Biomedical subjects

R P Farrar

Publications and source records attributed to R P Farrar.

At least 19 recordsLinked to original sources

PubMed2000

Maximal power across the lifespan.

BACKGROUND: Previous investigators have reported that maximal power increases during growth and decreases with aging. These age-related differences have been reported to persist even when power is scaled to body mass or muscle size. We hypothesized that age-related differences in maximal power were primarily related to differences in muscle size and fiber-type distribution rather than to age per se. METHODS: Maximum cycling power (Pmax) and optimal pedaling rate (Vopt, a surrogate measure for muscle fiber type) were determined for 195 boys and men, 8-70 years of age, by using inertial load cycle ergometry. Anthropometric dimensions were used to estimate lean thigh volume (LTVest) of all subjects, and magnetic resonance imagery was used to determine thigh and hip muscle volume (MRIvol) for 24 subjects. RESULTS: Pmax was highly related to the product of LTVest and Vopt (LTVest X Vopt; r2 = .83). Multiple regression revealed that Pmax was significantly related to both LTVest x Vopt and age (R2 = .84). Power scaled by LTVest X Vopt was stable during growth and exhibited a small but significant decrease with aging. MRIvol was highly correlated with LTVest, and the ratio of LTVest to MRIvol was independent of age. CONCLUSIONS: These results suggest that muscle volume and optimal pedaling rate are the main determinants of maximal power across the lifespan and that the contractile properties of muscle are developed early in childhood and remain nearly intact late into the lifespan.

Adolescent↗

PubMed1998

Effect of chronic electrical stimulation and beta-GPA diet on GLUT4 protein concentration in rat skeletal muscle.

The present study investigated whether alterations in the muscle high energy phosphate state initiates the contraction-induced increase in skeletal muscle GLUT4 protein concentration. Sprague-Dawley rats were provided either a normal or a 2% beta-guanidinoproprionic acid (beta-GPA) diet for 8 weeks and then the gastrocnemius of one hind limb was subjected to 0, 14 or 28 days of chronic (24 h day-1) low-frequency electrical stimulation (10 Hz). The beta-GPA diet, in the absence of electrical stimulation, significantly reduced ATP, creatine phosphate, creatine and inorganic phosphate and elevated GLUT4 protein concentration by 60% without altering adenylate cyclase activity or cAMP concentration. Following 14 days of electrical stimulation, GLUT4 protein concentration was elevated above non-stimulated muscle in both groups but was significantly more elevated in the beta-GPA group. Concurrent with this greater rise in GLUT4 protein concentration was a greater decline in the high energy phosphates and a greater rise in cAMP. After 28 days of electrical stimulation, GLUT4 protein concentration and cAMP stabilized and was not different between diet treatments. However, the high energy phosphates were significantly higher in the normal diet rats as opposed to the beta-GPA rats. These findings therefore suggest that a reduction in cellular energy supply initiates the contraction-induced increase in muscle GLUT4 protein concentration, but that a rise in cAMP may potentiate this effect.

Adenosine Triphosphate↗

PubMed1998

Higher mitochondrial fatty acid oxidation following intermittent versus continuous endurance exercise training.

It has been well documented that skeletal muscle fatty acid oxidation can be elevated by continuous endurance exercise training. However, it remains questionable whether similar adaptations can be induced with intermittent interval exercise training. This study was undertaken to directly compare the rates of fatty acid oxidation in isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria following these different exercise training regimes. Mitochondria were isolated from the gastrocnemius-plantaris muscles of male Sprague-Dawley rats following exercise training 6 days per week for 12 weeks. Exercise training consisted of either continuous, submaximal, endurance treadmill running (n = 10) or intermittent, high intensity, interval running (n = 10). Both modes of training enhanced the oxidation of palmityl-carnitine-malate in both mitochondrial populations (p < 0.05). However, the increase associated with the intermittent, high intensity exercise training was significantly greater than that achieved with the continuous exercise training (p < 0.05). Also, the increases associated with the IMF mitochondria were greater than the SS mitochondria (p < 0.05). These data suggest that high intensity, intermittent interval exercise training is more effective for stimulation of fatty acid oxidation than continuous submaximal exercise training and that this adaptation occurs preferentially within IMF mitochondria.

Adenosine Triphosphatases↗

PubMed1998

Effects of chronic moderate and heavy ethanol consumption on myocardial recovery from ischemia.

