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Biomedical subjects

Brian J Whipp

Publications and source records attributed to Brian J Whipp.

11 recordsLinked to original sources

Non-linear cardiac output dynamics during ramp-incremental cycle ergometry.

Published literature asserts that cardiac output (Q(.) = V(.) >O(2)x1/C((a-v))O(2)) increases as a linear function of oxygen uptake with a slope of approximately 5-6 during constant work rate exercise. However, we have previously demonstrated that C((a-v))O(2) has a linear relationship as a function of V(.)O(2) during progressively increasing work rate incremental exercise. Therefore, we hypothesized that Q(.) may indeed have a non-linear relationship with respect to V(.)O(2) during incremental, non-steady state exercise. To investigate this hypothesis, we performed five maximal progressive work rate exercise studies in healthy human subjects. Q(.) was determined every minute during exercise using measured breath-by-breath V(.) >O(2), and arterial and pulmonary artery measurements of PO(2), hemoglobin saturation, and content. Q(.) was plotted as a function of V(.) >O(2) and the linear and non-linear (first order exponential and hyperbolic) fits determined for each subject. Tests for linearity were performed by assessing the significance of the quadratic terms added to the linear relation using least squares estimation in linear regression. Linearity was inadequate in all cases (group P<0.0001). We conclude that cardiac output is a non-linear function of V(.)O(2 )during ramp-incremental exercise; the pattern of non-linearity suggests that while the kinetics of Q(.) > are faster than those of V(.) >O(2) they progressively slow as work rate (and V(.) >O(2)) increases.

Adult↗

Ventilatory responses to inhaled carbon dioxide, hypoxia, and exercise in idiopathic hyperventilation.

Idiopathic hyperventilation (IH) is a poorly understood condition of sustained hypocapnia and controversial etiology. Although behavioral/emotional factors may contribute, it is uncertain whether chemosensitivity is altered, hyperventilation is maintained during exercise, and the associated breathlessness reflects the hyperventilation. In 39 patients with IH and 23 control subjects, we described ventilatory responses to isocapnic-hypoxia, hyperoxic-hypercapnia, and exercise; breath-hold tolerance; breathlessness; and psychologic status. Patients demonstrated hyperventilation at rest, with hypocapnia (28 +/- 3.8 mm Hg), a normal (slightly alkaline) arterial pH and [H(+)]a, and a significant base excess (-4.5 +/- 2.7 mEq/L), consistent with compensated respiratory alkalosis. Hyperventilation was sustained during exercise, despite hyperoxic-hypercapnic ventilatory responsiveness being normal and isocapnic-hypoxic ventilatory responsiveness being low relative to control (but exceeding control [2.4 +/- 1.0 vs. 1.6 +/- 0.5 L/min/%, p < 0.05] with acute restoration to normocapnia). Hyperventilation was maintained during exercise, at the resting CO(2) "setpoint." Relative to control, the breath-hold tolerance was attenuated, and dyspnea during exercise was significantly greater and not simply ascribable to the high ventilation. These observations suggest that patients with IH have a sustained hyperventilatory and dyspneic drive that, although not attributable to central chemosensitivity, may possibly have peripheral chemoreflex contributions. The nature and etiology of this chronic hyperventilatory drive remain unclear.

Administration, Inhalation↗

Intensity-dependent tolerance to exercise after attaining V(O2) max in humans.

The tolerable duration of high-intensity, constant-load cycle ergometry is a hyperbolic function of power, with an asymptote termed critical power (CP) and a curvature constant (W') with units of work. It has been suggested that continued exercise after exhaustion may only be performed below CP, where predominantly aerobic energy transfer can occur and W' can be partially replenished. To test this hypothesis, six volunteers each performed cycle-ergometer exercise with breath-by-breath determination of ventilatory and pulmonary gas exchange variables. Initially, four exercise tests to exhaustion were made: 1). a ramp-incremental and 2). three high-intensity constant-load bouts at different work rates, to estimate lactate (theta(L)) and CP thresholds, W', and maximum oxygen uptake (Vo2 max). Subsequently, subjects cycled to the limit of tolerance (for approximately 360 s) on three occasions, each followed by a work rate reduction to 1). 110% CP, 2). 90% CP, and 3). 80% theta(L) for a 20-min target. W' averaged 20.9 +/- 2.35 kJ or 246 +/- 30 J/kg. After initial fatigue, 110% CP was tolerated for only 30 +/- 12 s. Each subject completed 20 min at 80% theta(L), but only two sustained 20 min at 90% CP; the remaining four subjects fatigued at 577 +/- 306 s, with oxygen consumption at 89 +/- 8% Vo2 max. The results support the suggestion that replenishing W' after fatigue necessitates a sub-CP work rate. The variation in subjects' responses during 90% CP was unexpected but consistent with mechanisms such as reduced CP consequent to prior high-intensity exercise, variation in lactate handling, and/or regional depletion of energy substrates, e.g., muscle glycogen.

