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[Ergospirometric studies of normal probands for an unsteady-state increment test program].

One-hundred-sixteen healthy subjects (60 female and 56 male) with normal height (L) and weight (w) were selected to provide an even distribution of age (A, 20-70 years). All underwent an unsteady state cycle ergometer test with work increments of 20 watts each minute to exhaustion. A commercially available exercise testing system (EOS SPRINT, Jäger Corp., FRG) with gas analysis from a mixing chamber was used to study oxygen uptake (VO2), carbon dioxide output (VCO2), heart rate (HR), tidal volume (VT), breathing frequency (BR) and arterial oxygen tension (PO2) with special regard to the ventilatory anaerobic threshold (VAT) and maximum power output. For all parameters multiple regression equations were determined. Furthermore, heart rate reserve (HR-reserve), breathing reserve (VE-reserve), O2-pulse (VO2/HR), the dead space/tidal volume ratio (VD/VT) and the alveolar-arterial PO2-difference (AaDO2) were calculated. Day-to-day reproducibility was proven in 21 subjects. VO2max in females was 1584 +/- 300 ml/min (VO2max = -17 A + 10 L + 10 G + 58, r = 0.75, p < 0.0001), VO2AT 957 +/- 159 ml/min (VO2AT = 0.35 VO2max + 0.40 l/min, r = 0.77, p < 0.0001). The ratio VO2AT/VO2max was 50 +/- 7%. In male, VO2max was 2452 +/- 529 ml/min (VO2max = -23 A + 23 L + 9.5 G - 1395, r = 0.78, p < 0.0001), VO2AT 1209 +/- 213 ml/min (VO2AT = 0.29 VO2max + 0.51 l/min, r = 0.71, p < 0.0001), and VO2AT/VO2max 62 +/- 9%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Non-invasive quantitative assessment of oxidative metabolism in quadriceps muscles by near infrared spectroscopy.

BACKGROUND: Near infrared spectroscopy can be used in non-invasive monitoring of changes in skeletal muscle oxygenation in exercising subjects. OBJECTIVE: To evaluate whether this method can be used to assess metabolic capacity of muscles. Two distinctive variables abstracted from a curve of changes in muscle oxygenation were assessed. METHODS: Exercise on a cycle ergometer was performed by 18 elite male athletes and eight healthy young men. A measuring probe was placed on the skin of the quadriceps muscle to measure reflected light at two wavelengths (760 and 850 nm), so that the relative index of muscle oxygenation could be calculated. Exercise intensity was increased from 50 W in 50 W increments until the subject was exhausted. During exercise, changes in muscle oxygenation and blood lactate concentration were recorded. The following two variables for assessment of muscle oxygenation were then abstracted and analysed by plotting curves of changes in muscle oxygenation: the rate of recovery of muscle oxygen saturation (R(R)) and the relative value of the effective decrease in muscle oxygenation (D(eff)). RESULTS: Data analysis showed a correlation between muscle oxygenation and blood lactate concentration at the various exercise intensities and verified the feasibility of the experiment. Data for the athletes were compared with those for the controls using the Aspin-Welch test of significance; t = 2.3 and 2.86 for R(R) and D(eff) respectively. There were significant differences (p = 0.05) between the athletes and the control group with respect to these two variables. CONCLUSION: R(R) and D(eff) may be distinctive variables that can be used to characterise muscle oxidative metabolism during human body movement.

Adult↗

Endocrine markers of semistarvation in healthy lean men in a multistressor environment.

