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PubMed2001

The contribution of chemoreflex drives to resting breathing in man.

The contribution of automatic drives to breathing at rest, relative to behavioural drives such as "wakefulness", has been a subject of debate. We measured the combined central and peripheral chemoreflex contribution to resting ventilation using a modified rebreathing method that included a prior hyperventilation and addition of oxygen to maintain isoxia at a P(ET,O2) (end-tidal partial pressure of oxygen) of 100 mmHg. During rebreathing, ventilation was unrelated to P(ET,CO2) (end-tidal partial pressure of carbon dioxide) in the hypocapnic range, but after a threshold P(ET,CO2) was exceeded, ventilation increased linearly with P(ET,CO2). We considered the sub-threshold ventilation to be an estimate of the behavioural drives to breathe (mean +/- S.E.M. = 3.1 +/- 0.5 l min(-1)), and compared it to ventilation at rest (mean +/- S.E.M. = 9.1 +/- 0.7 l min(-1)). The difference was significant (Student's paired t test, P < 0.001). We also considered the threshold P(CO2) observed during rebreathing to be an estimate of the chemoreflex threshold at rest (mean +/- S.E.M. = 42.0 +/- 0.5 mmHg). However, P(ET,CO2) during rebreathing estimates mixed venous or tissue P(CO2), whereas the resting P(ET,CO2) during resting breathing estimates P(a,CO2) (arterial partial pressure of carbon dioxide). The chemoreflex threshold measured during rebreathing was therefore reduced by the difference in P(ET,CO2) at rest and at the start of rebreathing (the plateau estimates the mixed venous P(CO2) at rest) in order to make comparisons. The corrected chemoreflex thresholds (mean +/- S.E.M. = 26.0 +/- 0.9 mmHg) were significantly less (paired Student's t test, P < 0.001) than the resting P(ET,CO2) values (mean +/- S.E.M. = 34.3 +/- 0.5 mmHg). We conclude that both the behavioural and chemoreflex drives contribute to resting ventilation. Experimental Physiology (2001) 86.1, 109-116.

Adult↗
PubMed1999

Resistance training affects GLUT-4 content in skeletal muscle of humans after 19 days of head-down bed rest.

This study assessed the effects of inactivity on GLUT-4 content of human skeletal muscle and evaluated resistance training as a countermeasure to inactivity-related changes in GLUT-4 content in skeletal muscle. Nine young men participated in the study. For 19 days, four control subjects remained in a -6 degrees head-down tilt at all times throughout bed rest, except for showering every other day. Five training group subjects also remained at bed rest, except during resistance training once in the morning. The resistance training consisted of 30 isometric maximal voluntary contractions for 3 s each; leg-press exercise was used to recruit the extensor muscles of the ankle, knee, and hip. Pauses (3 s) were allowed between bouts of maximal contraction. Muscle biopsy samples were obtained from the lateral aspect of vastus lateralis (VL) muscle before and after the bed rest. GLUT-4 content in VL muscle of the control group was significantly decreased after bed rest (473 +/- 48 vs. 398 +/- 66 counts. min-1. microgram membrane protein-1, before and after bed rest, respectively), whereas GLUT-4 significantly increased in the training group with bed rest (510 +/- 158 vs. 663 +/- 189 counts. min-1. microgram membrane protein-1, before and after bed rest, respectively). The present study demonstrated that GLUT-4 in VL muscle decreased by approximately 16% after 19 days of bed rest, and isometric resistance training during bed rest induced a 30% increase above the value of GLUT-4 before bed rest.

Adult↗
PubMed2005

Vascular adaptation to deconditioning and the effect of an exercise countermeasure: results of the Berlin Bed Rest study.

