Physical inactivity: an easily modified risk factor?
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Adult↗
Biomedical subjects
J H Mitchell
Publications and source records attributed to J H Mitchell.
Skeletal muscle afferent fibres release substance P in the nucleus tractus solitarii of anaesthetized cats.
1. The tachykinin substance P was recovered from the commissural subdivision of the nucleus tractus solitarii (cNTS) using in vivo microdialysis during activation of cardiorespiratory and skeletal muscle receptors in thirteen chloralose-anaesthetized cats. 2. Tetanic muscle contraction was evoked by stimulating L7-S1 ventral roots (n = 7). Electrically induced muscle contraction increased mean arterial pressure (MAP) by 55 +/- 10 mmHg and heart rate by 29 +/- 6 beats min-1. During contraction the dialysate concentration increased 154 % above resting control levels (from 0.217 +/- 0.009 to 0.546 +/- 0.023 fmol (100 microl)-1, control vs. contraction, P < 0.05). 3. Loss of cardiorespiratory input following disruption of the carotid sinus and vagus nerves significantly blunted, but did not abolish, the increase in substance P during muscle contraction (from 0.247 +/- 0.022 to 0.351 +/- 0.021 fmol (100 microl)-1, control vs. contraction, P < 0.05). Approximately 44 % of the substance P release during contraction was independent of cardiorespiratory input transmitted by carotid sinus and vagus nerves. 4. To determine the contribution of cardiorespiratory related neural input on substance P release, an intravascular balloon positioned in the thoracic aorta was inflated to increase arterial pressure (n = 6). Balloon inflation increased MAP by 50 +/- 5 mmHg and substance P increased from 0.251 +/- 0.025 to 0.343 +/- 0. 028 fmol (100 microl)-1 (control vs. balloon inflation, P < 0.05). This increase was completely abolished following interruption of vagal and carotid sinus nerves (from 0.301 +/- 0.012 to 0.311 +/- 0. 014 fmol (100 microl)-1, control vs. balloon inflation). This finding shows that neural input from cardiorespiratory receptors (primarily arterial baroreceptors) accounted for 37 % of the total substance P release during muscle contraction. 5. The findings from this study demonstrate that activation of skeletal muscle receptors and cardiorespiratory receptors (predominantly arterial baroreceptors) increases the extraneuronal concentration of substance P in the cNTS. Because substance P release was not completely abolished during muscle contraction following disruption of carotid sinus and vagus nerves it is proposed that: (1) afferent projections from contraction-sensitive skeletal muscle receptors may release substance P in the NTS; (2) neural input from muscle receptors activates substance P-containing neurones within the NTS; and (3) convergence of afferent input from skeletal muscle receptors and arterial baroreceptors onto substance P-containing neurones in the cNTS facilitates the release of substance P. The role of tachykininergic modulation of cardiorespiratory input is discussed.
Anesthesia↗
Effects of a soy milk supplement on plasma cholesterol levels and oxidative DNA damage in men--a pilot study.
BACKGROUND: Phytoestrogens are a major component of Asian diets and may be protective against certain hormone-dependent cancers (breast and prostate) and coronary heart disease. They may also have antioxidant function in scavenging potentially harmful free radicals and thus decreasing oxidative attack on DNA. AIMS OF THE STUDY: A pilot study to determine the effects of a phytoestrogen supplement, in the form of soy milk, on plasma LDL and HDL cholesterol levels and DNA damage in men. METHODS: Ten healthy men participated in the study and were assigned to one of three groups consuming 1 litre of either soy milk, rice dream (vegetable protein control) or semi-skimmed cow's milk (animal protein control) each day for 4 weeks. RESULTS: The soy supplement caused significant increases in plasma genistein and daidzein concentrations despite considerable inter-individual variation (P < 0.001). Supplementation with soy resulted in a decrease in oxidative damage to DNA bases detected using the comet assay compared with controls (P < 0.05). However, there was no significant effect of the soy supplement on plasma cholesterol or triglyceride levels in comparison with control groups. CONCLUSIONS: A 4 week soy milk supplementation in healthy volunteers does not alter serum cholesterol levels but can have a protective effect against oxidative DNA damage in lymphocytes.
