Local Muscle Tissue Research Articles

Training in hypoxia and its effects on skeletal muscle tissue

It is well established that local muscle tissue hypoxia is an important consequence and possibly a relevant adaptive signal of endurance exercise training in humans. It has been reasoned that it might be advantageous to increase this exercise stimulus by working in hypoxia. However, as long-term exposure to severe hypoxia has been shown to be detrimental to muscle tissue, experimental protocols were developed that expose subjects to hypoxia only for the duration of the exercise session and allow recovery in normoxia (live low-train high or hypoxic training). This overview reports data from 27 controlled studies using some implementation of hypoxic training paradigms. Hypoxia exposure varied between 2300 and 5700 m and training duration ranged from 10 days to 8 weeks. A similar number of studies was carried out on untrained and on trained subjects. Muscle structural, biochemical and molecular findings point to a specific role of hypoxia in endurance training. However, based on the available data on global estimates of performance capacity such as maximal oxygen uptake (VO2max) and maximal power output (Pmax), hypoxia as a supplement to training is not consistently found to be of advantage for performance at sea level. There is some evidence mainly from studies on untrained subjects for an advantage of hypoxic training for performance at altitude. Live low-train high may be considered when altitude acclimatization is not an option.

Inhibiting nitric oxide overproduction during hypotensive sepsis increases local oxygen consumption in rat skeletal muscle*

Although nitric oxide (NO) is a known regulator of cardiovascular function, the effect of NO overproduction during sepsis on capillary oxygen transport and local tissue oxygen consumption is not well understood. The objectives of this study were to determine whether sepsis-induced NO overproduction increased capillary stopped-flow and modulated tissue oxygen consumption in skeletal muscle. Prospective, controlled laboratory study. Animal laboratory in a university-affiliated research institute. Male Sprague-Dawley rats, 165-180 g body weight. Rats were made septic by cecal ligation and perforation (CLP) and were then ventilated and volume resuscitated (saline). The hind limb extensor digitorum longus (EDL) skeletal muscle was blunt dissected for in vivo microvascular imaging. The inducible NO synthase (iNOS) inhibitor L-N6-(1-iminoethyl)lysine dihydrochloride (L-NIL) was infused (3 mg/kg body weight per hour) starting 1 hr post-CLP to maintain arterial blood and EDL tissue NO(x)(-) (NO2(-) + NO3(-)) at baseline. Red blood cell hemodynamics, hemoglobin oxygen saturation, capillary geometry, and functional capillary density information were used to calculate capillary oxygen flux (the rate of oxygen diffusion from capillary to tissue) and indices of local oxygen delivery and tissue oxygen consumption. Over the first 5 hrs of septic injury, mean arterial pressure decreased while capillary stopped-flow and capillary oxygen flux both increased (p < .05). Inhibiting iNOS/NO overproduction partially restored mean arterial pressure and increased arterial pH. Within the microcirculation, inhibiting NO increased capillary red cell velocity and increased local tissue oxygen consumption (p < .05). Inhibiting NO failed, however, to prevent capillary stopped-flow. During the onset of sepsis, concurrent with the onset of microvascular dysfunction, there is an iNOS/NO-mediated reduction in local skeletal muscle tissue oxygen consumption.

Effects of 30 versus 60 min of low-load work on intramuscular lactate, pyruvate, glutamate, prostaglandin E2 and oxygenation in the trapezius muscle of healthy females

The aim of this study was to investigate the effects of duration of low-load repetitive work on intramuscular lactate, pyruvate, glutamate and prostaglandin E(2) (PGE(2)), and oxygen saturation in the trapezius muscle. Twenty healthy females were studied during baseline rest, during low-load repetitive work for either 30 (REP 30) or 60 min (REP 60) and 60 min recovery. Intramuscular microdialysate (IMMD) samples were obtained, and local muscle tissue oxygenation (%StO(2)) assessed with near-infrared spectroscopy (NIRS). Subjects rated their perceived exertion (Borg CR-10 scale) and capillary blood was sampled for lactate analysis. The results showed a significant increase in IMMD lactate in response to both REP 30 and REP 60 (P < 0.05 and P < 0.01, respectively) and glutamate (P < 0.0001), but no progressive increase with increasing work duration. Both IMMD pyruvate and lactate tended to be significantly increased during the recovery period. No corresponding increase in blood lactate was found. Local muscle %StO(2) did not change significantly in response to work and was not correlated to the IMMD lactate concentration. The ratings of perceived exertion increased in response to work, and remained increased after recovery for REP 60. In conclusion, the results of this study show significantly increased IMMD lactate and, glutamate concentrations in the trapezius muscle of healthy females in response to low-load work, but no progressive increase with increased work duration. Further, they do not indicate that the increased IMMD lactate concentration was caused by a locally decreased or insufficient muscle tissue oxygenation.