Deconditioning is a risk factor for cardiovascular disease. The physiology of vascular adaptation to deconditioning has not been elucidated. The purpose of the present study was to assess the effects of bed rest deconditioning on vascular dimension and function of leg conduit arteries. In addition, the effectiveness of resistive vibration exercise as a countermeasure for vascular deconditioning during bed rest was evaluated. Sixteen healthy men were randomly assigned to bed rest (BR-Ctrl) or to bed rest with resistive vibration exercise (BR-RVE). Before and after 25 and 52 days of strict horizontal bed rest, arterial diameter, blood flow, flow-mediated dilatation (FMD), and nitroglycerin-mediated dilatation were measured by echo Doppler ultrasound. In the BR-Ctrl group, the diameter of the common femoral artery decreased by 13 +/- 3% after 25 and 17 +/- 1% after 52 days of bed rest (P < 0.001). In the BR-RVE group this decrease in diameter was significantly attenuated (5 +/- 2% after 25 days and 6 +/- 2% after 52 days, P < 0.01 vs. BR-Ctrl). Baseline blood flow did not change after bed rest in either group. After 52 days of bed rest, FMD and nitroglycerin-mediated dilatation of the superficial femoral artery were increased in both groups, possibly by increased nitric oxide sensitivity. In conclusion, bed rest deconditioning is accompanied by a reduction in the diameter of the conduit arteries and by an increased reactivity to nitric oxide. Resistive vibration exercise effectively attenuates the diameter decrease of leg conduit arteries after bed rest.

Adaptation, Physiological↗
PubMed1981

Influence of resting left ventricular function on the left ventricular response to exercise in patients with coronary artery disease.

First-pass radionuclide angiocardiography was used to access the left ventricular response to submaximal exercise in 150 patients with coronary artery disease (CAD). To test the hypothesis that resting systolic left ventricular function as determined by left ventricular ejection fraction (LVEF) was a predictor of the hemodynamic response to exercise, the study group included patients with a wide range of resting LVEF (0.12-0.82). The influences of resting LVEF, resting end-diastolic volume, the number of diseased vessels, exercise end point and exercise double product on the change in LVEF (delta LVEF) during exercise were tested using multiple linear regression analyses. Resting LVEF was a highly significant predictor of the delta LVEF (p = 0.0001). Exercise duration was not related to either the resting LVEF or the delta LVEF. For the 112 patients in whom coronary anatomy was known, resting LVEF retained its significance as a predictor of delta LVEF (p = 0.002) even after adjustment for the significance of the extent of CAD (p = 0.0007) and the exercise end point (p = 0.06). Patients with normal resting LVEF showed the most profound decreases in LVEF, the highest frequency of new regional dysfunction and the largest relative increase in end-diastolic volume during exercise. As rest LVEF decreased, the magnitude of the delta LVEF and the frequency of new regional dysfunction decreased. Therefore, left ventricular function at rest is an important determinant of the direction and magnitude of change in left ventricular function during exercise.

Adult↗
PubMed2004

Intravenous pamidronate prevents femoral bone loss and renal stone formation during 90-day bed rest.

