Amrinone, a selective phosphodiesterase III inhibitor, improves microcirculation and flap survival: a comparative study with prostaglandin E1.
BACKGROUND
Amrinone, a selective phosphodiesterase (PDE) III inhibitor, is a newly developed agent that possesses a combination of positive inotropic and vasodilating properties as a result of preventing the degradation of cAMP and it has recently been licensed for treatment of heart failure alone. Amrinone is expected to be useful for the treatment not only of heart failure but also of peripheral circulatory disorders, including vascular disease, and for ischemic flaps, because it improves microcirculatory hemodynamics. To investigate potential therapeutic applications of amrinone, we evaluated its ability to improve microcirculatory hemodynamics and flap survival.


METHODS
The rat skinfold chamber technique was employed to quantify microcirculation directly in vivo. The improved survival area of random flaps in rats treated with amrinone was examined to assess therapeutic efficacy of this drug. Its effects were compared with those of prostaglandin E1 (PGE1), which has been widely approved as an agent for improving hemodynamics.


RESULTS
Microcirculatory blood flow and flap survival area were significantly increased in both amrinone- and PGE1-treated animals, compared to the saline-treated controls. The ameliorating effects of amrinone were comparable to those of PGE1.


CONCLUSIONS
The results of this study suggest amrinone to be a potentially useful drug not only for treating heart failure but also for improving microcirculation in patients with vascular diseases and for postoperative care after reconstructive surgery.
Ichioka
S
S
Department of Plastic and Reconstructive Surgery, Faculty of Medicine, University of Tokyo, Japan.
Nakatsuka
T
T
Sato
Y
Y
Shibata
M
M
Kamiya
A
A
Harii
K
K
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000527:Alprostadil / Q000494:pharmacology*; D000676:Amrinone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D007511:Ischemia; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013524:Surgical Flaps / Q000098:blood supply*; D014664:Vasodilation
D010726:Phosphodiesterase Inhibitors; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000527:Alprostadil; D000676:Amrinone