Excretion of resorption products from bioactive glass implanted in rabbit muscle

Bioactive glass granules were implanted in the paraspinal muscle of rabbits to determine the pathway of the silicon released from bioactive glass in vivo. We traced and quantified the silicon released by obtaining 24-h urine and blood samples for up to 6 months after implantation. Furthermore, local muscle tissue as well as the following organs were resected for chemical and histopathological analyses: brain, heart, kidney, liver, lung, lymph nodes, spleen, and thymus. The urinary silicon of the group with implanted granules was significantly higher than in the sham-operated, control group. The average excretion rate was 2.4 mg/day, and as such, 100% of the implanted silicon was excreted in 19 weeks. No elevated concentrations of silicon were found at the implant sites or in the other organs at sacrifice, that is, 24 weeks. The histological appearance of all organs was normal throughout. The concentrations of silicon measured in the urine were well below saturation and because no significant increase in silicon was found in any organ, including kidney, the increased silicon excretion rate was within the physiological capacity of rabbits. Therefore, it can be concluded that the resorbed silica gel is harmlessly excreted in soluble form through the urine.

Antithrombin III pretreatment reduces neutrophil recruitment into the lung and skeletal muscle tissues in the rat model of bilateral lower limb ischemia and reperfusion: a pilot study*

Anti-inflammatory action of Antithrombin III (AT III) is still not well understood in ischemia/reperfusion (I/R) injury. In the present study, we aimed to investigate the anti-inflammatory action of AT III on remote lung and local skeletal muscle tissue injury in a rat model of bilateral lower limb I/R model. Bilateral lower limb ischemia and reperfusion were produced by means of tourniquets occlusions and releases, respectively. Three groups of rats were used in this controlled study: sham group (sham, n=3) underwent 5 h of anesthesia only; control group (I/R, n=7) underwent 3 h of bilateral lower limb ischemia followed by 2 h of reperfusion; and AT III pretreated group (I/R-AT III, n=6) underwent the same procedure as the control group, but also received i.v. 250 U kg-1 AT III 30 min before ischemia induction under midazolam and fentanyl anesthesia. Lung and muscle tissue accumulation of polymorphonuclear leukocytes (PMN) were assessed by measuring tissue myeloperoxidase (MPO) activity. Histopathological changes in tissues were assessed by PMN counts in the lung, and muscle tissues and by histological lung injury score. Plasma 6-keto prostaglandin F(1alpha) and tumor necrosis factor alpha levels were measured by an enzyme immunoassay technique. Myeloperoxidase activity could not be detected in the muscle tissues of all groups. The lung and muscle tissue PMN counts in the I/R group were significantly higher compared with the I/R-AT III group (P<0.05). Data from the present study provides some evidence that AT III pretreatment attenuates remote lung and local skeletal muscle tissue injury caused by lower limb I/R.

Po‐Poster ‐ 34: Diffusion tensor imaging in the human calf muscle as a measure of the muscle disorder

The diffusion tensor imaging (DTI) is a method for the evaluation of water diffusion in organized tissues. In muscles the diffusion of water is expected to be anisotropic. It is hypothesized that diffusion is larger along muscle fibers compared to that across fibers. From a series of diffusion weighted images the diffusion tensor can be calculated. The obtained eigenvalues and eigenvectors of this tensor provide information about local muscle tissue anisotropy. The aim of this study was to determine whether DTI is a suitable method to characterize the extent of human calf muscle injuries such as tears, and the difference between immediate post‐exercise and at rest skeletal muscle. The data were collected using a GE‐3.0T shortbore scanner with a standard knee coil. Four subjects were investigated: one patient with chronic compartment syndrome affecting the posterior compartment of the calf, one patient with clinically apparent acute medial gastrocnemius tear, and two healthy volunteers. The diffusion anisotropy of water was characterized by the fractional anisotropy. The diffusion images demonstrate the anisotropy of the diffusion and the large contrast arising from the different orientations of the cells in the muscle tissue. The calculated eigenvalues of the diffusion tensor reflects the strong anisotropic character of the muscle tissue. The results of the fiber tractography method demonstrate disorder as expected for the muscle tear, while the healthy muscle shows the ordering in the fibers. As a conclusion, DTI and fibre tracking may be suitable techniques for analyzing skeletal muscle damage and evaluating lesion extent.

