Parikh V, Singh M
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, India.
Methods Find Exp Clin Pharmacol. 1999 May;21(4):269-74. doi: 10.1358/mf.1999.21.4.538177.
The present study was designed to investigate the role of cardiac mast cells in the cardioprotective effect of norepinephrine-induced preconditioning. Isolated rat heart was subjected to 30 min of global ischemia followed by 30 min of reperfusion. Both ischemic and norepinephrine (100 microM) preconditioning markedly reduced ischemia-reperfusion-induced release of lactate dehydrogenose (LDH) in the coronary effluent and the incidence of ventricular premature beats (VPBs) and ventricular tachycardia/fibrillation (VT/VF) during the reperfusion phase. Ischemic and norepinephrine preconditioning also significantly reduced ischemia-reperfusion-induced release of mast cell peroxidase (MPO), a marker of mast cell degranulation. However, MPO release increased immediately after ischemic or norepinephrine preconditioning. Histological study with ruthenium red (0.005%) staining confirmed cardiac mast cell degranulation in ischemic and norepinephrine preconditioned isolated rat hearts. These findings tentatively suggest that pharmacological preconditioning with norepinephrine produces a cardioprotective and antiarrhythmic effect similar to ischemic preconditioning through degranulation of resident cardiac mast cells.
本研究旨在探讨心脏肥大细胞在去甲肾上腺素诱导的预处理心脏保护作用中的作用。将离体大鼠心脏进行30分钟的全心缺血,随后再灌注30分钟。缺血预处理和去甲肾上腺素(100微摩尔)预处理均显著降低了缺血再灌注诱导的冠状动脉流出液中乳酸脱氢酶(LDH)的释放,以及再灌注期室性早搏(VPB)和室性心动过速/心室颤动(VT/VF)的发生率。缺血预处理和去甲肾上腺素预处理还显著降低了缺血再灌注诱导的肥大细胞过氧化物酶(MPO)的释放,MPO是肥大细胞脱颗粒的标志物。然而,缺血或去甲肾上腺素预处理后MPO释放立即增加。用钌红(0.005%)染色的组织学研究证实了缺血和去甲肾上腺素预处理的离体大鼠心脏中存在心脏肥大细胞脱颗粒。这些发现初步表明,去甲肾上腺素的药理学预处理通过驻留心脏肥大细胞的脱颗粒产生与缺血预处理相似的心脏保护和抗心律失常作用。