Defining the osteoarthritis patient: back to the future.

The history of osteoarthritis (OA) is important because it can help broaden our perspective on past and present controversies. The naming of OA, beginning with Heberden's nodes, is itself a fascinating story. According to Albert Hoffa, R. Llewellyn Jones and Archibald Edward Garrod, the name OA was introduced in the mid-nineteenth century by surgeon Richard von Volkmann who distinguished it from rheumatoid arthritis and gout. Others preferred the terms 'chronical rheumatism', 'senile arthritis', 'hypertrophic arthritis' or 'arthritis deformans'. A similar narrative applies to the concept of OA affecting the whole joint vs the 'wear-and-tear' hypothesis, inflammation and the role of the central nervous system (CNS). In the late nineteenth and early twentieth centuries, the Garrods (father and son) and Hermann Senator argued that OA was a whole joint disease, and that inflammation played a major role in its progression. Garrod Jnr and John Spender also linked OA to a neurogenic lesion 'outside the joint'. The remaining twentieth century was no less dynamic, with major advances in basic science, diagnostics, treatments, surgical interventions and technologies. Today, OA is characterized as a multi-disease with inflammation, immune and CNS dysfunction playing central roles in whole joint damage, injury progression, pain and disability. In the current 'omics' era (genomics, proteomics and metabolomics), we owe a great debt to past physicians and surgeons who dared to think 'outside-the-box' to explain and treat OA. Over 130 years later, despite these developments, we still don't fully understand the underlying complexities of OA, and we still don't have a cure.

Pulmonary function after hemorrhagic shock and resuscitation in a porcine model.

BACKGROUND: Hemorrhagic shock may trigger an inflammatory response and acute lung injury. The combination adenosine, lidocaine (AL) plus Mg(2+) (ALM) has organ-protective and anti-inflammatory properties with potential benefits in resuscitation.The aims of this study were to investigate: (1) pulmonary function and inflammation after hemorrhagic shock; (2) the effects of ALM/AL on pulmonary function and inflammation. METHODS: Pigs (38 kg) were randomized to: sham + saline (n = 5); sham + ALM/AL (n = 5); hemorrhage control (n = 11); and hemorrhage + ALM/AL (n = 9). Hemorrhage animals bled to a mean arterial pressure (MAP) of 35 mmHg for 90 min, received resuscitation with Ringer's acetate and 20 ml of 7.5% NaCl with ALM to a minimum MAP of 50 mmHg, after 30 min shed blood and 0.9% NaCl with AL were infused. Hemorrhage controls did not receive ALM/AL. Primary endpoints were pulmonary wet/dry ratio, PaO2 /FiO2 ratio (partial pressure of arterial oxygen to the fraction of inspired oxygen), cytokine and protein measurements in bronchoalveolar lavage fluid (BALF) and lung tissue, neutrophil invasion and blood flow in lung tissue. RESULTS: In the hemorrhage groups, wet/dry ratio increased significantly compared with the sham groups. PaO2 /FiO2 ratio decreased during shock but normalized after resuscitation. BALF did not indicate significant pulmonary inflammation, oxidative stress or increased permeability. Intervention with ALM caused a temporary increase in pulmonary vascular resistance and reduced urea diffusion across the alveolar epithelia, but had no effect on wet/dry ratio. CONCLUSION: Hemorrhagic shock and resuscitation did not cause acute lung injury or pulmonary inflammation. The question whether ALM/AL has the potential to attenuate acute lung injury is unanswered.

Physiological and metabolic effects of prophylactic treatment with the osmolytes glycerol and betaine on Bos indicus steers during long duration transportation.