The purpose of this study was to determine the effects of chronic moderate and heavy ethanol consumption on myocardial ischemia/ reperfusion injury. Three groups (n = 18) of 6-month-old female Sprague-Dawley rats were fed a nutritionally balanced liquid diet. Control, moderate alcohol, and heavy alcohol groups consumed 0%, 20%, and 35% of their calories from ethanol, respectively. After 10 weeks of feeding, hearts were isolated and subjected to 21.5 min of ischemia alone, or 21.5 min of ischemia followed by 30 min reperfusion. Hearts were evaluated for hemodynamic characteristics and high-energy phosphate content. Hearts from animals exposed to moderate and heavy amounts of ethanol recovered significantly less (30.61% and 29.45%, respectively) of their preischemic cardiac external work than control hearts (65.52%). Postischemic diastolic stiffness was increased approximately 7-fold, and high-energy phosphate content, both creatine phosphate and adenosine triphosphate, decreased >25% by both chronic moderate and heavy ethanol consumption. In conclusion, both chronic moderate and heavy ethanol consumption exacerbate myocardial ischemia/reperfusion injury. The ethanol-induced reduction in postischemic energy status may be the mechanism of increased diastolic stiffness and subsequent reduced cardiac external work.

Adenosine Triphosphate↗

PubMed1997

Contraction-induced intracellular signals and their relationship to muscle GLUT-4 concentration.

This investigation used a model of increased skeletal muscle contractile activity to evaluate whether the adenylate cyclase-adenosine 3',5'-cyclic monophosphate (cAMP) pathway and/or the high-energy phosphate state of the muscle might be temporally related to the contraction-induced increase in skeletal muscle GLUT-4 protein concentration. Plantaris and gastrocnemius muscles of Sprague-Dawley rats were subjected to 3, 7, 14, or 28 days of chronic low-frequency electrical stimulation (10 Hz, 24 h/day). GLUT-4 protein concentration was slightly reduced after 3 days of electrical stimulation, similar to control values at 7 days and significantly elevated above control at 14 days (53%, P < 0.05) and 28 days (338%, P < 0.05) of stimulation. ATP, creatine phosphate, creatine, and P, were inversely related to GLUT-4 protein concentration. Adenylate cyclase activity increased with electrical stimulation and was significantly related to the increased GLUT-4 protein. cAMP was significantly increased at 14 days of stimulation and remained elevated through 28 days. These results demonstrate that both the adenylate cyclase-cAMP pathway and the high-energy phosphate state of the muscle are temporally related to elevations in skeletal muscle GLUT-4 protein concentration in response to chronic low-frequency electrical stimulation and, as such, suggest that both may comprise a component of the intracellular signal that regulates the contraction-induced increase in skeletal muscle GLUT-4 protein concentration.

Adenylyl Cyclases↗

PubMed1996

Growth hormone supplementation increases skeletal muscle mass of old male Fischer 344/brown Norway rats.

Growth hormone (GH) supplementation can increase the body weight of old rats, but the individual tissues affected were previously unidentified. Therefore, the masses of the heart, spleen, kidney, epididymal fat pads, and five skeletal muscles were assessed in male Fischer 344/Brown Norway rats (9, 20, 31, months) injected with recombinant human GH (0.7 mg/kg) or vehicle twice daily for 10 days. Muscle composition (fiber type, protein concentration, dry weight/wet weight ratio, citrate synthase activity) was also evaluated. Muscle mass was increased with GH treatment, and this increment was undiminished in old age. Fiber type, protein concentration, and dry weight/wet weight ratio were unaffected by GH. Citrate synthase activity declined in the plantaris and increased in the soleus with GH treatment. GH supplementation elevated heart and spleen mass, but not fat pad or kidney weight. The data demonstrate that the capacity for GH-induced hypertrophy of skeletal muscle, myocardium, and spleen is retained during old age.

Aging↗

PubMed1994

Transcriptional regulation of muscle fatty acid-binding protein.

Heart fatty acid-binding protein (H-FABP) is present in a wide variety of tissues but is found in the highest concentration in cardiac and red skeletal muscle. It has been proposed that the expression of H-FABP correlates directly with the fatty acid-oxidative capacity of the tissue. In the present study, the expression of H-FABP was measured in red and white skeletal muscle under two conditions in which fatty acid utilization is known to be increased: streptozotocin-induced diabetes and fasting. Protein concentration, mRNA concentration and transcription rate were measured under both conditions. The level of both protein and mRNA increased approximately 2-fold under each condition. The transcription rate was higher in red skeletal muscle than in white muscle, was increased 2-fold during fasting, but was unchanged by streptozotocin-induced diabetes. In addition to supporting the hypothesis that H-FABP is induced during conditions of increased fatty acid utilization, these findings demonstrate that the regulation of H-FABP expression may or may not be at the level of transcription depending on the stimulus.

