SUMMARY1. Isometric contractions offast and slow twitch muscles ofrats were recorded 1-42 days after denervation.2. The major changes occurred over the period from 2 to 6 days after denervation. These changes were qualitatively similar in the two types of muscle. The most important effects were on the twitch: times to peak and half relaxation were prolonged, active tension and peak rate of rise of tension were increased. Tetanic tension per unit cross-sectional area and the maximum rate of rise of tension decreased during this period but, in the second week, the tension recovered substantially and the maximum rate recovered completely.3. Very small differences were seen between muscles denervated with short and long nerve stumps at day 4.4. In the late stage of denervation (7-42 days) twitch and tetanic tension fell more than cross-sectional area, but this may have been due to greater atrophy of fibres compared with other muscle tissue.5. Apart from this tension fall, there were only small changes in the fast muscle in the late stage of denervation. These were a fall in twitch-tetanus ratio and a prolongation of relaxation.6. In more than half of the soleus muscles there was a late reversal of some of the denervation changes, and these muscles showed a greater degree of atrophy. The less atrophied soleus muscles maintained a prolonged twitch and a low rate ofdevelopment of tension.7. It is concluded that denervation affects the contractile properties of muscle as early and as abruptly as it does the membrane properties, and that most of the contractile changes are a direct consequence of changes in excitation-contraction coupling alone.

Arterial hypertension produces changes along the vascular tree. However, there are few reports on its effect on human muscle capillaries. This study demonstrates the effects of essential hypertension on the capillaries of human quadriceps muscle.Muscle biopsy was taken from quadriceps femoris in eight men with recent diagnosis of essential hypertension, without treatment. Biopsies were also taken from eight normotensive men and were used as controls. Fiber types were classified by ATPase reaction, capillaries counted in ␣-amylase-PAS stained sections and ultrastructure studied by conventional methods of transmission electron microscopy.No changes were found in capillaries or muscle fiber types by histochemical methods. However, electron microscopy revealed abnormal capillaries with endothelial cells infoldings into the lumen, as well as occluded or degenerated capillaries. In some cases the endothelial cell area covered by pericytes was increased. Basement membrane of capillaries was frequently increased in width, sometimes irregularly, and in other instances it was reduplicated. In transversely sectioned capillaries lumen diameter was reduced and wall thickness was increased, although total diameter was unchanged.In hypertensive patients the finding of some degenerated capillaries adjacent to muscle fibers could be interpreted as the beginning of a process of rarefaction. Some capillaries showed morphological changes, and the ratio wall thickness/lumen was increased. Anat Rec 256: 425-432, 1999. 1999 Wiley-Liss, Inc.

Rat soleus muscles were denervated and stimulated in vivo for periods of up to 104 days. Stimuli used were trains of 1 ms pulses at 100 Hz delivered for periods of 1 s; trains were repeated every 10-100 s. In a majority of animals the tension of the muscles was maintained at about 10% of normal, equivalent to muscles denervated but unstimulated for 20 days. At the longest periods the stimulated muscles developed ten times more tension than ones that were denervated but not stimulated. In denervated and denervated-stimulated muscles twitch contraction and relaxation times were prolonged, compared with controls, for up to 3 weeks. Thereafter both sets showed a speeding of the isometric twitch that was greater in the stimulated muscles. At the longest periods the twitch was as short as that of a denervated fast muscle. Stimulation did not affect contralateral denervated muscles. Twitch: tetanus ratios remained high despite stimulation, and muscles showed little post-tetanic potentiation. Tension developed more rapidly in the tetani of the stimulated muscles, even allowing for larger final values. Maximum velocity of shortening was increased in many of the stimulated muscles, and there was a proportional flattening of the force-velocity curve, i.e. a/P 0 increased. Maximum velocity and a/P 0 increased reciprocally with twitch time to peak, so that those muscles that had twitches most changed by stimulation also had their isotonic properties modified to the greatest extent. Even at the longest period of stimulation, twitch time course and tetanic tension were not converted to those of normal fast muscle.

The damage to skeletal muscle capillaries in advanced Chagas' disease (stages II and III) was investigated in the vastus lateralis muscle of six patients and compared to that of six normal subjects. Capillaries were visualized by the PAS-amylase reaction and muscle fibres were classified by the ATPase histochemical method. Transmission electron microscopy was used to look for capillary alterations. The capillary-to-fibre ratio and number of capillaries adjacent to type I and type IIa fibres were decreased in the patient group. At the ultrastructural level, all patients showed capillary abnormalities, mainly basement membrane thickening and reduplication, capillary occlusion, proliferative endothelial cell cytoplasm with dense bodies, large vacuoles, altered mitochondria and prominent rough endoplasmic reticulum, as well as pericyte abnormalities. Capillary alterations are similar to those in patients affected by autoimmune diseases, suggesting an autoimmune component in the chronic phase of this disease. The reduction in capillarity may contribute to altered muscle performance in these patients.

suMMARyBrown widow spider (Latrodectus geometricus) venom (BrWSV) produces few local lesions and intense systemic reactions such as cramps, harsh muscle pains, nausea, vomiting and hypertension. Approximately 16 protein bands under reducing conditions and ~ 14 bands under non-reducing conditions on a 12.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis were observed. Neurotoxic clinical manifestations were confirmed in vivo, while proteolytic activity was demonstrated on gelatine film. Severe ultrastructural damages in mice skeletal muscles were observed at 3, 6, 12 and 24 h postinjection with at total of 45 µg of venom protein. Infiltration of eosinophils and ruptures of the cellular membranes were observed in the muscles along with swelling of the nuclear cover and interruption of the collagen periodicity. Altered mitochondrias and autophage vacuoles, nuclear indentation and mitochondria without cristae, slight increment of intermyofibrillar and subsarcolemic spaces and myelinic figures formation were also observed. In the capillary, endothelial membrane unfolding into the lumen was noticed; along with myelinic figures compatible with a toxic myopathy. Swollen sarcotubular systems with lysis of membrane, intense mitochondria autophagia and areas without pinocytic vesicles were observed. Swollen mitochondria surrounded by necrotic areas, myofibrillar disorganization and big vacuolas of the sarcotubular system, degenerated mitochondrium with formation of myelinic figure was seen. Glycogenosomes with small particulate, muscle type glycogen was noticed. Autophagic vacuole (autophagolysosomes) and necrotic areas were also noticed. These damages may be due to interactive effects of the multifactorial action of venom components. However, Latrodectus geometricus venom molecules may also be utilized as neuro therapeutic tools, as they affect neuronal activities with high affinity and selectivity. To our knowledge, the present study is the first ultrastructural report in the literature of muscle injuries and neurological and proteolytic activities caused by BrWSV.