporeal
membrane oxygenation. Twelve nonsplenectomized male mongrel dogs (23 to 30
kg) were randomized to treatment (n = 6) and control (n = 6) groups. The
treatment animals received an infusion of iloprost at a rate of 150
ng/kg/min with the infusion being terminated 30 minutes after the
initiation of extracorporeal membrane oxygenation, despite the fact that
all animals were maintained on extracorporeal membrane oxygenation for 3
hours. In the control group, platelet counts dropped to 54% +/- 8.9% (mean
+/- standard error of the mean) of initial levels at 30 minutes of
extracorporeal membrane oxygenation and gradually rose to 87.2% +/- 6.7% at
3 hours. In contrast, the platelet counts of the iloprost-treated dogs
remained stable throughout extracorporeal membrane oxygenation at 98.3% +/-
4.2% of initial counts. Platelet reactivity toward adenosine diphosphate
revealed a significant and permanent loss of platelet function in the
control group (37.0% +/- 2.1% inhibition). In contrast, the iloprost group
demonstrated significant inhibition of platelet reactivity (79.2% +/- 8.3%)
during the iloprost infusion but a return to normal function (4.2% +/- 6.7%
inhibition) after cessation of drug infusion which persisted throughout
extracorporeal membrane oxygenation. Plasma levels of the platelet-specific
protein thrombospondin rose progressively from 918 +/- 89 ng/ml to 1465 +/-
239 ng/ml (delta 548 +/- 179 ng/ml) at 30 minutes of extracorporeal
membrane oxygenation, which indicates extensive release of platelet granule
contents (p less than 0.05). In contrast, plasma thrombospondin levels in
the iloprost group demonstrated no additional rise after cessation of the
iloprost infusion. In conclusion, iloprost effectively preserves platelet
number and function during extracorporeal circulation. The fact that its
salutary effects outlast its presence in plasma suggests that prevention of
initial platelet-synthetic surface interactions permits the appearance of
reduced surface affinity for platelets and, thus, reduced synthetic surface
thrombogenicity.
