Membrane permeability alterations as manifestation of early cardiac muscle cell injury.

: Studies with extracellular fine structural diffusion protein tracers, horseradish peroxidase and ferritin, were carried out on catecholamine-induced cardiac muscle cell injury. Epinephrine, norepinephrine, and isoproterenol were administered in a dose of 4- 6 mug/100g body weight by continuous intravenous infusion. For follow-up studies, isoproterenol was also given subcutaneously in a dose of 8.5 mg/100 g body weight as a single injection. In contrast to saline-infused controls and following epinephrine infusion, where these tracers always remained extracellular, norepinephrine- and isoproterenol-infused animals exhibited alteration of sarcoplasmic membrane permeability to macromolecules in the early stage of evolution preceding fine structural changes of cardiac muscle cells. This was reflected by the intrasarcoplasmic presence of peroxidase in some cardiac muscle cells which otherwise showed no ultrastructural alteration. Deposition upon and selective binding of the extracellular protein tracer, peroxidase, to intact myofilament was also a characteristic early change that may affect the contraction-relaxation mechanism of the myofilaments and may contribute to the evolution of necrobiotic alteration. In structurally altered cells, peroxidase showed similar affinity to contraction bands and fragmented myofilaments. Furthermore, these studies disclosed different sensitivities of various membrane components of the cardiac muscle cell. While in the early pahse of cell damage no peroxidase could be detected in various intrasarcoplasmic compartments, with increasing severity of the lesion the external and internal mitochondrial membranes as well as the sarcoplasmic reticulum were also affected. When the large molecular tracer, ferritin, was used, the sequence of events in altered cardiac muscle cells followed that outlined for peroxidase. However, free ferritin molecules could not be demonstrated in the sarcoplasm of cardiac muscle cells which exhibited normal ultrastructure.