Cross-bridge kinetics modeled from myoplasmic [Ca2+] and LV pressure at 17{degrees}C and after 37{degrees}C and 17{degrees}C ischemia

1 Department of Biomedical Engineering, Marquette University, Milwaukee 53233; Departments of 2 Anesthesiology and 3 Physiology, 4 Cardiovascular Research Center, and 5 Department of Pulmonary Medicine and Critical Care, Medical College of Wisconsin, Milwaukee 53226; and 6 Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295 We modeled changes in contractile element kinetics derived from the cyclic relationship between myoplasmic [Ca 2+ ], measured by indo 1 fluorescence, and left ventricular pressure (LVP). We estimated model rate constants of the Ca 2+ affinity for troponin C (TnC) on actin (A) filament (TnCA) and actin and myosin (M) cross-bridge (A · M) cycling in intact guinea pig hearts during baseline 37°C perfusion and evaluated changes at 1 ) 20 min 17°C pressure, 2 ) 30-min reperfusion (RP) after 30-min 37°C global ischemia during 37°C RP, and 3 ) 30-min RP after 240-min 17°C global ischemia during 37°C RP. At 17°C perfusion versus 37°C perfusion, the model predicted: A · M binding was less sensitive; A · M dissociation was slower; Ca 2+ was less likely to bind to TnCA with A · M present; and Ca 2+ and TnCA binding was less sensitive in the absence of A · M. Model results were consistent with a cold-induced fall in heart rate from 260 beats/min (37°C) to 33 beats/min (17°C), increased diastolic LVP, and increased phasic Ca 2+ . On RP after 37°C ischemia vs. 37°C perfusion, the model predicted the following: A · M binding was less sensitive; A · M dissociation was slower; and Ca 2+ was less likely to bind to TnCA in the absence of A · M. Model results were consistent with reduced myofilament responsiveness to [Ca 2+ ] and diastolic contracture on 37°C RP. In contrast, after cold ischemia versus 37°C perfusion, A · M association and dissociation rates, and Ca 2+ and TnCA association rates, returned to preischemic values, whereas the dissociation rate of Ca 2+ from A · M was ninefold faster. This cardiac muscle kinetic model predicted a better-restored relationship between Ca 2+ and cross-bridge function on RP after an eightfold longer period of 17°C than 37°C ischemia. indo 1; ischemia-reperfusion injury; hypothermia; isolated hearts; four-state model