Salvatico E, Aliev G M, Novello D, Prosdocimi M
Fidia Research Laboratories, Abano Terme, PD, Italy.
J Cardiovasc Pharmacol. 1994 Oct;24(4):638-47. doi: 10.1097/00005344-199410000-00015.
Langendorff rat heart preparations were perfused with suspensions of human leukocytes containing approximately 65% polymorphonuclear cells (PMN). The cells were either unstimulated or activated with 1.6 x 10(-8) phorbol 12-myristate 13-acetate (PMA). Left ventricular developed pressure (LVDP), coronary flow (CF), and heart rate (HR) were recorded during PMN infusion (10 min) and for the recovery period (30 min). PMN were also pretreated with cloricromene (CLO 10-50 microM), a drug that inhibits platelet aggregation and PMN adhesion to endothelial cells (EC). Infusion of unstimulated cells did not affect cardiac function. Infusion of activated cells caused CF reduction (-44 +/- 4% at end of infusion; -24 +/- 4% at end of recovery, expressed as percentage of variation vs. basal value), LVDP decrease (-44 +/- 5% at end of infusion, -26 +/- 6% at end of recovery) endothelial damage, and leukocyte accumulation in heart as compared with hearts infused with unstimulated PMN and sham hearts. PMN accumulation was quantified as myeloperoxidase (MPO) activity (260 +/- 35, 39 +/- 6, 19 +/- 1 U/g, respectively). Superoxide dismutase (SOD 600 U/ml), catalase (2,200 U/ml), thiourea (10 mM) added to PMN suspension blunted CF decrease but not LVDP reduction and MPO increase. CLO (25-50 microM) pretreatment inhibited PMN accumulation, LVDP, and CF reduction by approximately 50%. These data suggest a role of leukocyte activation in the genesis of heart damage and raise the possibility of a pharmacologic intervention with drugs such as CLO that can interfere with this process.
采用Langendorff大鼠心脏灌流模型，用含约65%多形核细胞（PMN）的人白细胞悬液进行灌流。这些细胞要么未经刺激，要么用1.6×10⁻⁸佛波酯12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）激活。在输注PMN期间（10分钟）和恢复期（30分钟）记录左心室舒张末压（LVDP）、冠脉流量（CF）和心率（HR）。PMN还用氯克罗孟（CLO，10 - 50微摩尔）预处理，氯克罗孟是一种抑制血小板聚集和PMN与内皮细胞（EC）黏附的药物。输注未刺激的细胞不影响心脏功能。输注激活的细胞导致CF降低（输注结束时降低-44±4%；恢复期结束时降低-24±4%，以相对于基础值的变化百分比表示），LVDP降低（输注结束时降低-44±5%，恢复期结束时降低-26±6%），内皮损伤，与输注未刺激PMN的心脏和假手术心脏相比，心脏中有白细胞积聚。PMN积聚通过髓过氧化物酶（MPO）活性定量（分别为260±35、39±6、19±1 U/g）。向PMN悬液中添加超氧化物歧化酶（SOD 600 U/ml）、过氧化氢酶（2200 U/ml）、硫脲（10 mM）可减轻CF降低，但不能减轻LVDP降低和MPO增加。CLO（25 - 50微摩尔）预处理可使PMN积聚、LVDP和CF降低约50%。这些数据表明白细胞激活在心脏损伤发生过程中起作用，并增加了用CLO等药物进行药理干预以干扰这一过程的可能性。
