Mechanism of constant contractile efficiency under cooling inotropy of myocardium: simulationy
Geoffrey
Nunns
Auckland Bioengineering Institute, The University of Auckland
Model Status
This model is known to run in both OpenCell and COR. It is an accurate match to the paper equations but it does not recreate all the published results.
Model Structure
Abstract: We have reported that, in canine hearts, cardiac cooling to 29C 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.
model diagram
Schematic diagram of the Mikane et al model. The effect of calcium and troponin on cross bridge (CB) cycling is also demonstrated.
The complete original paper reference is cited below:
Mechanism of constant contractile efficiency under cooling inotropy of myocardium: simulation, Takeshi Mikane, Junichi Araki, Kunihisa Kohno, Yasunori Nakayama, Shunsuke Suzuki, Juichiro Shimizu, Hiromi Matsubara, Masahisa Hirakawa, Miyako Takaki, and Hiroyuki Suga, 1997, American Journal of Physiology, 273, H2891-H2898. PubMed ID: 9435629
$\mathrm{Ca\_release\_rate}=\begin{cases}0 & \text{if $\mathrm{time}> 0.1$}\\ 20\mathrm{Ca\_tot\_released}(1-10\mathrm{time}) & \text{otherwise}\end{cases}\frac{d \mathrm{Ca\_t}}{d \mathrm{time}}=\mathrm{Ca\_release\_rate}-\mathrm{k\_3}\mathrm{Ca\_t}-\mathrm{dTnCa\_t\_dt}\frac{d \mathrm{TnCa\_t}}{d \mathrm{time}}=\mathrm{k\_1}\mathrm{Ca\_t}(\mathrm{total\_Tn}-\mathrm{TnCa\_t})-\mathrm{k\_2}\mathrm{TnCa\_t}\mathrm{dTnCa\_t\_dt}=\mathrm{k\_1}\mathrm{Ca\_t}(\mathrm{total\_Tn}-\mathrm{TnCa\_t})-\mathrm{k\_2}\mathrm{TnCa\_t}\frac{d \mathrm{CB\_on\_t}}{d \mathrm{time}}=f\mathrm{TnCa\_t}(\mathrm{total\_CB}-\mathrm{CB\_on\_t})-g\mathrm{CB\_on\_t}\frac{d \mathrm{Ca\_released}}{d \mathrm{time}}=\mathrm{Ca\_release\_rate}\frac{d \mathrm{Ca\_sequestered}}{d \mathrm{time}}=\mathrm{k\_3}\mathrm{Ca\_t}\frac{d \mathrm{cumCB\_on\_t}}{d \mathrm{time}}=f\mathrm{TnCa\_t}(\mathrm{total\_CB}-\mathrm{CB\_on\_t})\frac{d \mathrm{cumCB\_off\_t}}{d \mathrm{time}}=g\mathrm{CB\_on\_t}$
Yasunori
Nakayama
Miyako
Takaki
This model is known to run in both PCEnv and COR. It is an accurate match to the paper equations, but it does not recreate all the published results.
9435629
This model is known to run in both PCEnv and COR. It is an accurate match to the paper equations, but it does not recreate all the published results.
Geoff Nunns
gnunns1@jhem.jhu.edu
Shunsuke
Suzuki
1997-00-00 00:00
Masahisa
Hirakawa
Hiroyuki
Suga
Juichiro
Shimuzi
Takeshi
Mikane
keyword
electrophysiology
cardiac
2008-06-20T00:00:00+12:00
American Journal of Physiology
Geoff Nunns
Hiromi
Matsubara
Mechanism of Constant Contractile Efficiency Under Cooling Intropy of Myocardium: Simulation
273
H2891
H2898
Auckland Bioengineering Institute
CellML Team
Geoffrey
Nunns
Rogan
Junichi
Araki
Kunihisa
Kohno