Cytoskeletal injury and subsarcolemmal bleb formation in dog heart during in vitro total ischemia.

In previous studies a two-step hypothesis explaining the mechanism of lethal ischemic injury to cardiac myocytes has been advanced. It proposes that damage to the myocyte cytoskeleton precedes, and predisposes the cell to, mechanical injury induced by cell swelling or by ischemic contracture. This study quantitated the prevalence of breakage of the major cytoskeletal attachment between the plasmalemma and peripheral myofibers as a function of the duration (0-180 minutes) of in vitro total ischemia in dog heart papillary muscle. Breakages of Z-band, plasmalemmal attachment complexes were few before 120 minutes of ischemia, but thereafter became more prevalent; the transition between the initial rate of appearance of the breaks and the later fast rates coincided with the appearance of severe cell swelling, ischemic contracture, and ultrastructural criteria of irreversible ischemic injury. Z-band, plasmalemmal attachment complex breakage and cell swelling resulted in formation of subsarcolemmal blebs. Two major bleb types have been discerned on ultrastructural appearance using as the criteria the preservation of integrity of the plasma-lemma and subplasmalemmal leptomeres. The identification of two types of blebs suggests two independent mechanisms of injury, the first directed at Z-band attachments, and the second at the cytoskeletal structures of A- and I-band regions of the plasmalemma.