THE SHAPE OF HUMAN ATRIAL ACTION-POTENTIAL ACCOUNTS FOR DIFFERENT FREQUENCY-RELATED CHANGES IN-VITRO

We aimed at investigating frequency-related changes of human atrial ac tion potential (AP) in vitro to see whether baseline AP shape might ac count for different responses to increasing stimulation rates. Human r ight atrial trabeculae (n=48) obtained from adult (n=38, mean age 59 /- 8, range 45-72 years) consecutive patients (congruent to 30% of tho se operated upon by a single surgeon; 1.26 preparations per patient, r ange 1-2) were superfused in an organ bath with oxygenated (O-2 conten t 16 ml/l) and modified (NaHCO, 25.7 mmol/l) Tyrode's solution at 31 d egrees C. Baseline electrophysiology (pacing: 1 ms duration, 2-4 mA cu rrent intensity) at cycle length (CL) of 1000 ms was recorded in 90% ( 43 out of 48) of the preparations. The frequency-related protocol (CL from 1600 to 300 ms) was, however, undertaken in 23 (48%) preparations because 20 (42%) became pacing unresponsive immediately after baselin e recordings. No statistical differences were seen when baseline elect rophysiological parameters (mean +/- SD) were grouped according to lat e pacing responsiveness (n=43 vs. n=23): respectively, resting membran e potential (RMP) was -74 +/- 6 vs. -75 +/- 4 mV, maximal upstroke vel ocity (Vmax) 172 +/- 60 vs. 173 +/- 39 V/s, AP amplitude (APA) 89 +/- 11 vs. 91 +/- 8 mV and AP durations were at 30% (APD30%) 10 +/- 13 vs. 13 +/- 18 ms, 50% (APD50%) 45 +/- 79 vs. 62 +/- 91 ms and 90% (APD90% ) 383 +/- 103 vs. 407 +/- 108 ms. To classify baseline AP shape, two c riteria were adopted: criterion 1 (''objective''), based on APA (cut-o ff 90 mV) and APD90% (cut-off 500 ms) computed values and criterion 2 (''visual'') derived from the literature. These criteria enabled us to differentiate three AP shape types: type 1 (spike and dome), type 3 ( no dome) and type 4 (extremely prolonged). At baseline, the two criter ia diagnosed different proportions of AP shape types. There were, howe ver, no intra-type statistical differences among electrophysiological parameters. By criterion 1, analysis of variance (ANOVA) showed signif icant inter-type differences of RMP, Vmax, APA, APD50 and 90% and by c riterion 2 of APA, APD30, (5)0 and 90%, respectively. To facilitate co mparisons with previous published data, criterion 2 was selected to an alyse frequency-related changes of AP shape types. At low stimulation rate, ANOVA for repeated measures (with Greenhouse-Geisser <(epsilon)o ver cap> correction) showed inter-type differences for APD30, 50 and 9 0% (P=0.00005). RMP, Vmax, APA and APD90% were overall frequency-relat ed (P=0.00005). Inter-type frequency-related differences were however seen only for APD90%. Human atrial AP durations (30, 50 and 90%) enabl e differentiation among AP shape types (1, 3 and 4). By a standardized use-dependent protocol overall RMP, Vmax, APA and APD90% are frequenc y-related. AP shape accounts for frequency-related changes of APD90% o nly. A type 4 AP shape with much prolonged AP duration had a flat freq uency dependence. At high stimulation rates, adult type 1 and 3 AP sha pes are indistinguishable. Use-dependent and pharmacological investiga tions in human atrial myocytes need to take AP shape into account.