Biomedical subjects

G D Marsh

Publications and source records attributed to G D Marsh.

At least 19 recordsLinked to original sources

PubMed2007

Effects of hyperventilation on phosphocreatine kinetics and muscle deoxygenation during moderate-intensity plantar flexion exercise.

The effects of controlled voluntary hyperventilation (Hyp) on phosphocreatine (PCr) kinetics and muscle deoxygenation were examined during moderate-intensity plantar flexion exercise. Male subjects (n = 7) performed trials consisting of 20-min rest, 6-min exercise, and 10-min recovery in control [Con; end-tidal Pco(2) (Pet(CO(2))) approximately 33 mmHg] and Hyp (Pet(CO(2)) approximately 17 mmHg) conditions. Phosphorus-31 magnetic resonance and near-infrared spectroscopy were used simultaneously to monitor intramuscular acid-base status, high-energy phosphates, and muscle oxygenation. Resting intracellular hydrogen ion concentration ([H(+)](i)) was lower (P < 0.05) in Hyp [90 nM (SD 3)] than Con [96 nM (SD 4)]; however, at end exercise, [H(+)](i) was greater (P < 0.05) in Hyp [128 nM (SD 19)] than Con [120 nM (SD 17)]. At rest, [PCr] was not different between Con [36 mM (SD 2)] and Hyp [36 mM (SD 1)]. The time constant (tau) of PCr breakdown during transition from rest to exercise was greater (P < 0.05) in Hyp [39 s (SD 22)] than Con [32 s (SD 22)], and the PCr amplitude was greater (P < 0.05) in Hyp [26% (SD 4)] than Con [22% (SD 6)]. The deoxyhemoglobin and/or deoxymyoglobin (HHb) tau was similar between Hyp [13 s (SD 8)] and Con [10 s (SD 3)]; however, the amplitude was increased (P < 0.05) in Hyp [40 arbitrary units (au) (SD 23)] compared with Con [26 au (SD 17)]. In conclusion, our results indicate that Hyp-induced hypocapnia enhanced substrate-level phosphorylation during moderate-intensity exercise. In addition, the increased amplitude of the HHb response suggests a reduced local muscle perfusion in Hyp compared with Con.

Adult↗

PubMed2005

NaHCO3-induced alkalosis reduces the phosphocreatine slow component during heavy-intensity forearm exercise.

During heavy-intensity exercise, the mechanisms responsible for the continued slow decline in phosphocreatine concentration ([PCr]) (PCr slow component) have not been established. In this study, we tested the hypothesis that a reduced intracellular acidosis would result in a greater oxidative flux and, consequently, a reduced magnitude of the PCr slow component. Subjects (n = 10) performed isotonic wrist flexion in a control trial and in an induced alkalosis (Alk) trial (0.3g/kg oral dose of NaHCO3, 90 min before testing). Wrist flexion, at a contraction rate of 0.5 Hz, was performed for 9 min at moderate- (75% of onset of acidosis; intracellular pH threshold) and heavy-intensity (125% intracellular pH threshold) exercise. 31P-magnetic resonance spectroscopy was used to measure intracellular [H+], [PCr], [Pi], and [ATP]. The initial recovery data were used to estimate the rate of ATP synthesis and oxidative flux at the end of heavy-intensity exercise. In repeated trials, venous blood sampling was used to measure plasma [H+], [HCO3-], and [Lac-]. Throughout rest and exercise, plasma [H+] was lower (P < 0.05) and [HCO3-] was elevated (P < 0.05) in Alk compared with control. During the final 3 min of heavy-intensity exercise, Alk caused a lower (P < 0.05) intracellular [H+] [246 (SD 117) vs. 291 nmol/l (SD 129)], a greater (P < 0.05) [PCr] [12.7 (SD 7.0) vs. 9.9 mmol/l (SD 6.0)], and a reduced accumulation of [ADP] [0.065 (SD 0.031) vs. 0.098 mmol/l (SD 0.059)]. Oxidative flux was similar (P > 0.05) in the conditions at the end of heavy-intensity exercise. In conclusion, our results are consistent with a reduced intracellular acidosis, causing a decrease in the magnitude of the PCr slow component. The decreased PCr slow component in Alk did not appear to be due to an elevated oxidative flux.

