Quantitative radiocardiographic evaluation of cardiac dynamics in man at rest and during exercise

113Inm radiocardiography in conjunction with a gamma camera and a digital computer is applied to measurements of cardiac output, stroke volume, ejection fraction, end-diastolic volume, pulmonary blood volume, pulmonary transfer time and dispersion both at rest and during muscular exercise. A modified gamma function is used in calculations of radiocardiographic curves. In twelve supine male subjects the maximal increase of cardiac output was 220%, stroke volume 30%, ejection fraction 15%, and pulmonary blood volume 30%. The present method provides a non-invasive tool for cardiovascular examinations during exercise.     

Ventilatory responses to inhaled carbon dioxide at rest and during exercise in man

1. Rapid steady-state CO2 responses were determined in six normal subjects at rest and five subjects at four different work loads up to 125 W, by injecting pure CO2 at constant flow into a small mixing chamber in the inspiratory limb of a breathing circuit. 2. The time course of the response of ventilation (V) and mean alveolar PCO2 (PACO2) was checked in separate experiments, where the flow rate of injected CO2 was changed abruptly and the effects were followed for 10 min. 3. V and PACO2 were measured every breath, and the results ensemble-averaged for each subject (two or three runs per subject) and then for the groups as a whole, in 30 s or 60 s time bins. 4. PACO2 during exercise was estimated by graphical reconstruction from the sloping alveolar plateau, and separately by the empirical equation of Jones, Robertson & Kane [1]. At rest, PACO2 was assumed equal to end-tidal PCO2 (PetCO2). 5. With the constant inflow technique, 4 min was required to reach steady-state V and PACO2 during exercise, and 6 min at rest. 6. At rest, with 4 min steps (doubtful steady state) the averaged CO2 response was concave up. With 6 min steps the response was almost linear. In neither case was the deviation from linearity statistically significant. 7. During exercise, the averaged CO2 responses were essentially isocapnic at work loads greater than 75 W with either method of deriving PACO2.     

Regional pulmonary clearance of inhaled C15O and C15O2 in man at rest and during exercise

Summary. The regional clearance of radioactive carbon monoxide (C¹⁵O₂) and carbon dioxide (C¹⁵O₂), after a single maximal inspiration, was investigated in six normal subjects seated on a bicycle, at rest and during exercise at 50 W. The clearances were measured sequentially during breath-holding by four pairs of scintillation counters vertically aligned over the right lung. The clearance rate (k) for C¹⁵O and C¹⁵O₂ increased from apex to base and from rest to exercise. On exercise, the apex base gradient (calculated over 11 cm vertical distance) for C¹⁵O decreased by 52% because of a larger increase in the upper zones but the C¹⁵O₂ gradient did not change. Thus the increase in blood flow (=kC¹⁵O₂) on exercise was accompanied by recruitment and/or distension of pulmonary capillary blood volume (=kC¹⁵O₂), most marked in the upper regions. The ratio of the clearance (C¹⁵O/C¹⁵O₂) decreased in the lower zones on exercise by 25% without significant change in the upper zone. This ratio reflects the product of capillary mean transit times and peripheral vascular and extravascular volumes. Since the latter increase on exercise, capillary transit times must have shortened considerably at a moderate level of exercise at all levels in the lung.     

Influence of age on pulmonary haemodynamics at rest and during supine exercise

To determine the effects of age on the pulmonary circulation at rest and on exercise we analysed the results of right heart catheterization studies performed in 125 asymptomatic subjects aged 14-68 years, who were healthy or had indispositions which did not impair cardiac or pulmonary function. Age accounted for less than 10% of total variation in resting values of right atrial, pulmonary artery and wedge pressures, and of cardiac output. The pulmonary artery-wedge pressure gradient and flow resistance at rest significantly increased with age. On exercise there were significant increases with age in right atrial, pulmonary artery and wedge pressures, pulmonary to wedge pressure gradient and flow resistance, but cardiac output was not influenced by age. Pulmonary circulation variables at rest are mainly influenced by sex and size, but during exercise significant effects of age are apparent.     

