Effects Of An Inhibitor Of Na～+/Ca～(2+) Exchange, KB-R7943, On Myocardium Inotropism And Cardiac Function

functionAIM: To study the properties of KB-R7943, a Na+/ Ca2+ exchange inhibitor, and its effects on myocardium inotropism and cardiac function in normal and hypertrophied rat heart.METHODS: Resting tension, developed tension, diastolic time, force - frequency relationship were measured during isolated papillary muscle perfusion. With Langendorff s perfusion, we observe changes of cardiac function in isolated rat hearts.RESULTS: KB-R7943 dose-dependently inhibited the increase of resting tension during a Na+-free perfusion, and its decrease during a Ca2+-free perfusion, and the inhibiting effects showed in the former were more intense than that in the latter. KB-R7943 attenuated developed tension and prolonged 75% diastolic time in rat papillary muscles under field stimulation at 1HZ; KB-R7943 dose-dependently exerts negative effects on LVSP-LVDP, +DP/DTmax, - DP/DTmax in isolated rat hearts. In hypertrophied myocardium and heart, KB-R7943 shows common pharmacologic profile but more intense than in normal myocardium and heart. A negative force - frequency relationship was seen in both normal and hypertrophied rat heart, and KB-R7943dose-dependently weakened it.CONCLUTION: In this study, we found that (1) KB-R7943 significantly inhibits the forward and reserve mode of Na+/ Ca2+ exchange, and the inhibiting effect on reserve mode is more intense than on forward mode. (2) The inhibitory effect of KB-R7943 on Na+/Ca2+ exchange is seen in both normal and hypertrophied myocardium, but more notable in hypertrophied one. (3) Inhibition of Na+/ Ca + exchange induces the suppression in systolic and diastolic function of myocardium, especially in hypertrophied heart.