Acid-Base Equilibrium↗

PubMed2002

Muscle size, strength, and bone geometry in the upper limbs of young and old men.

BACKGROUND: Bone loss in old men is associated with a decrease in muscle mass and strength. However, the influence of muscle size and strength on age-related changes in bone geometry has not been comprehensively described. Methods. Men in their third (group I, 23 +/- 3 y, n = 20), eighth (group II, 77 +/- 1 y, n = 10), and ninth (group III, 86 +/- 4 y, n = 13) decades of age were studied. The cross-sectional area (CSA) of the elbow flexors, elbow extensors, and forearm muscles, the total area (TA), cortical area (CA), and medullary area (MA) of the midhumerus, and distal third of the radius and ulna (n = 7 group II; n = 6 group III) were measured with magnetic resonance imaging. The maximal isometric strength (MVC) of the elbow flexors and elbow extensors was also determined. RESULTS: The CSA and MVC of the arm muscles (elbow flexors plus elbow extensors) were less in group II (-17% and -22%) and III (-32% and -39%), respectively, compared to group I. However, forearm CSA was less (-21%) in group III only. The TA and MA of all bones were greater in the older groups. The CA of the humerus (-14%) and ulna (-10%), but not the radius, was less in group III compared to group I, whereas CA was unchanged in group II. Stepwise multiple linear regression determined that arm muscle CSA (r = 0.52, p <.01) and forearm muscle CSA (r = 0.41, p <.05) provided the best prediction of CA in the humerus and forearm, respectively. CONCLUSIONS: Muscle size and strength are important determinants of CA in the humerus and forearm. The lower CA in the ninth decade may be explained, in part, by reduced bone strains due to a smaller muscle mass.

Adult↗

PubMed2001

Two-dimensional time correlation relaxometry of skeletal muscle in vivo at 3 Tesla.

A hybrid two-dimensional relaxometry (2DR) sequence was used to simultaneously measure both the spin-spin (R2) and spin-lattice relaxation rates (R1) of skeletal muscle in vivo. The 2DR sequence involved a 180 degrees inversion pulse followed by a variable delay time (30 values from 40 to 7000 ms); a projection presaturation (PP) scheme to localize a 16-ml cylindrical voxel; and a CPMG sequence (950 even echoes, effective echo spacing = 1.2 ms, equilibrium time = 12 s). The 2DR data were collected at 3.0 Tesla from the flexor digitorum profundus of eight healthy males, 26 +/- 2 years old. Analysis was performed with a 2D version of the non-negative least-squares algorithm and a one-way ANOVA. All subjects exhibited at least three spin-groups (R2 < 200 s(-1)), designated B, C, and D, with R2 values of 42.7, 26.5, and 8.1 s(-1), and fractional volumes of 52, 35, and 7%, respectively. The R1 values of B and C were similar, congruent with0.7 s(-1), but different from that of D (P < 0.001), which had an R1 of 1.0 s(-1). The results suggest that exchange between B and C ranges from 0.7-16.2 s(-1), while exchange between either of these spin-groups with D is slower. If the data are interpreted with a compartment model, in which spin-groups with short and long R2 values are attributed to extra- and intracellular fluid, respectively, the exchange of water across the cell membrane in living skeletal muscle is slow or intermediate relative to both R1 and R2.

Adult↗

PubMed2001

Neuromuscular properties and fatigue in older men following acute creatine supplementation.

