ALBERT

Description: Prolonged exposure of humans to hypogravity causes weakening of their skeletal muscles. This problem was studied in rats exposed to hypogravity for 7 days aboard Spacelab 3. Hindlimb muscles were harvested 12-16 hours postflight for histochemical, biochemical, and ultrastructural analyses. The majority of the soleus and extensor digitorum longus fibers exhibited simple cell shrinkage. However, approximately 1% of the fibers in flight soleus muscles appeared necrotic. Flight muscle fibers showed increased glycogen, lower subsarcolemmal staining for mitochondrial enzymes, and fewer subsarcolemmal mitochondria. During atrophy, myofibrils were eroded by multiple focal losses of myofilaments; lysosomal autophagy was not evident. Tripeptidylaminopeptidase and calcium-activated protease activities of flight soleus fibers were significantly increased, implying a role in myofibril breakdown. Simple fiber atrophy appears to account for muscle weakening during spaceflight, but fiber necrosis is also a contributing factor.

Description: Histochemical and ultrastructural analyses were performed postflight on hind limb skeletal muscles of rats orbited for 12.5 days aboard the unmanned Cosmos 1887 biosatellite and returned to Earth 2 days before sacrifice. The antigravity adductor longus (AL), soleus, and plantaris muscles atrophied more than the non-weight-bearing extensor digitorum longus, and slow muscle fibers were more atrophic than fast fibers. Muscle fiber segmental necrosis occurred selectively in the AL and soleus muscles; primarily, macrophages and neutrophils infiltrated and phagocytosed cellular debris. Granule-rich mast cells were diminished in flight AL muscles compared with controls, indicating the mast cell secretion contributed to interstitial tissue edema. Increased ubiquitination of disrupted myofibrils implicated ubiquitin in myofilament degradation. Mitochondrial content and succinic dehydrogenase activity were normal, except for subsarcolemmal decreases. Myofibrillar ATPase activity of flight AL muscle fibers shifted toward the fast type. Absence of capillaries and extravasation of red blood cells indicated failed microcirculation. Muscle fiber regeneration from activated satellite cells was detected. About 17% of the flight AL end plates exhibited total or partial denervation. Thus, skeletal muscle weakness associated with spaceflight can result from muscle fiber atrophy and segmental necrosis, partial motor denervation, and disruption of the microcirculation.

Description: Data obtained during Cosmos 2044 bisatellite mission are reviewed and found to be consistent with the results of previous rodent spaceflight experiments. Investigation was carried out of hindlimb muscles from flight rats killed as close to land as possible so that changes induced by spaceflight and early readaptation to weight bearing could be distinguished from the changes that resulted from the two-day postflight period during Cosmos 1887. Results presented pertain to muscle atrophy and fiber type changes, eccentric contraction-like lesions, microcirculatory changes and interstitial edema, and tissue damage.

Description: The effects of hindlimb unloading on rat-soleus histochemisty, ultrastructure, and electromyogram (EMG) activity were investigated. It was found that, after 14 days of tail suspension, the area of type I and type IIa muscle fibers decreased by 63 and 47 percent, respectively, mainly due to the degradation of subsarcolemmal mitochondria and myofibrils. After 10 days, 3 percent of type IIa fibers exhibited segmental necrosis. After four days, video monitoring revealed abnormal plantar flexion of the hindfeet, which shortened the soleus working range. The EMG activity shifted from tonic to phasic, and aggregate activity decreased drastically after only seven days. The results indictate that the pathological changes in the soleus resulted from unloaded contractions, reduced use, compromised blood flow, and shortened working length.

Description: Muscle atrophy in rats exposed to hypogravity for seven days aboard Spacelab 3 is examined. Hindlimb muscles were harvested 12-16 days postflight, and prepared for enzyme studies and electron microscopy. Simple cell shrinkage was found, with a mean fiber area decrease of 35.8 percent for soleus and 24.9 percent for extensor digitorum longus (EDL) flight muscle fibers, as compared with control muscle fibers. EDL and soleus muscles showed increases in alkaline myofibrillar ATPase, alpha glycerophosphate dehydrogenase, and glycogen, and a decrease in NADH dehydrogenase staining. The 26 percent increase in calcium activated protease suggests that the focal degradation of myofibrils is the key process of myofibril breakdown. The presence in the flight soleus muscles of one percent necrotic fibers is unexplained. The observed shift towards histochemical fast-muscle type properties is consistent with previous findings.

Description: We hypothesized that hindlimb suspension unloading of 8-day-old neonatal rats would disrupt the normal development of muscle fiber types and the motor innervation of the antigravity (weightbearing) soleus muscles but not extensor digitorum longus (EDL) muscles. Five rats were suspended 4.5 h and returned 1.5 h to the dam for nursing on a 24 h cycle for 9 days. To control for isolation from the dam, the remaining five littermates were removed on the same schedule but not suspended. Another litter of 10 rats housed in the same room provided a vivarium control. Fibers were typed by myofibrillar ATPase histochemistry and immunostaining for embryonic, slow, fast IIA and fast IIB isomyosins. The percentage of multiple innervation and the complexity of singly-innervated motor terminal endings were assessed in silver/cholinesterase stained sections. Unique to the soleus, unloading accelerated production of fast IIA myosin, delayed expression of slow myosin and retarded increases in standardized muscle weight and fiber size. Loss of multiple innervation was not delayed. However, fewer than normal motor nerve endings achieved complexity. Suspended rats continued unloaded hindlimb movements. These findings suggest that motor neurons resolve multiple innervation through nerve impulse activity, whereas the postsynaptic element (muscle fiber) controls endplate size, which regulates motor terminal arborization. Unexpectedly, in the EDL of unloaded rats, transition from embryonic to fast myosin expression was retarded. Suspension-related foot drop, which stretches and chronically loads EDL, may have prevented fast fiber differentiation. These results demonstrate that neuromuscular development of both weightbearing and non-weightbearing muscles in rats is dependent upon and modulated by hindlimb loading.