We tested the hypothesis that key endocrine responses to semistarvation would be attenuated by changing only the food intake in a multistressor environment that also included sustained workload, inadequate sleep, and thermal strain. Serum hormones were compared within and between two groups of healthy young male volunteers participating in the 8-wk US Army Ranger course, with four repeated cycles of restricted energy intakes and refeeding: group 1 (n = 49) and group 2 (n = 48); energy deficits averaged 1,200 and 1,000 kcal/day, respectively. After 8 wk, most of group 1 achieved a minimum body fat, serum 3,5,3'-triiodothyronine (T(3)) was below normal (78 +/- 20 ng/dl), testosterone (T) approached castrate levels (4.5 +/- 3.9 nmol/l), insulin-like growth factor I (IGF-I) declined by one-half (75 +/- 25 microg/l), and cholesterol rose from 158 +/- 31 to 217 +/- 39 mg/dl. Bioavailable T(3) and T were further reduced by increases in their specific binding proteins in response to declining insulin. Refeeding, even with continuation of the other stressors, produced prompt recovery of T(3), T, and IGF-I. Higher energy intakes in group 2 attenuated the subclinical hypothyroidism and hypercholesterolemia, whereas consistent luteinizing hormone suppression indicated centrally mediated threshold effects on gonadal hormone suppression. We conclude that low T, T(3), and IGF-I remained reliable markers of acute energy deficits in the presence of other stressors; elevated cholesterol and cortisol provided information about chronic status, corresponding to diminishing body fat stores.

Adult↗

Role of programmed electrical stimulation of the heart in risk stratification post-myocardial infarction.

Programmed electrical stimulation (PES) of the heart was evaluated as a method of identifying patients at risk of sudden death post-myocardial infarction (post-MI). Eighty-four patients (mean age, 56 +/- 10 years) underwent PES 6 to 8 weeks post-MI. PES was performed at the right ventricular apex at twice diastolic threshold. Prior to stimulation patients were studied with exercise stress testing, 24-hour Holter monitoring and radionuclide ejection fraction. The patients were placed into two groups, according to their responses to electrical stimulation. Group 1:65 patients in whom no arrhythmias were induced or who had repetitive responses that lasted less than six cycles; Group 2:19 patients in whom ventricular tachycardia was induced. At the end of follow-up (20 +/- 9 months) six patients from Group 1 had died. Complex ventricular ectopy and ventricular tachycardia were more frequently detected on Holter in Group 2 (9/19) than in Group 1 (14/65) (p less than 0.03). The results of exercise testing and radionuclide ejection fraction did not correlate with the response to PES. However all but one of the patients who died had a left ventricular ejection fraction (LVEF) under 40% and four out of six patients had ventricular tachycardia on Holter monitor. We draw the conclusion that PES did not contribute to the identification of high-risk patients post-MI, as none of the 19 patients in whom ventricular tachycardia was induced died during follow-up. In addition, high-risk patients were characterized by poor ventricular function and complex ventricular arrhythmias on Holter recording.

Electric Stimulation↗

Effects of exercise and insulin on insulin signaling proteins in human skeletal muscle.

Insulin and exercise independently increase glucose metabolism in muscle. Moreover, exercise training or a prior bout of exercise increases insulin-stimulated glucose uptake in resting skeletal muscle. The present study was undertaken to compare how physiological hyperinsulinemia and moderate intensity aerobic exercise affect the tyrosine phosphorylation state and activity of insulin signaling molecules in healthy, physically inactive volunteers. Subjects had biopsies of the vastus lateralis muscle before and immediately after 30 min of either hyperinsulinemia (euglycemic insulin clamp) or moderate-intensity exercise on a cycle ergometer (approximately 60% of VO2max). Insulin receptor and IRS-1 tyrosine phosphorylation, association of the p85 regulatory subunit of PI 3-kinase with IRS-1, IRS-1 associated PI 3-kinase activity, and glycogen synthase activity were determined in muscle biopsy specimens taken from healthy subjects before and after insulin or exercise. Physiological hyperinsulinemia increased the rate of glucose disposal from 11.4 +/- 1.5 to 25.6 +/- 6.7 micromol x kg(-1) x min(-1) (P < 0.01), insulin receptor and IRS-1 tyrosine phosphorylation (173 +/- 19% and 159 +/- 35% of basal values, respectively, P < 0.05), association of the p85 regulatory subunit of PI 3-kinase with IRS-1 (159 +/- 10%, P < 0.05), and glycogen synthase fractional velocity (136 +/- 11%, P < 0.01). Exercise also increased glucose disposal, from 10.4 +/- 0.5 to 15.6 +/- 1.7 micromol x kg(-1) x min(-1) (P < 0.01) and glycogen synthase fractional velocity (253 +/- 35% of basal, P < 0.01). The exercise-induced increase in glycogen synthase was greater than that due to insulin (P < 0.05). In contrast to insulin, exercise decreased tyrosine phosphorylation of the insulin receptor to 72 +/- 10% of basal values (P < 0.05 vs basal and P < 0.05 vs insulin) and had no effect on IRS-1 tyrosine phosphorylation, or association of p85 with IRS-1. The exercise-induced decreased insulin receptor tyrosine phosphorylation could explain the well-known effect of exercise to enhance the sensitivity of muscle to insulin.

