TY - JOUR
T1 - Possible contribution of acetylamrinone and its enhancing effects on platelet aggregation under shear stress conditions in the onset of thrombocytopenia in patients treated with amrinone
AU - Sadiq, Athar
AU - Tamura, Noriko
AU - Yoshida, Minako
AU - Hoshiba, Yasunari
AU - Kumagai, Asako
AU - Tanabe, Teruhisa
AU - Handa, Shunnosuke
AU - Ikeda, Yasuo
AU - Goto, Shinya
N1 - Funding Information:
This work was supported in part by a Grant-in-aid for Scientific Research in Japan (11770367, 13670744, 15590771); a grant from the Science Frontier Program of MESSC of Japan; a grant from the Japanese Medical Association 1998, a research fund of the Mitsukoshi Health and Welfare Foundation 1999, the Suzuken Memorial Fund 1999, a grant from Takeda Scientific Foundation 2003, and the Kanagawa Academy of Science and Technology Research 2003 (0031004), a Grant from NOVARTIS Foundation (Japan) for the Promotion of Science 2003.
PY - 2003
Y1 - 2003
N2 - Background: Thrombocytopenia is recognized as one of the most common complications when the patients with severe heart failure are treated with cardiotropic phosphodiesterase (PDE)-3 inhibitors. To understand the mechanism of the onset of this complication, we focused on the effects of various PDE-3 inhibitors and its stable metabolite of acetylamrinone on platelet aggregation occurring under physiological shear stress conditions. Method: Blood specimens were obtained from eight apparently healthy adult donors. Platelet-rich plasma was separated after anticoagulation by citrate. The effects of PDE-3 inhibitors of amrinone and olprinone, as well as the stable metabolite of the former of acetylamrinone, on platelet aggregation induced by its exposure to a shear rate of 1200 and 10,800 s-1 were determined by optically modified cone-plate viscometer. Results: Both olprinone and amrinone inhibited platelet aggregation at 10,800 s-1 in a dose-dependent manner with the IC 50 value of 14±1 and 61±8 μM (mean±S.D.), respectively, while amrinone significantly inhibited platelet aggregation at 1200 s-1 only at highest concentration tested (100 μM). Contrary to the effects shown with PDE-3 inhibitors, acetylamrinone did not inhibit platelet aggregation at all. Moreover, it even enhanced the aggregation at 1200 s-1 when used with 5 μM. Conclusions: Our results demonstrate possible contribution of the enhancing effects of acetylamrinone on platelet aggregation occurring under blood flow conditions, which reduced the platelet count when occurring in real circulation, to the higher incidence of thrombocytopenia in patients treated with amrinone.
AB - Background: Thrombocytopenia is recognized as one of the most common complications when the patients with severe heart failure are treated with cardiotropic phosphodiesterase (PDE)-3 inhibitors. To understand the mechanism of the onset of this complication, we focused on the effects of various PDE-3 inhibitors and its stable metabolite of acetylamrinone on platelet aggregation occurring under physiological shear stress conditions. Method: Blood specimens were obtained from eight apparently healthy adult donors. Platelet-rich plasma was separated after anticoagulation by citrate. The effects of PDE-3 inhibitors of amrinone and olprinone, as well as the stable metabolite of the former of acetylamrinone, on platelet aggregation induced by its exposure to a shear rate of 1200 and 10,800 s-1 were determined by optically modified cone-plate viscometer. Results: Both olprinone and amrinone inhibited platelet aggregation at 10,800 s-1 in a dose-dependent manner with the IC 50 value of 14±1 and 61±8 μM (mean±S.D.), respectively, while amrinone significantly inhibited platelet aggregation at 1200 s-1 only at highest concentration tested (100 μM). Contrary to the effects shown with PDE-3 inhibitors, acetylamrinone did not inhibit platelet aggregation at all. Moreover, it even enhanced the aggregation at 1200 s-1 when used with 5 μM. Conclusions: Our results demonstrate possible contribution of the enhancing effects of acetylamrinone on platelet aggregation occurring under blood flow conditions, which reduced the platelet count when occurring in real circulation, to the higher incidence of thrombocytopenia in patients treated with amrinone.
KW - Phoshodiesterase inhibitor
KW - Platelet
KW - Shear stress
UR - http://www.scopus.com/inward/record.url?scp=0346157309&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0346157309&partnerID=8YFLogxK
U2 - 10.1016/j.thromres.2003.09.024
DO - 10.1016/j.thromres.2003.09.024
M3 - Article
C2 - 14698653
AN - SCOPUS:0346157309
SN - 0049-3848
VL - 111
SP - 357
EP - 361
JO - Thrombosis Research
JF - Thrombosis Research
IS - 6
ER -