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Biomedical subjects

J E Graves

Publications and source records attributed to J E Graves.

At least 37 records · Page 2Linked to original sources

The lack of effect of aerobic exercise training on propranolol pharmacokinetics in young and elderly adults.

The effects of exercise training on the pharmacokinetics of orally administered propranolol were studied in young and elderly healthy volunteers. Twenty-three young (30 +/- 5 years of age) and 20 elderly (67 +/- 5 years of age) adults were randomly assigned to endurance training (N = 12 young subjects, 10 elderly subjects) or nonexercising control (N = 11 young subjects, 10 elderly subjects) groups. Training consisted of treadmill walking, stair climbing, or both three times per week for 40 minutes at 70-85% of maximal heart rate reserve for 16 weeks. Resting plasma propranolol concentrations after a single dose of 80 mg of oral propranolol were measured by high performance liquid chromatography with fluorescence detection, and estimated hepatic blood flow measured was measured using indocyanine green during supine test. Aerobic training increased maximal oxygen uptake (VO2 max) by 13% and 14% in the exercising young and elderly groups, respectively. There was no change in VO2 max in either control group. Adjusted mean estimated hepatic blood flow after exercise corrected for body weight for the young subjects who did not exercise (15.6 mL/min/Kg) and those who did (18.2 mL/min/Kg) groups were of borderline significance. No statistical differences were detected in the experimental propranolol pharmacokinetic parameters (maximal concentration, time of maximal concentration, terminal half-life, area under the curve, and protein binding) or derived pharmacokinetic parameters (intrinsic clearance, bioavailability, clearance, and volume of distribution). These results provide evidence that changes in aerobic fitness do not produce corresponding changes in propranolol pharmacokinetics in young or elderly adults.

Administration, Oral↗

The short- and long-term effects of methotrexate on the rat skeleton.

Both clinical and laboratory studies have shown that the chemotherapy drug, Methotrexate (MTX), has adverse short-term effects on bone. There are no studies that demonstrate the long-term response of bone to MTX. The purpose of this study was to determine the short- and long-term effects of MTX on bone volume, turnover, mineralization and strength. Three-month-old Sprague-Dawley rats were randomly assigned to a control (CTL) or MTX group and were given either daily MTX or saline injections for two separate 5-day courses (5 on/9 off/5 on). Fluorochrome compounds were injected prior to killing to label actively mineralizing bone surfaces. One CTL and MTX group were killed at 30, 80 and 170 days after treatment. Both femurs and tibiae were harvested for cancellous and cortical bone histomorphometry and biomechanical testing (torsion). Standard cancellous and cortical histomorphometric parameters were measured from undecalcified, methyl-methacrylate-embedded sections from the right proximal tibia and tibial and femoral diaphyses. The contralateral femur and tibia were torsionally loaded to failure and standard mechanical parameters were measured. All bone responses were statistically analyzed using a two-way ANOVA followed by Duncan's multiple comparison procedure (significance: p = 0.05). Cancellous bone volume was significantly lower in the MTX-treated group at 80 and 170 days. Cancellous mineralizing surface and longitudinal bone growth were significantly depressed at all time points yet mineral apposition rate was only depressed at the 170-day point. Cancellous osteoclast surface was increased at all time points for the MTX-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Selective impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated resistance arteries of the streptozotocin-induced diabetic rat.