UNLABELLED: Long-term bed rest has potential risks of bone loss and renal stone formation. We examined the effects of resistive exercise and intravenous pamidronate on BMD, bone turnover, urinary calcium, and renal stone formation in 25 healthy males during 90-day bed rest. Pamidronate prevented femoral bone loss and renal stone formation, but resistive exercise showed little effects. INTRODUCTION: Long-term bed rest increases the risks of bone loss and urinary stone formation. Resistive exercise increases bone formation, and bisphosphonates reduce bone resorption. However, the effects of muscle exercise and bisphosphonates have not been examined side-by-side. The objectives of this study are to compare the effects of pamidronate with resistive exercise on BMD and renal stone formation during prolonged bed rest. MATERIALS AND METHODS: Twenty-five male white volunteers, 26-45 years of age, were randomly assigned to the control (n = 9), exercise (n = 9), and pamidronate (n = 7) groups and underwent 90-day 6 degrees head-down tilt bed rest. Exercise group performed squats and heel raises on a flywheel device for 30 minutes every 3 days. Pamidronate (60 mg) was administered intravenously 14 days before bed rest. BMD of the head, forearm, lumbar spine, and proximal femur; biochemical bone markers; calcium (Ca) metabolism; and abdominal radiographs were examined during 90 days of bed rest and 360 days of reloading. RESULTS: In controls, proximal femoral BMD decreased, and bone resorption markers and urinary Ca increased during bed rest, along with development of renal stones in two of nine subjects. Resistive exercise increased bone formation but was unable to prevent femoral BMD decrease and increases in bone resorption and urinary Ca during bed rest, with formation of renal stones in four of nine subjects. Pamidronate maintained femoral BMD, reduced bone resorption and urinary Ca, and completely prevented renal stone formation. CONCLUSIONS: Resistive exercise increased bone formation but could not reduce bone resorption and the risk of renal stones. In contrast, inhibition of bone resorption by pamidronate could preserve bone mineral and reduce the risk of renal stone formation during prolonged bed rest.

Adult↗
PubMed2006

The effect of rest interval length on the sustainability of squat and bench press repetitions.

The purpose of this study was to compare the effect of 3 different rest intervals on the sustainability of squat and bench press repetitions over 5 consecutive sets performed with a 15 repetition maximum (RM)-load. Fifteen college-age men with previous resistance training experience were tested weekly over a period of 3 weeks. During each testing session, 5 consecutive sets of the squat and the bench press were performed with a 30-second, 1-minute, or 2-minute rest interval between sets. For each exercise, significant declines in repetitions occurred between the first and the fifth sets (p = 0.000). For the squat, a significant difference in the ability to sustain repetitions occurred between the 30-second and 2-minute rest condition (p = 0.003). However, differences were not significant between the 30-second and 1-minute rest conditions (p = 0.986) and between the 1-minute and 2-minute rest conditions (p = 0.042). For the bench press, significant differences in the ability to sustain repetitions occurred between the 30-second and 2-minute rest conditions (p = 0.000) and between the 1-minute and 2-minute rest conditions (p = 0.000). However, differences were not significant between the 30-second and 1-minute rest conditions (p = 0.019). For each exercise, the number of repetitions completed on the first set was not sustained over subsequent sets, irrespective of the rest condition. These results suggest that when short rest intervals are used to develop muscular endurance, the intensity should be lowered over subsequent sets to sustain repetitions within the range conducive to this training goal.

Adult↗
PubMed2001

Does bed rest after cervical or lumbar puncture prevent headache? A systematic review and meta-analysis.

BACKGROUND: Headache after cervical or lumbar puncture has long been attributed to early mobilization; however, there is little evidence for this. We performed a systematic literature review and meta-analysis of randomized controlled trials to assess whether longer bed rest is better than immediate mobilization or short bed rest in preventing headache. METHODS: We searched EMBASE (1988 to March 2001), MEDLINE (1966 to May 2001), Pascal Biomed (1996 to February 2001), Current Contents (1997 to September 1999), PsycINFO (1966 to May 2001), the Cochrane Controlled Trial Register (last search May 15, 2001), textbooks and references of the papers selected. Studies were eligible if patients underwent cervical or lumbar puncture for any reason and were randomly assigned to either a long or a short period of bed rest. Data were abstracted independently by 2 investigators to a predefined form. RESULTS: We found 16 randomized controlled trials involving 1083 patients assigned to immediate mobilization or a short period of bed rest (up to 8 hours) and 1128 patients assigned to a longer period of bed rest (0.5 to 24 hours). Puncture was performed for anesthesia (5 trials), myelography (6 trials) and diagnostic reasons (5 trials). None of the trials showed that longer bed rest was superior to immediate mobilization or short bed rest for preventing headache after puncture. When pooling the results of the trials in the myelography group and the diagnostic group, the relative risks of headache after puncture were 0.93 (95% confidence interval [CI] 0.81-1.08) and 0.97 (95% CI 0.79-1.19) respectively. We did not pool the results from the trials in the anesthesia group because of clinical heterogeneity, but shorter bed rest appeared to be superior. INTERPRETATION: There was no evidence that longer bed rest after cervical or lumbar puncture was better than immediate mobilization or short bed rest in reducing the incidence of headache.