Application of near infrared spectroscopy to exercise sports science.

Over the past 15 years the use of near infrared spectroscopy in exercise and sports science has increased exponentially. The majority of these studies have used this noninvasive technique to provide information related to tissue metabolism during acute exercise. This has been undertaken to determine its utility as a suitable tool to provide new insights into the heterogeneity and regulation of local tissue metabolism, both in cerebral and skeletal muscle tissue. In the accompanying articles in this symposium, issues related to the principles, techniques, limitations (Ferrari et al., 2004), and reliability and validity of NIRS in both cerebral and skeletal muscle tissue (Bhaambhani, 2004), mostly during acute exercise, have been addressed and will not be discussed here. Instead, the present paper will focus specifically on the application of NIRS to exercise sports science, with an emphasis on how this technology has been applied to exercise training and sport, and how it can be used to design training programs for athletes.

Efficiency of small-volume resuscitation in restoration of disturbed skeletal muscle microcirculation after soft-tissue trauma and haemorrhagic shock.

Despite advances in primary care, trauma in conjunction with shock remains the leading cause for morbidity and mortality of young adults in western countries. Herein, we report on the efficiency of small-volume resuscitation to improve compromised perfusion of traumatised skeletal muscle tissue in shock. In pentobarbital anaesthetised, mechanically ventilated rats, closed soft-tissue trauma of the right hind limb was induced, followed by induction of haemorrhagic shock [mean arterial blood pressure (MAP) 40 mmHg for 1 h]. For resuscitation, animals received saline (four-times the shed blood volume/20 min), 10% hydroxyethyl starch (HES) 200/0.5 (equal to shed blood volume/5 min) or 7.2% sodium chloride/6% hydroxyethyl starch 200/0.5 (HyperHES; 10% of shed blood volume/2 min). At 2 h of resuscitation, traumatised skeletal muscle tissue was analysed by in vivo microscopy. Non-resuscitated animals served as shock controls. Despite incomplete restoration of systemic blood pressure, HyperHES was superior to saline, but not to HES, with respect to amelioration of nutritive perfusion. Inflammatory cell response within the traumatised skeletal muscle tissue escaped from the anti-adhesive properties of HyperHES when applied for resuscitation from hypovolaemic shock, and did not differ from values in HES-treated and saline-treated animals. Resuscitation with HyperHES is as effective as HES in improving capillary perfusion in traumatised skeletal muscle during haemorrhagic shock. However, because values of functional capillary density in the HyperHES-treated and HES-treated animals were still markedly below those reported in traumatised skeletal muscle of normovolaemic animals, further tools are needed to enhance efficiency in treatment of local skeletal muscle tissue injury during haemorrhagic shock.

Tissue Tolerance of Diclofenac Sodium Encapsulated in Liposomes After Intramuscular Administration

ABSTRACTIn this work the effect of the encapsulation of diclofenac sodium within liposomes on the reduction of the myotoxicity after intramuscular administration in rats was studied. Diclofenac sodium was encapsulated in small unilamellar liposomes obtained from phosphatidylcholine, cholesterol, and α-tocopherol (40:10:0.04 mM), and administered by intramuscular injection in the quadriceps femoral muscle of male Wistar rats. After a single dose of 0.2 mg diclofenac formulations the local tissue damage was assessed by plasma creatine kinase (CPK) activity and histological analysis. It was demonstrated that formulations containing free diclofenac produced a higher increase in CPK activity, while those encapsulated in liposomes exhibited CPK activity similar to the control groups. Histopathological analysis of local muscle tissue performed on the third and seventh days following the injection showed intense cellular damage when free drug solution was used, while encapsulation in liposome protected the tissue against the local tissue inflammation.

Naked DNA vaccination differentially modulates autoimmune responses in experimental autoimmune encephalomyelitis

Vaccination with naked DNA represents a therapeutic strategy currently under consideration in multiple sclerosis (MS). In this study, we tested the potential therapeutic effect of vaccination with a naked DNA construct encoding proteolipid protein (pRc/CMV-PLP) upon the outcome of subsequent sensitization for experimental autoimmune encephalomyelitis (EAE) actively-induced in SJL mice with PLP139–151 peptide in adjuvant. Intramuscular vaccination with the naked DNA pRc/CMV-PLP construct led to PLP expression in local muscle tissue that persisted for about 8 weeks. Early sensitization for EAE (4 weeks after DNA vaccination) caused recipient mice to develop a severe, exacerbated form of disease (in comparison to control mice), while late sensitization (>10 weeks) resulted in a milder, ameliorated form. In the groups sensitized <10 weeks post-DNA vaccination with pRc/CMV-PLP induction of a Th1-type cytokine response was noted. In contrast, sensitization >10 weeks post-DNA vaccination led to peripheral tolerance as evidenced by a decrease in T cell proliferation and cytotoxic T cell response, no Th2 response, and no increase in apoptosis. These data are novel in that they demonstrate a differential effect of DNA vaccination and have important implications for its use as a mechanism to enhance or modulate immune reactivity.

