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1 Abteilung Kardiologie und Pneumologie, Zentrum Innere Medizin, and 2 Abteilung Thorax-, Herz-, Gefäßchirurgie, Zentrum Chirurgie, Georg-August-Universität Göttingen, 37075 Göttingen, Germany
Physiologically, human atrial and ventricular myocardium are coupled by an identical beating rate and rhythm. However, contractile behavior in atrial myocardium may be different from that in ventricular myocardium, and little is known about intracellular Ca2+ handling in human atrium under physiological conditions. We used rapid cooling contractures (RCCs) to assess sarcoplasmic reticulum (SR) Ca2+ content and the photoprotein aequorin to assess intracellular Ca2+ transients in atrial and ventricular muscle strips isolated from nonfailing human hearts. In atrial myocardium (n = 19), isometric twitch force frequency dependently (0.25-3 Hz) increased by 78 ± 25% (at 3 Hz; P < 0.05). In parallel, aequorin light signals increased by 111 ± 57% (P < 0.05) and RCC amplitudes by 49 ± 13% (P < 0.05). Similar results were obtained in ventricular myocardium (n = 13). SR Ca2+ uptake (relative to Na+/Ca2+ exchange) frequency dependently increased in atrial and ventricular myocardium (P < 0.05). With increasing rest intervals (1-240 s), atrial myocardium (n = 7) exhibited a parallel decrease in postrest twitch force (at 240 s by 68 ± 5%, P < 0.05) and RCCs (by 49 ± 10%, P < 0.05). In contrast, postrest twitch force and RCCs significantly increased in ventricular myocardium (n = 6). We conclude that in human atrial and ventricular myocardium the positive force-frequency relation results from increased SR Ca2+ turnover. In contrast, rest intervals in atrial myocardium are associated with depressed contractility and intracellular Ca2+ handling, which may be due to rest-dependent SR Ca2+ loss (Ca2+ leak) and subsequent Ca2+ extrusion via Na+/Ca2+ exchange. Therefore, the influence of rate and rhythm on mechanical performance is not uniform in atrial and ventricular myocardium.
force-frequency relation; postrest behavior; human myocardium
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