Animals↗

PubMed1993

Effect of chronic electrical stimulation on GLUT-4 protein content in fast-twitch muscle.

Insulin- and contraction-stimulated skeletal muscle glucose transport is governed largely by the GLUT-4 isoform of the glucose transporter. Recently, it has been demonstrated that denervated muscle has decreased GLUT-4 protein content, suggesting that regulation of GLUT-4 protein is related to neuromuscular activity. However, until now the effects of the opposite situation, enhanced neuromuscular activity, could only be speculated on from exercise training studies. In the present investigation the effect of chronic low-frequency electrical stimulation (10 Hz, 8 h/day) on GLUT-4 protein content and citrate synthase activity was determined in the predominantly fast-twitch plantaris. Chronic electrical stimulation enhanced GLUT-4 protein content and citrate synthase activity in the muscles stimulated for 10-20 days. Electrical stimulation lasting 30-40 days resulted in no further enhancement of GLUT-4 protein content while citrate synthase activity continued to increase. Further prolongation of electrical stimulation (60-90 days) resulted in a plateauing of citrate synthase activity. The results suggest that increased neuromuscular activity can act independently of systemic changes to increase total GLUT-4 protein content. They also suggest that both GLUT-4 protein content and citrate synthase activity are positively related to increased neuromuscular activity but that their rates of increase differ substantially.

Animals↗

PubMed1992

Exercise training improves cardiac function after ischemia in the isolated, working rat heart.

The aim of this study was to determine whether exercise training produces a myocardium intrinsically more tolerant to ischemic-reperfusion injury. Male Fischer 344 rats were treadmill trained for 11-16 wk at one of the following intensities: LOW (20 m/min, 0% grade, 60 min/day), moderate (MOD; 30 m/min, 5% grade, 60 min/day) or intensive (INT; 10 bouts of alternating 2-min runs at 16 and 60 m/min, 5% grade). Cardiac function was evaluated both before and after 25 min of global, zero-flow ischemia in the isolated, working heart model. Compared to hearts from sedentary (SED) rats, postischemic cardiac output (CO) and work were significantly higher in all trained groups. Percent recovery of CO (relative to preischemia) was 36.0 +/- 7.1 in SED and 61.2 +/- 6.5, 68.1 +/- 9.3, and 73.2 +/- 5.0 in LOW, MOD, and INT, respectively. Postischemic increases in stroke volume with increased preload and cardiac work at high work load were significantly higher in INT compared with SED. Coronary flow during initial retrograde reperfusion was significantly enhanced with training and correlated with subsequent recovery of CO (R2 = 0.613). Furthermore, trained hearts had higher phosphocreatine (P less than 0.05) and ATP (P less than 0.01) contents after 45 min reperfusion. It is concluded that exercise training results in an intrinsic myocardial adaptation, allowing greater recovery of cardiac pump function after global ischemia in the isolated rat heart.

Adenosine Triphosphate↗

PubMed1991

Enhancement of spatial learning in F344 rats by physical activity and related learning-associated alterations in hippocampal and cortical cholinergic functioning.

The effects of physical activity on spatial memory performance and associated cholinergic function were examined in F344 rats. Cholinergic analysis included resting and depolarization-induced activation of high-affinity choline uptake and muscarinic receptor binding in the hippocampus, parietal cortex and frontal cortex. Rats that were physically trained, using chronic treadmill running, demonstrated significantly enhanced performance on the spatial learning task, both in second trial latency and first and second trial proximity ratio scores (P less than 0.002). Concomitant with enhanced behavioral performance were neurochemical changes of a reduction in hippocampal high-affinity choline uptake, an upregulation of muscarinic receptor density, and an increase in high-affinity choline uptake 24 h after spatial memory testing (P less than 0.05). Spatial memory tested rats demonstrated enhanced depolarization-induced activation of high-affinity choline uptake (P less than 0.001). Rats that were yoked for swim time to spatial memory tested rats did not show any spatial learning-induced alterations in high affinity choline uptake. These spatial learning- and physical activity-induced cholinergic alterations were observed only in the hippocampus, not in the parietal or frontal cortex. These data indicate that the chronic running-induced alterations in hippocampal high-affinity choline uptake and upregulation of muscarinic receptor density, in combination with enhancement of high-affinity choline uptake related to spatial learning, may contribute to the enhanced spatial learning performance of chronic-run rats.

