普罗帕酮对豚鼠心肌力学的影响

目的研究普罗帕酮心肌变力性作用并从组织水平探讨其作用机制。方法采用离体乳头肌灌流的方法观察普罗帕酮对豚鼠乳头肌主动张力(DT)、主动张力上升最大速度(+dT/dtmax)、主动张力下降最大速度(-dT/dtmax)的影响。经钙通道阻滞剂尼卡地平及Na+/Ca2+交换体阻滞剂KBR7943预处理后,分别观察普罗帕酮的上述作用。结果①在场刺激引起收缩的乳头肌,0.1、1、10、30μmol·L-1普罗帕酮分别使DT由对照(0.18±0.05)g降至(0.14±0.03)、(0.12±0.03)、(0.08±0.02)、(0.05±0.02)g(P<0.01),IC50为10μmol·L-1;+dT/dtmax由对照(1.79±0.45)mg·s-1降至(1.58±0.37)、(1.46±0.29)、(1.26±0.19)、(0.97±0.15)mg·s-1(P<0.01);-dT/dtmax由对照(1.61±0.29)mg·s-1降至(1.45±0.28)、(1.26±0.19)、(0.92±0.26)、(0.78±0.22)mg·s-1。②尼卡地平(2.0μmol·L-1)阻断L型钙通道后,普罗帕酮(10μmol·L-1)使DT、+dT/dtmax、-dT/dtmax由(0.10±0.02)g、(1.32±0.24)mg·s-1、(1.24±0.17)mg·s-1分别降低至(0.06±0.01)g、(1.11±0.23)mg·s-1、(0.89±0.23)mg·s-1(P<0.01)。③KBR7943(1.0μmol·L-1)阻断Na+/Ca2+交换体后,普罗帕酮(10μmol·L-1)使DT、+dT/dtmax、-dT/dtmax由(0.18±0.02)g、(1.48±0.28)mg·s-1、(1.63±0.23)mg·s-1分别降低至(0.09±0.01)g、(1.16±0.01)mg·s-1、(1.05±0.23)mg·s-1(P<0.01)。结论①普罗帕酮剂量依赖性抑制豚鼠乳头肌力学各项指标,显示有负性肌力作用。②普罗帕酮对L型钙通道及反向Na+/Ca2+交换的抑制作用参与其负性肌力的作用,且前者作用较大。

Effects of propafenone on myocardium inotropism in isolated papillary muscle of guinea pig

Aim To investigate the effects of propafenone on myocardium inotropism and explore it’s possible mechanism in isolated papillary muscle of guinea pig. Methods Developed tension (DT), maximum rate of contraction (+dT/dt_ max) and maxi-mum rate of relaxation (-dT/dt_ max) were measured during propafenone perfusion before and after administration of L-type calcium channel blocker, nicardipine and selective Na+/Ca 2+ exchanger inhibitor, KB-R7943. Results ①At concentration of 0.1,1,10,30 μmol·L -1,propafenone attenuated DT from control (0.18±0.05) g to (0.14±0.03), (0.12±0.03), (0.08±0.02), (0.05±0.02) g respectively (P<0.01). The IC_ 50 was 10 μmol·L -1. +dT/dt_ max decreased from (1.79±0.45) mg·s -1 to (1.58±0.37),(1.46±0.29),(1.24±0.19),(0.97±0.15) mg·s -1 respectively (P<0.01); -dT/dt_ max from (1.61±0.25) mg·s -1 to (1.45±0.28),(1.26±0.19),(0.92±0.26),(0.78±0.22) mg·s -1 respectively (P<0.01). ② After administration of L-type calcium channel blocker, nicardipine (2.0 μmol·L -1), propafenone (10 μmol·L -1) further decreased DT, +dT/dt_ max, -dT/dt_ max from (0.10±0.02) g,(1.32±0.24) mg·s -1,(1.24±0.17) mg·s -1 to (0.06±0.01) g,(1.11±0.23) mg·s -1,(0.89±0.23) mg·s -1 respectively (P<0.01). ③ After administration of selective Na+/Ca 2+ exchanger inhibitor, KB-R7943 (1.0 μmol·L -1), propafenone (10 μmol·L -1) decreased DT, +dT/dt_ max, -dT/dt_ max from (0.18±0.02) g,(1.48±0.28) mg·s -1,(1.63±0.23) mg·s -1 to (0.09±0.01) g,(1.16±0.01) mg·s -1,(1.05±0.23) mg·s -1 respectively (P<0.01). Conclusion ① Propafenone has significant negative inotropic effect in isolated papillary muscle of guinea pig . ② The inhibition of L-type calcium channel and Na+/Ca 2+ exchange of propafenone may contribute to its negative inotropic effect.