Adult↗

Estimating pesticide exposure in tidal streams of Leadenwah Creek, South Carolina.

This article estimates the potential exposure of estuarine organisms to two pesticides (azinphosmethyl and fenvalerate) in a tidal stream of Leadenwah Creek near the Edisto River, South Carolina, during four runoff episodes. Exposure is calculated from simulation runs of the one-dimensional transport equation solved by an implicit finite difference method. Calibration was done for each episode by adjusting three conditions (runoff starting time, duration, and flow) and a correction to the dispersion coefficient in order to match the continuously measured salinity transients. First-order rate constants used by the fate component were calculated from half-life values reported in the literature. Baseline scenarios for each episode and each pesticide were derived by using the same conditions obtained in the salinity runs and adjusting the pesticide loading in order to mimic the few data points of measured pesticide concentrations. In all baseline scenarios, pesticide concentration rises following the initial burst of runoff (also noticeable as an abrupt drop in salinity) and then oscillates, forced by the tidal cycle. These oscillations are dominated by transport, while fate imposes a secular decaying trend. Ten additional scenarios for each episode were obtained from the baseline scenario by randomly varying three pesticide load parameters (starting time and duration of runoff, and pesticide discharge) using a Latin hypercubes design. Two exposure metrics were calculated from the simulated and the measured pesticide concentration: maximum and time average, which was obtained by integrating the curve and dividing by the time period. The metrics calculated from the baseline runs are relatively close to the data-derived metrics, because the baseline runs attempted to mimic the data. For each one of the two metrics and all pesticide-episode combinations, several statistics of the set of 11 scenarios were also calculated: minimum and maximum, mid-range, mean, standard deviation, and median. The mean +/- standard deviation interval of the simulation-derived value consistently brackets the data-derived value for the maximum metric, but not for the time-average metric. This may indicate that even if the maximum value is correctly captured in the field sample, the time-average exposure could be in error when calculated directly from the field data due to undersampling of the pesticide time series. The methodology developed here attempts to reconstruct the possible exposure from the sparse sampling of the pesticide concentration during the runoff episodes; only when the number of field samples is high and regularly spaced is it possible to have confidence in the reconstruction of the curve. The shape of the curve cannot be inferred from the field measurements alone; as expected, tidal movement makes the pesticide concentration swing up and down. This result has important implications because the biological community would be subject to repetitive pulses of exposure to the chemicals. The baseline simulations can be used to derive a pulse-exposure metric by calculating the sum of ratios of the time average of the threshold-exceeding concentrations to the time average of the toxic threshold during intervals of above-threshold concentration. This metric is species specific and extrapolates laboratory toxicity data in order to compare pulse exposure to mortality rates measured in the field.

Azinphosmethyl↗

[Rehabilitation of patients with chronic cardiac insufficiency. Immediate and midterm effects].

OBJECTIVES: While physical training is known to improve cardiac performance in patients with chronic congestive heart failure, we conducted this study to evaluate the effect of such training programmes. METHODS: The study group included 48 untrained patients with stable chronic heart failure controlled with the same daily oral regimen including 0.25 mg digitoxin, 40 mg furosemide and 50 mg captopril. Halt of the patients (n = 24) entered a physical rehabilitation programme for a 3-week period. Each daily session included passive mobilization of the limbs (10 min), respiratory exercises (10 min) and endurance exercise on an ergometric cycle with a maximum work load of 50, 60 and 70% of the theoretical maximal load for weeks 1, 2 and 3 respectively. The other 24 patients did not change their physical activity level and served as controls. The immediate and medium term effects (3 months after the end of the training programme) were assessed using exercise tests, left ventricular isotopic ejection fraction and plethysmography of the lower limbs. The quality of life was compared using the NYHA functional classification and the Goldsman questionnaire. RESULTS: At the end of the 3-week training period, and compared with the control group, there was a moderate improvement of VO2max (p < 0.02) and a 10% improvement in the ejection fraction (p < 0.05) in the trained patients. There was a clearly significant improvement in the anaerobic threshold and arterial blood flow rate (p < 0.001) and lowered vascular resistance (p < 0.001) and venous tone (p < 0.001). The quality of life was also improved in the training group. However, 3 weeks after the end of the training period, these differences disappeared. CONCLUSION: Patients with chronic heart failure can benefit from physical training showing functional improvement and no deleterious effect on left ventricular function. This beneficial effect is nonetheless temporary and would appear to be due to improved skeletal muscle oxidative capacity and peripheral haemodynamics.