Bed Rest↗
PubMed1992

Mechanisms underlying the genesis of post-rest contractions in cardiac muscle.

1. Post-rest potentiation reflects basic cellular mechanisms that control cardiac muscle contraction. Transmembrane calcium influx, the Na+/Ca2+ exchange and the function of intracellular stores that liberate activator calcium upon activation are some of the mechanisms involved. 2. Three aspects of the post-rest potentiated phenomenon were investigated, using isometrically contracting rat papillary muscles and toad ventricle strips: dependence on 1) inotropic state of steady-state contractions, 2) pause duration and Na+/Ca2+ exchange activity, and 3) the extent of transmembrane calcium influx. 3. The results suggest that the potentiated state of post-rest contractions increases linearly with the inotropic state of preceding steady-state control contractions. As the pause duration increases from 5 to 240 s, the post-rest potentiation also increases, attaining a steady level after 30-s pauses. During the pause, the Na+/Ca2+ exchange mechanism operates at an activity level that can alter the amount of activator calcium used for post-rest contractions. Interventions that increase intracellular Na+, such as the increase of the stimulation rate from 0.5 to 1 Hz or the increase of extracellular NaCl concentration to 160 mM, reduce the Na+/Ca2+ activity, increasing intracellular Ca2+ and post-rest potentiation. The decrease of transmembrane Ca2+ influx during activation increases the relative participation of the sarcoplasmic reticulum in the development of post-rest potentiation. Reduction of extracellular Ca2+ concentration from 1.25 mM to 0.25 mM or the use of 1 microM verapamil and 2 mM manganese increases the relative potentiation of post-rest contractions. This is particularly observed in toad ventricle strips since post-rest potentiation, which does not develop under control conditions, is observed after verapamil or manganese treatment. The results suggest that the excitation-contraction coupling process operating for post-rest contraction activation, unlike that operating for steady-state contraction activation, depends more on the calcium stored at intracellular sites than on transmembrane calcium influx.

Animals↗
PubMedDate not supplied

The relationship of resting and exercise blood pressure in subjects with essential hypertension before and after drug treatment with propranolol.

OBJECTIVE: To investigate the relationship between clinic resting blood pressure (BP) and exercise BP in subjects with established essential hypertension during placebo and propranolol-treated phases. DESIGN: Prospective, placebo-controlled, cross-over trial. SETTING: University-affiliated medical center. PATIENTS: A convenience sample of 38 patients with essential hypertension, 34 men and four women, who ranged in age from 22 to 62 years (mean = 44 years, SD = 10.7). Subjects were diagnosed with mild to moderate diastolic or mixed systolic/diastolic essential hypertension at least 1 year before study entry. They had no clinical evidence of secondary hypertension, diabetes, heart, liver, pulmonary, or renal disease. OUTCOME MEASURES: Resting and exercise BP. INTERVENTION: Antihypertensive medication was tapered off and subjects were free of all prescription drug treatment for 2 weeks. They received placebo for an additional 2 weeks. Subjects then received treatment with propranolol at a dose necessary to control resting blood pressure for 4 to 6 weeks. At the end of both the untreated and treated phases, subjects were given a graded maximal exercise test on a bicycle ergometer. RESULTS: Propranolol effectively reduced mean resting and maximal exercise BP. The nonsignificant correlation between clinic resting and maximal exercise systolic BP was low in both phases. The correlation between clinic resting and maximal exercise diastolic BP was only moderate, but statistically significant (untreated, r = 0.43; p < 0.01; treated, r = 0.53; p < 0.001). For systolic BP or diastolic BP, there were no significant relationships between percent drop in BP because of propranolol at rest or maximal exercise. Clinic resting BP was not a valid predictor of maximal exercise BP. Degree of control of clinic resting BP was not a valid predictor of control observed at maximal exercise. CONCLUSIONS: Resting BP should not be used as a predictor of BP during maximal exercise in the untreated condition or with treatment with propranolol.

