Tetrandrine ameliorates ischaemia-reperfusion injury of rat myocardium through inhibition of neutrophil priming and activation

1 We have previously shown that tetrandrine (TTD), a bisbenzyltetrahydroios quinoline isolated from the Chinese herb Stephania tetrandra, inhibits neut rophil adhesion, Mac-1 expression, and reactive oxygen species (ROS) produc tion. To examine whether inhibition of neutrophil function may confer upon TTD the ability to prevent myocardial ischaemia-reperfusion (MI/R) injury, experiments were performed on rats subjected to coronary ligation followed by reperfusion for induction of MI/R injury. 2 Intravenous administration of TTD (0.1 and 1.0 mg kg(-1)) 15 min prior to coronary ligation completely prevented MI/R-associated mortality. TTD pret reatment also significantly reduced MI/R-induced ventricular tachyarrhythmi a, myocardial infarct size, and neutrophil infiltration. 3 However, TTD pretreatment did not influence mean arterial blood pressure, heart rate, or product of pressure-rate, indicating that T-TD extenuated M I/R through mechanisms independent of modulating haemodynamics or myocardia l oxygen demand. 4 Peripheral blood neutrophils were isolated for ex vivo examination of sha pe change and Mac-1 upregulation of neutrophils, two sensitive indicators o f proinflammatory priming, as well as N-formyl-methionyl-leucyl-phenylalani ne (fMLP)-induced adhesion and ROS production, parameters commonly used for the assessment of neutrophil activation. 5 Neutrophils from MI/R animals showed significant shape change and Mac-1 u pregulation, both of which were prevented by TTD-pretreatments. On the othe r hand, fMLP-induced adhesion and ROS production of neutrophils were marked ly enhanced by MI/R but diminished in TTD-pretreated animals. 6 These data suggest that the protective effect of TTD against MI/R injury can be accounted for by inhibition of neutrophil priming and activation, th ereby abolishing subsequent infiltration and ROS production that cause MI/R injury.