Ultrastructural damage associated with the Ca2+ paradox. The protective effect of Mn2+

Hearts repleted with Ca2+-containing buffers after only a few minutes of Ca2+-free perfusioN display extensive ultrastructural damage and accumulate Ca2+. Ultrastructural damage includes separation of the intercalated disks, development of contracture bands, and splitting of the internal and external layers of the glycocalyx. In this study, the authors have used isolated spontaneously beating Langendorff perfused hearts to investigate whether Mn2+ alters the ultrastructural damage associated with Ca2+ repletion after Ca2+-free perfusion, previous studies having shown that it attenuates or abolishes the gain in Ca2+ which normally occurs under these conditions. Mn2+ added only at the time of Ca2+ repletion did not attenuate the ultrastructural damage. When Mn2+ (2 mM) was added during the Ca2+-free period or the Ca2+-free and Ca2+ repletion periods, however, the hearts were not as extensively damaged. The myofibrils were relaxed, and the intercalated disks were intact. However, splitting of the glycocalyx still occurred and was a prominent feature. These results indicate that splitting of the glycocalyx per se does not necessarily result in a massive gain in Ca2+ when Ca2+ is returned to Ca2+-depleted hearts. Possible mechanisms of action of Mn2+ are discussed.