Effect of inotropic interventions on contraction and Ca21 transients in the human heart

Brixius, Klara, Marcus Pietsch, Susanne Hoischen, Jochen Müller-Ehmsen, and Robert H. G. Schwinger. Effect of inotropic interventions on contraction and on Ca21 transients in the human heart. J. Appl. Physiol. 83(2): 652–660, 1997.—The present study investigated the influences of inotropic intervention on the intracellular Ca21 transient 5intracellular Ca21 concentration ([Ca]i)6 and contractile twitch. Isometric twitch and [Ca]i (fura 2 ratio method) were measured simultaneously (1 Hz, 37°C) after stimulation with Ca21 (0.9–3.2 mM), the cardiac glycoside ouabain (Oua; 0.1 μM), the b1and b2-adrenoceptor-agonist isoprenaline (Iso; 1–10 nM), and the Ca21 sensitizer EMD57033 (30 μM) by using isolated human nonfailing right auricular trabeculae (n 5 19). Inotropic interventions increased force of contraction and peak rate of tension rise (1T) significantly. Only Iso stimulated peak rate of tension decay (2T) higher than 1T (P , 0.05), thereby reducing time of contraction (Ttwitch). EMD-57033 increased 1T more effectively than 2T and prolonged Ttwitch (P , 0.05). Ca21, Oua, and Iso, but not EMD-57033, increased systolic Ca21. Diastolic Ca21 increased after stimulation with Oua or Ca21, but not in the presence of EMD-57033. Iso shortened the Ca21 transient and did not influence diastolic Ca21. In conclusion, positive inotropic agents differently affect force and [Ca]i depending on their mode of action. Inotropic interventions influence diastolic Ca21 and thusmay be less advantageous in a situation with altered intracellular Ca21 homeostasis (e.g., heart failure due to dilated cardiomyopathy).