Changes in excitation-contraction coupling in an isolated ventricular myocyte model of cardiac stunning

To investigate cardiac stunning, we recorded intracellular [Ca²⁺], contractions, and electrical activity in isolated guinea pig ventricular myocytes exposed to simulated ischemia and reperfusion. After equilibration, ischemia was simulated by exposing myocytes to hypoxia, acidosis, hyperkalemia, hyper-capnia, lactate accumulation, and substrate deprivation for 30 min at 37°C. Reperfusion was simulated by exposure to Tyrode solution. Field-stimulated myocytes exhibited stunning upon reperfusion. By 10 min of reperfusion, contraction amplitude decreased to 43.0 ± 5.5% of preischemic values (n = 15, P < 0.05), although action potential configuration and sarcoplasmic reticulum Ca²⁺ stores, assessed with caffeine, were normal. Diastolic [Ca²⁺] and Ca²⁺ transients (fura 2) were also normal in stunned myocytes. In voltage-clamped cells, peak L-type Ca²⁺ current was reduced to 47.4 ± 4.5% of preischemic values at 10 min of reperfusion (n = 21, P < 0.05). Contractions elicited by Ca²⁺-induced Ca²⁺ release and the voltage-sensitive release mechanism were both depressed in reperfusion. Our observations suggest that stunning is associated with reduced L-type Ca²⁺ current but that alterations in Ca²⁺ homeostasis and release are not directly responsible for stunning.