Adult↗
Decreased rate of back injuries through a wellness program for offshore petroleum employees.
High rates of injury, particularly those for back injuries, at an offshore petroleum unit were addressed through an intensive wellness program initiated in 1991. The number of all types of injuries, including back injuries, decreased between 1991 and 1995. The number of back injuries decreased from nine in 1987 to four in 1992 and was zero in 1993. Although there are inadequate data to provide power for a significant result, other criteria suggest a causal relationship. The results are consistent with the few published studies that suggest a decrease in the number of injuries in association with exercise and perhaps with modification of psychosocial risk factors. Calculations suggest a cost savings of over $800,000 and a return on investment of $2.51, as well as avoidance of pain and injury.
Back Injuries↗
Activation of the insular cortex is affected by the intensity of exercise.
The purpose of this investigation was to determine whether there were differences in the magnitude of insular cortex activation across varying intensities of static and dynamic exercise. Eighteen healthy volunteers were studied: eight during two intensities of leg cycling and ten at different time periods during sustained static handgrip at 25% maximal voluntary contraction or postexercise cuff occlusion. Heart rate, blood pressure (BP), perceived exertion, and regional cerebral blood flow (rCBF) distribution data were collected. There were significantly greater increases in insular rCBF during lower (6.3 +/- 1.7%; P < 0.05) and higher (13.3 +/- 3.8%; P < 0.05) intensity cycling and across time during static handgrip (change from rest for right insula at 2-3 min, 3.8 +/- 1.1%, P < 0.05; and at 4-5 min, 8.6 +/- 2.8%, P < 0.05). Insular rCBF was decreased during postexercise cuff occlusion (-5.5 +/- 1.2%; P < 0.05) with BP sustained at exercise levels. Right insular rCBF data, but not left, were significantly related, with individual BP changes (r(2) = 0.80; P < 0.001) and with ratings of perceived exertion (r(2) = 0.79; P < 0.01) during exercise. These results suggest that the magnitude of insular activation varies with the intensity of exercise, which may be further related to the level of perceived effort or central command.
Adult↗
Antioxidant efficacy of phytoestrogens in chemical and biological model systems.
Phytoestrogens (PEs) are diphenolic compounds from plants which can bind to estrogen receptors and have estrogen and antiestrogen effects in man and animals. Like other plant phenolics, PEs may have antioxidant properties through hydrogen/electron donation via hydroxyl groups. They might therefore act as free radical scavengers and inhibit development of coronary heart disease and cancers. The hydrogen-donating ability of a range of phytoestrogens was assessed using electron spin resonance spectroscopy, the ferric-reducing ability of plasma assay, and the Trolox equivalent antioxidant capacity. In addition, the ability of compounds to inhibit lipid peroxidation was examined in vitamin E-deficient liver microsomes. Genistein had the highest activity of the isoflavones; however, the isoflavones were relatively poor hydrogen donors compared with the other estrogenic compounds examined. Coumestrol and equol were more effective antioxidants than genistein but had relatively limited activity in comparison with Trolox. The only estrogenic compound with significant antioxidant activity was kaempferol which is better known as a dietary antioxidant than a phytoestrogen. As the concentrations of PEs used in this study exceed the estimated serum concentrations, their relatively poor antioxidant ability in vitro may indicate little significance as antioxidants in vivo.
Animals↗
Synchronization of somato-sympathetic outflows during exercise: role for a spinal rhythm generator.
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Animals↗
Cardiovascular response to submaximal stationary cycling during hemodialysis.