Aged↗

Near infrared spectroscopy and changes in skeletal muscle oxygenation during incremental exercise in chronic heart failure: a comparison with healthy subjects.

Near infrared spectroscopy (NIRS) is a noninvasive technique of monitoring tissue oxygen saturation by detecting changes in tissue absorbance of two wavelengths (850 and 760 nm) reflecting the relative oxygenation of hemoglobin and myoglobin. Aim of the present study was to determine whether changes in skeletal muscle oxygen saturation during incremental exercise detected by NIRS can reflect an impared oxygen delivery and an early onset of anaerobic metabolism in patients with chronic heart failure (CHF). We studied 19 subjects (mean age 43 +/- 16 years). Seven patients had a history of CHF with a diagnosis of ischemic cardiomyopathy (Group A) and 12 were healthy sedentary (Group B). All patients had a history of dyspnea on exertion (NY-HA II), peripheral edema, pulmonary rales and cardiac gallop sounds over the last 6 months. They were in sinus rhythm and stable clinical condition in the last 3 months. They were well matched regarding age, sex and body surface area. All subjects performed an incremental work rate test in a ramp pattern on a upright cycle ergometer until volitional fatigue. Gas exchange was measured breath by breath with a metabolic chart. Muscle oxygenation was determined, transcutaneously, during the exercise test over the vastus lateralis muscle with NIRS. At peak exercise, work rate, VO2, anaerobic threshold (LAT), heart rate and systolic blood pressure were significantly lower in Group A compared to Group B (92 +/- 28 vs 232 +/- 17 watts; 14 +/- 2 vs 21 +/- 2 ml/kg/min; 868 +/- 225 vs 1317 +/- 354 ml/min; 149 +/- 7 vs 172 +/- 18 b/min; 145 +/- 18 vs 195 +/- 21 mm Hg, respectively; p < 0.0001 for all). In both groups, as work rate increased, tissue oxygenation initially either remained constant near resting levels or decreased. In both groups, muscle oxygenation decreased more steeply near the work rate where lactic acidosis (LAT) was detected. However, patients with CHF had an earlier acceleration in muscle deoxygenation compared to the other group, indicating a premature onset of anaerobic metabolism. Moreover, Group A had a flatter increase in both heart rate and systolic blood pressure and a steeper slope of oxygenation profile at all matched workloads compared to normals (Group A: -0.13 +/- 0.03 ml/min; Group B: -0.06 +/- 0.015 ml/min; p < 0.0001). The LAT correlated with the work rate at which the rate of tissue O2 desaturation accelerated (r = 0.94; p < 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

The zone of vulnerability to T wave shocks in humans.