The purpose of this study was to investigate the effects of creatine (Cr) supplementation in 12 older (65-82 years) men. The subjects were randomly assigned to a Cr or a placebo (P) group. Seven men were supplemented with 5 g of Cr and 5 g maltodextrin four times a day for 5 days (Cr), and 5 men consumed 5 g of maltodextrin four times a day for 5 days (P). Following this treatment body mass increased significantly in the Cr group (1 kg), but did not change in the P group, and measurements of arm anthropometry were not affected in either group. Prior to and following supplementation maximal isometric voluntary force (MVC), muscle activation, contractile properties and surface electromyography (EMG) were measured in the elbow flexor muscles at baseline, during a fatiguing task and over 10 min of recovery. The fatigue protocol involved both voluntary and contractile stimulated. Stimulated contractile properties, MVC, and muscle activation were not affected by Cr supplementation. Furthermore, there were no changes in time to fatigue, decline in MVC force, muscle activation, EMG or contractile properties during the fatigue protocol. The rates of recovery of voluntary force, and stimulated contractile force did not change following Cr supplementation. These results indicate that short-term Cr supplementation in older men does not influence isometric performance of the elbow flexor muscles.

Aged↗

PubMed2001

Normalized force, activation, and coactivation in the arm muscles of young and old men.

The purpose of this study was to determine whether the loss of muscle strength in the elderly could be explained entirely by a decline in the physiological cross-sectional area (PCSA) of muscle. Isometric force, muscle activation (twitch interpolation), and coactivation (surface electromyograph) were measured during maximal voluntary contractions (MVCs) of the elbow flexors (EFs) and extensors (EEs) in 20 young (23 +/- 3 yr) and 13 older (81 +/- 6 yr) healthy men. PCSA was determined using magnetic resonance imaging, and normalized force (NF) was calculated as the MVC/PCSA ratio. The PCSA was smaller in the old compared with the young men, more so in the EEs (28%) compared with the EFs (19%) (P < 0.001); however, the decline in MVC (approximately 30%) with age was similar in the two muscle groups. Muscle activation was not different between the groups, but coactivation was greater (5%) (P < 0.001) in the old men for both muscles. NF was less (11%) in the EFs (P < 0.01) and tended to be unchanged in the EEs of the old compared with young subjects. The relative maintenance of NF in the EEs compared with the EFs may be related to age-associated changes in the architecture of the triceps brachii muscle. In conclusion, although the decline in PCSA explained the majority of strength loss in the old men, additional factors such as greater coactivation or reduced specific tension also may have contributed to the age-related loss of isometric strength.

Adult↗

PubMed2000

Effects of exercise on muscle transverse relaxation determined by MR imaging and in vivo relaxometry.

The purpose of this study was to determine the effects of intense exercise on the proton transverse (T(2)) relaxation of human skeletal muscle. The flexor digitorium profundus muscles of 12 male subjects were studied by using magnetic resonance imaging (MRI; 6 echoes, 18-ms echo time) and in vivo magnetic resonance relaxometry (1,000 echoes, 1.2-ms echo time), before and after an intense handgrip exercise. MRI of resting muscle produced a single T(2) value of 32 ms that increased by 19% (P < 0.05) with exercise. In vivo relaxometry showed at least three T(2) components (>5 ms) for all subjects with mean values of 21, 40, and 137 ms and respective magnitudes of 34, 49, and 14% of the total magnetic resonance signal. These component magnitudes changed with exercise by -44% (P < 0.05), +52% (P < 0.05), and +23% (P < 0.05), respectively. These results demonstrate that intense exercise has a profound effect on the multicomponent T(2) relaxation of muscle. Changes in the magnitudes of all the T(2) components synergistically increase MRI T(2), but changes in the two shortest T(2) components predominate.

Adult↗

PubMed2000

Forearm muscle metabolism studied using (31)P-MRS during progressive exercise to fatigue after Acz administration.

