In this study we determined whether contractile function becomes uncoupled during reperfusion of ischemic hearts from mitochondrial tricarboxylic acid (TCA) cycle activity or myocardial O2 consumption (MVO2). Isolated working rat hearts perfused with buffer containing 1.2 mM palmitate and 11 mM glucose were subjected to 30 min of global ischemia followed by 60 min of aerobic reperfusion. During reperfusion, cardiac work recovered to 26.5 +/- 5.4% (n = 29) of preischemic levels, even though TCA cycle activity, fatty acid beta-oxidation, glucose oxidation, glycolysis, and MVO2 rapidly recovered. As a result, the efficiency of coupling between cardiac work and TCA cycle activity and between cardiac work and mitochondrial respiration decreased during reperfusion. In contrast, coupling of TCA cycle activity to MVO2 during reperfusion recovered to preischemic values. Addition of 1 mM dichloroacetate at reperfusion resulted in a significant increase in both cardiac work and cardiac efficiency during reperfusion. This was associated with a significant decrease in H+ production due to an improved balance between glycolysis and glucose oxidation. These data demonstrate that mitochondrial function and overall myocardial ATP production quickly recover in rat hearts after a 30-min period of global ischemia. However, mitochondrial ATP production is not efficiently translated into mechanical work during reperfusion. This may be due to an imbalance between glycolysis and glucose oxidation, resulting in an increase in H+ production and a decrease in cardiac efficiency.
The Ca2+ uptake by isolated cardiac sarcoplasmic reticulum (SR) was compared between Richardson's ground squirrels and rats at 37, 25, 15, and 5 degrees C. The rate of SR Ca2+ uptake in ground squirrels was significantly higher than in rats over the temperature range. This marked species difference was observed over a Ca2+ concentration range from 0.1 to 10 microM. The Arrhenius plot for Ca2+ uptake was linear for ground squirrels between 37 and 5 degrees C but showed a depression from linearity for rats at 5 degrees C. This temperature sensitivity was also reflected in rat SR Ca2+-adenosinetriphosphatase activity. Analysis of [3H]ryanodine binding in SR suggests that more Ca2+ release channels are in an open state at low temperatures in rats than in ground squirrels. Together, these results suggest that species differences in the response of SR to low temperature may account for the rise in cytosolic free Ca2+ in cold-sensitive species and may be responsible, at least in part, for the inability of cold-sensitive hearts to function at low temperature.
Chemically skinned papillary muscles from active and hibernating ground squirrels were used to determine whether the enhanced cardiac contractility observed in hibernation is due to a change in myofilament Ca2+ sensitivity. A similar preparation from rats was used to reflect the changes in a nonhibernator. When examined at pH 7.00 in all three groups and under physiological pH with varying temperatures in the ground squirrels, the calcium concentration at which muscle tension is at 50% maximum (pCa2+50) decreased significantly (P < 0.05) with decreasing temperature (25, 15, and 5 degrees C). When hibernating and active ground squirrels were compared, no significant difference in pCa2+50 was observed at 25 degrees C; however, the values at 15 and 5 degrees C were significantly higher (P < 0.05) in the hibernating squirrels. The results indicate that cardiac myofilament Ca2+ sensitivity decreases significantly at low temperature in both active and hibernating ground squirrels; however, the higher Ca2+ sensitivity in the hibernating squirrels at 15 and 5 degrees C could partially contribute to the enhanced cardiac contractility typically seen during hibernation.
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