Mechanism of constant contractile efficiency under cooling inotropy of myocardium: simulation.
We have reported that, in canine hearts, cardiac cooling to 29 degrees C enhanced left ventricular contractility but changed neither the contractile efficiency of cross-bridge (CB) cycling nor the excitation-contraction coupling energy. The mechanism of this intriguing energetics remained unknown. To get insights into this mechanism, we simulated myocardial cooling mechanoenergetics using basic Ca2+ and CB kinetics. We assumed that both adenosinetriphosphatase (ATPase)-dependent sarcoplasmic reticulum (SR) Ca2+ uptake and CB detachment decelerated with cooling. We also assumed that all the ATPase-independent SR Ca2+ release, Ca2+ binding to and dissociation from troponin, and CB attachment remained unchanged. The simulated cooling shifted the CB force-free Ca2+ concentration curve to a lower Ca2+ concentration, increasing the Ca2+ responsiveness of CB force generation, and increased the maximum Ca(2+)-activated force. The simulation most importantly showed that these cooling effects combined led to a constant contractile efficiency when Ca2+ uptake and CB detachment rate constants changed appropriately. This result seems to account for our experimentally observed constant contractile efficiency under cooling inotropy.
Mikane
T
T
Department of Physiology II, Okayama University Medical School, Japan.
Araki
J
J
Kohno
K
K
Nakayama
Y
Y
Suzuki
S
S
Shimizu
J
J
Matsubara
H
H
Hirakawa
M
M
Takaki
M
M
Suga
H
H
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D006321:Heart / Q000502:physiology*; D007700:Kinetics; D008955:Models, Cardiovascular; D009200:Myocardial Contraction; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D014336:Troponin / Q000502:physiology*; D019209:Troponin C / Q000378:metabolism; D016277:Ventricular Function, Left
D014336:Troponin; D019209:Troponin C; D000251:Adenosine Triphosphatases; D002118:Calcium