The effects of acetazolamide (Acz)-induced carbonic anhydrase inhibition (CAI) on muscle intracellular thresholds (T) for intracellular pH (pH(i)) and inorganic phosphate-to-phosphate creatine ratio (P(i)/PCr) and the plasma lactate (La(-)) threshold were examined in nine adult male subjects performing forearm wrist flexion exercise to fatigue. Exercise consisted of raising and lowering (1-s contraction, 1-s relaxation) a cylinder whose volume increased at a rate of 200 ml/min. The protocol was performed during control (Con) and after 45 min of CAI with Acz (10 mg/kg body wt iv). T(pH(i)) and T(P(i)/PCr), determined using (31)P-labeled magnetic resonance spectroscopy (MRS), were similar in Acz (722 +/- 50 and 796 +/- 75 mW, respectively) and Con (855 +/- 211 and 835 +/- 235 mW, respectively). The pH(i) was similar at end-exercise (6.38 +/- 0.10 Acz and 6.43 +/- 0.22 Con), but pH(i) recovery was slowed in Acz. In a separate experiment, blood was sampled from a deep arm vein at the elbow for determination of plasma lactate concentration ([La(-)](pl)) and T(La(-)). [La(-)](pl) was lower (P < 0.05) in Acz than Con (3.7 +/- 1.7 vs. 5.0 +/- 1.7 mmol/l) at end-exercise and in early recovery, but T(La(-)) was higher (1,433 +/- 243 vs. 1,041 +/- 414 mW, respectively). These data suggest that the lower [La(-)](pl) seen with CAI was not due to a delayed onset or rate of muscle La(-) accumulation but may be related to impaired La(-) removal from muscle.

Acetazolamide↗

PubMed2000

Contractile properties, fatigue and recovery are not influenced by short-term creatine supplementation in human muscle.

There have been several studies on the effect of short-term creatine (Cr) supplementation on exercise performance, but none have investigated both voluntary and stimulated muscle contractions in the same experiment. Fourteen moderately active young men (19-28 years) were randomly assigned, in a double blind manner, to either a creatine (Cr) or placebo (P) group. The subjects supplemented their regular diet 4 times a day for 5 days with either 5 g Cr + 5 g maltodextrin (Cr group), or 5 g maltodextrin (P group). Isometric maximal voluntary contraction (MVC), muscle activation, as assessed using the modified twitch interpolation technique, electrically stimulated contractile properties, electromyography (EMG), endurance time and recovery from fatigue were measured in the elbow flexors. The fatigue protocol involved both voluntary and stimulated contractions. Following supplementation there was a significant weight gain in the Cr group (1.0 kg), whereas the P group did not change. For each group, pre-supplementation measures were not significantly different from post-supplementation for MVC, twitch and tetanic tensions at rest, time to peak tension, half-relaxation time and contraction duration. Prior to Cr supplementation time to fatigue was 10 +/- 4 min (mean +/- S.E.M.) for both groups, and following supplementation there was a non-significant increase of 1 min in each group. MVC force, muscle activation, EMG, stimulated tensions and durations were similar for the Cr and P groups over the course of the fatigue protocol and did not change after supplementation. Furthermore, recovery of MVC, stimulated tensions and contractile speeds did not differ as a result of Cr supplementation. These results indicate that short-term Cr supplementation does not influence isometric elbow flexion force, muscle activation, stimulated contractile properties, or delay time to fatigue or improve recovery.

Adult↗

PubMed1999

Multicomponent T2 relaxation of in vivo skeletal muscle.

In vivo spin-spin (T2) relaxation measurements were acquired from the flexor digitorum profundus (FDP) of 13 subjects. A standard imaging T2 measurement technique [number of points (N) = 6, TE = 18 msec, signal-to-noise ratio (SNR) approximately equal to 300] yielded a single T2 value of 31 msec. A novel technique, projection presaturation combined with a CPMG sequence, was used to acquire data (N = 1000, TE = 1.2 msec, SNR 3500) from a cylindrical voxel (2 cm diameter, 5 cm length) within the FDP. All 13 subjects had at least four T2 components, at < 5, 21 +/- 4, 39 +/- 6, and 114 +/- 31 msec, with fractional areas of 11 +/- 2, 28 +/- 15, 46 +/- 12, and 11 +/- 5% respectively. The shortest and longest components have been observed in ex vivo muscle studies, probably corresponding to water associated with macromolecules and extracellular water, respectively. The middle T2 components are suggestive of an organization of in vivo intracellular water.