Adult↗
PubMed2004

The effects of rest interval and resistance training on quadriceps femoris muscle. Part II: EMG and perceived exertion.

AIM: The purpose of this study was to examine the effects of rest interval on quadriceps femoris muscle activation and perceived exertion, during short-term resistance training. METHODS: Vastus medialis (VM) and vastus lateralis (VL) muscle electromyograms (EMG) were assessed in 15 males during a sustained 80% maximal voluntary contraction (MVC). During the pre-training evaluation, the absolute value of the 80% MVC (N.m) and contraction duration (s) was performed at 2, 4, and 6 weeks during the training period. Perceived exertion was measured via the Borg category-ratio scale every 5 s during the 80% MVC. Subjects were randomly assigned to 3 groups: group 1 received a 40 s rest interval in between exercise sets, group 2 received a rest period of 160 s, and the control group did not participate in training. Groups 1 and 2 performed isokinetic knee extensions at 180 deg.s(-1) 2 days per week for 6 weeks. RESULTS: The results demonstrated a significant decrease in VM EMG within the initial portion of the 80% MVC across the training period in the short rest interval group. The long rest interval and control groups showed no significant changes in VM EMG during 1st part of the contraction across the training period, whereas the control group exhibited a significant reduction in VL EMG across weeks 4 to 6. VL EMG increased during the 80% MVC in the control group across the training period. VM EMG increased during the sustained contractions in the long rest interval and control groups across the training period. The perceived exertion response was lower in the 1st part of the 80% MVC in the short and long rest interval groups, but not in the control group, across the training period. The results also showed a significant decrease in perceived exertion at the end of the sustained contraction in the short rest interval group, but not in the long rest interval group or the control group. CONCLUSIONS: The findings from this study suggest that the application of relatively short rest intervals in between sets of resistance exercise induced a greater neuromuscular response of the VM muscle during short-term training.

Adult↗
PubMed1988

Mechanical behavior of rest contractions in cardiac muscle.

The effects of increasing rest periods on rest contractions and rest potentiation were analysed on isometric contractions of guinea pig papillary muscles at room temperature. Rest contraction amplitude is dependent on pause duration and potentiated for short pauses, which decreases as the rest period increases. their inotropic state is also dependent on the inotropic state of steady state control contractions. This statement is validated by the interdependence between control contractions and rest contractions amplitude and also because positive (5.0 mM CaCl2) and negative (0.5 mM NiCl2)inotropic interventions do not change the time course of dF/dt pause duration curves. They also show a slow activation characterized by a prolonged TTP that depends on pause duration being observed even in contractions occurring after short pauses. Rest contractions can be elicited under depolarized conditions produced by TKBa (Tyrode with high potassium and barium) and TKAdr (Tyrode with high potassium and adrenaline), showing that they are dependent on calcium influx occurring during the slow response of the cardiac action potential. The present study, carried out under depolarized conditions and in low extracellular Na+, shows that Na+ entry during the Na-dependent fast component of the action potential is necessary for the occurrence of rest potentiation. These findings suggest that the intracellular Na+, that can be exchanged by external calcium with the Na/Ca exchange mechanism, is necessary for the occurrence of the rest potentiation and to avoid the accelerated depression of the rest contractions with increasing pause duration.

Animals↗
PubMed1994

Relationships between resting and total energy expenditure in injured and septic patients.

