TY  - JOUR
AU  - Arteaga, GM
AU  - Warren, CM
AU  - Milutinović-Smiljanić, Sanja
AU  - Martin, AF
AU  - Solaro, RJ
PY  - 2005
UR  - https://smile.stomf.bg.ac.rs/handle/123456789/1249
AB  - Alteration in myofilament response to Ca2+ is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to Ca2+ are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament Ca2+ sensitivity in which the adult form of cardiac troponin I (cTnI) is stoichiometrically replaced with the embryonic/neonatal isoform, slow skeletal TnI (ssTnI). We also studied mouse hearts with EMD-57033, which acts specifically to enhance myofilament response to Ca2+. We subjected isolated, perfused hearts to an I/R protocol consisting of 25 min of no-flow ischemia followed by 30 min of reperfusion. After I/R, developed pressure and rates of pressure change were significantly depressed and end-diastolic pressure was significantly elevated in nontransgenic (NTG) control hearts. These changes were significantly blunted in TG hearts and in NTG hearts perfused with EMD-57033 during reperfusion, with function returning to nearly baseline levels. Ca2+- and cross bridge-dependent activation, protein breakdown, and phosphorylation in detergent-extracted fiber bundles were also investigated. After I/R NTG fiber bundles exhibited a significant depression of cross bridge-dependent activation and Ca2+-activated tension and length dependence of activation that were not evident in TG preparations. Only NTG hearts demonstrated a significant increase in cTnI phosphorylation. Our results support the hypothesis that specific increases in myofilament Ca2+ sensitivity are able to diminish the effect of I/R on cardiac function.
PB  - Amer Physiological Soc, Bethesda
T2  - American Journal of Physiology - Heart & Circulatory Physiology
T1  - Specific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia-reperfusion dysfunction
VL  - 289
IS  - 5
SP  - H2183
EP  - H2192
DO  - 10.1152/ajpheart.00520.2005
ER  - 

@article{
author = "Arteaga, GM and Warren, CM and Milutinović-Smiljanić, Sanja and Martin, AF and Solaro, RJ",
year = "2005",
abstract = "Alteration in myofilament response to Ca2+ is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to Ca2+ are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament Ca2+ sensitivity in which the adult form of cardiac troponin I (cTnI) is stoichiometrically replaced with the embryonic/neonatal isoform, slow skeletal TnI (ssTnI). We also studied mouse hearts with EMD-57033, which acts specifically to enhance myofilament response to Ca2+. We subjected isolated, perfused hearts to an I/R protocol consisting of 25 min of no-flow ischemia followed by 30 min of reperfusion. After I/R, developed pressure and rates of pressure change were significantly depressed and end-diastolic pressure was significantly elevated in nontransgenic (NTG) control hearts. These changes were significantly blunted in TG hearts and in NTG hearts perfused with EMD-57033 during reperfusion, with function returning to nearly baseline levels. Ca2+- and cross bridge-dependent activation, protein breakdown, and phosphorylation in detergent-extracted fiber bundles were also investigated. After I/R NTG fiber bundles exhibited a significant depression of cross bridge-dependent activation and Ca2+-activated tension and length dependence of activation that were not evident in TG preparations. Only NTG hearts demonstrated a significant increase in cTnI phosphorylation. Our results support the hypothesis that specific increases in myofilament Ca2+ sensitivity are able to diminish the effect of I/R on cardiac function.",
publisher = "Amer Physiological Soc, Bethesda",
journal = "American Journal of Physiology - Heart & Circulatory Physiology",
title = "Specific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia-reperfusion dysfunction",
volume = "289",
number = "5",
pages = "H2183-H2192",
doi = "10.1152/ajpheart.00520.2005"
}

Arteaga, G., Warren, C., Milutinović-Smiljanić, S., Martin, A.,& Solaro, R.. (2005). Specific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia-reperfusion dysfunction. in American Journal of Physiology - Heart & Circulatory Physiology
Amer Physiological Soc, Bethesda., 289(5), H2183-H2192.
https://doi.org/10.1152/ajpheart.00520.2005

Arteaga G, Warren C, Milutinović-Smiljanić S, Martin A, Solaro R. Specific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia-reperfusion dysfunction. in American Journal of Physiology - Heart & Circulatory Physiology. 2005;289(5):H2183-H2192.
doi:10.1152/ajpheart.00520.2005 .

Arteaga, GM, Warren, CM, Milutinović-Smiljanić, Sanja, Martin, AF, Solaro, RJ, "Specific enhancement of sarcomeric response to Ca2+ protects murine myocardium against ischemia-reperfusion dysfunction" in American Journal of Physiology - Heart & Circulatory Physiology, 289, no. 5 (2005):H2183-H2192,
https://doi.org/10.1152/ajpheart.00520.2005 . .