Adult↗

PubMed1999

Anaerobic power of the arms and legs of young and older men.

The purpose of this study was to examine differences in the anaerobic exercise performance of young and older men. Eight healthy, active older (68.5 +/- 2.4 years old, mean S.D.) and eight healthy, active young (30.6 +/- 4.5 years old) subjects were assessed for peak and mean power output (PP and MP, respectively) of the legs and arms, during 30 s Wingate tests. PP during leg exercise was significantly (P < 0.05) higher in the young (14.6 +/- 1.6 W kg-1) compared with the older (10.7 +/- 1.0 W kg-1) group. MP of the legs was also greater in the young subjects (10.7 +/- 0.7 vs. 7.4 +/- 0.9 W kg-1). These differences in PP and MP remained significant when expressed relative to lean leg volume. PP during arm cranking was significantly greater in the young subjects (8.9 +/- 0.7 vs. 7.5 +/- 0.6 W kg-1) as was MP (6.4 +/- 0.7 vs. 5.0 +/- 0.7 W kg-1). Post-exercise blood lactate concentration in the older group (7.0 +/- 1.6 mmol l-1) was less (P < 0.05) than in the young group (10.6 +/- 2.0 mmol l-1), for leg work only. The significant loss of anaerobic power in the older group could not be explained by a difference in muscle mass. Power output was also lower in the arms, but to a lesser extent. The results of this study suggest that a reduction in the ability to perform high intensity exercise may be an inevitable consequence of ageing. The extent, however, of this decline varies with different muscle groups.

Adult↗

PubMed1998

Evaluation of muscle oxidative potential by 31P-MRS during incremental exercise in old and young humans.

The purpose of this study was to compare muscle oxidative capacity between moderately active young and old humans by measuring intracellular threshold (IT) during exercise with 31P-magnetic resonance spectroscopy (31P-MRS). Changes in phosphocreatine, inorganic phosphate, and intracellular pH were measured by 31P-MRS during a progressive unilateral ankle plantar flexion exercise protocol in groups of moderately active old (n = 12, mean age 66.7 years) and young (n = 13, mean age 26.2 years) individuals. From muscle biopsy samples of the lateral gastrocnemius, citrate synthase (CS) activity was determined in six subjects from each group, and fibre type composition was determined in nine old and ten young subjects. The old group had a lower IT for pH, as a percentage of peak work rate (P < 0.05), despite a similar CS activity compared to the young. IT was significantly correlated with CS activity (R = 0.59; P < 0.05), but not with fibre type composition. It was concluded that metabolic responses to exercise are affected by ageing, as indicated by a lower IT in old compared to young individuals.

Adult↗

PubMed1998

The effects of age on kinetics of oxygen uptake and phosphocreatine in humans during exercise.

We compared the kinetics of oxygen uptake (VO2) and phosphocreatine (PCr) during the adjustment to and recovery from plantar flexion exercise in moderately active older (n = 10, 66.9 years) and younger (n = 10, 27.5 years) individuals. VO2 kinetics were similar in the two groups, with time constants (tau) averaging 46.3 +/- 10.2 s (younger, on-transient), 38.1 +/- 14.4 s (younger, off-transient), 46.3 +/- 17.8 (older, on-transient) and 40.7 +/- 19.2 s (older, off-transient). These were similar to corresponding PCr kinetics, measured by 31P nuclear magnetic resonance spectroscopy, which averaged 50.6 +/- 24.0 s (younger, on-transient), 42.0 +/- 16.1 s (younger, off-transient), 39.8 +/- 22.0 s (older, on-transient) and 37.6 +/- 21.6 s (older, off-transient). On-transient tau values for VO2 and PCr were correlated, for combined groups (r = 0.53; P = 0.015). We conclude that: (1) VO2 and PCr kinetics during exercise of a muscle group accustomed to daily activity are not compromised in physically active older humans, and (2) PCr kinetics reflect the kinetics of muscle O2 consumption, and are expressed at the lung (VO2 kinetics) after a transit delay.

