A. Bernabei et al., ILOPROST AND ECHISTATIN PROTECT PLATELETS DURING SIMULATED EXTRACORPOREAL-CIRCULATION, The Annals of thoracic surgery, 59(1), 1995, pp. 149-153
Temporary, reversible inhibition of platelets during cardiopulmonary b
ypass is an attractive strategy to protect platelets and normalize pos
toperative bleeding times. Iloprost, an analogue of prostacyclin, and
the disintegrins reversibly inhibit platelets by different mechanisms.
We tested the hypothesis that reduced doses of iloprost and either ec
histatin, a natural disintegrin, or R043-5054, a peptidomimetic, in co
mbination provide better platelet protection than any drug alone durin
g simulated extracorporeal circulation. Thirty-five recirculation stud
ies using fresh, heparinized human blood in an extracorporeal perfusio
n circuit that contained a 0.45-m(2) spiral coil membrane oxygenator w
ere performed. Iloprost, but neither echistatin nor R043-5054, increas
ed platelet cyclic adenosine monophosphate. Combinations of iloprost a
nd either fibrinogen receptor platelet cyclic adenosine monophosphate.
Platelet adhesion and release of beta-thromboglobulin antigen was com
pletely inhibited by combinations of the two classes of drugs, but onl
y partially inhibited by each drug alone. Combinations of drugs also c
ompletely inhibited platelet aggregation to adenosine diphosphate; the
se platelets retained full sensitivity to adenosine diphosphate after
90 minutes of recirculation when drugs were removed by gel filtration.
We conclude that combinations of iloprost and a fibrinogen receptor a
ntagonist at doses that are unlikely to produce clinical side effects
completely inhibit platelet activation and preserve platelet function
during in vitro extracorporeal circulation.