Adult↗

Behavioral influences and physiological indices of ventilatory control in subjects with idiopathic hyperventilation.

Idiopathic hyperventilation has been defined as a respiratory-related psychophysiological complaint. This study attempted to clarify relationships between psychological and physiological variables in this condition. Participants demonstrated increased anxiety, depression, and symptoms consistent with hyperventilation. This was associated with a reduced peripheral chemosensitivity (isocapnic hypoxic rebreathe; -0.84 +/- 0.5 min-1.%O2(-1)), which was normalized with experimentally increased pCO2. Resting CO2 sensitivity was close to normal (2.1 +/- 1.0 min-1.mmHg-1). Breath hold time was significantly reduced versus controls (20.4 s +/- 12 s vs. 63 s +/- 31 s), and resting PETCO2 was correlated with the anxiety score. Also, the ventilatory response to moderate intensity exercise was augmented (vs. controls). The normalcy of pulmonary and chemoreceptor responses suggests that psychological factors may initiate this hyperventilation, which may become a conditioned response with an increased drive to breathe.

Anxiety↗

The curvature constant parameter of the power-duration curve for varied-power exercise.

INTRODUCTION: The tolerable duration (t) for high-intensity cycle ergometry bears a hyperbolic relationship to the power output (P) with an asymptote termed the critical power (CP), and a curvature constant (W') that is numerically equivalent to an amount of work that can be performed above CP. The physiological nature of W' has received little consideration compared with CP, e.g., whether the total amount of work above CP remains constant when the power actually changes during the high-intensity task. PURPOSE: The purpose of this study was to compare W' derived from the standard estimation method, consisting of several different constant-P tests, and the total amount of work above CP during an exhausting exercise bout using a variable-P protocol. METHODS: Eleven healthy male subjects (age: 21-40 yr) volunteered to participate in this study. Each initially performed four-to-six high-intensity square-wave exercise bouts for estimation of CP [mean (SD); 213.3 (22.4) W] and W' [12.68 (3.08) kJ]. The subjects subsequently performed two variable-P tests to the limit of tolerance. During the first part, P was 117% or 134% of CP for a duration that expended approximately half of W'. The work rate was then abruptly increased to 134% (UP protocol) or decreased to 117% (DOWN protocol) of CP for the second part. RESULTS: There were no significant differences between W' [12.68 (3.08) kJ] and the total amount of work above CP during the UP [12.14 (4.18) kJ] and DOWN [12.72 (4.05) kJ] protocols (P > 0.05). CONCLUSION: We conclude that the work equivalent of W' is not affected by power variations during exhausting cycle ergometry, at least in the P range of 100-134% of CP.

Adult↗

A treadmill ramp protocol using simultaneous changes in speed and grade.

INTRODUCTION: A treadmill exercise test requiring a low initial metabolic rate that then increments the work rate linearly to reach the subject's limit of tolerance in approximately 10 min would have significant advantages for exercise testing and rehabilitation of subjects with impaired exercise tolerance. METHODS: We developed such a treadmill protocol that uses a linear increase in walking speed coupled with a curvilinear increase in treadmill grade to yield a linear increase in work rate. RESULTS: Twenty-two healthy, sedentary subjects performed both this new treadmill protocol and a standard cycle ergometry ramp protocol eliciting similar work rate profiles. The low initial treadmill speed and grade resulted in a low initial metabolic rate, commensurate with unloaded pedaling on a cycle ergometer (average [OV0312]O2 = 0.54 +/- 0.16 vs 46 +/- 0.12 l x min(-1)). This combination of simultaneous increase in speed and grade yielded a linear work rate and its oxygen uptake response (R2 = 0.96 +/- 0.03) with a slope of 11.4 +/- 2.4 ml x min(-1) x W(-1)-slightly, but significantly, higher than on the cycle (9.6 +/- 2.0 ml x min(-1) x W(-1)). This difference was attributed to unmeasured work associated, for example, with additional limb movements and frictional losses. As previously demonstrated, both the peak oxygen uptake and the estimated lactate threshold were higher on the treadmill than for cycle ergometry (averaging 23% and 27%, respectively, in these subjects). CONCLUSION: This treadmill protocol provides a linear profile of work rate as is currently standard for cycle ergometry and is appropriate for testing of subjects with low exercise tolerance.

Adolescent↗

Breath-by-breath fluctuations of pulmonary gas exchange and ventilation in COPD patients.

