A novel mechanism for myocardial stunning involving impaired Ca²⁺ handling

The mechanism of myocardial stunning has been studied extensively in rodents and is thought to involve a decrease in Ca²⁺ responsiveness of the myofilaments, degradation of Troponin I (TnI), and no change in Ca²⁺ handling. We studied the mechanism of stunning in isolated myocytes from chronically instrumented pigs. Myocytes were isolated from the ischemic (stunned) and nonischemic (normal) regions after 90-minute coronary stenosis followed by 60-minute reperfusion. Baseline myocyte contraction was reduced, P< 0.01, in stunned myocytes (6.3±0.4%) compared with normal myocytes (8.8±0.4%). The time for 70% relaxation was prolonged, P<0.01, in stunned myocytes (131±8 ms) compared with normal myocytes (105±5 ms). The impaired contractile function was associated with decreased Ca²⁺ transients (stunned, 0.33±0.04 versus normal, 0.49±0.05, P<0.01). Action potential measurements in stunned myocytes demonstrated a decrease in plateau potential without a change in resting membrane potential. These changes were associated with decreased L-type Ca²⁺-current density (stunned, -4.8±0.4 versus normal, -6.6±0.4 pA/pF, P<0.01). There were no differences in TnI, sarcoplasmic reticulum Ca²⁺ ATPase (SERCA2a), and phospholamban protein quantities. However, the fraction of phosphorylated phospholamban monomer was reduced in stunned myocardium. In rats, stunned myocytes demonstrated reduced systolic contraction but actually accelerated relaxation and no change in Ca²⁺ transients. Thus, mechanisms of stunning in the pig are radically different from the widely held concepts derived from studies in rodents and involve impaired Ca²⁺ handling and dephosphorylation of phospholamban, but not TnI degradation.