INTRODUCTION: Shocks during the vulnerable period of the cardiac cycle induce ventricular fibrillation (VF) if their strength is above the VF threshold (VFT) and less than the upper limit of vulnerability (ULV). However, the range of shock strengths that constitutes the vulnerable zone and the corresponding range of coupling intervals have not been defined in humans. The ULV has been proposed as a measure of defibrillation because it correlates with the defibrillation threshold (DFT), but the optimal coupling interval for identifying it is unknown. METHODS AND RESULTS: We studied 14 patients at implants of transvenous cardioverter defibrillators. The DFT was defined as the weakest shock that defibrillated after 10 seconds of VF. The ULV was defined as the weakest shock that did not induce VF when given at 0, 20, and 40 msec before the peak of the T wave or 20 msec after the peak in ventricular paced rhythm at a cycle length of 500 msec. The VFT was defined as the weakest shock that induced VF at any of the same four intervals. To identify the upper and lower boundaries of the vulnerable zone, we determined the shock strengths required to induce VF at all four intervals for weak shocks near the VFT and strong shocks near the ULV. The VFT was 72 +/- 42 V, and the ULV was 411 +/- V. In all patients, a shock strength of 200 V exceeded the VFT and was less than the ULV. The coupling interval at the ULV was 19+/- 11 msec shorter than the coupling interval at the VFT (P < 0.001). The vulnerable zone showed a sharp peak at the ULV and a less distinct nadir at the VFT. A 20-msec error in the interval at which the ULV was measured could have resulted in underestimating it by a maximum of 95 +/- 31 V. The weakest shock that did not induce VF was greater for the shortest interval tested than for the longest interval at both the upper boundary (356 +/- 108 V vs 280 +/- 78 V; P < 0.01) and lower boundary (136 +/- 68 msec vs 100 +/- 65 msec; P < 0.05). CONCLUSIONS: The human vulnerable zone is not symmetric with respect to a single coupling interval, but slants from the upper left to lower right. Small differences in the coupling interval at which the ULV is determined or use of the coupling interval at the VFT to determine the ULV may result in significant variations in its measured value. An efficient strategy for inducing VF would begin by delivering a 200-V shock at a coupling interval 10 msec before the peak of the T wave.

Aged↗

Normal standards for an incremental progressive cycle ergometer test.

One hundred healthy subjects (50 male and 50 female), selected to provide an even distribution of age (15 to 71 yr) and height (165 to 194 cm in males and 152 to 176 cm in females), underwent a progressively incremental (100 kpm/min each min) exercise test to a symptom-limited maximum. Measurements were made of O2 intake and CO2 output, ventilation and breathing pattern, heart rate and blood pressure, and rating of perceived exertion. The ventilatory anaerobic threshold was identified. Predictive data were derived for measurements at maximal and submaximal exercise. Maximal power output (Wmax) and oxygen intake (VO2max) varied with sex (0, male; 1, female), age (yr), and height (Ht, cm): Wmax = 20.4 (Ht) - 8.74 (Age) - 288 (Sex) - 1,909 kpm/min (SEE, 216; r, 0.858); VO2max = 0.046 (Ht) - 0.021 (Age) - 0.62 (Sex) - 4.31 L/min (SEE, 0.458; r, 0.869). The extent of leisure time activity exerted a positive influence on VO2max (r, 0.47; p less than 0.001); VO2max was also related to lean thigh volume (r, 0.79). Maximal heart rate (HR) declined as a function of age: HRmax = 202 - 0.72 (Age) beats/min (SEE, 10.3; r, 0.72). Maximal O2 pulse (O2Pmax) was related to height and was systematically higher in males than in females: O2Pmax = 0.28 (Ht) - 3.3 (Sex) - 26.7 ml/beat (SEE, 2.8; r, 0.86). Ventilation was closely related to CO2 output, and the maximal tidal volume was related to vital capacity. The VO2 increased linearly with power throughout the test; in an individual subject, the intercept of this relationship was positively influenced by weight and height.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effects of exercise training on cardiorespiratory function in men and women older than 60 years of age.

This study reports the physiologic effects of up to 14 months of aerobic exercise in 101 older (greater than 60 years) men and women. After an extensive baseline physiologic assessment (Time 1), in which aerobic capacity and blood lipids were measured, subjects were randomized to an aerobic exercise condition (cycle ergometry, 3 times per week for 1 hour), nonaerobic yoga (2 times per week for 1 hour), or a waiting list nonexercise control group for 4 months, and then underwent a second (Time 2) assessment. At the completion of the second assessment, all remaining subjects completed 4 months of aerobic exercise and were reevaluated (Time 3). Subjects were given the option of participating in 6 additional months of supervised aerobic exercise, and all available subjects completed a fourth assessment (Time 4) 14 months after their initial baseline evaluation. Results indicated that subjects generally exhibited a 10 to 15% improvement in peak oxygen consumption after 4 months of aerobic exercise training, and a 1 to 6% improvement in aerobic power with additional aerobic exercise training. On the other hand, subjects, especially men, continued to have improvements in submaximal exercise performance (i.e., anaerobic threshold). In addition, aerobic exercise was associated with an improved lipid profile; subjects participating in aerobic exercise for up to 14 months exhibited increased levels of high-density lipoprotein cholesterol. Maintenance of regular aerobic exercise for an extended time interval is associated with greater cardiovascular benefits among older adults than has been reported previously.

