Effects Of Class I C Antiarrhythmic Agent, Propafenone On Myocardium Inotropism In Isolated Papillary Muscle Of Guinea Pig

AIM: To investigate the effects of class Ⅰc antiarrhythmic agent , 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/dtmax), maximum rate of relaxation (-dT/dtmax) were measured during isolated papillary muscle perfusion with propafenone. Observed the effects of propafenone after administration of L-type calcium channel blocker, nicardipine and selective Na+/Ca2+ exchange inhibitor, KB-R7943.RESULTS: (1) At concentration of 0.1, 1, 10, 30μmol L-1, propafenone could attenuate DT from control 0.176±0.050 g to 0.141±0.032,0.116±0.029,0.083±0.018,0.053±0.015 g, respectively (P<0.01). The IC50 was 10μmol L-1; +dT/dtmax was decreased from control 1.788±0.452 mg s-1 to 1.580±0.371,1.458±0.289,1.235±0.189,0.970±0.149 mg s-1, respectively (P<0.01); -dT/dtmax was suppressed from control 1.606±0.248 mg s-1 to 1.452±0.276,1.255±0.190,0.915±0.262,0.784±0.221 mg s-1 respectively (P<0.01). (2) After administration of L-type calcium channel blocker, nicardipine (2.0μmol L-1), propafenone (10μmol L-1) further decreased DT, +dT/dtmax, -dT/dtmax from 0.099±0.017 g,1.316±0.242 mg s-1,1.241±0.171 mg s-1 to 0.061±0.010 g,1.107±0.226 mg s-1,0.894±0.234 mg s-1, respectively (P<0.01). (3) After the administration of selective Na+/Ca2+ exchange inhibitor, KB-R7943 (1.0μmol L-1), propafenone (10μmol L-1) decreased DT, +dT/dtmax, -dT/dtmax from 0.177±0.021 g,1.484±0.278 mg s-1,1.631±0.234 mg s-1 to 0.087±0.009 g,1.164±0.006 mg s-1,1.045±0.230 mg s-1, respectively (P<0.01).CONCLUSION: In this study, we found that (1) Propafenone has significant negative inotropic effect in isolated papillary muscle in the normal guinea pig . (2) The inhibition of L-type calcium channel and Na+/Ca2+ exchange of propafenone may contribute to its negative inotropic effect.