Protamine inhibits capillary formation in growing rat hearts.

Various indices of capillary supply to the rat heart were studied in neonatal rats injected for 2 or 4 weeks with protamine sulfate in saline (subcutaneously, 60 mg/kg body weight, 2 times/day). Cardiac capillarization was evaluated not only by traditional indices for the capillary supply, such as mean capillary density and myocyte-to-capillary ratio, but also by a more advanced morphometric method of capillary domains. This method allows the estimation of both the average radius of the Krogh tissue cylinder and its variability, which reflects the heterogeneity of capillary spacing found to be an independent morphological determinant of oxygen diffusion in the tissue. The results were evaluated with respect to regional differences (subendocardial vs. middle section), age differences, and the effect of protamine. No regional differences in capillary supply were found in this experimental situation. Hearts from older rats had significantly decreased capillary supply, expressed as lower capillary density, larger capillary domains, and greater radius of the tissue cylinder. On the other hand, the heterogeneity of capillary spacing decreased significantly with age. Protamine-injected animals, when compared to their control littermates, had a significantly higher cell-to-capillary ratio, lower capillary density, larger capillary domains, greater radius of the tissue cylinder, and larger variability in capillary spacing. Thus, protamine was effective in impeding rapid capillary growth in the hearts from rats in the early postnatal period. Close to half of all the existing capillaries in the adult rat hearts are formed during the first 3-4 postnatal weeks.