Dipyridamole-induced neoformation of capillaries in the rat heart. Quantitative stereological study on papillary muscles.

Eighteen young male Wistar rats were randomly divided into two groups of equal size. Each experimental animal was treated with the powerful vasodilating drug dipyridamole (4 mg kg-1 intraperitoneally twice daily) for a period of 6 weeks. The control animals received sham injections with saline. The rats were fixed by retrograde vascular perfusion. Seven transverse and two longitudinal sections per animal were randomly selected from the left ventricular papillary muscles for stereological investigation. Length density of capillaries (length of capillaries per unit of tissue volume), surface density of capillaries (surface area of capillaries per unit of tissue volume) and the "true" three-dimensional capillary-fiber ratio (length of capillaries per unit length of myocardial fibers) were estimated by means of the Dimroth-Watson distribution, a mathematical model of directional statistics which assumes that the capillary directions scatter around the longitudinal axis of the muscle. This model was recently introduced into the stereology of myocardial capillaries and leads to a more accurate quantitation of the capillary network than parameters used hitherto, such as the "capillary density" (number of capillary profiles per mm2 of cross sectional area) and the "capillary-fiber ratio" (number of capillary profiles per number of myofiber profiles in cross sections). After chronic dipyridamole treatment, the length density of myocardial capillaries (+5%; p less than 0.02), the surface density of capillaries (+8%, p less than 0.01) and the three-dimensional capillary-fiber ratio (+6%, p less than 0.05) were increased. It is therefore concluded that the vasodilating drug dipyridamole evokes capillary growth in the heart which may be induced by mechanical factors via the enhanced myocardial blood flow. Investigation of the frequency distribution of capillary directions in space in both groups provided evidence that the capillary growth resulted from neoformation of capillaries.