The structures present in the rabbit myocardial interstitium have been defined and quantified. Stereological methods were used for the quantification. The extracellular space contains abundant ground substance (23%) distributed in a homogeneous mat throughout the space and within the T tubules. The remainder of the space contains 59% blood vessels, 6% "empty" space, 4.0% collagen, and 7.0% connective tissue cells. The arrangement of the interstitium in relation to the myocardial cells and the capillaries has been described. In addition, the extracellular space was measured using extracellular markers: 14C sucrose (neutrally charged), 35SO4 (negatively charged), and 140La (positively charged). The La+++ space differed markedly from the other two (P << 0.001), indicating extensive binding of La+++ to polyanionic extracellular structures. Cetylpyridinium chloride, a cationic detergent specific for polysaccharides, caused precipitation of the ground substance and marked decrease in the La+++ space. This study indicates the considerable structural complexity of the interstitium. The effects of an abundant negatively charged protein-polysaccharide within the interstitium has been discussed in terms of cation exchange in arterially perfused tissue.

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