Animals↗

PubMed1991

Physical activity effects on hippocampal and parietal cortical cholinergic function and spatial learning in F344 rats.

In the present investigation, the effects of physical activity on hippocampal cholinergic function, parietal cortical cholinergic function, and spatial memory were examined in F344 rats. Single bouts of physical activity elevated hippocampal and cortical high affinity choline uptake, whereas chronic physical activity significantly reduced only hippocampal high affinity choline uptake (HACU) and elevated muscarinic (QNB) receptor density. Three weeks prior to the end of the 14-week chronic treadmill running protocol, a group of chronic-run rats and their non-run controls were tested on a stringent version of Whishaw's place learning-set task. Chronic-run rats exhibited enhanced performance on the spatial task by significantly reduced second trial latencies and elevated first and second trial proximity ratio scores. Chronic-run spatial memory tested rats also showed enhanced hippocampal HACU and muscarinic receptor binding. These data indicate that chronic physical activity improves spatial learning performance. This improvement may be due, in part, to a chronic running-induced enhancement of hippocampal cholinergic functioning.

Animals↗

PubMed1991

Effect of physical activity on hippocampal high affinity choline uptake and muscarinic binding: a comparison between young and old F344 rats.

Normal aging has been associated with a progressive decline in hippocampal cholinergic function. In the present study, specific markers of hippocampal cholinergic function, high-affinity choline uptake (HACU) and muscarinic quinuclidinylbenzilate (QNB) binding, were shown to be altered by endurance training (6 months of treadmill running, 5 days/week, 30 min/day). HACU and QNB binding were determined in synaptosomes of endurance trained F344 rats and their age-matched sedentary controls. Comparison of synaptosomes of sedentary rats ages 3 months, 12 months and 25 months (distinguished in this paper as young (Y), middle age (MA) and old (O), respectively) showed maximum HACU at 12 months and subsequent reduction in HACU and QNB binding at 25 months (P less than 0.05). This decline at 25 months is consistent with previous reports of an age-related decline in cholinergic function. Endurance trained rats (trained from 6 months to 12 months of age) showed a reduction (P less than 0.02) in HACU and an increase (P less than 0.05) in QNB binding compared to their age-matched sedentary controls whereas endurance trained rats (trained from 19 months to 25 months of age) showed no significant difference in either parameter from their age-matched sedentary controls. From these results, it appears that while both training and normal aging reduce HACU, the reductions may be different in presynaptic mechanism and postsynaptic consequence.

Adrenal Glands↗

PubMed1991

Compensation of the age-related decline in hippocampal muscarinic receptor density through daily exercise or underfeeding.

A decline in muscarinic receptor density of the hippocampus during aging has been previously observed. In the present investigation, the physiological treatments of underfeeding (every-other-day feeding) and exercise (daily treadmill running), initiated at 3 months or 10 months of age, compensated for this age-related decline in hippocampal muscarinic receptor density in F344 rats. Muscarinic receptor density in aged rats, 27 or 24 months of age, was maintained to levels comparable to rats 12 or 10 months of age, respectively. In addition, with the protocols used in this study, underfeeding appeared to be more effective than exercise in muscarinic receptor upregulation.

Aging↗

PubMed1991

Influence of electrical stimulation on a fast-twitch muscle in aging rats.

Recently we observed that the flexor digitorum longus muscle of the Fischer 344 rat, which is comprised primarily of type IIb muscle, does not change in size, fiber type, or physiological characteristics during senescence [Am. J. Physiol. 258 (Cell Physiol. 27): C1031-C1035, 1990]. This muscle was utilized to determine whether a predominantly fast-twitch glycolytic muscle would respond to tonic electrical stimulation (ES) with the same degree of fiber-type transformation in aging and young rats. The extent of transformation was quantified by measuring the contractile and metabolic properties, as well as the fiber-type composition, of the flexor digitorum longus muscle after ES (10 Hz, 8 h/day) imposed on the tibial nerve for periods of 0-90 days in young adult (YG; 6-8 mo), middle-aged (MA; 16-18 mo), and senescent (SN; 26-28 mo) male Fischer 344 rats. Although ES induced a IIb-to-IIa fiber-type shift in all groups, in the SN rats the shift was significantly less pronounced at the intermediate time points and remained incomplete after 90 days, compared with YG and MA rats. ES resulted in a reduction in tetanic tension (Po), which in the YG and MA rats was due to a reduction in muscle cross-sectional area. In the SN rats the reduced Po was due to a combined loss of cross-sectional area and specific tension (Po, N/cm2). Contraction and half-relaxation times were largely unaffected by ES, and maximal velocity of unloaded shortening declined throughout ES in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

PubMed1990

Aging does not affect contractile properties of type IIb FDL muscle in Fischer 344 rats.