1. There is growing evidence that an impairment in the function of nitric oxide synthase may play a role in the vascular complications of diabetes mellitus. The relaxation of resistance arteries from the mesenteric and hindlimb circulations of streptozotocin-induced diabetic rats and age-matched controls were investigated using two endothelium-dependent vasodilators, bradykinin and acetylcholine, and the endothelium-independent vasodilator sodium nitroprusside. The contractile responses to the alpha 1-adrenergic agonist phenylephrine were also studied. 2. Endothelium-dependent relaxation to acetylcholine was impaired in the diabetic rats in arteries from both mesenteric and hindlimb circulations (hindlimb pEC50, 7.93 +/- 0.08 in the control compared with 7.38 +/- 0.10 in the diabetic rat; mesenteric pEC50, 7.47 +/- 0.04 in the control compared with 6.65 +/- 0.06 in the diabetic rat; unpaired t-test P < 0.0001). Bradykinin elicited relaxation in only the mesenteric arteries, and this was not attenuated in the diabetic rats compared with controls. 3. Endothelium-independent relaxation to sodium nitroprusside was similar in the two circulations and was not abnormal in the diabetic rats. There was no significant difference in constrictor responses to phenylephrine between diabetic rats and controls in either the hindlimb or mesenteric arteries, in contrast to an earlier study in which we showed increased sensitivity to noradrenaline. 4. The diabetic rats therefore demonstrated a specific impairment of receptor-mediated endothelium-dependent relaxation to acetylcholine. These results suggest that, in this diabetic model, the ability of the endothelium to relax arteries via nitric oxide may involve a defect of a specific signal transduction pathway, leading to reduced production of nitric oxide.

Acetylcholine↗

Hormonal responses in elders experiencing pre-syncopal symptoms during head-up tilt before and after exercise training.

BACKGROUND: Hormonal responses of elderly individuals experiencing pre-syncopal symptoms during head-up tilt testing (HUT) were compared with responses of nonsymptomatic subjects both before (T1) and after (T2) 6 months of endurance training. METHODS: Based on responses to HUT at T1, 35 men and women (ages 61-79 years) were placed into symptomatic and nonsymptomatic groups for analysis. Symptomatic subjects (n = 5) experienced lightheadedness, nausea, sweating, or syncope during T1 HUT but completed 15 minutes of HUT at T2. Training consisted of treadmill walking or stairclimbing 3 x/wk, 30-45 min/day, at 75-85% of maximal heart rate reserve. Adrenocorticotropic hormone (ACTH), vasopressin, aldosterone, norepinephrine, epinephrine, hemoglobin, and hematocrit were measured during supine rest prior to HUT, and either at the end of the 15-minute HUT or at symptom onset. Plasma volume (PV) was measured at supine rest; tilt-induced changes in PV were calculated from changes in hemoglobin and hematocrit. RESULTS: During T1 HUT, symptomatic subjects had greater increases in vasopressin and a greater rate of PV loss (p < .05). Increases in ACTH and aldosterone were greater in symptomatic subjects at T1 and T2, while increases in norepinephrine were greater at T2 (p < .05). Reductions in tilt-induced vasopressin concentration and a decreased rate of PV loss were seen at T2 in symptomatic subjects. CONCLUSIONS: T1 results from symptomatic subjects are consistent with greater stimulation of volume-sensitive receptors induced by a greater rate of fall in PV. Exercise training resulted in increased tilt tolerance for symptomatic subjects associated with reductions in vasopressin concentration and rate of PV loss during tilt.

Aged↗

Effect of 6 months of exercise training on cardiovascular responses to head-up tilt in the elderly.

The purpose of this investigation was to evaluate the effect of 6 months of exercise training on cardiovascular responses to 70 degrees head-up tilt (HUT) in the elderly. Forty-four elderly men and women (ages 60-82 years) were assigned to endurance training alone (n = 18), endurance training in combination with selected resistance exercises (n = 17), or to a non-exercising control group (n = 9). Head-up tilt testing at the start (T1) and end (T2) of 26 weeks of training consisted of 30 min of supine rest, 15 min of 70 degrees HUT, and 15 min of supine recovery. Endurance training consisted of uphill treadmill walking or stair climbing exercise 3 times per week, 30-45 min/day, at 75-85% of maximal heart rate reserve. In addition, the endurance/resistance group completed one set of 8-15 repetitions of biceps curl (BC), triceps extension (TE), and leg press, 3 times per week. After 26 weeks, increases in VO2max averaged 16.2% and 12.3% for endurance and endurance/resistance groups, respectively. In addition, the endurance/resistance group increased BC and TE strength by 25.3% and 26.1%, respectively. Results from the HUT test indicated that only the endurance group increased supine resting stroke volume (SV) and cardiac output (Q) from T1 to T2; however, SV and Q during HUT were not augmented as a result of training. Training did not affect heart rate, blood pressure, or peripheral resistance responses at rest or during HUT in any of the groups. These results suggest that 6 months of endurance training, alone or in combination with selected resistance exercises, is not detrimental to blood pressure controlling mechanisms to head-up tilt in the elderly.