The purpose of the study was to characterise statistically the inherent fluctuations in breath-by-breath measurements of pulmonary gas exchange (oxygen uptake and carbon dioxide output, V*O2 and V*CO2, respectively) and pulmonary ventilation (V*E) in patients with chronic obstructive pulmonary disease (COPD) and to compare them with those of healthy control subjects. Thirty subjects with COPD [mean (SD): 67 (6) years old; forced expiratory volume in 1 min, FEV1 1.25( 0.18) l; 42 (6)% predicted FEV1] and 12 healthy subjects [31 (3) years old; FEV1 3.62 (0.54) l; 99 (8)% predicted FEV1] performed exercise tests on a cycle ergometer at a constant work rate of moderate intensity. Steady-state exercise values for V*O2, V*CO2 and V*E were 905 (96) ml.min(-1), 847(90) ml.min(-1) and 23 (3) l.min(-1), respectively for the COPD patients and 1239(89) ml.min(-1), 1191(84) ml.min(-1)and 37(3) l.min(-1), respectively, for the healthy controls. The breath-by-breath fluctuations were well characterised by a Gaussian density-probability function with breath-to-breath autocorrelations that were not significantly different from 0, up to four subsequent breaths. Its magnitude varied among variables, but was independent of the signal amplitude for the same subject and variable. With ratios of amplitude of fluctuation:signal of around 10%, typical of the patients studied, the resolution of time constants and amplitude were congruent with 9 s and congruent with 100 ml.min(-1), respectively for V*O2 or V*CO2 with one repetition.

Adult↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗

The effect of resistive breathing on leg muscle oxygenation using near-infrared spectroscopy during exercise in men.

The effect of added respiratory work on leg muscle oxygenation during constant-load cycle ergometry was examined in six healthy adults. Exercise was initiated from a baseline of 20 W and increased to a power output corresponding to 90% of the estimated lactate threshold (moderate exercise) and to a power output yielding a tolerance limit of 11.8 min (+/- 1.4, S.D.) (heavy exercise). Ventilation and pulmonary gas exchange were measured breath-by-breath. Profiles of leg muscle oxygenation were determined throughout the protocol using near-infrared (NIR) spectroscopy (Hamamatsu NIRO 500) with optodes aligned midway along the vastus lateralis of the dominant leg. Four conditions were tested: (i) control (Con) where the subjects breathed spontaneously throughout, (ii) controlled breathing (Con Br) where breathing frequency and tidal volume were matched to the Con profile, (iii) increased work of breathing (Resist Br) in which a resistance of 7 cmH2O l(-1) s(-1) was inserted into the mouthpiece assembly, and (iv) partial leg blood flow occlusion (Leg Occl), where muscle perfusion was reduced by inflating a pressure cuff (approximately 90 mmHg) around the upper right thigh. During Resist Br and Leg Occl, subjects controlled their breathing pattern to reproduce the ventilatory profile of Con. An approximately 3 min period with respiratory resistance or pressure cuff was introduced approximately 4 min after exercise onset. NIR spectroscopy data for reduced haemoglobin-myoglobin (delta[Hb]) were extracted from the continuous display at specific times prior to, during and after removal of the resistance or pressure cuff. While the delta[Hb] increased during moderate- and heavy-intensity exercise, there was no additional increase in delta[Hb] with Resist Br. In contrast, delta[Hb] increased further with Leg Occl, reflecting increased muscle O2 extraction during the period of reduced muscle blood flow. In conclusion, increasing the work of breathing did not increase leg muscle deoxygenation during heavy exercise. Assuming that leg muscle O2 consumption did not decrease, this implies that leg blood flow was not reduced consequent to a redistribution of flow away from the working leg muscle.

Adult↗

Effects of training on the tolerance to high-intensity exercise in patients with severe COPD.

BACKGROUND: There has been no systemic investigation of the effects of training on endurance at different high-intensity work rates in patients with COPD to date. OBJECTIVES: We wanted to determine the effects of intense endurance training on tolerance to several high-intensity work rates and to establish the relationship between power (WR) and its tolerable duration (t) (t = W'/(WR - CP), being W', the curvature constant, thought to be reflective of anaerobic energy availability and/or tolerance to the uncomfortable sensations associated with the high-intensity exercise, and CP the critical power. METHODS: We studied 27 patients: age 62 +/- 5 years; FEV(1) 1.2 +/- 0.2 liters. Before and after the intervention, the subjects randomly underwent 4 high-intensity constant WR exercise tests. The endurance times of the highest 3 tests were used. RESULTS: Ventilation reached approximately the same level in each of the tests. In response to the training, the average peak increased by 9 +/- 5% (p < 0.0001), CP by 14 +/- 12% (p < 0.0001) and W' 18 +/- 22% (p = 0.002). In 67% of the patients, CP increased, accompanied by changes in other related physiological variables of aerobic capacity. In the remaining 33%, W' increased but not CP. Smaller or no changes in the other variables of aerobic capacity were found in those subjects. This latter group was significantly older and had more hyperinflation (i.e. higher RV/TLC%). CONCLUSIONS: Our results suggest that neither an incremental nor a single endurance test at constant WR provides an adequate characterisation of exercise tolerance at other WRs. CP and W' appear to be important parameters characterizing exercise tolerance over a range high-intensity work rates and identifying two distinct types of response to training.

Exercise↗