Aged↗

Aerobic and anaerobic power characteristics of competitive cyclists in the United States Cycling Federation.

The purpose of this study was to characterize the aerobic and anaerobic capabilities of United States Cycling Federation cyclists in different categories. To determine aerobic and anaerobic power, 38 competitive road cyclists (32 males, 6 females) performed a VO2max test and a Wingate anaerobic test, respectively. Male cyclists in category II had the highest VO2max, both in absolute and relative terms. Their VO2max was 6% and 10% higher than category III and IV cyclists, respectively (4.98 +/- 0.14 vs 4.72 +/- 0.15 vs 4.54 +/- 0.12 l/min). A significant difference existed between category II and IV male cyclists (p < 0.05). VO2max for female cyclists (3.37 +/- 0.13 l/min) was significantly (p < 0.05) lower than those for males. The Wingate anaerobic test revealed that male cyclists in category II also had the highest anaerobic power output. The peak power output in category II, III and IV was 13.86 +/- 0.23, 13.55 +/- 0.25, and 12.80 +/- 0.41 W/kg, respectively. The mean power output in category II, III, and IV was 11.22 +/- 0.18, 11.06 +/- 0.15, and 10.40 +/- 0.30 W/kg, respectively. The difference in the mean power output between category II and IV was significant (p < 0.05). Female cyclists recorded significantly less peak and mean power output than their male counterparts (p < 0.05). However, when expressed relative to lean body mass, anaerobic power was similar for both sexes. No inter-correlation was found in any measurement between the aerobic and anaerobic power values. On the whole, category II male cyclists were characterized by higher aerobic and anaerobic power outputs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Brain and central haemodynamics and oxygenation during maximal exercise in humans.

During maximal exercise in humans, fatigue is preceded by reductions in systemic and skeletal muscle blood flow, O(2) delivery and uptake. Here, we examined whether the uptake of O(2) and substrates by the human brain is compromised and whether the fall in stroke volume of the heart underlying the decline in systemic O(2) delivery is related to declining venous return. We measured brain and central haemodynamics and oxygenation in healthy males (n= 13 in 2 studies) performing intense cycling exercise (360 +/- 10 W; mean +/-s.e.m.) to exhaustion starting with either high (H) or normal (control, C) body temperature. Time to exhaustion was shorter in H than in C (5.8 +/- 0.2 versus 7.5 +/- 0.4 min, P < 0.05), despite heart rate reaching similar maximal values. During the first 90 s of both trials, frontal cortex tissue oxygenation and the arterial-internal jugular venous differences (a-v diff) for O(2) and glucose did not change, whereas middle cerebral artery mean flow velocity (MCA V(mean)) and cardiac output increased by approximately 22 and approximately 115%, respectively. Thereafter, brain extraction of O(2), glucose and lactate increased by approximately 45, approximately 55 and approximately 95%, respectively, while frontal cortex tissue oxygenation, MCA V(mean) and cardiac output declined approximately 40, approximately 15 and approximately 10%, respectively. At exhaustion in both trials, systemic VO(2) declined in parallel with a similar fall in stroke volume and central venous pressure; yet the brain uptake of O(2), glucose and lactate increased. In conclusion, the reduction in stroke volume, which underlies the fall in systemic O(2) delivery and uptake before exhaustion, is partly related to reductions in venous return to the heart. Furthermore, fatigue during maximal exercise, with or without heat stress, in healthy humans is associated with an enhanced rather than impaired brain uptake of O(2) and substrates.

Adenosine Triphosphate↗

Aerobic and functional capacity in a group of healthy women: reference values and repeatability.