Removal Pathway of Bioactive Glass Resorption Products from the Body

AbstractWe traced and quantified the silicon released from bioactive glass (BG) granules in vivo (45S5, 300–355 μm). 1500 mg of BG granules were implanted in the paraspinal muscle of 7 four kg rabbits. Blood samples and 24-hour urine samples were obtained over a 24 week period. Local muscle tissue as well as the following organs were harvested for chemical and histological analyses: brain, heart, kidney, liver, lung, lymph nodes, spleen, and thymus. Flame atomic absorption spectrophotometry was used to measure the concentration of elemental silicon in all the samples after digestion. Tissues and fluids from a sham group of 7 rabbits (underwent surgical procedure but received no implants) were obtained in a similar manner.The urinary silicon of the implanted group was significantly higher than in the control group. From the data, the calculated average excretion rate was approximately 2.4 mg/day, and as such, 100 percent of the implanted silicon was excreted in 19 weeks. No elevated concentrations of silicon were found at the implant site or in the other organs after 24 weeks. Histological appearance of all major organs was normal for all animals in the study.The concentrations of silicon measured in the urine were well below saturation and since no significant increase in silicon was found in the kidney or in the other organs, the increased silicon excretion rate was within the physiological capacity of rabbits. Therefore, it can be concluded that the resorbed silica gel is harmlessly excreted in soluble form through the urine.

Significance of injection solution temperature on local muscle tissue damage in pigs.

Pharmacology & ToxicologyVolume 82, Issue 6 p. 301-303 Free Access Significance of Injection Solution Temperature on Local Muscle Tissue Damage in Pigs Ove Svendsen, Ove Svendsen Department of Pharmacology and Pathobiology, The Royal Veterinary and Agricultural University, DK–1870 Frederiksberg C, DenmarkSearch for more papers by this authorHenrik Bo Hansen, Henrik Bo Hansen Department of Pharmacology and Pathobiology, The Royal Veterinary and Agricultural University, DK–1870 Frederiksberg C, DenmarkSearch for more papers by this authorKarin Damm Jørgensen, Karin Damm Jørgensen Department of Pharmacology and Pathobiology, The Royal Veterinary and Agricultural University, DK–1870 Frederiksberg C, DenmarkSearch for more papers by this author Ove Svendsen, Ove Svendsen Department of Pharmacology and Pathobiology, The Royal Veterinary and Agricultural University, DK–1870 Frederiksberg C, DenmarkSearch for more papers by this authorHenrik Bo Hansen, Henrik Bo Hansen Department of Pharmacology and Pathobiology, The Royal Veterinary and Agricultural University, DK–1870 Frederiksberg C, DenmarkSearch for more papers by this authorKarin Damm Jørgensen, Karin Damm Jørgensen Department of Pharmacology and Pathobiology, The Royal Veterinary and Agricultural University, DK–1870 Frederiksberg C, DenmarkSearch for more papers by this author First published: 25 March 2009 https://doi.org/10.1111/j.1600-0773.1998.tb01577.xCitations: 1 Ove Svendsen, Department of Pharmacology and Pathobiology, The Royal Veterinary and Agricultural University, DK–1870 Frederiksberg C, Denmark (fax +45 35313114). AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume82, Issue6June 1998Pages 301-303 ReferencesRelatedInformation

Tibialis anterior turnover flap coverage of exposed tibia in a severely burned patient

A case report of a longitudinally split tibialis anterior turnover flap reconstruction of an exposed tibia in a burn patient is presented here. The patient had sustained deep partial- and fullthickness burns to 70 per cent of his total body surface area (TBSA), resulting in an exposed left patella and upper two-thirds of the left tibia. Although full thickness loss of skin occurred on the left lower leg, no muscle trauma was sustained. Reconstruction was therefore deemed possible using local muscle tissue to provide transposed flap coverage. A gastrocnemius muscle flap was used to cover the exposed patella and superior aspect of the tibia. A portion of the tibialis anterior muscle was split longitudinally and turned over medially to cover the remaining exposed tibia. The advantages offered by this infrequently used flap include technical simplicity, reliability, minimal donor site dysfunction and the allowance of future use of the soleus flap. The tibialis anterior turnover flap may therefore have wide applicability for reconstruction of the severely burned lower extremity.