The physiological and metabolic effects of prophylactic treatment with osmolytes were investigated using twenty-four 2.5-yr-old Bos indicus steers. Animals were allocated to 1 of 4 treatment groups: 1) control, feed and water deprived for 48 h (n = 6); 2) transported, transported for 48 h (n = 6); 3) glycerol, dosed with glycerol (2 g/kg of BW) and then transported for 48 h (n = 6); and 4) betaine, dosed with betaine (0.25 g/kg of BW) then transported for 48 h (n = 6). Body water, electrolytes, blood pH and gases, plasma lactate, glucose, albumin, total protein, anion gap, strong ion difference, total weak acids, and BW were determined at the conclusion of 24 and 48 h of transportation. The glycerol group had greater body water volumes than the control (P = 0.05) and transported (P = 0.02) groups. The glycerol, transported, and betaine groups had lower (P = 0.02) plasma Mg concentrations than the control group at 24 h, whereas the glycerol group maintained lower (P = 0.04) plasma concentrations of Ca than the control group. The betaine group had lower (P = 0.04) hematocrit than the control group at 24 and 48 h. Plasma bicarbonate and pCO2 were 13 and 17% greater (P = 0.01 and 0.04, respectively) in the glycerol group at 24 h compared with control and transported groups. However, the ratio of [HCO3]/[CO2] in the glycerol group did not differ from the other groups and thereby maintained pH. The glycerol group maintained a 30% greater (P < 0.001) plasma concentration of glucose than the control group, and 14% greater (P = 0.05) than the transported and betaine groups. In contrast, betaine had little effect on increasing blood glucose compared with glycerol. Glycerol-linked hyperhydration at 24 h may not only help to conserve water loss during long distance transportation, but the increased blood glucose may have an important protein-sparing effect due, in part, to greater insulin concentrations inhibiting the breakdown of muscle proteins, thus, countering the amino-acid mobilizing effect of cortisol after 24 h. Therefore, the osmolyte glycerol shows promise as a prophylactic treatment for attenuating the effects of long distance transportation by maintaining body water, decreasing the energy deficit, and preserving health and muscle quality.

31P NMR quantitation of phosphorus metabolites in rat heart and skeletal muscle in vivo.

The aim of this study was to examine two methods of 31P NMR quantitation of phosphocreatine (PCr), ATP, and P(i) in rat heart and skeletal muscle in vivo. The first method employed an external standard of phenylphosphonic acid (PPA; 10 mM), and the second method used an enzymatic measurement of tissue ATP equated to the area under the betaATP peak. With the use of the external standard, the concentrations of ATP, PCr, and P(i) in the rat heart were 4.48 +/- 0.33, 9.21 +/- 0.65, and 2.25 +/- 0.16 micromol/g wet wt, respectively. With the use of the internal ATP standard, measured on the same tissue, the contents (means +/- SE) were 4.78 +/- 0.19, 9.83 +/- 0.18, and 2.51 +/- 0.33 micromol/g wet wt, respectively (n = 7). In skeletal muscle, ATP, PCr, and P(i) were 6.09 +/- 0.19, 23.44 +/- 0.88, and 1.81 +/- 0.18 micromol/g wet wt using the PPA standard and 6.03 +/- 0.19, 23.30 +/- 1.30, and 1.82 +/- 0.19 micromol/g wet wt using the internal ATP standard (n = 6). There was no significant difference for each metabolite as measured by the two methods of quantification in heart or skeletal muscle. The results validate the use of an external reference positioned symmetrically above the coil and imply that each has similar NMR sensitivities (similar signal amplitude per mole of 31P between PPA and tissue phosphorus compounds). We conclude that PCr, ATP, and P(i) are nearly 100% visible in the normoxic heart and nonworking skeletal muscle given the errors of measurement.

Force reduction uncoupled from pH and H(2)PO(-)(4) in rat gastrocnemius in vivo with continuous 2-Hz stimulation.

The aim of this study was to examine the effect of the products of ATP hydrolysis on the fatigue process in rat gastrocnemius in vivo. Adult male Sprague-Dawley rats (300-400 g) were anesthetized and ventilated in a custom-built cradle fitted with a force transducer that could be placed into a 7-T NMR magnet. The muscle was stimulated continuously at 2 Hz for 20 min (n = 7). Isometric twitch force increased in the first 4 min of stimulation accompanied by changes in twitch duration (20% increase in relaxation time). Prolonged relaxation was associated with changes in cytosolic pH (6.91 to 6.58), lactate (1.8 to 12.6 micromol/g wet wt), and H(2)PO (7.57 to 13.99 mM). After 4 min, relaxation time, pH, lactate, and H(2)PO returned toward control values as twitch force progressively decreased. No correlation was found between force decline (or twitch broadening) and total phosphate (3 to 23 mM), free [ADP] (18 to 95 microM), free [Mg(2+)] (0.58 to 0.96 mM), or free energy of ATP hydrolysis (-65 to -55 kJ/mol). We conclude that force decline is not due to increased pH and/or H(2)PO but to fatigue of the fast-twitch fibers, possibly linked to glycogen depletion and/or failure of nerve impulse transmission in these fibers.

