Effect of inotropic interventions on contraction and Ca2+ transients in the human heart.
The present study investigated the influences of inotropic intervention on the intracellular Ca2+ transient (intracellular Ca2+ concentration ([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 ouabain (Oua; 0.1 microM), the beta1- and beta2-adrenoceptor-agonist isoprenaline (Iso; 1-10 nM), and the Ca2+ sensitizer EMD-57033 (30 microM) 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 (Ttwitch). EMD-57033 increased +T more effectively than -T and prolonged Ttwitch (P < 0.05). Ca2+, Oua, and Iso, but not EMD-57033, increased systolic Ca2+. Diastolic Ca2+ increased after stimulation with Oua or Ca2+, but not in the presence of EMD-57033. Iso shortened the Ca2+ transient and did not influence diastolic Ca2+. In conclusion, 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 altered intracellular Ca2+ homeostasis (e.g., heart failure due to dilated cardiomyopathy).
Brixius
K
K
Medizinische Klinik III, Universität zu Köln, D-50924 Cologne, Germany.
Pietsch
M
M
Hoischen
S
S
Müller-Ehmsen
J
J
Schwinger
R H
RH
D000328:Adult; D000368:Aged; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007537:Isometric Contraction; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D013829:Thiadiazines / Q000494:pharmacology
D002316:Cardiotonic Agents; D011804:Quinolines; D013829:Thiadiazines; C070609:EMD 53998; D010042:Ouabain; D007545:Isoproterenol; D002118:Calcium