Non-invasive determination of the distribution of cardiac output in man at rest and during exercise

Summary. The distribution of cardiac output, as expressed by the regional uptake of thallium-201 following injection, has been studied by whole body scanning with a gamma-camera in six healthy persons and eight patients with aortic valvular disease. In the patients, cardiac output at rest and during exercise was also measured by the dye dilution technique. Combining the values of cardiac output and regional thallium uptake enabled the calculation of organ blood flow. The myocardial uptake of thallium at rest was 3·2 ± 0·32% in the control group, which is significantly lower than 8·3 ± 1·52%, found in the patients. The corresponding values measured in the kidneys were 12·5 ±1·91% in the healthy subjects and 7·1 ± 0·50% in the patient material. Myocardial uptake increased and kidney uptake decreased in both groups following injection at peak exercise. Thallium uptake in the legs increased from about 13% at rest to about 39% at exercise in both groups. Distribution of thallium after injection at peak exercise did not, however, vary significantly between the two groups in the kidneys, abdominal area or the legs. Further methodological work is required before it can be ascertained to what extent the regional thallium uptake reflects the distribution of cardiac output. We nevertheless propose that the technique should be explored further, since it appears to be a simple non-invasive means of visualizing the distribution of the cardiac output in man under certain conditions.     

A proposal for scientific validation of instruments for indirect blood pressure measurement at rest,during exercise,and in critical care

Objective. The purpose of this study was to provide a critical review and comprehensive outline of published guidelines for the validation of monitors for indirect blood pressure (BP) measurement in light of recent research and practical clinical experienceMethods. Studies testing the reliability and validity of BP monitors and available guidelines for validation have been reviewed and comparedResults. The validation studies of instruments for indirect BP measurement have used a wide variety of sample pools, BP ranges, protocols, reference instruments, and statistical procedures, thereby making it impossible to reach a consensus Few existing recommendations for validation have been found to be incomplete with respect to BP in various physiological states, sequence of procedures, sample, and statistical analysisConclusions. A new sequence of procedures for validation, including assessment of instruments during exercise and in critical care, is introduced Previously suggested sample sizes for study subjects, age, and BP groups, as well as margins of error, are statistically challenged Insufficiency of linear relationship and aggregate agreement alone in determining the interchangeability between a reference and test instrument is demonstrated by quantification of agreement     

Nasal, pulmonary and autoinhaled nitric oxide at rest and during moderate exercise

Objective: To investigate nasal nitric oxide (NO) excretion, pulmonary NO excretion, and autoinhalation of nasally released NO at rest compared with that during moderate exercise in smokers and non-smokers.¶Design: Prospective observational study.¶Setting: University laboratory.¶Participants: Fourteen healthy adult volunteers.¶Interventions: Breathing of NO-purified air supplied via a tube system at rest and during a bicycle-ergometer workload of 60 Watt over a time of 10 min.¶Measurement and results: We examined nasal and pulmonary NO excretion in smoking (n = 7) and non-smoking (n = 7) adult human volunteers. At rest, we measured constant nasal NO excretion rates of 311 ± 89 nl/min for non-smokers and 261 ± 142 nl/min for smokers (mean ± SD, n. s.). During 60 W exercise, nasal NO release remained unchanged, while pulmonary NO excretion doubled compared with the rates at rest (non-smokers: 40 ± 21 nl/min versus 23 ± 14 nl/min, p < 0.05; smokers: 41 ± 8 nl/min versus 22 ± 8 nl/min, p < 0.05). The differences between smokers and non-smokers in nasal or pulmonary NO excretion were not significant. To determine the autoinhaled amount of nasally released NO, we also measured the NO concentration within the nasopharynx of five volunteers during nasal breathing. The average inhaled NO concentration was 17.8 ± 3.1 ppb at rest and this decreased to 9.3 ± 1.8 ppb during exercise of 60 W, while minute ventilation approximately doubled from 9 ± 2 to 21 ± 3 l/min.¶Conclusion: Our results demonstrate that moderate exercise increased exclusively pulmonary NO excretion. Nasal NO release, which is 10 times higher at rest, was not changed. The decrease in autoinhaled NO concentration during exercise results from dilution of the continuous nasal release by the increased respiratory gas flow. The individual NO release allows no conclusion about smoking habits.     

Timing of deep breaths during rest and light exercise in man

1. We used digital filtering techniques and segmental analysis to dissect a series of respiratory variables into three components: (a) outlying values, including deep breaths or sighs; (b) random variation; (c) non-stationary baseline variation. 2. Records of about 30 min breathing were obtained from normal adults at rest and at 50 W exercise. 3. Deep breaths were defined as having a tidal volume greater than 2.5 sd above the mean. 4. We related these deep breaths to preceding trends in tidal volume and end-tidal partial pressure of CO2. 5. At rest, there was no relation between deep breaths and tidal volume, but the deep breaths were significantly clustered around the troughs in end-tidal partial pressure of CO2. 6. At 50 W exercise, there was no relation between deep breaths and end-tidal partial pressure of CO2, but the deep breaths were significantly clustered around tidal volume troughs. 7. Results obtained by pneumography were concordant with those obtained by using a mouthpiece to measure ventilation.     