Exercise intolerance is a problem in renal failure. Stationary cycle training during hemodialysis treatment is recommended as safe, effective, and practical, but requires compensations for both exercise and acute changes in uremia. Eight patients pedalled for 5 minutes, at 60% of VO2peak, at 0, 1, 2, and 3 hours of a hemodialysis treatment. Fluid removed, blood pressure, cardiac output, heart rate, O2 uptake, hematocrit, and arterial O2 content were measured. Mean arterial blood pressure, systemic vascular resistance, stroke volume, (a-v)O2 difference, and mixed-venous O2 content were calculated. Fluid removed was 1,356 mL/hr (P < 0.002 for each hour), but with no significant cardiovascular effects during the first 2 hours. At 3 hours, decreasing cardiac output, stroke volume, and mean arterial pressure all reached significance at rest (P < 0.05), and five of eight patients could not exercise. We conclude that the cardiovascular exercise response is superimposed on hemodynamic effects of dialysis and is adequately stable during the first 2 hours of treatment. After 2 hours, cardiovascular decompensation may preclude exercise.
Analysis of Variance↗
Effect of barodenervation on c-Fos expression in the medulla induced by static muscle contraction in cats.
A previous study has shown increased Fos-like immunoreactivity (FLI), a marker of neural activation, in the nucleus of the solitary tract (NTS) and the ventrolateral medulla (VLM) after static muscle contraction elicited by electrical stimulation of L7 and S1 ventral roots of the spinal cord in anesthetized, baroreceptor-intact cats. Because the electrically induced static muscle contraction reflexly increased arterial blood pressure, the concomitant activation of the arterial baroreceptor reflex during static muscle contraction may have resulted in some of the FLI labeling that was observed in the medulla. The purpose of this study was to determine regions in the medulla that are activated by muscle contraction in the absence of arterial baroreceptor input. Electrical stimulation of L7 and S1 ventral roots of the spinal cord was used to elicit static muscle contraction, and FLI in the medulla was determined in barointact and barodenervated cats. In barointact contraction cats, FLI was observed in the lateral reticular nucleus (LRN), NTS, lateral tegmental field (FTL), subretrofacial nucleus (SRF), and A1 region of the medulla. In barodenervated contraction cats, FLI increased in the same regions; however, the number of FLI-labeled cells in the NTS, FTL, and A1 region was significantly less than in barointact contraction animals. No significant difference in the number of FLI-labeled cells was found in the LRN and SRF between the two groups. These results clearly demonstrate that cardiovascular regions in the medulla are activated by input from afferent activity originating in skeletal muscle independently of concomitant arterial baroreceptor reflex activation.
Afferent Pathways↗
Rapid resetting of carotid baroreceptor reflex by afferent input from skeletal muscle receptors.
Resetting of the arterial baroreflex is mediated by central (central command) or peripheral (exercise pressor reflex) mechanisms. The purpose of this study was to determine the effect of somatosensory input from skeletal muscle receptors on resetting of the carotid baroreceptor reflex. Resetting of the baroreflex was determined by measuring carotid sinus threshold pressure (Pth) during a ramp protocol that consisted of a linear increase in sinus pressure from 50 to 250 mmHg at approximately 3 mmHg/s. Experiments were performed in seven alpha-chloralose-anesthetized and vagotomized dogs. To determine the effect of skeletal muscle afferent input on resetting, electrically induced muscle contraction was used to activate mechanically and metabolically senstive afferent fibers, whereas passive stretch of the hindlimb was used to activate predominantly mechanically sensitive afferent fibers. Pth for heart rate (HR) and arterial blood pressure (BP) during the control ramp protocol was 110 +/- 4 and 118 +/- 7 mmHg, respectively. Electrically induced muscle contraction increased hindlimb tension (5.7 +/- 0.4 kg) and significantly increased Pth-HR and Pth-BP above control (135 +/- 6 and 141 +/- 5 mmHg, respectively; P < 0.05). Muscle paralysis prevented the increase in Pth-HR and Pth-BP during ventral root stimulation (104 +/- 7 and 116 +/- 5 mmHg, respectively; P = not significant). Passive muscle stretch (n = 3) increased hindlimb tension (5.9 +/- 0.9 kg) and significantly increased Pth-BP (125 +/- 21 vs. 159 +/- 16 mmHg, control vs. contraction; P < 0.05). There was no difference in the magnitude of Pth resetting between muscle contraction or stretch. The present study demonstrates that activation of skeletal muscle afferent fibers, by either muscle contraction or stretch, increases Pth of the carotid baroreflex. Therefore, neural input from skeletal muscle receptors resets the carotid baroreflex in a manner similar to that ascribed by central command.