Aged↗

Body fat and muscle thickness distributions in untrained young females.

Brightness-mode (B-mode) ultrasound was used to measure fat and muscle thicknesses on 44 untrained females (age = 18-29 yr, body density = 1.050 +/- 0.009 (SD)g.ml-1, %fat = 21.5 +/- 4.1%) at eight sites (triceps, biceps, forearm, subscapular, abdomen, quadriceps, hamstrings, and posterior calf). The correlation coefficients between fat and muscle thickness were not significant at any measurement site except for the triceps (r = -0.32, P < 0.05). Intercorrelation analyses among the eight sites were significant (P < 0.05) in almost all cases for fat thickness, while mainly between adjoining sites for muscle thickness. However, both tissues had a low degree of generality in thickness among sites. Fat thickness at all measurement sites was significantly correlated with body density except for the posterior calf; the best correlation was found with the quadriceps (r = -0.73). On the other hand, for muscle thickness, only the forearm and triceps were significantly correlated with body density. These results show 1) the extent of muscled and fat thicknesses are independent each of other within the same region, 2) fat and muscle thicknesses have a high degree of specificity in site distribution, and 3) fat thickness measurements determined from B-mode ultrasound may be of significant value assessing total body composition.

Adipose Tissue↗

Effects of running on the torsional strength, morphometry, and bone mass of the rat skeleton.

Intensity and duration effects of weight-bearing exercise on the rat skeleton were investigated. Eighty-four 3-month-old female Sprague-Dawley rats were assigned to control and nine exercise groups. Exercised rats were run on a treadmill for either 30, 60, or 90 min.d-1 at low (Vo2max approximately 55%), medium (VO2max approximately 65%), or high (VO2max approximately 75%) intensity 4 d.wk-1 for 10 wk. Rat femurs, tibias, and vertebrae were harvested for torsional mechanical tests, bone density assessment, and morphometry. Our results indicate exercise has a significant effect (P < 0.05) on the femoral mechanical response (energy absorbed and twist angle), tibial morphometry (cortical bone area and thickness), and tibial and vertebral bone density measurements but had no effect (P > 0.05) on bone strength when compared with control values. Higher intensity exercise decreased tibial and femoral torque (P < 0.05). Long duration exercise increased tibial and femoral stiffness and decreased twist angle and energy absorbed (P < 0.05). These results indicate bone adapts to its loading environment by increasing bone mineral density, increasing cortical bone area, increasing stiffness, decreasing energy absorbed, and decreasing twist angle. High-intensity exercise decreased the maximum force the bone could withstand, whereas long duration exercise made the bone more brittle.

Absorptiometry, Photon↗

Effect of training on blood volume and plasma hormone concentrations in the elderly.

The purpose of this investigation was to determine the effects of 6 months of endurance training on resting plasma (PV) and blood volume (BV), and resting hormone and electrolyte concentrations in the elderly. Thirty-eight elderly men and women (ages 60-82 yr) were assigned to endurance exercise training (N = 29) or to control (N = 9) groups. Resting plasma levels of adrenocorticotropic hormone, vasopressin, aldosterone, norepinephrine, epinephrine, sodium, potassium, and protein were measured at the start (T1) and end (T2) of 26 wk of training. PV measurement was performed using the Evan's blue dye technique. Endurance training consisted of uphill treadmill walking or stairclimbing exercise 3 times.wk-1, 30-45 min.d-1, at 75-84% of maximal heart rate reserve. The exercise group increased VO2max by 11.2% (P < or = 0.05) and increased resting PV and BV by 11.2% and 12.7% (P < or = 0.05), respectively. Hormone and electrolyte levels in the exercise group remained unchanged; all variables were unchanged in the control group. These results are similar to findings in younger individuals. Because plasma hormone concentrations were maintained despite a chronically elevated BV, endurance training in healthy, elderly subjects may be associated with a resetting of volume receptors.