Muscle Toxicity of Diatrizoate and Iohexol in Rabbits

The potential tissue irritating effect of diatrizoate and iohexol was studied by injecting the contrast media into the right longissimus dorsi muscle of rabbits. The left muscle served as control. The animals were sacrificed 3 days after the injection, at which time muscle tissue was examined for macroscopic changes and loss of the muscle enzyme creatine kinase (CK) from the injection site was determined. An irregular area of necrotic muscle tissue and a hemorrhage was found at the injection site in rabbits given diatrizoate, whereas iohexol only caused hemorrhage. The local loss of CK activity following diatrizoate (0.64 g muscle tissue) was statistically significantly greater than following iohexol (0.18 g muscle tissue). It is concluded that this model seems to be useful for identification of the irritating potential of contrast media. It is also concluded that diatrizoate caused more damage to the local muscle tissue than iohexol.

The effect of unilateral isokinetic strength training on local adipose and muscle tissue morphology, thickness, and enzymes

One-leg exercise of 5 weeks duration in 10 healthy middleaged women resulted in a significant increment of muscle force in the exercising leg and in a less, but at some angular velocities also significant, increase in the nonexercising leg. The thickness of subcutaneous tissue measured by ultrasound and skinfold caliper decreased, while muscle thickness increased in the exercising leg only. The increased thickness of muscle tissue was associated with an increase in the relative number and relative fiber area of type II fibers in the exercising leg. The mean fiber area of type IIB fibers increased significantly as well as the activity of lactate dehydrogenase and myokinase. The decrease of thickness of subcutaneous adipose tissue was not associated with a significant decrease in fat cell size and was probably due to geometrical factors secondary to hypertrophy of the underlying muscle. It is concluded that the relationship between lean and fat components of the human thigh is significantly influenced by changes in the activity of the thigh skeletal muscles, but a local dynamic strength training program can hardly be used for local emptying of the fat depot over the exercising muscles.

Lactate dehydrogenase activity in muscle after prolonged severe exercise in man.

