Alpha adrenergic-mediated accumulation of calcium in reperfused myocardium.

A D Sharma; J E Saffitz; B I Lee; B E Sobel; P B Corr

doi:10.1172/JCI111051

Published September 1, 1983 - More info

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Abstract

Reperfusion of ischemic myocardium is associated with increases in total myocardial calcium (Ca+2), which may influence the ultimate extent of ischemic damage as well as the development of arrhythmias. Since reperfusion is also associated with enhanced alpha-adrenergic responsivity, this study was performed to determine the potential interactions between alpha-adrenergic receptors and myocardial calcium during reperfusion. Cats were subjected to 35 min of left anterior descending coronary artery occlusion and 10 min of reperfusion. Total myocardial calcium was measured by atomic absorption spectrometry. Intracellular calcium was calculated from measurements of extracellular space [( 3H]inulin). In control animals with reperfusion, total calcium increased from 0.32 +/- 0.03 to 0.65 +/- 0.05 mmol/100 g dry tissue (P less than 0.0001), while intracellular calcium increased from 0.15 +/- 0.03 to 0.40 +/- 0.05 mmol/100 g dry tissue (P less than 0.001). Pretreatment with the alpha-adrenergic blocking agents phentolamine or prazosin prevented the increase in total and intracellular calcium. Phentolamine and the aqueous soluble alpha 1-adrenergic antagonist BE-2254 administered as late as 2 min before reperfusion similarly attenuated the increase in tissue calcium. Although administration of BE-2254 2 min before reperfusion failed to block the reperfusion-induced increase in extracellular space, the increase in calculated intracellular calcium was prevented. beta-Adrenergic blockade with propranolol partially attenuated but did not prevent an increase in total tissue calcium. Labetalol, a combined alpha- and beta-adrenergic blocking agent completely blocked the increase in tissue calcium during reperfusion. Additional experiments performed after 70 min of ischemia with reperfusion demonstrated a 49% attenuation of the increase in tissue calcium with alpha-adrenergic blockade. Electron microscopy with pyroantimonate and x-ray microprobe analysis demonstrated a large increase in calcium precipitate in mitochondria after reperfusion in untreated animals. Though alpha-adrenergic blockade prevented the calcium deposition in mitochondria, other criteria of ischemia persisted. Thus, alpha-adrenergic blockade specifically prevents the increase in intracellular calcium during reperfusion in reversibly injured tissue, independent of alterations in extracellular space and tissue water.

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