Adrenocorticotropic Hormone↗

Moderate- and high-intensity exercise lowers blood pressure in normotensive subjects 60 to 79 years of age.

To investigate the effects of exercise intensity on resting blood pressure (BP) in normotensive elderly subjects, 44 sedentary healthy subjects aged 60 to 79 years of age were studied during 6 months of walking exercise. Subjects were ranked according to maximal oxygen consumption and randomly stratified to groups that trained at 70% (n = 19) or 80% to 85% (n = 14) of maximal heart rate reserve, or to a control group (n = 11) that did not train. Initial BP was established during a 2- to 3-week control period. During the first 3 months, both exercise groups progressed to 70% of heart rate reserve for 40 minutes 3 times each week. The moderate-intensity group continued to train at 70% (45-minute duration) for an additional 3 months, whereas the high-intensity group progressed to training at 85% of heart rate reserve (35-minute duration). Maximal oxygen consumption increased (p < or = 0.05) during the initial 3 months in both exercise groups (25.2 to 28.1 ml.kg-1.min-1 and 26.3 to 29.3 ml.kg-1.min-1) and continued to increase (p < or = 0.05) after 3 additional months of training, but the increase was greater (p < or = 0.05) in the high-intensity group (28.1 to 29.4 ml.kg-1.min-1 and 29.3 to 32.8 ml.kg-1.min-1). Systolic BP decreased (p < or = 0.05) similarly at 6 months in both training groups (120 to 111 mm Hg and 120 to 112 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Functional assessment for prediction of lifting capacity.

OBJECTIVE: This study investigated the ability to predict maximal functional lifting capacity from peak isometric lumbar extension torque and submaximal lifting mechanics. METHODS: Peak isometric lumbar extension torques were measured on 26 healthy men and women, ages 18 to 39 years. In addition, their lifting mechanics were evaluated while they lifted a submaximal load. Each subject's maximal lifting capacity (kg) then was predicted from the peak torque and submaximal kinetic analysis using a linear regression model. RESULTS: Mean values for the predicted and actual maximum weight the subjects lifted were not significantly different (50.3 +/- 15.6 kg and 48.5 +/- 17.0 kg, respectively, P > or = 0.05). The correlation between predicted and criterion values was high (r = 0.96), and the total error of the prediction was 5.1 kg, which represented 10.5% of the actual maximum value. CONCLUSIONS: This multi-faceted functional assessment model involving biomechanical analysis of a submaximal lift and maximal isometric lumbar extension strength accurately predicted a subject's maximum functional lifting capacity.

Adult↗

Endurance exercise training improves body composition and plasma insulin responses in 70- to 79-year-old men and women.

Forty-two men and women aged 70 to 79 years were studied to assess the effects of 6 months of endurance or resistance training and subsequent cessation of training on glucose tolerance, plasma insulin responses, serum triglyceride and cholesterol levels, and plasma dehydroepiandrosterone (DHEA) levels. The endurance training group (n = 16) exercised at 75% to 85% heart rate reserve for 35 to 45 minutes three times per week; the resistance training group (n = 17) completed one set of eight to 12 repetitions on 10 Nautilus machines three times per week. No significant changes in any variables occurred in a control group (n = 9). Maximal oxygen consumption (VO2max) increased by 20% with endurance training, but did not change with resistance training. Upper- and lower-body strength increased in the resistance training group, but did not change with endurance training. Neither group changed their body weight with training, but the endurance training group elicited a significant reduction in their sum of seven skinfolds and percent body fat. Neither group altered their glucose tolerance with training; however, the endurance training group had lower plasma insulin responses after training compared with the other two groups. Serum lipid and plasma DHEA levels did not change in either the endurance or resistance training groups. Ten days of no exercise following training did not significantly alter body weight or composition, glucose tolerance, plasma insulin responses, or plasma DHEA levels in either the endurance training (n = 10) or resistance training (n = 14) group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Exercise, age, and skeletal muscle function.