The purpose of this study was to examine the influence of aging on the contractile, metabolic, and histochemical properties of the predominantly fast-twitch flexor digitorum longus muscle (FDL) in the Fischer 344 (F344) rat strain. Contractile measurements were made in situ by stimulating the motoneuron while the animals were under pentobarbital sodium anesthesia. Fiber-type composition, capillarity, aerobic capacity, and myosin light chain composition were also examined. The results of this investigation were striking in that there was no alteration in any parameter measured. Collectively, these results suggest that aging does not induce a functional alteration in the neuromuscular relationship in the predominantly fast-twitch FDL of F344 rats, and consequently, there is no loss of functional capacity of the muscle. This study demonstrates that alteration in predominantly fast-twitch muscle is not a universal phenomenon and that care must be taken when generalizing about the influence of aging on skeletal muscle. Some of the conflicting results regarding the influence of aging on predominantly fast-twitch muscle in rodents may be either strain or muscle specific.

Aging↗

PubMed1989

Development of tolerance in brain mitochondria for calcium uptake following chronic ethanol ingestion.

Brain mitochondria isolated from rats following 10 weeks of chronic exposure to ethanol were not deficient in respiratory function or in rates of calcium uptake under control conditions. Ethanol (80 mM) in the incubation medium caused significant depression in the respiratory and ATP-dependent rates of calcium uptake in control mitochondria, but did not affect mitochondria from ethanol-tolerant rats. Chronic exposure to ethanol causes mitochondria to take calcium up at a normal rate when challenged acutely by ethanol.

Animals↗

PubMed1989

Aging does not alter cytosolic calcium levels of cortical synaptosomes in Fischer 344 rats.

Several lines of experimental evidence support an association between altered Ca2+ regulation and aging. It has been supposed that free cytosolic Ca2+ concentrations ([Ca2+]i) may decrease or increase in aged animals. In this study, both resting and KCl-stimulated [Ca2+]i were measured in purified cortical synaptosomes from young (3 mo.), middle-aged (12 mo.), and old (24 mo.) Fischer 344 rats. Two additional groups of rats were included, one middle-aged and one old which were trained on a treadmill for 6 months prior to experimentation. The [Ca2+]i was determined using the fluorescent Ca2+ chelator fura-2. Net KCl-dependent changes (delta K) in [Ca2+]i were determined by the difference between stimulatory (100 microM Ca2+/60 mM KCl) and resting (100 microM Ca2+/5 mM KCl buffer) conditions among the 3 age groups. Significant increases in [Ca2+]i were observed in each age group upon depolarization with 60 mM KCl. However, there were no significant age-dependent differences in either resting [Ca2+]i or KCl-stimulated [Ca2+]i.

Aging↗

PubMed1989

Effectiveness of two synthetic fiber filters for removing white cells from AS-1 red cells.

Two commercially available synthetic fiber filters were studied for their effectiveness at removing white cells (WBCs) from AS-1-preserved red cells (RBCs) stored less than or equal to 14 days. In all, 65 filtrations were performed. An automated microprocessor-controlled hydraulic system designed for use with cellulose acetate fiber filters was employed to prepare filtered RBCs before release for transfusion. Studies were also carried out on polyester fiber filters, which are designed to be used in-line during transfusion. Residual WBCs were below the accurate counting range of Coulter counters and of conventional manual chamber counts. An isosmotic ammonium chloride RBC lysis method, plus a modified chamber counting technique, permitted a 270-fold increase over the number of WBCs counted by the conventional manual method. For the polyester fiber-filtered products, residual WBCs per unit were not affected by speed of filtration, prior length of storage, or mechanical tapping during filtration. The effectiveness of WBC removal (mean 99.7%), total residual WBCs (means, 4.8 and 5.5 x 10(6], and RBC recovery (mean, 93%) was the same for both filters. The majority of residual WBCs were lymphocytes. WBC removal and RBC recovery were strikingly superior to results reported with nonfiltration methods.

Adenine↗