Temporary inhibition of platelet function with iloprost (ZK36374) preserves canine platelets during extracorporeal membrane oxygenation.
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.
Cottrell
E D
ED
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104.
Kappa
J R
JR
Stenach
N
N
Fisher
C A
CA
Tuszynski
G P
GP
Switalska
H I
HI
Addonizio
V P
VP
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D004285:Dogs; D011464:Epoprostenol / Q000627:therapeutic use*; D015199:Extracorporeal Membrane Oxygenation; D006023:Glycoproteins / Q000097:blood; D016285:Iloprost; D008297:Male; D010976:Platelet Count / Q000187:drug effects; D010979:Platelet Function Tests; D019699:Thrombospondins; D013997:Time Factors
D002317:Cardiovascular Agents; D006023:Glycoproteins; D019699:Thrombospondins; D011464:Epoprostenol; D016285:Iloprost