Abstract
Breakdown of the excitation-contraction coupling system has been proposed to play a pivotal role in myocardial dysfunction during the course of acute ischemia. We tested this hypothesis by characterizing the function of the sarcoplasmic reticulum (SR) at pH 7.1 and 6.4 after 7.5, 15 and 30 minutes of canine normothermic global ischemia. At pH 7.1, isolated SR demonstrated a 55% depression of oxalate supported calcium uptake at 7.5 minutes which progressed to 87% at 30 minutes. At pH 6.4, control calcium uptake rates were significantly depressed accompanied by a further depression in the ischemic groups. Whole heart homogenate calcium uptakes mirrored the effects of the isolated SR. Calcium stimulated-Mg dependent ATPase activity was significantly depressed by both ischemia and acidosis with a decrease in the coupling ratio (μmoles Ca/μmoles ATP) at 15 and 30 minutes of ischemia. Acidosis (pH 6.4) significantly shifted the SR pCa-ATPase curve to the right increasing 50% activation from pCa 6.0 to 5.5 and depressing Vmax (pH 7.1 = 2.06 ± 0.14; pH 6.4 = 1.41 ± 0.05ymol Pi/mg-min; p < 0.01). With ischemia, there was a progressive decrease in maximal activation of the Ca2+ -ATPase enzyme and a shift in calcium sensitivity to a higher concentration. Hill plot analysis demonstrates a decrease in the Hill coefficient with ischemia. Steady-state calcium uptake, in the absence of oxalate demonstrated a similar depression following 7.5 minutes of ischemia at both pH 7.1 and 6.4. It is concluded that during short term, normothermic ischemia, there is significant and progressive sarcoplasmic reticulum dysfunction which is magnified at pH 6.4 characterized by a decrease in calcium uptake and ATPase activity which is due in part to a loss of enzyme activity and a probable increase in permeability of the SR membrane. It is postulated that during primary myocardial ischemia, this breakdown in sarcoplasmic reticulum function may serve as the source of intracellular calcium overload.
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© 1984 Martinus Nijhoff Publishing, Boston
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Hess, M.L., Krause, S.M. (1984). Characterization of Cardiac Sarcoplasmic Reticulum: Dysfunction during primary myocardial ischemia: A potential source for intracellular calcium overload. In: Sperelakis, N., Caulfield, J.B. (eds) Calcium Antagonists. Developments in Cardiovascular Medicine, vol 39. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3810-9_25
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DOI: https://doi.org/10.1007/978-1-4613-3810-9_25
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