Skeletal muscle strength, muscle mass, and psychomotor performance decline with age. These declines are associated with reduced functional capacity and an increased risk of musculoskeletal injury and dependent care. Resistance exercise training is generally safe and effective for improving muscle strength and increasing muscle mass in the elderly. The magnitude of improvement depends on the intensity of training and the initial level of fitness. Because many elderly persons have low levels of muscular strength, they show a greater than average potential for relative improvement. Whether an exercise program can enhance psychomotor performance in the elderly is equivocal. Participating in a well-rounded program of physical activity throughout life may be the best approach to attenuating the decline in skeletal muscle function associated with aging.

Aged↗

Exercise training and prescription for the elderly.

Most exercise programs designed for healthy persons older than 65 emphasize fitness development, but the maintenance of functional capacity and quality of life are equally important. The basic guidelines for frequency, intensity, and duration of training and the mode of activity recommended by the American College of Sports Medicine for healthy adults are also appropriate for the elderly. The difference in the exercise prescription for the elderly participant is the manner in which it is applied. Given that the elderly person is more fragile and has more physical-medical limitations than the middle-aged participant, the intensity of the program is usually lower while the training frequency and duration are increased. The mode of training should avoid high-impact activities, and the progression of training should be more gradual. The prescribed training heart rate for the elderly at 40% to 80% of maximal heart rate reserve is slightly lower than the 50% to 85% recommended for young and middle-aged participants, but its relationship to relative metabolic work (50% to 85% of maximal oxygen uptake) and rating of perceived exertion are similar to those found for younger participants. Because of the importance of maintaining muscle mass and bone in middle and old age, a well-rounded program including strength/resistance exercise of the major muscle groups is recommended. Hence the exercise prescription for the elderly should emphasize low to moderate intensity and low-impact activities, avoid heavy static-dynamic lifting, and allow a gradual progression in training.

Activities of Daily Living↗

Pelvic stabilization during resistance training: its effect on the development of lumbar extension strength.

The purpose of this study was to evaluate and compare resistance exercise training with and without pelvic stabilization on the development of isolated lumbar extension strength. Isometric torque of the isolated lumbar extensor muscles was measured at seven positions through a 72 degree range-of-motion on 47 men and 30 women before and after 12 weeks of variable resistance lumbar extension training. Subjects were assigned to either a group that trained with pelvic stabilization (P-STAB, n = 21), a group that trained without pelvic stabilization (NO-STAB, n = 41), or a control group that did not train (n = 15). Subjects trained once a week with 8 to 12 repetitions to volitional exhaustion. The P-STAB and NO-STAB groups showed significant (p < or = 0.05) and similar increases in the weight load used for training (P-STAB = 24.1 +/- 9.4kg; NO-STAB = 19.4 +/- 11.0kg) during the 12-week training period. In contrast, posttraining isometric torque values describing isolated lumbar extension strength improved only for the P-STAB group (23.5%, p < or = 0.05) and not for the NO-STAB group (-1.2%, p > 0.05) relative to controls. These data indicate that pelvic stabilization is required to effectively train the lumbar extensor muscles. The increased training load for the NO-STAB group is probably the result of exercising the muscles involved in pelvic rotation (hamstring and buttock muscles).

Adult↗

Using the exercise test to develop the exercise prescription in health and disease.

