Duration and intensity of training is obviously a very important factor.In human muscles, however, increased capillarization could not be main tained without training, since bed rest for wk led to decreased activity of oxidative enzymes within wk and a return of CF to pretraining values within wk. A higher CD and CF in subjects trained for wk returned to control values within wk of de training, and in welltrained crosscountry skiers, pretraining values in CF were reached after only wk of detraining, the activity of oxidative enzymes return ing to control values long before this. How ever, hypoxia per se does not stimulate capillary prolif eration.Also, endurance training increased, diphos phoglycerate in red blood cells, resulting in decreased binding affinity for oxygen and increased Secnidazole availability of oxygen for muscle metabolism, and muscle PO, was found to be actually higher in trained athletes as well as in trained guinea pigs. A possible stimulus initiating capillary growth could be linked with in creased blood flow during muscle activity.Maximal flow is greater in long distance runners than in sprinters, and there is no increase in capillarization in the latter.Increased blood flow could lead to increased shear stress or increased capillary pressure and thus wall tension, and these fac tors could trigger changes in capillary endothelial base ment membrane resulting in its breakage, which is the first step necesssary for capillary growth.Experi ments were therefore designed to stimulate capillary growth by a drastic reduction in heart rate by either electrical bradycardial pacing or drugs with predomi nantly negative chronotropic effects.Bradycardial pacing eliminated every second heart beat and led to higher CD in comparison with control hearts of a simi lar weight were changed, so the in crease in CD and CF based on histochemical local ization of alkaline phosphatase in capillary endothelium and electron microscopy can only be interpreted as due to the growth of capillaries, Piperonyl butoxide equally distributed between subendocardial and subepicardial regions, an increased volume density of mitochondria, and a higher maximal oxygen con sumption, which was met by increased oxygen extrac tion. Thus increased CD did not result in increased maximal blood flow but rather in a greater homogeneity offlow that was also confirmed by measurements of capillary permeabilitysurface area product to be. in control hearts similar to that found in human hearts with myocardial infarction. It is possible that in this model prolonged diastole, resulting in an increased capillary wall tension, in combination with the angio genie factor is responsible for capillary growth.Longterm bradycardia was also induced by a wk administration of alinidine to rats, and, as in paced hearts, there was no heart hypertrophy and no change in maximal coro nary blood flow.In agreement with this hypothesis, longterm ad ministration of dobutamine, a drug with a positive ino tropic effect, also resulted in capillary growth. Activity in selective fiber groups can be increased by different types of training, but all fibers are very rarely activated at the same time.Longterm electrical stimulation, on the other hand, usually acti vates all fibers indiscriminately.