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.