Simulated moderate altitude elevates serum erythropoietin but does not increase reticulocyte production in well-trained runners.

The purpose of this study was to investigate whether the modest increases in serum erythropoietin (sEpo) experienced after brief sojourns at simulated altitude are sufficient to stimulate reticulocyte production. Six well-trained middle-distance runners (HIGH, mean maximum oxygen uptake, VO2max = 70.2 ml x kg(-1) x min(-1) spent 8-11 h per night for 5 nights in a nitrogen house that simulated an altitude of 2650 m. Five squad members (CONTROL, mean VO2max= 68.9 ml x kg(-1) x min(-1) undertook the same training, which was conducted under near-sea-level conditions (600 m altitude), and slept in dormitory-style accommodation also at 600 m altitude. For both groups, this 5-night protocol was undertaken on three occasions, with a 3-night interim between successive exposures. Venous blood samples were measured for sEpo after 1 and 5 nights of hypoxia on each occasion. The percentage of reticulocytes was measured, along with a range of reticulocyte parameters that are sensitive to changes in erythropoiesis. Mean serum erythropoietin levels increased significantly (P < 0.01) above baseline values [mean (SD) 7.9 (2.4) mU x ml(-1)] in the HIGH group after the 1st night [11.8 (1.9) mU x ml(-1), 57%], and were also higher on the 5th night [10.7 (2.2) mU x ml(-1), 42%] compared with the CONTROL group, whose erythropoietin levels did not change. After athletes spent 3 nights at near sea level, the change in sEpo during subsequent hypoxic exposures was markedly attenuated (13% and -4% change during the second exposure; 26% and 14% change during the third exposure; 1st and 5th nights of each block, respectively). The increase in sEpo was insufficient to stimulate reticulocyte production at any time point. We conclude that when daily training loads are controlled, the modest increases in sEpo known to occur following brief exposure to a simulated altitude of 2650 m are insufficient to stimulate reticulocyte production.

Free [ADP] and aerobic muscle work follow at least second order kinetics in rat gastrocnemius in vivo.

The relationship between free cytosolic [ADP] (and [P(i)]) and steady-state aerobic muscle work in rat gastrocnemius muscle in vivo using (31)P NMR was investigated. Anesthetized rats were ventilated and placed in a custom-built cradle fitted with a force transducer that could be placed into a 7-tesla NMR magnet. Muscle work was induced by supramaximal sciatic nerve stimulation that activated all fibers. Muscles were stimulated at 0.1, 0.2, 0.3, 0.4, 0.5, 0.8, 1.0, and 2.0 Hz until twitch force, phosphocreatine, and P(i) were unchanged between two consecutive spectra acquired in 4-min blocks (8-12 min). Parallel bench experiments were performed to measure total tissue glycogen, lactate, total creatine, and pyruvate in freeze-clamped muscles after 10 min of stimulation at each frequency. Up to 0.5 Hz, there was no significant change in muscle glycogen, lactate, and the lactate/pyruvate ratios between 8-12 min. At 0.8 Hz, there was a 17% fall in glycogen and a 65% rise in the muscle lactate with a concomitant fall in pH. Above this frequency, glycogen fell rapidly, lactate continued to rise, and ATP and pH declined. On the basis of these force and metabolic measurements, we estimated the maximal mitochondrial capacity (V(max)) to be 0.8 Hz. Free [ADP] was then calculated at each submaximal workload from measuring all the reactants of the creatine kinase equilibrium after adjusting the K'(CK) to the muscle temp (30 degrees C), pH, and pMg. We show that ADP (and P(i)) and tension-time integral follow a Hill relationship with at least a second order function. The K(0.5) values for free [ADP] and [P(i)] were 48 microM and 9 mM, respectively. Our data did not fit any form of the Michaelis-Menten equation. We therefore conclude that free cytosolic [ADP] and [P(i)] could potentially control steady-state oxidative phosphorylation in skeletal muscle in vivo.

Detection and quantification of free cytosolic inorganic phosphate and other phosphorus metabolites in the beating mouse heart muscle in situ.

