title: Mechanism of constant contractile efficiency under cooling inotropy of myocardium: simulation.
abstract: 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.
authors.affiliation: Department of Physiology II, Okayama University Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mikane
authors.forename: J
authors.initials: J
authors.lastname: Araki
authors.forename: K
authors.initials: K
authors.lastname: Kohno
authors.forename: Y
authors.initials: Y
authors.lastname: Nakayama
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: J
authors.initials: J
authors.lastname: Shimizu
authors.forename: H
authors.initials: H
authors.lastname: Matsubara
authors.forename: M
authors.initials: M
authors.lastname: Hirakawa
authors.forename: M
authors.initials: M
authors.lastname: Takaki
authors.forename: H
authors.initials: H
authors.lastname: Suga
mesh_terms: 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
chemical_list: D014336:Troponin; D019209:Troponin C; D000251:Adenosine Triphosphatases; D002118:Calcium