TY - JOUR
T1 - Positive inotropic effects of calcium sensitizers on normal and failing cardiac myocytes
AU - Tsutsui, H.
AU - Kinugawa, S.
AU - Ide, T.
AU - Hayashidani, S.
AU - Suematsu, N.
AU - Satoh, S.
AU - Nakamura, R.
AU - Egashira, Kensuke
AU - Takeshita, A.
PY - 2001
Y1 - 2001
N2 - Calcium sensitizers increase myocardial contractile function without affecting Ca2+ homeostasis, which might be beneficial in the treatment of patients with heart failure. However, it remains uncertain whether Ca sensitizers induce quantitatively similar inotropic responses in control and failing hearts. To compare their effects in normal versus failing hearts at the cellular level, shortening mechanics and intracellular calcium ([Ca2+]i) transient were simultaneously measured in the left ventricular myocytes isolated from normal dogs (n = 8) and dogs with rapid pacing-induced heart failure (n = 7). CGP 48506 and EMD 57033 exerted a positive inotropic effect in a dose (0.1-3 μM)-dependent manner in both normal and heart failure myocytes. The percent increase of cell shortening magnitude was comparable between the two groups. CGP 48506 and EMD 57033 did not affect the diastolic cell length and resting [Ca2+]i level. They did not affect the duration of [Ca2+]i transient dynamics. Thus Ca2+ sensitizers exerted comparable positive inotropic effects without affecting the rest cell length and rest [Ca2+]i in normal and heart failure myocytes.
AB - Calcium sensitizers increase myocardial contractile function without affecting Ca2+ homeostasis, which might be beneficial in the treatment of patients with heart failure. However, it remains uncertain whether Ca sensitizers induce quantitatively similar inotropic responses in control and failing hearts. To compare their effects in normal versus failing hearts at the cellular level, shortening mechanics and intracellular calcium ([Ca2+]i) transient were simultaneously measured in the left ventricular myocytes isolated from normal dogs (n = 8) and dogs with rapid pacing-induced heart failure (n = 7). CGP 48506 and EMD 57033 exerted a positive inotropic effect in a dose (0.1-3 μM)-dependent manner in both normal and heart failure myocytes. The percent increase of cell shortening magnitude was comparable between the two groups. CGP 48506 and EMD 57033 did not affect the diastolic cell length and resting [Ca2+]i level. They did not affect the duration of [Ca2+]i transient dynamics. Thus Ca2+ sensitizers exerted comparable positive inotropic effects without affecting the rest cell length and rest [Ca2+]i in normal and heart failure myocytes.
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U2 - 10.1097/00005344-200101000-00003
DO - 10.1097/00005344-200101000-00003
M3 - Article
C2 - 11152370
AN - SCOPUS:0035188809
VL - 37
SP - 16
EP - 24
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 1
ER -