Abstract
To investigate cardiac stunning, we recorded intracellular Ca(2+),
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, hypercapnia, lactate accumulation, and substrate deprivation
for 30 min at 37 degrees 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
Ca(2+) stores, assessed with caffeine, were normal. Diastolic Ca(2+)
and Ca(2+) transients (fura 2) were also normal in stunned myocytes.
In voltage-clamped cells, peak L-type Ca(2+) current was reduced
to 47.4 +/- 4.5\% of preischemic values at 10 min of reperfusion
(n = 21, P < 0.05). Contractions elicited by Ca(2+)-induced Ca(2+)
release and the voltage-sensitive release mechanism were both depressed
in reperfusion. Our observations suggest that stunning is associated
with reduced L-type Ca(2+) current but that alterations in Ca(2+)
homeostasis and release are not directly responsible for stunning.
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