Twenty-five randomly selected, low or moderately fit and healthy women (22-44 years) rated their perceived physical capacity and performed an incremental cycle exercise test with respiratory gas analysis. The aerobic and functional capacity did not decrease with age. However, tauVo(2) increased with age. The mean value of the perceived physical capacity was 10 metabolic equivalents and that of Vo(2max) 2075 ml min(-1). The increasing anaerobic metabolism was determined at three points DX (where the rate of Vco(2) increase just exceeds the rate of Vo(2) increase), PX (where Vco(2)/Vo(2) = 1.0) and PQ (where ventilation increase disproportionately in relation to Vco(2)). The mean Vo(2) (% of Vo(2max)) at DX, PX and PQ were 1263 (63%), 1528 (73%) and 1620 (78%) ml min(-1), respectively. The mean value of deltaVo(2)/deltaW was 10.2 ml min(-1) W(-1) while that of tauVo(2) was 0.578 (age) + 15.6. Ten women performed a test and re-test on two consecutive days, and eight of these performed another re-test 4 weeks later. The repeatability was analysed and the variations were expressed as 2 SD of the differences between the tests. The variation was greater for the 4-week re-test than the day-to-day re-test regarding Vo(2max), o(2) at DX, PX and PQ, deltaVo(2)/deltaW and HR. The variation in Vo(2max), PX and deltaVo(2)/deltaW for the 4-week re-test was more than twice that of the previously reported 4-week variation for men. The considerable variation, especially for 4-week re-testing for women should be considered when evaluating the effects of exercise and rehabilitation.

Adult↗

Studies on the chronopharmacology of ethanol.

Male subjects (n = 10) were given ethanol (0.75 g/kg) at four equally spaced times in the 24 hr cycle (9 am, 3 pm, 9 pm 3 am) in random order. Blood ethanol concentrations were monitored by breath analysis and measurements were made of the blood or plasma levels of ethanol, acetaldehyde, acetate, pyruvate, lactate and cortisol. Blood pressure, heart rate and body temperature were measured before and at 60 and 120 min after ethanol administration and the effects of ethanol on a number of behavioural parameters and mood were studied. After ethanol ingestion, there was a significant decrease in body temperature, systolic blood pressure, plasma cortisol and pyruvate levels, whilst acetate levels and the lactate:pyruvate ratio were significantly increased. Standing steadiness, critical flicker fusion threshold and divided attention tracking control were significantly impaired under ethanol and self-report data indicated a significant decrease in alertness, co-ordination, concentration and attentiveness. Although a significantly higher peak blood ethanol concentration was attained at the 9 am session, other time-of-day differences did not reach significance and the pharmacokinetics of ethanol were essentially unchanged. Since the only significant diurnal variations in the response to ethanol identified in this study (apart from the subjective results) were for plasma cortisol concentrations and body temperature (both of which are well known to exhibit diurnal rhythmicity), it appears that major circadian variability in the metabolic and/or behavioural effects of ethanol is unlikely to occur.

Adolescent↗

Intracellular glutathione heterogeneity in L1210 murine leukemia sublines made resistant to DNA-interacting anti-neoplastic agents.

Intracellular glutathione (GSH) content was measured by flow cytometry using monochlorobimane (mBCl) and by the enzymatic assay in a set of 6 sublines of murine L1210 leukemia cells made resistant to DNA-interacting agents having distinct mechanisms of action: L-phenylalanine mustard (L-PAM), 1,3-bis(2-chloroethyl)-I-nitrosourea (BCNU), cisplatin (DDP), N-deformyl-N-(4-N,N-bis(2-chloroethylamino) benzoyl) distamycin A (FCE 24517), doxorubicin (DX) and 3'-deamino-3' (2-methoxy-4-morpholinyl)-doxorubicin (FCE 23762). A significant correlation was demonstrated between the mean intracellular mBCl fluorescence values measured by flow cytometry and levels of GSH measured by the classical enzymatic assay, despite the possible influence of glutathione-S-transferases and of other thiols on the mBCl fluorescence. Although less specific, the flow cytometric method is more informative than the enzymatic assay, allowing detection of fluorescence distributions, which we proved to be characteristic of each subline. In order to assess a procedure enabling a quantitative analysis to be made of intercellular GSH heterogeneity, we propose the use of appropriate thresholds and parameters of the mBCl flow cytometric distribution. By use of this analysis procedure, distinct types of alterations, with respect to the heterogeneity distribution of the parental L1210 cell line, have been evidenced in resistant cells. A uniform increase in mBCl fluorescence was observed among cells of the sublines resistant to L-PAM and FCE-24517. The mean mBCl fluorescence increase in sublines resistant to DX and DDP was due to a higher number of cells with fairly high mBCl fluorescence, but still within the range spanned by the parental cell line. A less heterogeneous mBCl fluorescence distribution was found in the L1210 subline resistant to FCE 23762, which was, however, similar to a cloned sensitive line. Though GSH was linked to the principal cause of drug resistance only in the L-PAM-resistant cell line, alterations in heterogeneity, as detected by mBCl fluorescence distributions, were found in 5 out of 6 resistant lines.