OBJECTIVE: To quantify resting and total energy expenditure in patients who have suffered severe trauma and sepsis. DESIGN: Prospective, unblinded, observational, nonrandomized study. SETTING: Critical care unit of a Level I adult trauma center. PATIENTS: Immediate posttrauma patients or trauma patients exhibiting signs of sepsis with multiple organ dysfunction. INTERVENTIONS: An indirect calorimeter was used to measure energy expenditure at rest (resting energy expenditure) at 0700 and 1900 hrs. The energy expenditure measurement was then continued for up to 12 hrs (total energy expenditure). Clinical data were collected for computation of an illness severity score. RESULTS: Thirteen trauma and 20 septic patients were studied 240 times. All patients were mechanically ventilated. Morphine or fentanyl was infused during 99% of studies. Neuromuscular blocking agents were used in 42% of septic studies. Both the trauma and septic groups were hypermetabolic (mean trauma resting energy expenditure, 36 +/- 6 kcal/kg; mean septic resting energy expenditure, 44 +/- 8 kcal/kg; p < .05). Total energy expenditure was similar to resting energy expenditure (trauma total energy expenditure = resting energy expenditure x 1.035 +/- 0.078, septic total energy expenditure = resting energy expenditure x 1.039 +/- 0.071). Total energy expenditure and resting energy expenditure were linearly related (r2 = .89, p < .0001). CONCLUSIONS: Trauma and septic patients are hypermetabolic, even when heavily sedated or medically paralyzed. A measurement of resting energy expenditure is a close approximation of total energy expenditure in most patients.

Adult↗
PubMed2000

In vitro formation of resting spores by the insect pathogenic fungus Entomophaga maimaiga.

Field-collected resting spores (azygospores) of the fungal pathogen of Lymantria dispar (gypsy moth), Entomophaga maimaiga, have been used to release this biological control agent in areas where this pathogen is not established. We have found that E. maimaiga can produce resting spores in vitro using Grace's insect tissue culture medium (95%) plus fetal bovine serum (5%). The majority of spores become mature between 7 and 21 days after cultures are initiated. Spore production varies by fungal isolate; of 38 isolates tested, 10 produced no resting spores while 7 produced >1000 resting spores/ml. Resting spore production was not affected when isolates were mixed. Glycerol (used for fungal storage), trehalose, and selected amino acids each inhibited resting spore formation. Fetal bovine serum was required for spore production but the presence of >5% yielded lower resting spore densities. A large surface area:volume ratio (12.5 cm(2):ml versus 4.2 cm(2):ml) was required for abundant formation of resting spores. At present, resting spores have only been produced in small volumes with a maximum of 3 x 10(4) resting spores/ml.

Animals↗
PubMed1995

Regional differences in rest decay and recoveries of contraction and the calcium transient in rabbit ventricular muscle.

The rates of rest decay (for rest periods of between 0.5 min and 10 min) and recovery from the rested state (following 10 min of rest) of cell shortening and the amplitude of the intracellular calcium transient were compared in epicardial and endocardial ventricular myocytes isolated from rabbit hearts. The object of these experiments was to determine whether reported transmural differences in action potential duration, myosin type expression and metabolic enzyme content are able to influence the control of contraction. Cells isolated from these two regions of the ventricular wall displayed almost identical twitch shortening and calcium transient characteristics during steady-state electrical stimulation at 0.5 Hz. Despite this, rest decay of cell shortening was faster and recovery from the rested state slower in endocardial cells than in epicardial cells. Neither of these differences could be explained in terms of changes of calcium transient amplitude or time course. We tried to mimic the effect of prolonged rest by application of caffeine to empty the sarcoplasmic reticulum of calcium. The regional differences in recovery of contraction from the rested state were not reproduced in the recovery of contraction after caffeine application, suggesting that the effect is produced by something other than refilling of the sarcoplasmic reticulum. It is suggested that changes in factors that affect myofilament calcium sensitivity produce the regional differences in rest decay and post-rest recovery of contraction.

