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Am J Physiol Heart Circ Physiol 273: H2891-H2898, 1997;
0363-6135/97 $5.00
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Vol. 273, Issue 6, H2891-H2898, December 1997

MODELING IN PHYSIOLOGY
Mechanism of constant contractile efficiency under cooling inotropy of myocardium: simulation

Takeshi Mikane1, Junichi Araki1, Kunihisa Kohno1, Yasunori Nakayama1, Shunsuke Suzuki1, Juichiro Shimizu1, Hiromi Matsubara1, Masahisa Hirakawa2, Miyako Takaki3, and Hiroyuki Suga1

Departments of 1 Physiology II and 2 Anesthesiology and Resuscitology, Okayama University Medical School, Shikatacho, Okayama 700; and 3 Department of Physiology II, Nara Medical University, Shijocho, Kashihara 634, Japan

We have reported that, in canine hearts, cardiac cooling to 29°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 Ca2+-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.

temperature; inotropism; contractility; energetics; responsiveness


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