Myocardial Protection by Recombinant Soluble P-selectin Glycoprotein Ligand-1 Suppression of Neutrophil and Platelet Interaction Following Ischemia and Reperfusion

• 영문명: Myocardial Protection by Recombinant Soluble P-selectin Glycoprotein Ligand-1 Suppression of Neutrophil and Platelet Interaction Following Ischemia and Reperfusion
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Sang Soo Ham Yoon Young Jang Jin Ho Song Hyang Mi Lee Kwang Joon Kim Jun Sik Hong Yong Kyoo Shin
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제4권 제6호, 507~513쪽, 전체 7쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2000.01.01

영문 초록

Polymorphonuclear leukocytes (PMNs) play an important role in myocardial ischemia/reperfusion (MI/R) injury. Moreover, platelets are also important blood cells that can aggravate myocardial ischemic injury. This study was designed to test the effects of PMNs and platelets separately and together in provoking cardiac dysfunction in isolated perfused rat hearts following ischemia and reperfusion. Additional control rat hearts were perfused with 75⁓10⁶ PMNs, with 75⁓10⁶ platelets, or with 75⁓10⁶ PMNs⁢75⁓10⁶ platelets over a five minute perfusion followed by a 75 min observation period. No significant reduction in coronary flow (CF), left ventricular developed pressure (LVDP), or the first derivative of LVDP (dP/dt max) was observed at the end of the observation period in any non-ischemic group. Similarly, global ischemia (I) for 20 min followed by 45 minutes of reperfusion (R) produced no sustained effects on the final recovery of any of these parameters in any group of hearts perfused in the absence of blood cells. However, I/R hearts perfused with either PMNs or platelets alone exhibited decreases in these variables of 5∼10% (p＜0.05 from control). Furthermore, I/R hearts perfused with both PMNs and platelets exhibited decreases of 50 to 60% in all measurements of cardiac function (p＜0.01). These dual cell perfused I/R hearts also exhibited marked increases in cardiac myeloperoxidase (MPO) activity indicating a significant PMN infiltration, and enhanced P-selectin expression on the coronary microvascular endothelium. All cardiaodynamic effects as well as PMN accumulation and P-selectin expression were markedly attenuated by a recombinant soluble PSGL-1 which inhibits selectin mediated cell adhesion. These results provide evidence that platelets and PMNs act synergistically in provoking post-reperfusion cardiac dysfunction, and that this may be largely due to cell to cell interactions mediated by P-selectin. These results also demonstrate that a recombinant soluble PSGL-1 reduces myocardial reperfusion injury by platelet and PMNs interaction.

키워드

P-selectin Neutrophils Platelets Cardiac dysfunction Ischemia and reperfusion