Action Potentials↗
PubMed1995

A comparison of resting images from two myocardial perfusion tracers.

We have compared stress-redistribution and delayed rest thallium-201 with rest technetium-99m methoxyisobutylisonitrile (MIBI) tomograms in order to compare the tracers for the assessment of myocardial viability and to validate a rapid protocol combining the two tracers. We studied 30 consecutive patients with known or suspected coronary artery disease [group 1: 16 with normal left ventricular function, mean left ventricular ejection fraction (LVEF) 55%, SD 6%; group 2: 14 with abnormal function, mean LVEF 28%, SD 8%]. 201Tl was injected during infusion of adenosine followed by acquisition of conventional stress and redistribution tomograms. On a separate day, 201Tl was injected at rest with imaging 4 h later. 99mTc-MIBI was then given at rest and imaging was performed. Three images were compared: redistribution 201Tl, rest 201Tl, and rest 99mTc-MIBI. Tracer activity was classified visually and quantitatively in nine segments and segments with > 50% activity were defined as containing clinically significant viable myocardium. Mean (+/- SD) global tracer uptake as a percentage of maximum was similar in group 1 (rest 201Tl 69% +/- 12%, redistribution 201Tl 69% +/- 15%, rest 99mTc-MIBI 70% +/- 13%, ANOVA P > 0.05), but in group 2 mean tracer uptake was significantly greater in the rest 201Tl images (59% +/- 16%) than in redistribution 201Tl images (53% +/- 17%) or rest 99mTc-MIBI images (53% +/- 19%) (ANOVA P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed2006

Parallel mechanisms for resting nucleo-cytoplasmic shuttling and activity dependent translocation provide dual control of transcriptional regulators HDAC and NFAT in skeletal muscle fiber type plasticity.

Skeletal muscle fibers exhibit plasticity of their physiological and biochemical properties in response to the firing pattern from the innervating motor neuron. In particular, the gene expression pattern generally characteristic of a slow twitch fiber can be induced in a fast twitch fiber by chronic slow fiber type electrical stimulation. We have studied the nucleo-cytoplasmic distribution of two transcriptional regulators of slow fiber type genes, HDAC4 and NFATc1, both in response to slow fiber type stimulation and in resting conditions using cultured fast twitch skeletal muscle fibers. HDAC4 is present in both cytoplasm and nuclei of resting fibers, and moves out of the nuclei in response to slow fiber type stimulation. The stimulation-dependent nuclear efflux of HDAC4 requires activation of nuclear CaMKII, which phosphorylates nuclear HDAC4 and thus allows its exit of the nucleus. In unstimulated resting fibers, a balance of nuclear efflux and influx of HDAC4 establishes the resting level of nuclear HDAC4. However, the nuclear efflux of HDAC4 in resting fibers does not involve CaMKII. Slow fiber type stimulation also causes NFATc1 translocation from the cytoplasm into muscle fiber nuclei following dephosphorylation by calcineurin (CaN) activated by the elevated cytosolic Ca2+ accompanying fiber stimulation. In resting fibers, NFATc1 exhibits balanced shuttling between cytoplasm and nucleus, but during this shuttling NFATc1 influx does not require CaN and NFATc1 efflux does not require the kinases involved in removing nuclear NFATc1 following prior activity. Thus different enzymes are responsible for HDAC4 nuclear efflux in resting and active fibers, and different pathways mediate NFATc1 nuclear influx and efflux in resting and active fibers. Such dual mechanisms for resting shuttling and active movements provide the potential for the resting level and the rate of translocation during fiber stimulation to be controlled independently for both of the transcriptional regulators HDAC4 and NFATc1.

Animals↗
PubMed1989

Value of normal electrocardiographic findings in predicting resting left ventricular function in patients with chest pain and suspected coronary artery disease.