The aim of this study was the quantification of inorganic phosphate (Pi) and other phosphorus metabolites by (31)P NMR spectroscopy in the mouse heart muscle in situ, beating at around 600 min(-1). Male adult Quacker-bush mice (mean weight 32 +/- 7 g) were anaesthetized, ventilated and placed in a temperature-controlled animal holder. A purpose-built (31)P NMR surface coil was positioned against the exposed left ventricular myocardium. Partial signal overlap of Pi with 2,3-DPG from chamber blood was minimized using a DEPTH pulse sequence (180 degrees -90 degrees -180 degrees -180 degrees -acq.). Quantification of phosphorus metabolites was performed using an external standard positioned directly above the surface coil. We report for the mouse myocardium in situ an intracellular free [Pi] of <0.4 mM, pH of 7.32 +/- 0.1, free [Mg2+] of 0.41 +/- 0.1 mM, free [ADP] of 13 +/- 1.5 microM, [ATP] of 5 +/- 0.5 mM and [PCr] of 14 +/- 1.5 mM. The phosphorylation ratio (ATP/ADP Pi) was 1005 +/- 200 mM (-1) for a PCr/ATP ratio of 2.7 +/- 0.3. It was concluded that the detection of free [Pi] in the mouse myocardium in situ can be greatly enhanced using a DEPTH pulse sequence. Quantification of compounds using an external standard positioned directly above the surface coil gave comparable results to estimations using internal ATP that was quantified enzymatically. The close agreement between the external and internal methods indicates that ATP is 100% NMR visible in the mouse heart in situ.

"Live high, train low" does not change the total haemoglobin mass of male endurance athletes sleeping at a simulated altitude of 3000 m for 23 nights.

The purpose of this study was to document the effect of 23 days of "live high, train low" on the haemoglobin mass of endurance athletes. Thirteen male subjects from either cycling, triathlon or cross-country skiing backgrounds participated in the study. Six subjects (HIGH) spent 8-10 h per night in a "nitrogen house" at a simulated altitude of 3000 m in normobaric hypoxia, whilst control subjects slept at near sea level (CONTROL, n = 7). Athletes logged their daily training sessions, which were conducted at 600 m. Total haemoglobin mass (as measured using the CO-rebreathing technique) did not change when measured before (D1 or D2) and after (D28) 23 nights of hypoxic exposure [HIGH 990 (127) vs 972 (97) g and CONTROL 1042 (133) vs 1033 (138) g, before and after simulated altitude exposure, respectively]. Nor was there any difference in the substantial array of reticulocyte parameters measured using automated flow cytometry prior to commencing the study (D1), after 6 (D10) and 15 (D19) nights of simulated altitude, or 1 day after leaving the nitrogen house (D28) when HIGH and CONTROL groups were compared. We conclude that red blood cell production is not stimulated in male endurance athletes who spend 23 nights at a simulated altitude of 3000 m.

Effects of a 12-day "live high, train low" camp on reticulocyte production and haemoglobin mass in elite female road cyclists.

The aim of this study was to document the effect of "living high, training low" on the red blood cell production of elite female cyclists. Six members of the Australian National Women's road cycling squad slept for 12 nights at a simulated altitude of 2650 m in normobaric hypoxia (HIGH), while 6 team-mates slept at an altitude of 600 m (CONTROL). HIGH and CONTROL subjects trained and raced as a group throughout the 70-day study. Baseline levels of reticulocyte parameters sensitive to changes in erythropoeisis were measured 21 days and 1 day prior to sleeping in hypoxia (D1 and D20, respectively). These measures were repeated after 7 nights (D27) and 12 nights (D34) of simulated altitude exposure, and again 15 days (D48) and 33 days (D67) after leaving the altitude house. There was no increase in reticulocyte production, nor any change in reticulocyte parameters in either the HIGH or CONTROL groups. This lack of haematological response was substantiated by total haemoglobin mass measures (CO-rebreathing), which did not change when measured on D1, D20, D34 or D67. We conclude that in elite female road cyclists, 12 nights of exposure to normobaric hypoxia (2650 m) is not sufficient to either stimulate reticulocyte production or increase haemoglobin mass.

Glycerol hyperhydration improves cycle time trial performance in hot humid conditions.