Afferent Pathways↗
Central interaction between carotid baroreceptors and skeletal muscle receptors inhibits sympathoexcitation.
To determine the potential of an inhibitory interaction between the carotid sinus baroreflex (CSB) and the exercise pressor reflex (EPR), both pathways were activated to produce sympathoexcitation. It was hypothesized that, under conditions when the baroreflex increased sympathetic outflow, the interaction between CSB and EPR would be inhibitory. Bilateral carotid occlusion (BCO), electrically induced muscle contraction (EMC), and passive muscle stretch (PMS) were used to evoke sympathoexcitation. BCO decreased sinus pressure 50 +/- 5 mmHg, and the levels of muscle tension generated by EMC and PMS were 7 +/- 2 and 8 +/- 1 kg, respectively. This resulted in significant increases in mean arterial pressure (MAP) of 55 +/- 9, 50 +/- 7, and 50 +/- 6 mmHg (P = not significant, BCO vs. EMC vs. PMS) and in heart rate (HR) of 7 +/- 2, 19 +/- 4, and 17 +/- 2 beats/min (P < 0. 05, BCO vs. EMC and PMS). When BCO was combined with EMC or PMS, the reflex increase in MAP was augmented (80 +/- 8 and 79 +/- 10 mmHg; BCO+EMC and BCO+PMS, respectively; P < 0.05). However, summation of the individual MAP responses was greater than the response evoked during coactivation (106 +/- 11 and 103 +/- 12 mmHg, respectively, P < 0.05). Because summing the individual blood pressure responses exceeded the response during coactivation, the net effect was that the CSB and EPR interacted in an occlusive manner. In contrast, summation of the individual chronotropic responses was the same as the response evoked during coactivation. Moreover, there was no difference in summation of the individual MAP or HR responses when muscle afferents were activated by either EMC or PMS. In conclusion, the interaction between the CSB and the EPR in control of MAP was occlusive when both reflexes were stimulated to evoke sympathoexcitation. However, summation of the reflex changes in HR was simply additive.
Animals↗
Selenoprotein expression and brain development in preweanling selenium- and iodine-deficient rats.
Selenium deficiency causes further impairment of thyroid hormone metabolism in iodine-deficient rats and therefore could have a role in the aetiology of both myxoedematous and neurological cretinism in humans. Thyroidal type I iodothyronine deiodinase (ID-I), cytosolic glutathione peroxidase and phospholipid hydroperoxide glutathione peroxidase activities were increased in iodine-deficient adult rats and their offspring at 11 days of age. Thyroidal ID-I activity was unchanged and thyroidal cytosolic glutathione peroxidase activity was decreased by more than 75% by combined selenium and iodine deficiency in 11-day-old rats, indicating that, while the thyroid retained an ability to produce 3,3',5-triiodothyronine (T3), the gland was probably more susceptible to peroxidative damage caused by increased hydrogen peroxide concentrations driven by increased thyrotrophin. Thyroidal atrophy, common in myxoedematous cretinism, did not occur in iodine- or selenium and iodine-deficient rat pups. Iodine deficiency increased brain type II iodothyronine deiodinase activity 1.5-fold in 4-day-old rats and 3-fold in 11-day-old rats, regardless of selenium status. Thus rats were able to activate compensatory mechanisms in brain that would maintain T3 concentrations in selenium and iodine deficiencies. Surprisingly, however, selenium deficiency had a greater effect than iodine deficiency on markers of brain development in rat pups. Expression of the brain-derived neurotrophic factor (BDNF) mRNA was decreased in selenium deficiency in 4- and 11-day-old pups and in combined selenium and iodine deficiency in 4-day-old pups. Iodine deficiency caused an increase in BDNF expression in 11-day-old pups but had no effect on 4-day-old pups. Myelin basic protein mRNA expression in brain was decreased by combined selenium and iodine deficiency in 11-day-old rats.
Animals↗
Activation of the insular cortex during dynamic exercise in humans.