Adult↗

PubMed1996

Early detection of cancer cachexia in the rat using 31P magnetic resonance spectroscopy of the liver and a fructose stress test.

The dynamic metabolic effects of a fructose infusion challenge on hepatic intracellular levels of adenosine 5'-triphosphate (ATP), inorganic phosphate (Pi) and phosphomonoesters (PME) were monitored noninvasively by 31P MRS in a remote tumour-bearing rat model. Fisher male rats were inoculated with a methylcholanthrene-induced sarcoma. Seventeen rats were randomized into three groups: control (n = 6), low tumour burden (LTB, n = 6), or moderate tumour burden (MTB, n = 5). The LTB group had tumour burdens of 0.2-2.0% while the MTB group had tumour burdens of 2.6-5.7%. All rats were in the pre-clinical phase of cancer cachexia as determined by food intake and body weight. Rats were infused with 1.2 g/kg of fructose i.v. and the metabolic response of the liver was monitored with time over 1 h via 31P MRS. In all groups an immediate increase in hepatic levels of PME was noted, which returned to baseline values over the course of the experiment, reflecting the phosphorylation of fructose to fructose 1-phosphate. For the MTB rats, the return to baseline levels was more rapid than in the control or LTB group. All groups experienced a 20% decrease in hepatic ATP levels which did not return to baseline over the 1 h observation period. As well, all groups experienced an initial fall in Pi, which recovered to prefructose levels or greater. MTB rats demonstrated a 30-40% increase in Pi concentration and a 60-70% increase in Pi/ATP ratio after infusion with fructose as compared to LTB and control rats (ANOVA;p<0.05). This is consistent with cachexia-induced enhancement of hepatic gluconeogenic activity, and hence more rapid release of Pi from the phosphorylated metabolites in the MTB rats. Thus fructose infusion and hepatic 31P MRS permit pre-clinical detection of cancer cachexia as reflected by increased Pi generation and more rapid removal of PME.

Analysis of Variance↗

PubMed1996

Metabolic response of forearm muscle to graded exercise in type II diabetes mellitus: effect of endurance training.

In this study, 31P nuclear magnetic resonance spectroscopy was used to monitor muscle metabolism in Type II diabetic subjects (n = 10) during an incremental exercise test. Also the exercise responses of diabetic subjects (n = 4) following submaximal endurance training were assessed and compared to healthy controls (n = 5). Responses to incremental exercise in the diabetic subjects were consistent over time despite minor fluctuations in metabolic control. In the diabetic and control groups, after 12 weeks of training the forearm flexor muscles, power output at the intracellular threshold of acidosis (IT) increased (p < .01) similarly: T0 versus T12: 0.90 +/- 0.09 versus 1.20 +/- 0.13 and 1.03 +/- 0.07 versus 1.22 +/- 0.10 W, respectively. Minimum intracellular pH reached at peak exercise was unchanged after training. The control group, however, became more acidic versus the diabetic group (p < .05) in response to progressive exercise. This difference was maintained over time. Endurance training elicited similar adaptations in forearm muscles of Type II diabetic and control subjects, although there were differences between the two groups in intracellular pH during exercise.

Acidosis↗

PubMed1996

Kinetics of pulmonary oxygen uptake and muscle phosphates during moderate-intensity calf exercise.

