Korean J Physiol Pharmacol.  2004 Feb;8(1):43-50.

Effect of Amrinone, a Selective Inhibitor of Phosphodiesterase III, on PMNs-induced Cardiac Dysfunction in Ischemia/reperfusion

• Oh BK
• Kim HK
• Choi SR
• Song JH
• Park ES
• Choi BS
• Park JD
• Shin YK

Abstract

Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. Amrinone, a specific inhibitor of phosphodiesterase 3, has an antioxidant activity against PMNs. Therefore, we hypothesized that amrinone could attenuate PMNs-induced cardiac dysfunction by suppression of reactive oxygen species (ROS) produced fby PMNs. In the present study, we examined the effects of amrinone on isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. Amrinone at 25microM, given to hearts during the first 5 min of reperfusion, significantly improved coronary flow, left ventricular developed pressure (P< 0.001), and the maximal rate of development of left ventricular developed pressure (P< 0.001), compared with ischemic/reperfused hearts perfused with PMNs in the absence of amrinone. In addition, amrinone significantly reduced myeloperoxidase activity by 50.8%, indicating decreased PMNs infiltration (p< 0.001). Superoxide radical and hydrogen peroxide production were also significantly reduced in fMLP- and PMA-stimulated PMNs pretreated with amrinone. Hydroxyl radical was scavenged by amrinone. fMLP-induced elevation of [Ca2+]i was also inhibited by amrinone. These results provide evidence that amrinone can significantly attenuate PMN-induced cardiac contractile dysfunction in the ischemic/ reperfused rat heart via attenuation of PMNs infiltration into the myocardium and suppression of ROS release by PMNs.

Keyword

Amrinone; Ischemia; Polymorphonuclear leukocyte; Reperfusion

MeSH Terms

Amrinone*
Animals
Cyclic Nucleotide Phosphodiesterases, Type 3*
Heart
Hydrogen Peroxide
Hydroxyl Radical
Ischemia
Myocardium
Neutrophils
Peroxidase
Rats
Reactive Oxygen Species
Reperfusion
Superoxides
Amrinone
Cyclic Nucleotide Phosphodiesterases, Type 3
Hydrogen Peroxide
Hydroxyl Radical
Peroxidase
Reactive Oxygen Species
Superoxides