Effect of Amrinone, a Selective Inhibitor of Phosphodiesterase III, on PMNs-induced

• 영문명: Effect of Amrinone, a Selective Inhibitor of Phosphodiesterase III, on PMNs-induced
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Byung Kwon Oh Hyoung Ki Kim Soo Ran Choi Jin Ho Song Eon Sub Park Byung
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제8권 제1호, 43~50쪽, 전체 8쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2004.01.01

영문 초록

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 25μM, 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 [Ca^2⁢]_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.

키워드

Amrinone Ischemia Polymorphonuclear leukocyte Reperfusion,