ArticleLactate dehydrogenase activity in muscle after prolonged severe exercise in man.J Karlsson, B Diamant, and B SaltinJ Karlsson, B Diamant, and B SaltinPublished Online:01 Jul 1968https://doi.org/10.1152/jappl.1968.25.1.88MoreSectionsPDF (758 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByPATHOPHYSIOLOGICAL A SPECTS OF OLIGOELEMENT SUPPLEMENTATION IN A THLETES15 March 2018 | Acta Medica Medianae, Vol. 57, No. 2Lactate oxidation in human skeletal muscle mitochondriaRobert A. Jacobs, Anne-Kristine Meinild, Nikolai B. Nordsborg, and Carsten Lundby1 April 2013 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 304, No. 7Effects of High-Intensity Training and Resumed Training on Macroelement and Microelement of Elite Basketball Athletes22 April 2012 | Biological Trace Element Research, Vol. 149, No. 2Plasma trace elements levels are not altered by submaximal exercise intensities in well-trained endurance euhydrated athletesJournal of Trace Elements in Medicine and Biology, Vol. 25Magnesium, zinc, and chromium nutriture and physical activityThe American Journal of Clinical Nutrition, Vol. 72, No. 2Lactate as a fuel for mitochondrial respiration5 April 2002 | Acta Physiologica Scandinavica, Vol. 168, No. 4Skeletal muscle energy substrates, metabolic products and enzyme activity in infants with symptomatic ventricular septal defectActa Paediatrica, Vol. 85, No. 11Serum lactate dehydrogenase and creatine kinase during marathon training.British Journal of Sports Medicine, Vol. 19, No. 3MUSCLE SUBSTRATE LEVELS, MUSCLE ENZYME ACTIVITIES AND MUSCLE MORPHOLOGY IN THE VASTUS LATERALIS AND DELTOIDEUS MUSCLES IN NORMAL CHILDREN AND IN CHILDREN WITH COARCTATION OF THE AORTAActa Paediatrica, Vol. 72, No. 6Physiological Profiles of Two Champion Ultramarathoners11 July 2016 | The Physician and Sportsmedicine, Vol. 11, No. 5Blood lactate concentration following maximum exercise in trained subjects.British Journal of Sports Medicine, Vol. 15, No. 3Comparisons of muscle substrate levels, muscle enzyme activities and muscle morphology in arm and leg muscles in normal subjects and in patients operated upon for coarctation of the aorta in childhood8 July 2009 | Scandinavian Journal of Clinical and Laboratory Investigation, Vol. 41, No. 7The effect of unilateral isokinetic strength training on local adipose and muscle tissue morphology, thickness, and enzymesEuropean Journal of Applied Physiology and Occupational Physiology, Vol. 42, No. 4The Influence of Thoracic Epidural Analgesia on the Circulation at Rest and During Physical Exercise in ManActa Anaesthesiologica Scandinavica, Vol. 22, No. 5Effect of Physical Training on LDH Activity and LDH Isozyme Pattern in Human Skeletal MuscleActa Physiologica Scandinavica, Vol. 97, No. 2LDH Isozymes in Skeletal Muscles of Endurance and Strength Trained AthletesActa Physiologica Scandinavica, Vol. 93, No. 2Serum and Erythrocyte Zinc Concentrations After Prolonged Heavy ExerciseSubstrate Activation and Product Inhibition of LDH Activity in Human Skeletal MuscleActa Physiologica Scandinavica, Vol. 92, No. 1Human soleus muscle: A comparison of fiber composition and enzyme activities with other leg musclesPfl�gers Archiv European Journal of Physiology, Vol. 348, No. 3Changes in enzyme activities in smooth muscle after contractile activity in vitroInternational Journal of Biochemistry, Vol. 4, No. 22Percutaneous needle-biopsy of skeletal muscle in diagnosis and researchThe Lancet, Vol. 298, No. 7724Lactate in Working Muscles after Prolonged ExerciceActa Physiologica Scandinavica, Vol. 82, No. 1 More from this issue > Volume 25Issue 1July 1968Pages 88-91 https://doi.org/10.1152/jappl.1968.25.1.88PubMed4385564History Published online 1 July 1968 Published in print 1 July 1968 Metrics

STUDIES ON THE PATHOGENESIS OF RINDERPEST IN EXPERIMENTAL CATTLE. 3. PROLIFERATION OF AN ATTENUATED STRAIN IN VARIOUS TISSUES FOLLOWING SUBCUTANEOUS INOCULATION.

Twenty-five grade cattle were infected subcutaneously with 1040to 104·6TCD 50 of a highly-attenuated strain of rinderpest virus which is used as a vaccine. No clinical reaction was observed but the proliferation of virus was studied in twenty-two tissues harvested at daily intervals from the first to the 10th days after inoculation. Serum samples collected at the same times were examined for rinderpest-neutralizing antibody.There was an ‘eclipse’ phase of 3 days during which no infectivity could be demonstrated in any tissue. On the 4th day virus had generalized, as shown by its detection in lymphoid tissues which were not associated with the site of inoculation; occasional animals showed evidence of viral proliferation in the local muscle and subcutaneous tissue. A considerable growth of virus, with peak titres between 104·0and 105·0TDC50/g., was demonstrated in the prescapular, pharyngeal and mesenteric lymph nodes, also in the palatal tonsils and Peyer's patches of the ileum. Highest titres (105·4TCD50/g.) were recorded in the prescapular haemo-lymph nodes, but less virus (up to 103·4TCD50/g.) appeared in the spleen.A low-level viraemia was detected in eight of the thirteen cattle killed on the 5th to 8th days inclusive. Minimal quantities of virus were found on two occasions each in the bone marrow and lung. No virus was recovered from the mucosae of the base of the tongue, abomasum, ileum, caecum and colon; liver, heart, kidney and brain tissue also failed to support its multiplication.Neutralizing antibody was present in all cattle by the 10th day after inoculation, its appearance being associated with the abrupt decline in virus titres, which was usually demonstrable on the 8th day.The behaviour of the attenuated virus was compared with that of virulent strains, and it was concluded that its lack of pathogenicity was due primarily to its failure to proliferate in the mucosae of the gastro-intestinal and respiratory tracts. Vaccine virus was, in fact, exclusively ‘lymphotropic’, a characteristic which may account for the solid, lasting immunity it confers and for the considerable antibody response it provokes in inoculated cattle. Inability to spread by contact amongst susceptible cattle may be a result of the absence of virus in mucosae or parenchymatous organs and hence in excretions.