Animals↗

Effect of pacing current strength on indexes of myocardial activation in humans: influence of chronic infarction and polarity of pacing.

The effects of current strength (threshold to 20 mA) and pacing polarity (bipolar versus unipolar) on indexes of ventricular activation during endocardial pacing (cycle length 400 to 500 ms) from 10 normal and 17 abnormal left ventricular sites were assessed in 19 patients. Abnormal sites were infarcted and demonstrated an electrogram duration greater than 70 ms and amplitude less than 3 mV during sinus rhythm. Bipolar pacing was performed from poles 1 (cathode) and 3 (1 cm interelectrode distance) of a quadripolar catheter. Unipolar cathodal pacing was performed from the tip electrode (pole 1). Local activation was indexed by the interval from the pacing stimulus to 1) the onset of the QRS complex, 2) the largest rapid deflection of the local electrogram, and 3) the end (total duration) of the local electrogram recorded from poles 2 and 4 of the quadripolar catheter used for left ventricular pacing. Distant activation was indexed by the interval from pacing stimulus to electrograms recorded at the right ventricular apex and outflow tract. Bipolar and unipolar pacing of normal sites produced a modest homogeneous reduction of all activation times by 3 to 11 ms (median) with increments in current strength from threshold (0.8 mA) to 20 mA. Bipolar pacing of abnormal sites showed marked (up to 110 ms) and heterogeneous changes in local (median 22 to 30 ms) as well as distant (median 14 to 23 ms) activation times with increases in current strength from threshold (2.7 mA) to 20 mA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Three-dimensional mapping of earliest activation after near-threshold ventricular defibrillation shocks.

INTRODUCTION: Following shocks with a 50% defibrillation success (DFT50) delivered from electrodes at the right ventricular (RV) apex and superior vena cava (SVC), the earliest epicardial postshock activation always appears focally in the left ventricular (LV) apex for both successful and failed shocks. Because the heart is a three-dimensional (3D) structure, questions remain whether this activation truly arises from a focus or the focal pattern represents epicardial breakthrough resulting from intramural reentry. To answer these questions, 3D electrical mapping was performed. METHODS AND RESULTS: In six pigs, 60 to 84 epoxy fiberglass needles (0.7-mm-diameter), each containing six electrodes 2 mm apart, were inserted into the LV with 3- to 5-mm spacing around the apex and 5- to 10-mm spacing near the base. Ten DFT50 shocks (RV-->SVC, biphasic, 6/4 msec) were delivered after 10 seconds of fibrillation in each animal. The first five activations after each shock were mapped. Of 60 DFT50 shocks, 31 were successful, of which the first postshock cycle was a sinus beat in 13. In the other 18 successful shock episodes, the first postshock activation was detected 63 +/- 16 msec after the shock, which was not significantly different from the 58 +/- 23 msec postshock interval for the 29 failed shock episodes. In these 47 successful and failed shock episodes, the earliest postshock activation always arose focally from the LV apex. Its origin was in the subepicardium in 76% +/- 17%, midmyocardium in 16% +/- 12%, and subendocardium in 8% +/- 6% of cases. CONCLUSION: Following near-DFT50 shocks, the first postshock cycles did not arise by macroreentry. Instead, they originated from a true focus or microreentry, most commonly near the epicardium.

Animals↗