Responses of the systemic circulation and of the renin-angiotensin-aldosterone system to ketanserin at rest and exercise in normal man

The systemic circulation at rest and during exercise was studied in ten normal male volunteers, after placebo on one occasion and after acute intravenous administration of the serotonergic antagonist ketanserin on another occasion. The effects of ketanserin on the components of the renin-angiotensin-aldosterone system, on plasma catecholamines and on exercise capacity for graded uninterrupted exercise were also investigated. At rest in recumbency rapid intravenous injection of 10 mg of ketanserin, followed by a continuous infusion of 2 mg/h, produced an acute but transient fall in mean intra-arterial pressure of 6 mmHg compared with placebo. After 15 min the mean arterial pressure with ketanserin was within 2 mmHg of the mean pressure with placebo. In the sitting position both at rest and up to 30% of maximal work rate, the mean arterial pressure during ketanserin did not differ from the pressure on placebo. However, at higher levels of physical activity the rise in mean arterial pressure was lower with ketanserin; the pressure achieved with placebo was 7.5 mmHg higher at maximal work rate. Heart rate and cardiac output were significantly higher during ketanserin. When the subjects were lying down and resting, plasma noradrenaline and adrenaline levels, plasma renin activity and angiotensin II concentration were not affected by ketanserin; however, these values were higher in the sitting position both at rest and during exercise. Plasma aldosterone was reduced by ketanserin during exercise and also when the subject was resting in the recumbent position.(ABSTRACT TRUNCATED AT 250 WORDS)     

高肺血流幼猪模型的建立及其肺动脉血流动力学和肺组织学变化

目的研究高肺血流幼猪动物模型的建立的方法及探讨肺动脉血流动力学与结构关系。方法采用生后2-3月龄的幼猪,体重8-10kg,分为两组,每组6只。对照组(Control-group,n=6):即假手术组,只开胸无手术处理;高肺血流组(shunt-group,n=6):全部行左侧开胸,降主动脉与左肺动脉搭桥术。所有动物正常饲养3个月。然后正中开胸,检测肺动脉收缩压(PASP)、肺血管阻力(PVR),观察肺动脉标本的结构和组织学变化。结果 高肺血流组肺动脉收缩压(PASP)、肺血管阻力(PVR)显著升高(P<0.01);左肺动脉出现平滑肌细胞显著增生,部分血管中膜及内膜增厚,官腔狭窄。对照组无明显变化。结论在幼猪动物模型中,高肺血流可导致肺动脉结构重塑,可导致肺动脉压力的升高。为进一步研究高肺血流先天性心脏病肺动脉高压的形成过程,以期在治疗上提供新的方法。     

Abnormal vascular reactivity at rest and exercise in obese boys

Background Obese children exhibit vascular disorders at rest depending on their pubertal status, degree of obesity, and level of insulin resistance. However, data regarding their vascular function during exercise remain scarce. The aims of the present study were to evaluate vascular morphology and function at rest, and lower limb blood flow during exercise, in prepubertal boys with mild‐to‐moderate obesity and in lean controls. Materials and methods Twelve moderately obese prepubertal boys [Body Mass Index (BMI: 23·9 ± 2·6 kg m^?2)] and thirteen controls (BMI:17·4 ± 1·8 kg m^?2), matched for age (mean age: 11·6 ± 0·6 years) were recruited. We measured carotid intima‐media thickness (IMT) and wall compliance and incremental elastic modulus, resting brachial flow‐mediated dilation (FMD) and nitrate‐dependent dilation (NDD), lower limb blood flow during local knee‐extensor incremental and maximal exercise, body fat content (DEXA), blood pressure, blood lipids, insulin and glucose. Results Compared to lean controls, obese boys had greater IMT (0·47 ± 0·06 vs. 0·42 ± 0·03 mm, P < 0·05) but lower FMD (4·6 ± 2·8 vs. 8·8 ± 3·2%, P < 0·01) in spite of similar maximal shear rate, without NDD differences. Lower limb blood flow (mL min^?1·100 g^?1) increased significantly from rest to maximal exercise in both groups, although obese children reached lower values than lean counterparts whatever the exercise intensity. Conclusions Mild‐to‐moderate obesity in prepubertal boys without insulin resistance is associated with impaired endothelial function and blunted muscle perfusion response to local dynamic exercise without alteration of vascular smooth muscle reactivity.     