Eight competitive cyclists [mean peak oxygen consumption, (VO2(peak)) = 65 ml x min(-1) x kg(-1)] undertook two 60-min cycle ergometer time trials at 32 degrees C and 60% relative humidity. The time trials were split into two 30-min phases: a fixed-workload phase and a variable-workload phase. Each trial was preceded by ingestion of either a glycerol solution [1 g x kg(-1) body mass (BM) in a diluted carbohydrate (CHO)-electrolyte drink] or a placebo of equal volume (the diluted CHO-electrolyte drink). The total fluid intake in each trial was 22 ml x kg(-1) BM. A repeated-measures, double blind, cross over design with respect to glycerol was employed. Glycerol ingestion expanded body water by approximately 600 ml over the placebo treatment. Glycerol treatment significantly increased performance by 5% compared with the placebo group, as assessed by total work in the variable-workload phase (P < 0.04). There were no significant differences in rectal temperature, sweat rate or cardiac frequency between trials. Data indicate that the glycerol-induced performance increase did not result from plasma volume expansion and subsequently lower core temperature or lower cardiac frequencies at a given power output as previously proposed. However, during the glycerol trial, subjects maintained a higher power output without increased perception of effort or thermal strain.

Thermodynamics of the arginine kinase reaction.

The effect of temperature, pH, free [Mg(2+)], and ionic strength on the apparent equilibrium constant of arginine kinase (EC 2.7.3.3) was determined. At equilibrium, the apparent K' was defined as [see text] where each reactant represents the sum of all the ionic and metal complex species. The K' at pH 7.0, 1.0 mM free [Mg(2+)], and 0. 25 M ionic strength was 29.91 +/- 0.59, 33.44 +/- 0.46, 35.44 +/- 0. 71, 39.64 +/- 0.74, and 45.19 +/- 0.65 (n = 8) at 40, 33, 25, 15, and 5 degrees C, respectively. The standard apparent enthalpy (DeltaH degrees') is -8.19 kJ mol(-1), and the corresponding standard apparent entropy of the reaction (DeltaS degrees') is + 2. 2 J K(-1)mol(-1) in the direction of ATP formation at pH 7.0, free [Mg(2+)] =1.0 mM, ionic strength (I) =0.25 M at 25 degrees C. We further show that the magnitude of transformed Gibbs energy (DeltaG degrees ') of -8.89 kJ mol(-1) is mostly comprised of the enthalpy of the reaction, with 7.4% coming from the entropy TDeltaS degrees' term (+0.66 kJ mol(-1)). Our results are discussed in relation to the thermodynamic properties of its evolutionary successor, creatine kinase.

Can reticulocyte parameters be of use in detecting iron deficient erythropoiesis in female athletes?

BACKGROUND: The purpose of this study was to investigate whether monitoring reticulocyte profiles, which are known to respond to iron store depletion in sedentary populations, could also be utilised with intensely training athletes. METHODS: A retrospective study of blood samples from 134 national level athletes (61 males, 73 females) at the Australian Institute of Sport were analysed, from which reference ranges were calculated. To ascertain the stability of reticulocyte profiles during periods of intense physical training, the intra-individual variation of these parameters in 12 iron-replete female athletes over a four month period of training was documented. The precision with which the analyzer measured these parameters was also determined using duplicate samples from 37 female athletes. To establish whether reticulocyte parameters were sensitive to iron deficient erythropoiesis in athletes, reticulocyte profiles of five female athletes diagnosed by medical personnel as having depleted iron stores were compared before and after iron therapy to seven controls. RESULTS: Corpuscular hemoglobin concentration mean (CHCMr) and mean corpuscular volume (MCVr) showed little variation over time in iron-replete females, with 95% of all fluctuations being within 5.8% and 4.3% of original values, respectively. Iron supplementation in athletes with depleted iron stores elicited an increase in CHCMr (p = 0.01), and a decrease in the distributions of reticulocyte volume (RDWr, p = 0.01) and cell hemoglobin concentration (HDWr, p < 0.01). The ratios of reticulocyte to mature cell MCV (p < 0.01) and CHCM (p < 0.01) also changed following iron therapy. No such changes occurred in non-supplemented controls with normal iron stores. CONCLUSIONS: These data lend support to the thesis that monitoring of reticulocyte parameters can be of use in detecting iron deficient erythropoiesis in female athletes.

Skin-prick blood samples are reliable for estimating Hb mass with the CO-dilution technique.

