EFFECT OF INOTROPIC INTERVENTIONS ON CONTRACTION AND CA2+ TRANSIENTS IN THE HUMAN HEART

The present study investigated the influences of inotropic interventio n on the intracellular Ca2+ transient (intracellular Ca2+ concentratio n ([Ca2+](i))} and contractile twitch. Isometric twitch and [Ca2+](i) (fura 2 ratio method) were measured simultaneously (1 Hz, 37 degrees C ) after stimulation with Ca2+ (0.9-3.2 mM), the cardiac glycoside ouab ain (Oua; 0.1 mu M), the beta(1)- and beta(2)-adrenoceptor-agonist iso prenaline (Iso; 1-10 nM), and the Ca2+ sensitizer EMD-57033 (30 mu M) by using isolated human nonfailing right auricular trabeculae (n = 19) . Inotropic interventions increased force of contraction and peak rate of tension rise (+T) significantly. Only Iso stimulated peak rate of tension decay (-T) higher than +T (P < 0.05), thereby reducing time of contraction (T-twitch) EMD-57033 increased +T more effectively than - T and prolonged T-twitch (P < 0.05). Ca2+, Oua, and Iso, but not EMD-5 7033, increased systolic Ca2+. Diastolic Ca2+ increased after stimulat ion with Oua or Ca2+, but not in the presence of EMD-57033. Iso shorte ned the Ca2+ transient and did not influence diastolic Ca2+. In conclu sion, positive inotropic agents differently affect force and [Ca2+](i) depending on their mode of action. Inotropic interventions influence diastolic Ca2+ and thus may be less advantageous in a situation with a ltered intracellular Ca2+ homeostasis (e.g., heart failure due to dila ted cardiomyopathy).