1. The insular cortex has been implicated as a region of cortical cardiovascular control, yet its role during exercise remains undefined. The purpose of the present investigation was to determine whether the insular cortex was activated during volitional dynamic exercise and to evaluate further its role as a site for regulation of autonomic activity. 2. Eight subjects were studied during voluntary active cycling and passively induced cycling. Additionally, four of the subjects underwent passive movement combined with electrical stimulation of the legs. 3. Increases in regional cerebral blood flow (rCBF) distribution were determined for each individual using single-photon emission-computed tomography (SPECT) co-registered with magnetic resonance (MR) images to define exact anatomical sites of cerebral activation during each condition. 4. The rCBF significantly increased in the left insula during active, but not passive cycling. There were no significant changes in rCBF for the right insula. Also, the magnitude of rCBF increase for leg primary motor areas was significantly greater for both active cycling and passive cycling combined with electrical stimulation compared with passive cycling alone. 5. These findings provide the first evidence of insular activation during dynamic exercise in humans, suggesting that the left insular cortex may serve as a site for cortical regulation of cardiac autonomic (parasympathetic) activity. Additionally, findings during passive cycling with electrical stimulation support the role of leg muscle afferent input towards the full activation of leg motor areas.
Adult↗
Identification of hypothalamic vasopressin and oxytocin neurons activated during the exercise pressor reflex in cats.
Blood pressure and heart rate reflexly increase during static muscle contraction in anesthetized cats. Previous studies have demonstrated that vasopressin (AVP) and oxytocin (OT) may act as neuromodulators to regulate cardiovascular responses elicited by contraction of skeletal muscle. In this study, we tested the hypothesis that neurons containing AVP and OT in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus are activated during static muscle contraction. A laminectomy was performed to expose the spinal cord and the peripheral cut ends of L7 and S1 ventral roots were stimulated electrically to induce muscle contraction. Hypothalamic neurons activated during the muscle contraction were identified by Fos-like immunoreactivity (FLI). Static muscle contraction significantly increased FLI in the PVN and SON, compared with sham-operated cats. Double-staining of neurons in the PVN for AVP and OT showed that 22 +/- 4% of the AVP and 26 +/- 3% of the OT neurons in the PVN expressed FLI. In contrast, only 4 +/- 1% of the AVP and 3 +/- 1% of the OT neurons in the PVN were labeled with FLI in sham-operated animals. These results indicate that neurons in the PVN and SON of the hypothalamus were activated during static muscle contraction. Furthermore, as FLI was present in AVP and OT neurons, this suggests these neurons may constitute a part of the neural pathway involved in cardiovascular regulation during static muscle contraction.
Animals↗
Static muscle contraction elicits a baroreflex-dependent increase in glutamate concentration in the ventrolateral medulla.
In anesthetized cats, static contraction of the hindlimb reflexly increases mean arterial pressure (MAP). This cardiovascular adjustment is reduced by the arterial baroreflex. Both of these reflex responses are mediated through activation of ventrolateral medullary (VLM) regions. We tested the hypothesis that the concentration of glutamate (Glu) increases in the caudal ventrolateral medulla (cVLM) during static hindlimb contractions in anesthetized cats, and that barodenervation reduces this elevation in Glu levels. Static contractions of the triceps surae muscle of one hindlimb were evoked by electrical stimulation of the peripheral ends of cut L7 and S1 ventral roots. After the insertion of the microdialysis probes and a 3-h recovery period, a 2-min static contraction increased MAP by 47 +/- 7 mmHg. The concentration of Glu increased from 606 +/- 189 to 1042 +/- 228 nM. These results were repeatable in that Glu, as well as MAP, rose by a similar amount in two subsequent contractions. By contrast, in a subset of cats paralyzed prior to the third contraction, neither MAP nor Glu were significantly increased over baseline levels during the third stimulation period. In a third group of cats, hindlimb contraction increased MAP and Glu levels. However, the Glu release was attenuated in subsequent contractions after these cats were barodenervated. During the same periods of stimulation, the denervation accentuated the rise in MAP. These data demonstrate that static contraction of the hindlimb increases the extracellular concentration of Glu in the cVLM. Further, our study implicates this neurotransmitter in the baroreflex mediated reduction of the pressor reflex response to static muscle contraction.