Investigation of the impact of environmental stimuli such as altitude exposure on hemoglobin mass currently rely on invasive techniques that require venous blood sampling. This study assessed the feasibility of lancet skin pricks as an alternative to venepuncture to estimate hemoglobin mass with the carbon monoxide (CO) dilution technique, with the intent of making the technique accessible to technicians without phlebotomy training. Sixteen healthy volunteers rebreathed CO via a small-volume rebreathing apparatus. Blood was sampled simultaneously with a glass syringe (VEN) from a superficial forearm vein and with a capillary tube from either a lanced fingertip or earlobe (CAP). As a control, VEN blood was then aliquoted into capillary tubes (CONTROL-CAP). Samples were assayed for carboxy-hemoglobin (HbCO) using a diode-array spectrophotometer. Mean %HbCO was higher in CAP than VEN (bias 0.3+/-0.2%HbCO, p < 0.01), but VEN and CONTROL-CAP were not different (p = 0.55). Compared to VEN, Hb mass derived from CAP samples was overestimated by 1.7% (15+/-22 g Hb, p = 0.01). CAP samples to estimate Hb mass demonstrated a technical error of measurement of 2.7%, which is comparable to the 1.9% reported previously with VEN samples. We conclude that using CAP samples gives a reliable measure of %HbCO, and will make the estimation of Hb mass with the CO-technique accessible to technicians without phlebotomy training.

The haematological response to an iron injection amongst female athletes.

The aim of this study was to monitor the haematological response of female athletes with moderately low ferritin values to an iron injection. We measured the total haemoglobin mass of 11 female basketballers with a range of ferritin values who lived and trained together for the duration of the study (age 18+/-1, range 16-19 yrs), [Hb] 12.4+/-1.3, 11.5-16.1 g x dL; ferritin 35.6+/-15.6, 9-58 microg x L). A total dose of 2.5 mL Ferrum H was administered to six squad members who were matched with the remaining five controls based on ferritin measures obtained three weeks earlier. Venous blood samples were drawn weekly to obtain full blood counts, reticulocyte parameters as well as iron profiles. There was no change detected in any of the haematological parameters measured in the treatment group compared to controls. A repeated measures ANOVA (treatment x time) demonstrated that neither total haemoglobin mass (P = 0.91) nor [Hb] (P = 0.79) altered significantly between groups, whilst the mean haemoglobin content of reticulocytes also showed no response (P = 0.17). Because a positive haematological response is definitive evidence of impaired red cell production, our results indicate that none of the athletes were iron deficient at the time of the injection. This suggests that low ferritin values in trained female athletes are not always associated with impaired red cell production.

Sensitivity of reticulocyte indices to iron therapy in an intensely training athlete.

Iron deficiency anaemia, and its debilitating effect on performance, is an area of concern for many female athletes. Automated technologies that analyse individual reticulocytes may provide a sensitive measure of bone marrow response to iron supplementation. The reticulocyte characteristics of a female volleyball player with frank iron deficiency anaemia, and her subsequent response to oral iron therapy, are reported.

Tissue spaces in rat heart, liver, and skeletal muscle in vivo.

Tissue spaces were determined in rat heart, liver, and skeletal muscle in vivo using isotopically labeled [14C]inulin. Tracer was injected into the jugular vein of pentobarbital-anesthetized male Sprague-Dawley rats. After a 30-min equilibration period, a blood sample was taken, and heart, liver, and gastrocnemius muscle were excised and immediately freeze clamped at liquid nitrogen temperatures. The extracellular inulin space was 0.209 +/- 0.006 (n = 13), 0.203 +/- 0.080 (n = 7), and 0.124 +/- 0.006 (SE) ml/g wet wt tissue (n = 8) for heart, liver, and skeletal muscle, respectively. Total tissue water was 0.791 +/- 0.005 (n = 9), 0.732 +/- 0.002 (n = 9), and 0.755 +/- 0.005 ml/g wet wt tissue (n = 10) for heart, liver, and skeletal muscle, respectively. Expressed as a percentage of total tissue water, the intracellular space was 73.6, 72.2, and 83. 7% for heart, liver, and skeletal muscle, respectively. With use of 2,3-diphospho-D-glyceric acid as a vascular marker, the interstitial space was calculated by subtracting the counts in tissue due to whole blood from total tissue counts and dividing by plasma counts. The interstitial space was 18.8, 22.4, and 14.5% of total tissue water, with accompanying plasma spaces of 7.7, 5.3, and 1.8% for heart, liver, and gastrocnemius muscle, respectively. The tracer method used in this study provides a quantitative assessment of water distribution in tissues of nonnephrectomized rats that has applications for calculation of tissue ion and metabolite concentrations, gradients, and fluxes under normal and pathophysiological conditions.

