[Hypoxia and wound healing (author's transl)].
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Biomedical subjects
Publications and source records attributed to A Réffy.
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Ischemic-hypoxic changes in muscles with experimental tenotomy and human tendon ruptures have been examined. The so-called capillarization of the muscles is greatly reduced, following tendon injury and the accumulation of fibrous tissue is to be observed, around the muscle cells. The decreased blood supply and the elongation of the capillary muscle cell distance lead to hypoxic lesions (mitochondrial destruction, intramitochondrial calcification, accumulation of lysosomes etc.).
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The ultrastructural alterations in human liver cells have been studied in reversible acute hypoxia. After thoracic and/or craniocerebral injury, the arterial oxygen saturation was under 60 mm Hg, and the circulation was intact, in all 20 patients. The hepatic cells were characterized by depletion of glycogen, swelling of the mitochondria with some irregularity of their membranes, and swelling of the endoplasmic reticulum, as well as by the appearance of large hypoxic vacuoles.
The fibre composition of 5 hand and 3 arm muscles were investigated by histochemical methods. The hand muscles of the dominant side (right side by the right-handed and left side by the left-handed persons) had a significantly higher amount of type 2 fibre than type 1 fibre. In the same subjects the fibre composition of the 3 investigated arm muscles were practically the same on the dominant and on the non-dominant side. It is suggested that the different movements of the dominant hand causes the difference in the fibre ratio of the hand muscles, while the different mechanical demands did not influence the composition of the arm muscles.
The authors examined 119 tendons with light-, and 34 tendons with electron microscope, excised within 48 h after spontaneous rupture of tendon. By light microscopic study 9, and by electron microscopic examination 18 cases of calcifying tendinopathy could be detected. The calcification occurred without necrosis or inflammation. The authors concluded, that calcifying tendinopathy is a hypoxic alteration of the tendon.
Alterations in the capillary density of the M. biceps brachii was studied in 20 cases during 2 months after spontaneous rupture of the tendon. The fiber typing was done using succinic dehydrogenase and myofibrillar ATP-ase at pH 9.4 for the staining, the capillaries were visualized with alkaline phosphatase and PAS reactions, and in each case 1,000 muscle fibers with their capillaries were estimated. In the intact muscles the capillary count ranged from 1,500 to 1,910 (mean 1,740) per 1,000 fibers. During the 1st month following the rupture the decrease in the capillary count of the muscle occurred rapidly, being after 4-7, 8-10, and 18-29 days 36%, 52%, and 66%, respectively, as compared to the contralateral muscles. After 2 months a decrease of approx. 70% was found in the amount of capillaries compared with the contralateral muscles. The obliteration of the capillaries was particularly pronounced in the amount of anastomoses. These results indicate that the capillary supply of the human M. biceps brachii decreases enormously during the 1st month after a tenotomy.
The myocardial alterations were investigated in dogs after hemorrhagic hypotension. Development of metabolic acidosis with increased lactate concentration was observed in all cases. Focal hemorrhages and hypoxic changes developed in the subendocarial region. Typical so-called zonal lesions were demonstrable in the mural myocardium of both ventricles. The hypoxia, increased level of catecholamines, metabolic disturbances, and probably cardiotoxic products may play a role in the pathomechanism. The alterations which are potentially reversible are transformed into irreversible damage only in most severe cases. The necrosis is of hypercontraction type, and is associated with rapid calcification and mononuclear cell infiltration. The morphologic changes may explain the circulatory disturbances of cardiac origin and may represent the basis of development of the low cardiac output syndrome in hemorrhagic shock.
A series of non-progressive myopathies have been found (central core disease, centronuclear myopathy, myofibrillar dysproportion) when muscles of patients with spontaneous tendon ruptures were examined. Pathological muscle actions, uneven pulling force on the tendons, disturbances in the nervous feed-back between tendons and muscles and the role of myopathies in the alteration of resting and working muscle tone by affecting the type--I. muscle fibers are thought to be pathogenic factors in the spontaneous tendon ruptures associated with non-progressive myopathies.
