Novelli Gp

Spin-trappers and vitamin E prolong endurance to muscle fatigue in mice

The involvement of free radicals in endurance to muscle effort is suggested by experimental and clinical data. Therefore, experiments have been performed to observe the effect of trapping free radicals on endurance to swimming in mice. Animals were injected intraperitoneally with each of three spin-trappers [N-tert-Butyl-alpha-Phenyl-Nitrone (PBN),alpha-4-Pyridyil-1-Oxide-N-tert-Butyl-Nitrone (POBN) and 5,5-Dimethyl-1-Pirrolyn-N-Oxide (DMPO): 0.2 ml of 10(-1) molar solution]. Each mouse was submitted to a swimming test to control resistance to exhaustion a) without any treatment, b) after administration of each spin-trapper in a random order c) after saline. Control experiments were performed with saline and with vitamin E. Endurance to swimming was greatly prolonged by pretreatment with all the spin-trappers (DMPO less than 0.0001; POBN less than 0.0001; PBN less than 0.001) and with Vitamin E. Experiments state that compared to treatment with spin-trappers or Vitamin E, administration of saline alone did not enhance time to exhaustion so that the increase in time to exhaustion with the various free radical scavengers was not the effect of training. Therefore, free radicals could be considered as one of the factors terminating muscle effort in mice.

Vitamin E protects human skeletal muscle from damage during surgical ischemia-reperfusion.

PURPOSE The biochemical and morphological alterations induced in lower limb skeletal muscle by ischemia-reperfusion (I-R) during aortic surgery and the effect of vitamin E pretreatment were investigated. METHODS Two groups of patients undergoing aortic aneurysm resection, one untreated and one treated with vitamin E, were examined. Quadricep muscle biopsies were taken after induction of anesthesia, at the end of ischemia, and after reperfusion. The malondialdehyde (MDA) content and morphology of biopsies were examined to assess peroxidative processes. RESULTS Ischemia did not induce an increase in MDA content but did increase neutrophil infiltration in muscle fibers of untreated patients. Reperfusion led to a significant increase in MDA content and to intermyofibrillar edema and mitochondrial swelling. The MDA content was not increased during ischemia and neutrophil infiltration was minimal in vitamin E treated patients. At reperfusion, the MDA content, the ultrastructural injuries and neutrophil infiltration were significantly reduced by the treatment. CONCLUSIONS Vitamin E is effective in reducing the oxidative muscle damage occurring after a period of I-R.

Exogenous glutathione increases endurance to muscle effort in mice

Many data suggest an involvement of toxic oxygen radicals in the termination of endurance to muscle fatigue. Being reduced glutathione (GSH), an efficient intracellular physiological antioxidant, experiments have been performed to discover whether exogenous GSH modifies endurance to exhaustive swimming in mice. GSH was administered to mice as a single dose (250, 500, 750 or 1000 mg/kg i.p.) or as repeated doses (250 mg/kg i.p. once a day during 7 days) 10 min before a swimming test to exhaustion. GSH 500, 750 and 1000 mg/kg, increased endurance to swimming by respectively 102.4%, 120.0% and 140.7%. GSH 250 mg/kg did not affect endurance when injected in a single dose but increased it by 103.7% when injected once a day for 7 days.

Neutrophils as mediators of human skeletal muscle ischemia-reperfusion syndrome

Nine patients with aortic aneurysm undergoing arterial reconstruction with temporary aortic occlusion were studied. Since a typical condition of ischemia-reperfusion of the muscles of the lower limbs was created during this surgery, muscle biopsies from the right femoral quadriceps as well as blood samples from the homolateral saphenous vein were taken: (1) before clamping of the aorta, (2) just before declamping, and (3) 30 minutes after reperfusion. Light microscopy revealed a consistent granulocyte infiltration in the ischemic and reperfused skeletal muscle. Ultrastructural damage to the muscle fibers was seen during ischemia and became more severe upon reperfusion. The recruitment of granulocytes into the muscle tissue paralleled the activation of the blood complement system and an increase in circulating neutrophils. Although a spontaneous superoxide anion (O2-) generation from such granulocytes cannot be proved, upon stimulation with formyl-methionyl-leucyl-phenylalanine neutrophils showed a reduced ability in O2 free radical production at the end of ischemia and enhanced O2- generation at reperfusion as compared with the controls. All these findings indicate an active role of granulocytes in the genesis of reperfusion-induced tissue injuries.