The objective of an exercise program for persons with or without disease should be the development or maintenance of cardiorespiratory fitness, strength and muscular endurance, and flexibility. The basic principles of prescribing exercise--frequency, intensity, and duration of training--and the mode of activity as recommended by the ACSM for healthy adults are also appropriate for persons with disease. The difference in the exercise prescription for persons with disease is the manner in which these principles are applied. Usually, the more fragile the patient, the lower the intensity of exercise and the slower the progression of training. The role of cardiopulmonary exercise testing is to determine a safe and effective level of exercise for healthy persons as well as those with disease. GXT is useful in identifying individuals with disease and in providing information regarding the level of supervision needed during exercise training. In addition, exercise testing can be used to clear a person for participation in a resistance training program. Resistance training should be integrated as part of a well-rounded program, because of the importance of maintaining strength, muscle mass, and bone mineral density. Generally, the starting intensity for persons with disease is lower, the frequency and duration higher, and the progression of exercise slower to allow a more gradual adaptation to exercise training.

Exercise↗

Carbon dioxide induced vasorelaxation in rat mesenteric small arteries precontracted with noradrenaline is endothelium dependent and mediated by nitric oxide.

Hypercapnia induces initial constriction and prolonged relaxation of rat small mesenteric arteries. The mechanism of the relaxation is unknown, but has been attributed to lowering of pHi in the vascular smooth muscle. In this study we have investigated the response to raised PCO2 at constant pHo, in mesenteric small arteries precontracted with noradrenaline. 10% CO2 led to a fall in pHi associated with acute potentiation of tension, and subsequent relaxation. The relaxation did not occur in arteries in which the endothelium had been removed, nor in arteries pretreated with the nitric oxide synthase inhibitor, L-NAME (10(-4)M, NG-nitro-L-arginine methyl ester). The D-enantiomer, D-NAME, was without effect. We conclude that hypercapnic-induced vasodilatation in this circulation occurs via endothelium derived nitric oxide production.

Amino Acid Oxidoreductases↗

Frequency and volume of resistance training: effect on cervical extension strength.

Quantification of cervical extension (CERV EXT) strength is complicated by the inability to stabilize the torso and isolate the CERV EXT muscles. A newly developed machine designed to stabilize the torso and isolate the CERV EXT muscles was used to evaluate the effect of frequency and volume of resistance training on CERV EXT strength. Fifty men (age, 26 +/- 9 years; height, 174 +/- 16 cm; weight, 74 +/- 9 kg) and 28 women (age, 30 +/- 9 years; height, 152 +/- 32 cm; weight, 62 +/- 7 kg) volunteered to participate. Subjects were randomly stratified to one of four training groups or a control group (CONT, n = 19) that did not train. Each training group exercised for 12 weeks as follows; once per week using one set of dynamic exercise (DYN 1x/wk, n = 14), once per week using one set of DYN and one set of maximal isometric (IM) exercise at eight angles through a 126 degrees-range of CERV EXT (DYN-IM 1x/wk, n = 16), DYN 2x/wk (n = 19), or DYN-IM 2x/wk (n = 10). Maximal IM torque was measured at eight angles initially and after 12 weeks of training. All training groups improved CERV EXT strength (p < or = 0.05) at all angles tested compared to the CONT except for DYN once per week at 0 degree of CERV flexion. A greater increase in strength was found when the groups that trained two times a week were compared to those that trained once per week.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of sodium-transport inhibition in human resistance arteries.

It is hypothesized that endogenous inhibitors of active sodium transport may lead to an increase in peripheral vascular resistance. From studies in animal conduit arteries there is substantial evidence that cardiac glycosides may increase tension. A number of studies from our laboratory demonstrate that inhibition of active sodium transport may also increase tension in human resistance arteries, and that reduced Ca efflux via Na/Ca exchange could be a contributory mechanism. Further experiments also have suggested that endogenous inhibitors of sodium transport could lead to an increase in peripheral vascular resistance by reducing endothelium-dependent relaxation.

Arginine↗