Abstract-Hydroxyl radicals (OH) are involved in the development of reperfusion injury and myocardial failure. In the acute phase of the OH-mediated diastolic dysfunction, increased intracellular Ca 2ϩ levels and alterations of myofilaments may play a role, but the relative contribution of these systems to myocardial dysfunction is unknown. Intact contracting cardiac trabeculae from rabbits were exposed to OH, resulting in an increase in diastolic force (F dia ) by 540%. Skinned fiber experiments revealed that OH-exposed preparations were sensitized for Ca 2ϩ (EC 50 : 3.27Ϯ0.24ϫ10Ϫ6 versus 2.69Ϯ0.15ϫ10 Ϫ6 mol/L; PϽ0.05), whereas maximal force development was unaltered. Western blots showed a proteolytic degradation of troponin T (TnT) with intact troponin I (TnI). Blocking of calpain I by MDL-28.170 inhibited both TnT-proteolysis and Ca 2ϩ sensitization, but failed to prevent the acute diastolic dysfunction in the intact preparation. The OH-induced diastolic dysfunction was similar in preparations with intact (540Ϯ93%) and pharmacologically blocked sarcoplasmic reticulum (539Ϯ77%), and was also similar in presence of the L-type Ca 2ϩ -channel antagonist verapamil. In sharp contrast, inhibition of the reverse-mode sodium-calcium exchange by KB-R7943 preserved diastolic function completely. Additional experiments were performed in rat myocardium; the rise in diastolic force was comparable to rabbit myocardium, but Ca 2ϩ sensitivity was unchanged and maximal force development was reduced. This was associated with a degradation of TnI, but not TnT. Electron microscopic analysis revealed that OH did not cause irreversible membrane damage. We conclude that OH-induced acute diastolic dysfunction is caused by Ca 2ϩ influx via reverse mode of the sodium-calcium exchanger. Degradation of troponins appears to be species-dependent but does not contribute to the acute diastolic dysfunction.
. The potential involvement of actin and fodrin (brain spectrin) in secretory events has been assessed in primary cultured guinea pig parotid acinar cells, using as a tool affinity purified anti-alpha-fodrin antibody, phalloidin, and immunofluorescence techniques. In resting parotid acinar cells fodrin and actin appeared as a continuous ring under the plasma membrane of most of the cells . Upon stimulation with secretagogues fodrin and actin labeling at the level of the plasma membrane disappeared almost completely. To establish a correlation between secretion and cytoskeletal changes at the individual cell level, anti-alphaamylase-antibodies were used to label secreted amylase exposed at the surface of secreting cells. The number THEcytoskeletalproteinsa ctin and fodrin (brain spectrin) are widely distributed among different cell types. Fodrin is a heterodimer composed of an alpha (240 kD) and a beta (235 kD) subunit. The main characteristics ofthe proteins ofthe fodrin-spectrin family are self-assembly and binding to actin filaments, this latter property being inhibited by calcium (for review see references 8 and 9). The existence of F-actin-fodrin networks in vitro and in vivo has been reported . In most cell types, actin filaments and fodrin are colocalized under the plasma membrane, a notable exception being epithelial and endothelial cells where fodrin is mainly detected along the actin cables within the cell (4, 12) . The existence of F-actin-fodrin networks under the plasma membrane of secretory cells raises the question of whether a reorganization of this network is required for secretory vesicles to get access to the plasma membrane during regulated secretion.The first demonstration of such a reorganization during stimulated secretion came from experiments in chrornaffin cells of the adrenal medulla . Following stimulation of chrornaffin cells, a dramatic redistribution of fodrin (7,14) and a reduction in the amount of actin associated with the cytoskeleton (3) was observed. Furthermore, the introduction of anti-alpha-fodrin antibodies into permeabilized chrornaffin cells induced a 50% inhibition of catecholamine release (15) . As nicotine-and potassium-induced secretion ® The Rockefeller University Press, 0021-9525/92/01/127/8 $2 .00 TheJournal ofCell Biology, Volume 116, Number 1, January 1992127-134 of cells expressing alpha-amylase on their surface followed bulk secretion of alpha-amylase . A strict correlation between secretion and alteration of the actinfodrin labeling was observed at the individual cell level. The cytoskeletal changes occurred in parallel with secretion independently of the secretagogue used (carbamoylcholine in the presence of Caz+, isoproterenol in presence or absence of Ca 2+' forskohn, or dibutyryl-cyclic-AMP) . The changes were reversible upon removal of the secretagogue.Since Caz+, as well as CAMP-mediated secretion, was associated with the same kind of cytoskeletal changes, a reorganization of the cytoskeleton may play an essential part in regulated secretion .in...
Tako-tsubo cardiomyopathy is a distinctive form of regional left ventricular dysfunction triggered by psychologically stressful events, which has a favorable clinical outcome. With a remarkable frequency of 7.5% especially in women, tako-tsubo cardiomyopathy should be included in the differential diagnosis of acute myocardial infarction.
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