Áreas funcionales

The post denervation hypertrophy of the rat

hemidiaphragin is a complex process. Of the many explan­ ations that have been put forward to account for the

phenomenon perhaps the most plausible is that the hyper­ trophy is caused by the passive rhythmic stretching which is experienced by the paralysed muscle whilst the animal

respires (Sola & Martin, 1953)o Thus diaphragms that

are bilaterally phrenicectomized (Peng & Lu, 1965) or unilaterally phrenicectomized but also costotoraized

(Gutmann et 1966) fail to hypertrophy because the

stretch effect is reduced. Further evidence in

support of this suggestion comes from the observation that the resting metabolism of isolated muscle increases during passive stretch (Feng, 1932) and that rates of in vitro protein synthesis are increased when the muscle is kept under tension (Buresova, Gutmann & Klicpera, 1969). Stewart (1968) found that tenotomy of denervated limb

muscles enhances the atrophic response only when the limb bones are rapidly elongating, i.e. the passive stretch of the denervated muscle that is released on tenotomy seems

to exert a trophic influence on the muscle. Increased tension has also been suggested as a cause for the compensatory hypertrophy of limb muscles following tenotomy of the synergist; the phenomenon occurs in­ dependently of innervation and points to a non-neural factor as a causative agent (Schiaffino & Hanzlikova, 1970).

A particular feature of the denervation hyper­ trophy of the rat hemidiaphragin is that the hypertrophy does not take place in all the fibre types present in the

muscle (Feng & Lu, 1965). Available evidence suggests

that the "white" fibres begin to atrophy immediately after nerve section and that the "red" and/or "inter­ mediate" fibre types are the ones that undergo the hyper­

trophy. Schiaffino & Hanzlikova (1970) showed that com­

pensatory hypertrophy occurs to an almost equal extent in "red" & "white" muscles, the .hypertrophy of the rat soleus being only fractionally greater than that of the plantaris.

In the hypertrophying denervated diaphragm therefore some factor other than passive rhythmic stretch must account for the differential fibre response.

An increased blood flow has been suggested as

being an early consequence of denervation. Schreiber and. his co-workers (Schreiber, Oratz & Rothschild, 1966;Schreib Evans, Oratz & Rothschild, 1967) have demonstrated in the isolated perfused working rat heart that increased ven­ tricular perfusion rate or a rise in aortic pressure re­ sulted in an increased rate of incorporation of radio­

active amino acid into protein. This effect could also

be observed when the normal perfusion medium was made hyperbaric with respect to oxygen tension; increased oxygen availability thus appeared to stimulate protein

synthesis in the working rat heart. Romanul (1965) has

shown that in mixed skeletal muscles the capillary density around mitochondrial-rich fibres is appreciably greater than that around the "white" muscle fibres. The fibre selective hypertrophy of the denervated diaphragm may thus be a manifestation of the greater capillary supply to the non-white fibre types, the increased blood flow permitting a greater availability of oxygen to the red fibres and thus stimulating protein synthesis. G arrow. Brown & van Huss (1967) subjected rats to a lengthy

hind limb muscles. "Red" muscle fibres hypertrophied to a greater extent than did the "white" fibres, but nevertheless a statistically significant increase in fibre diameter was found for the "white" fibres after the enforced exercise. . More surprisingly it was found that the number of capillaries available to each fibre type increased more for the "white" fibres as a result of the exercise than was the case for the "red" fibres. Thus under conditions in which hypertrophy of white fibres takes place an augmentation of the capillary

supply to these fibres is observed. If it is a neces­

sary condition for the hypertrophy of the white fibre that there be an increased blood supply then the situa­ tion occurring in the denervated rat hemidiaphragm, in which possibly all the fibre types are stimulated to hypertrophy by the stretch effect, will act adversely against the white fibres because of the inability within the time available to augment the capillary supply to

these fibres. Of course the situation is probably com­

plicated still further by the extent that control over blood flow through the tissue still remains to the vaso­

On the other hand, the differential response of the various fibre types may be due to some intrinsic

property of the fibres themselves. Bajusz (1964)

found that in denervation atrophy the "white" fibres decreased in size earlier than did the "red" fibres and therefore proposed the greater dependence of the "white" fibres on neuromuscular integrity, since he found that if muscles were immobilized (in plaster casts, or by tenotoraj^) both "red" and "white" fibres atrophied at the

same rate. In support of this concept is the finding of

Brust (1966) that in mice with muscular dystrophy the per­ centage reduction in weight of the soleus muscle was only half that of the gastrocnemius, whilst the contraction characteristics of the soleus were much less severely

affected by the dystrophy. Goldberg (l96?) has demon-

14

strated that the upLake of 0-AIB, and incorporation of

14

in red skeletal muscle than in white muscle. Unfortunately these results could be interpreted as indicating that red muscles have a greater blood flow than white ones, but re­ cently studies of the protein synthetic capacity of indi­ vidual fibres 3^ vitro have confirmed Goldberg’s conclusion