PURPOSE: Characterization of left ventricular function is important in managing patients with coronary artery disease. Although many methods are available to assess left ventricular function, most are either expensive, invasive, or both. In this study, we examined the ability of normal or near-normal resting electrocardiographic findings to predict resting left ventricular ejection fraction, measured by resting radionuclide angiography, in 874 patients with chest pain and suspected coronary artery disease. PATIENTS AND METHODS: A retrospective review was undertaken of 4,410 Mayo Clinic patients who underwent rest and exercise radionuclide ventriculography for the evaluation of chest pain and known or suspected coronary artery disease; of these, 874 patients met the inclusion criteria for the current study. A 15-lead electrocardiogram, which was interpreted by the cardiologist or cardiology trainee working in the laboratory, was obtained at the same evaluation as the radionuclide study. RESULTS: In 590 patients with no previous history of a myocardial infarction and entirely normal resting electrocardiographic results without nonspecific ST-T wave abnormalities, the mean left ventricular ejection fraction was 0.63 +/- 0.004, and 559 patients (95%) had a normal resting ejection fraction (defined as 0.50 or more). Both nonspecific ST-T wave abnormalities (p less than 0.001) and, to a lesser degree, a history of myocardial infarction (p = 0.06) were independent predictors of an abnormal resting ejection fraction. In 185 patients with nonspecific ST-T wave abnormalities and no history of myocardial infarction, the mean left ventricular ejection fraction was 0.61 +/- 0.009, and 85% had a normal resting ejection fraction. In 36 patients with nonspecific ST-T wave abnormalities and a history of myocardial infarction, the mean left ventricular ejection fraction was 0.53 +/- 0.021, and 72% had a normal resting ejection fraction. CONCLUSION: Thus, an entirely normal result on a resting 12-lead electrocardiogram in patients with suspected coronary disease but no history of a previous myocardial infarction is a reliable (95%) predictor of normal left ventricular function. If nonspecific ST-T wave abnormalities are noted, particularly if there is a history of a previous infarction, the predictive value of the electrocardiographic findings is diminished.

Angina Pectoris↗
PubMed2003

Enabling bone formation in the aged skeleton via rest-inserted mechanical loading.

The mild and moderate physical activity most successfully implemented in the elderly has proven ineffective in augmenting bone mass. We have recently reported that inserting 10 s of unloaded rest between load cycles transformed low-magnitude loading into a potent osteogenic regimen for both adolescent and adult animals. Here, we extended our observations and hypothesized that inserting rest between load cycles will initiate and enhance bone formation in the aged skeleton. Aged female C57BL/6 mice (21.5 months) were subject to 2-week mechanical loading protocols utilizing the noninvasive murine tibia loading device. We tested our hypothesis by examining whether (a) inserting 10 s of rest between low-magnitude load cycles can initiate bone formation in aged mice and (b) whether bone formation response in aged animals can be further enhanced by doubling strain magnitudes, inserting rest between these load cycles, and increasing the number of high-magnitude rest-inserted load cycles. We found that 50 cycles/day of low-magnitude cyclic loading (1200 microepsilon peak strain) did not influence bone formation rates in aged animals. In contrast, inserting 10 s of rest between each of these low-magnitude load cycles was sufficient to initiate and significantly increase periosteal bone formation (fivefold versus intact controls and twofold versus low-magnitude loading). However, otherwise potent strategies of doubling induced strain magnitude (to 2400 microepsilon) and inserting rest (10 s, 20 s) and, lastly, utilizing fivefold the number of high-magnitude rest-inserted load cycles (2400 microepsilon, 250 cycles/day) were not effective in enhancing bone formation beyond that initiated via low-magnitude rest-inserted loading. We conclude that while rest-inserted loading was significantly more osteogenic in aged animals than the corresponding low-magnitude cyclic loading regimen, age-related osteoblastic deficits most likely diminished the ability to optimize this stimulus.

Age Factors↗