Animals↗
Cardiovascular and catecholamine responses to static exercise in partially curarized humans.
Neural control of the circulation was evaluated during static exercise in 19 subjects by the determination of heart rate (HR), mean arterial pressure (MAP), cardiac output (CO) and plasma catecholamines. Influence from central command was evaluated during contractions with weakened muscles following partial curarization and reflex influence from metaboreceptors was assessed by post-exercise muscle ischaemia. Static handgrip increased HR and more so MAP and CO and MAP remained elevated during post-exercise muscle ischaemia. With partial curarization plasma catecholamines were also increased (P < 0.05). Two-leg extension increased all variables and during post-exercise muscle ischaemia elevations of HR, MAP and CO were maintained (P < 0.05). With partial curarization HR, MAP and plasma noradrenaline were even greater during the contraction. With the involvement of both legs during static exercise, reflex influence from the muscles elevated blood pressure by way of HR and CO and the importance of central command was detectable for HR and MAP as plasma catecholamines became elevated. However, the results indicate a separation between a central command influence on HR and CO related to an increase in plasma catecholamines during a handgrip, while the reflex influence on blood pressure was directed towards total peripheral resistance.
Adult↗
c-Fos expression in the medulla induced by static muscle contraction in cats.
In this study, we examined Fos-like immunoreactivity (FLI) in the medulla after static muscle contraction induced by stimulation of L7 and S1 ventral roots of the spinal cord in anesthetized cats. The results show that FLI increases in the lateral reticular nucleus, nucleus of the solitary tract, lateral tegmental field, vestibular nucleus, subretrofacial nucleus, and A1 region of the medulla in comparison with these same areas in sham-operated animals (P < 0.05 in each region). In the rostral ventrolateral medulla, FLI distribution in neurons containing phenylethanolamine-N-methyltransferase (PNMT, the synthetic enzyme for epinephrine) was also observed utilizing double-labeling methods. The majority of neurons with PNMT also expressed FLI (66 +/- 4%). These data are in contrast to the results from sham-operated animals showing that 24 +/- 3% of the neurons costained with PNMT (P < 0.05). Our findings indicate that expression of FLI can be used to identify neurons activated during static muscle contraction and support previous studies implicating the ventrolateral medulla as a critical region for expression of the exercise pressor reflex. Furthermore, neurons in the rostral ventrolateral medulla containing PNMT were activated during static muscle contraction.
Animals↗
Central injection of physostigmine attenuates exercise-induced pressor response in conscious cats.
The effects of intracerebroventricular administration of physostigmine, a cholinesterase inhibitor, on the cardiovascular responses evoked by static voluntary exercise were investigated using conscious cats. Four cats were trained to press a bar (200-650 g) with one forelimb for at least 20 s. The changes in mean arterial pressure (MAP), heart rate (HR), and developed force during the first five trials in 30 min by each individual cat were averaged, and a mean of the four values was then calculated. After the cats exercised for 30 min, either artificial cerebrospinal fluid (CSF) or physostigmine (5 micrograms) was administered intracerebroventricularly. Before physostigmine, exercise trials by the cats increased MAP and HR by 17 +/- 3 mmHg and 42 +/- 4 beats/min, respectively. Administration of physostigmine did not alter the resting MAP and HR but attenuated the MAP and HR responses to exercise (5-30 min postphysostigmine: MAP = 8 +/- 3 mmHg, HR = 25 +/- 7 beats/min; 30-60 min postphysostigmine: MAP = 4 +/- 3 mmHg, HR = 19 +/- 8 beats/min). Intracerebroventricular administration of CSF had no effect on the cardiovascular responses to static exercise. Pretreatment with the muscarinic antagonist, atropine (25 micrograms icv), blocked the attenuating effects of subsequent intracerebroventricular administration of physostigmine. These results demonstrate that stimulation of central muscarinic receptors attenuates the cardiovascular responses to static exercise by conscious cats. In addition, the present study suggests that there is no tonic effect of central muscarinic receptors on the cardiovascular responses to voluntary exercise.
Analysis of Variance↗