The oxygen and carbon dioxide tension were studies with Silastic tonometer technique in skeletal muscle and subcutaneous tissue of rat. The high initial pO2 was caused by airborne contamination during implantation and declined rapidly. Tissue gas tensions measured with a Silastic tonometer reflect the healing sequences of implantation trauma and stable readings are not obtained until 14 days after implantation. After healing of implantation injury 42 to 47 mmHg pO2 and 50 to 57 mmHg pCO2 were measured in muscle and 23 to 26 mmHg pO2 and 51 to 57 mmHg pCO2 in subcutaneous tissue of rat.
The alterations of oxygen and carbon dioxide tensions in crush-injured muscles were determined by means of a Silastic-tonometer. Immediately after crush-injury the oxygen tension was elevated, then declined and 2 hours after trauma a value of 10 to 14 mmHg was reached. The oxygen tension was 8 to 15 mmHg the next four days after injury, from 5th day the tissue pO2 elevated rapidly. On 14th day the tissue oxygen tension was 60-72 mmHg, thereafter decreased gradually to 40-50 mmHg by the 19th day. The tissue pCO2 elevated within 2 hours after injury to 95-105 mmHg. From 5th day decreased gradually to 50 mmHg by the 21st day.
Ruptured liver injury was produced in dogs. For arresting the bleeding and for the tissue unifying GRF adhesive was used instead of the traditional wound treatment. The experiences obtained during the wound healing were positive. On the 4th week the adhesive was well markedly emerged from the liver surface, but on the 20th postoperative week the adhesive could not be noticed even by microscopy. The necrosis spread over 10-15 cell lines has nearly disappeared by the end of the 15th week. By this time the granulation tissue filling up the wound transformed into native connective tissue.
The authors determined the wear products in tissues following hip prostheses implantations in 40 cases. The interval between prostheses implantation and histochemical examinations varied from 3 weeks to 15 years. The authors found that on the inner layer of the neighbouring joint capsule immediate to the implant a metal-protein layer developed and cobalt, chrom, nickel particles were demonstrated later in the connective and scar tissues as well. In the connective and fat tissues around the hip prostheses (from 4 cm) cobalt and chrom, in the regional lymph nodes cobalt, chrom nickel and in some cases manganese particles were found. Bone cement and plastic materials were found in the joint capsule, in the bone marrow of the distal part of the femur, but they were not present in the lymph nodes.
The authors describe a new preparation technique for scanning electron microscopic study of the internal structure of skeletal muscle cells. The specimens were fixed, dehydrated and imbibed with Epon or Durcupan--without polymerisation--and thereafter they were freeze-fractured.
A tissue adhesive composed of gelatin-resorcinol-formaldehyde was prepared. The factors, influencing its properties were discussed and compared with other preparation methods. Incised rat skin wounds were unified with adhesive applied between the wound edges or on the wound surface. Sutured skin wounds served as controls. After a week, the skin wounds with adhesive on their surface had a tensile strength twice as much as the sutured wounds. The granulation tissue was narrow, scarcely was inflammation reaction, no formaldehyde necrosis occurred.
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The authors have studied the enzymhistochemical and ultrastructural pictures of tenocytes of adult human tendons. High succinate dehydrogenase, cytochrome oxidase, TPN-diaphorase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase activity were found, as indicated both oxidativ, anaerobic and pentose-phosphate shung activity. Phosphorylase and glutamate dehydrogenase activity was medial, lipase and alcaline phosphatase activity was slight. In tenocytes well developed rough endoplasmic reticulum and GOLGI apparatus, large amount of free ribosomes were found.
The authors studied the histochemical alterations of human skeletal muscles after tenotomy and after spontaneous rupture of the tendon. Both succinate dehydrogenase (in type I fibers), and myofibrillar ATP-ase (in type 2 fibers) activity was decreased in all injured muscles. In the intact antagonists and contralateral muscles alterations were not found. The creatine phosphokinase and aldolase activity were decreased also in injured muscles. The lactate dehydrogenase activity was various both in affected and in unaffected muscles. Two weeks or more after the injury of the tendon in injured muscles the number of type 1 fibers were decreased and therefore a mathematically significant type 2 fibre predominance occurred. Atrophy involve both type 1 and type 2 fibers, but type 1 fibre atrophy was more pronunced as type 2 fibre atrophy.