Expression of E-Selectin in Ischemic and Reperfused Human Skeletal Muscle

This work was undertaken to assess the role of endothelial E-selectin in the development of neutrophil accumulation into the ischemic and reperfused human skeletal muscle and eventually in the genesis of ischemia-reperfusion syndrome. Twelve patients affected by abdominal aortic aneurysm who were undergoing reconstructive vascular surgery were studied. Muscle biopsies from the right femoral quadriceps were taken (1) immediately after anesthesia, as control samples, (2) before declamping the aorta, as ischemic samples, and (3) 30 minutes after reperfusion and then processed for immunohistochemical and ultrastructural analysis. Immunohistochemistry revealed a strong positive reaction for E-selectin on the venular endothelium during ischemia and reperfusion. Ultrastructural investigation showed that reactivity for E-selectin matched neutrophil accumulation of the skeletal muscle tissue. This phenomenon was dependent upon a complex series of events that included neutrophil adhesion to the inner surface of the postcapillary venules, passage through endothelial intercellular junctions, and migration distally into the interstitial spaces of the skeletal muscle tissue. Neutrophil tissue infiltration was also associated with ultrastructural signs of tissue damage at reperfusion. This is in agreement with accumulating evidence indicating a role for tissue infiltrating neutrophils in the genesis of toxic O2 free radicals. Our data suggest that E-selectin expression on the vascular endothelium of human skeletal muscle may represent a key regulatory point in the process of neutrophil tissue accumulation and indicate an active role for the venular endothelium in the development of human ischemia-reperfusion syndrome.

The Role of Splancnic Adrenergic Vasoconstriction in the Development of Irreversibility of Hemorrhagic Shock

In the indefinite picture of the hypoteses related to the pathogenetic events of experimental shock and its irreversibility, some Authors give particular importance to the effects of bacterial endotoxins and to their deficient detoxification from reticuloendothelial system (RES).

Free Radicals and Circulatory Shock

Circulatory shock is a severe pathologic state caused by several agents (trauma, sepsis, surgery, etc.) and characterized by diffuse tissue hypoperfusion and ischemic damage. The search for mediator/s of circulatory shock is relevant, as they are thought to be identical to those of all ischemia-related conditions.

Liver function following hypovolemic hypotension in rats anaesthetized with halothane or enflurane.

Rats which had approximately 25-30% of their calculated blood volume removed were exposed to halothane (1%) or enflurane (2%) in 33% oxygen for 30 min. Hepatic function was evaluated by determining, at various time intervals, serum activities of glutamic-oxalacetic and glutamic-pyruvic transaminase, acid phosphatase and gamma-glutamyl-transpeptidase. In this model serum enzyme activities and animal mortality were significantly increased when hypovolemic hypotension was induced during halothane anaesthesia. The same events did not occur in bleeding animals anaesthetized with enflurane. The marked disparity in hepatic dysfunction and mortality between halothane and enflurane-anaesthetized rats during hypovolemic hypotension may be explained by the more pronounced decrease of oxygen available for the liver and production of reductive toxic intermediates in animals exposed to halothane.

The activity of microsomal enzymatic system as a limiting factor upon the effects of althesin, a new intravenous steroid anaesthetic,

Abstract The effects of Althesin (a new steroid intravenous anaesthetic which undergoes a rapid glucuronoconjugation) on sleeping time and circulation were studied in rats, in which the glucuronyl-transferase activity had been increased (with phenobarbital) or depressed (with ethionine). Induction of the enzymatic activity reduces the effects of Althesion, whereas its depression lenghtens them.