NA-FREQUENCY-RELATIONSHIP IN HUMAN MYOCARDIUM( CHANNEL MODULATION ANDFORCE)

The enhancement of force of contraction (FOC) following increasing fre quencies of stimulation is an important mechanism of positive inotropy in human myocardium. The present study aimed to investigate the influ ence of alterations in Na+ influx on FFR in human myocardium. Isometri c FOC of electrically stimulated right auricular trabeculae (AUT, n=12 ) from human nonfailing hearts (n=8) was measured at different stimula tion rates (0.5-3 Hz) under control conditions, after increasing Na+ i nflux by the addition of (+/-)BDF 9148 (BDF, 3 mu mol l(-1)) and after decreasing Na+ influx by the addition of lidocaine (LIDO, 10 mu mol l (-1)). Additionally, the rate dependent changes in diastolic tension ( DT) were measured in all experiments. Under control conditions FOC inc reased with increasing frequencies of stimulation. The rate at which m aximal FOC was observed (SFmax) was 2.0+/-0.2 Hz and maximal increase in FOC (PFmax) by increasing frequency of stimulation was +1.5+/-0.5 m N. After increase of Na+ influx by BDF (3 mu mol l(-1)) SFmax was decr eased to 0.8+/-0.1 Hz (p<0.05 versus control) and PIEmax was +0.1+/-0. 3 mN (p<0.05). When Na+ influx was diminished by LIDO (10 mu mol l(-1) ) SFmax and PIEmax were increased compared to control (2.4+/-0.1 Hz an d +4.1+/-0.9 mN, p<0.05 versus control). The diastolic tension (DT) of AUT at 3 Hz was not changed at higher rates in the control group and after application of LIDO (10 mu mol l(-1)), whereas after enhancement of Na+ influx by BDF there was an increase in DT of +0.7+/-0.2 at 3 H z (p<0.05 versus control and LIDO). An enhanced Na+ influx leads to a decrease in the optimal frequency and to a smaller force potentiation by higher stimulation rates which could be at least partly due to inco mplete relaxation at higher frequencies, whereas a reduced Na+ influx is followed by opposite alterations. It is concluded that besides Ca2 handling also Na+ influx and Na+ homeostasis might determine the freq uency-induced force potentiation in human myocardium. Thus, the negati ve FFR in diseased human myocardium might result from changes in cellu lar Ca2+ or Na+ regulatory sites.