Serum ferritin and anemia in trained female athletes.

The aim of this study was to establish whether extremely low serum ferritin values in female athletes were associated with indications of iron deficiency anemia and whether serum ferritin values were influenced by the type of training or participants' body size. Hematological data collected during 6 years at the Australian Institute of Sport were reviewed to quantify changes in serum ferritin concentration associated with training and to establish whether decrements in serum ferritin were associated with any change in hemoglobin concentration, mean corpuscular volume, or mean corpuscular hemoglobin concentration. Mean serum ferritin concentrations of 7.5 microg x L(-1) were not associated with any indication of iron-deficiency anemia. Serum ferritin declined by approximately 25% with the onset of rigorous daily training (p < .01) whether training was predominantly weight-bearing or non-weight-bearing. Rowers had significantly higher ferritin concentrations than basketball players of similar stature (p=.02). We conclude that considerable background information such as the stage of training, specific sport, and previous blood results should be sought when interpreting serum ferritin concentrations in female athletes.

Skeletal muscle histology and biochemistry of an elite sprinter, the African cheetah.

To establish a skeletal muscle profile for elite sprinters, we obtained muscle biopsy samples from the vastus lateralis, gastrocnemius and soleus of African cheetahs (Acinonyx jubatus). Muscle ultrastructure was characterized by the fiber type composition and mitochondrial volume density of each sample. Maximum enzyme activity, myoglobin content and mixed fiber metabolite content were used to assess the major biochemical pathways. The results demonstrate a preponderance of fast-twitch fibers in the locomotor muscles of cheetahs; 83% of the total number of fibers examined in the vastus lateralis and nearly 61% of the gastrocnemius were comprised of fast-twitch fibers. The total mitochondrial volume density of the limb muscles ranged from 2.0 to 3.9% for two wild cheetahs. Enzyme activities reflected the sprinting capability of the cheetah. Maximum activities for pyruvate kinase and lactate dehydrogenase in the vastus lateralis were 1519.00 +/- 203.60 and 1929.25 +/- 482.35 mumol min-1.g wet wt-1, respectively, and indicated a high capacity for glycolysis. This study demonstrates that the locomotor muscles of cheetahs are poised for anaerobically based exercise. Fiber type composition, mitochondrial content and glycolytic enzyme capacities in the locomotor muscles of these sprinting cats are at the extreme range of values for other sprinters bred or trained for this activity including greyhounds, thoroughbred horses and elite human athletes.

Epinephrine enhances glycogen turnover and depresses glucose uptake in vivo in rat heart.

In vivo effects of epinephrine on glucose uptake and glycogen turnover in rat heart were studied and compared to liver and skeletal muscle. Fasted ketamine-anesthetized rats were intravenously infused with saline or epinephrine. Both the low and high doses of epinephrine resulted in hyperglycemia (40-50%) and hyperlactemia (threefold) at the end of infusion. Glucose uptake, determined by the phosphorylation of the intravenously injected [14C]2-deoxyglucose, was found to decrease in the heart and skeletal muscle of epinephrine-infused rats. Glycogen in livers, skeletal muscles, and hearts of the epinephrine-infused rats decreased to varying degrees relative to the saline-infused rats, indicating enhanced glycogenolysis in all three organs. Glycogen synthesis, determined by the incorporation of the co-infused [3-(3)H]glucose into glycogen, was found to decrease in liver and skeletal muscle. However, glycogen synthesis in the heart was found to increase 50% in Epi-1 and 280% in Epi-2 compared to the saline-infused rats. We conclude that glucose utilization in the in vivo heart may be preferentially channeled through glycogen turnover in the presence of epinephrine. That both synthesis and degradation of glycogen can be simultaneously activated appears to be unique to the heart and is protective against a loss of glycogen at a time of enhanced glucose utilization.