The purpose of this study is to directly compare the dynamic responses of phosphocreatine (PCr) and P(i) to those oxygen uptake (VO2) measured at the lung during transitions to and from moderate-intensity exercise. Changes in PCr and P(i) were measured by 31P-nuclear magnetic resonance spectroscopy, and changes in VO2 were measured breath by breath by mass spectroscopy during transitions to and from moderate-intensity square-wave ankle plantar flexion exercise in 11 subjects (7 men and 4 women; mean age 27 yr). Three repeated transitions were averaged for improvement in signal-to-noise ratio of phosphate data, and 12 transitions were averaged for VO2 measurements. Averaged transitions were fit with a monoexponential curve for determination of the time constant (tau) of the responses. Mean tau values for on transients of PCr, P(i), and phrase 2 VO2 were 47.0, 57.7, and 44.5 s, respectively, whereas means tau values for off transients were 44.8, 42.1, and 33.4 s, respectively. There were no significant differences between tau values for phosphate- and VO2-measured transients or on and off transients. The similarity of on and off kinetics supports linear first-order respiratory control models. Measurement of phase 2 pulmonary VO2 kinetics to and from moderate-intensity small-muscle-mass exercise reflect muscle phosphate kinetics (and muscle oxygen consumption).

Adult↗

PubMed1996

Effect of anaemia correction on skeletal muscle metabolism in patients with end-stage renal disease: 31P magnetic resonance spectroscopy assessment.

Skeletal muscle metabolism during exercise was compared in 5 patients with end-stage renal disease (ESRD) and 8 healthy controls, using a noninvasive technique, 31P magnetic resonance spectroscopy (MRS). After 3 months of anaemia correction with recombinant human erythropoietin (rHuEPO) these patients were re-evaluated. Maximal power achieved by the ESRD patients during a dynamic wrist flexion exercise test was 33% lower (p < 0.05) than the controls. Similarly in the ESRD group, the power at the onset of metabolic acidosis (the intracellular threshold) was 29% less than controls. The metabolic differences observed in the patients indicated a lower aerobic capacity. Three months of rHuEPO treatment resulted in a 55% increase in mean haematocrit but conferred no significant improvement in metabolic parameters at rest or during exercise. The lack of any significant changes in muscle metabolism following the correction of anaemia suggests that oxygen availability is not the exclusive limiting factor for aerobic metabolism in ESRD patients.

Adult↗

PubMed1994

Insulin protects against hepatic bioenergetic deterioration induced by cancer cachexia: an in vivo 31P magnetic resonance spectroscopy study.

The bioenergetic effects of cancer cachexia on the livers of male Fischer rats inoculated with a methylcholanthrene-induced sarcoma were assessed using serial in vivo 31P magnetic resonance spectroscopy. Rats were randomized into three groups: tumor-bearing controls (n = 7); an insulin-treated group receiving 2 units/100 g body weight/day starting 21 days after implantation (n = 8); and a chronic insulin-treated group receiving insulin every day after implantation (n = 3). During the 32-day study, serial measurements of food intake, body weight, and tumor volume were taken, and 31P magnetic resonance spectroscopy analyses of the livers were conducted every 7 days after tumor implantation. Neither the short-term nor the chronic insulin treatment regimens stimulated the progress of tumor growth. However, both treatments prevented body weight loss, and the short-term insulin treatment prevented tumor-induced decrease in food intake relative to the control group. Liver bioenergetic deterioration was evaluated from the increase in the ratio of Pi to ATP obtained from the hepatic 31P magnetic resonance spectra. At day 28 postimplantation, control rats exhibited appreciable hepatic bioenergetic deterioration, i.e., a Pi/ATP ratio of 1.41 +/- 0.35 (SE), significantly higher (P < 0.05) than the Pi/ATP ratio for short-term or chronic insulin treatment groups (Pi/ATP 0.92 +/- 0.22 and 0.84 +/- 0.22, respectively) or rats before tumor implantation (Pi/ATP 0.76 +/- 0.14). This insulin-induced bioenergetic protection occurred at any given tumor burden up to at least 10%. Thus, both short-term insulin given just prior to the frank manifestations of cancer cachexia and chronic insulin treatment given throughout tumor growth ameliorated host hepatic bioenergetic deterioration without significantly stimulating tumor growth. Insulin may act by altering the host metabolism (stimulation of liver glucose uptake and utilization, decreased energy-requiring gluconeogenesis, and general protein-sparing action) at the expense of the tumor.

Adenosine Triphosphate↗