Atrial natriuretic factor: comparability of venous and arterial plasma measurements in man at rest and during exercise

1. Simultaneously obtained arterial and venous plasma atrial natriuretic factor (ANF) concentrations were compared at supine rest and during graded dynamic leg exercise in 10 healthy male subjects (aged 33-51 years). 2. Arterial ANF concentrations ranged between 12 and 179 pg/ml and venous concentrations between 9 and 177 pg/ml. 3. A positive correlation between arterial and venous concentrations was found (r = 0.984). 4. Arterial ANF concentrations were higher than venous concentrations in all pairs of samples (n = 31), but the difference was small and changed little with exercise: the mean difference was 5 pg/ml at rest, 12 pg/ml during submaximal exercise and 6 pg/ml during maximal exercise. 5. The extraction ratios for ANF varied greatly, but were in general lower (P less than 0.05) during maximal exercise (median 0.07, range 0.01-0.32) than at rest (median 0.22, range 0.05-0.33). 6. It was concluded that the plasma ANF concentration in a peripheral arm vein is a good indicator of the systemic peptide concentration at rest as well as during dynamic leg exercise.     

Beat-to-beat measurement of the finger arterial pressure pulse shape index at rest and during exercise

Arterial pressure waveform can be characterized by the pulse shape index kpulse determined as kpulse = (Pmean - Pdiast) / (Psyst - Pdiast). For brachial artery, the shape index value of 0.33 is usually applied to approximate Pmean from the measured Psyst and Pdiast. Our purpose was to test whether this value can validly be applied to finger vascular beds under different experimental conditions. By using Finapres, we non-invasively estimated the beat-to-beat values of kpulse in the fingers of young healthy persons in supine position at rest and during a 4-min moderate exercise (rhythmical exercise with the quadricep muscles in combination with handgrip compression). To detect intensive peripheral vasoconstrictions, a laser-Doppler probe was attached to the thumb pulp of the same hand. Periods of 30 s without intensive vasoconstriction for rest, different stages of exercise and recovery were involved in the analysis in every subject. The results demonstrated that the group-averaged value of kpulse (median with a 95% confidence interval) in the fingers of 11 healthy volunteers aged from 20 to 24, equalled 0.33 (0.31- 0.34), 0.31 (0.28-0.34), 0.35 (0.33-0.39) and 0.38 (0.34-0.43) for rest, first and second stages of exercise and recovery, respectively. We conclude that in the fingers of young healthy persons in supine position formula Pmean = Pdiast + 1/3 (Psyst - Pdiast) gives an adequate approximation for rest and low intensity exercise (first stage), and slightly underestimates the actual finger mean blood pressure during moderate exercise (second stage) and recovery.     

Mucociliary clearance in healthy men at rest and during exercise

Summary. We measured mucociliary clearance at rest and during exercise in 11 healthy non-smoking men. The subjects inhaled an aerosol containing [⁹⁹Tc^m]albumin millimicrospheres with deep inhalations. Four sets of scintigraphic images were obtained with 15-min intervals. Lung retention of radioactivity was quantified using a gamma camera and the clearance of particles from the lungs calculated for each 15-min period. The first image was obtained directly after inhalation, the second after a period of 15-min rest, the third after a period of exercise on a bicycle ergometer (workload approximately 80% of predicted maximum capacity) and the final fourth image after another period of rest. We found small differences in clearance rate at rest and during exercise indicating that there is no substantial change in the clearance rate during exercise in normal subjects.     

Influence of oxygen administration on pulmonary haemodynamics and tissue oxygenation during exercise in COPD patients with different ACE genotypes

We previously found that the angiotensin-converting enzyme (ACE) DD genotype is associated with exaggerated pulmonary hypertension and disturbance of tissue oxygenation during exercise in chronic obstructive pulmonary disease (COPD) patients. This study was designed to compare the effect of oxygen administration on pulmonary haemodynamics and tissue oxygenation during exercise in COPD patients with different ACE genotypes. Forty-three COPD patients (II=16, ID=12, DD=15) underwent right heart catheterization, and then performed an exercise test with room air or oxygen. We measured pulmonary haemodynamic variables and indices of tissue oxygenation such as mixed venous oxygen tension (PVO2) and arterial lactate concentration, both at rest and after exercise. The magnitude of difference in mean pulmonary arterial pressure and pulmonary vascular resistance after exercise between breathing of room air and breathing of oxygen did not significantly differ among the three groups. PVO2 after exercise with room air or oxygen was significantly higher in patients with the II genotype than in those with the ID or DD genotype. In contrast, lactate concentration after exercise with room air or oxygen was significantly lower in patients with the II genotype than in those with the ID or DD genotype. Moreover, the magnitude of difference in PVO2 and lactate concentration after exercise between breathing of room air and breathing of oxygen was the II>ID>DD genotype. These findings suggest that the ability of oxygen administration to improve tissue oxygenation during exercise is associated with the ACE genotypes in COPD patients.     

The degree of exercise hypoxemia reflects pulmonary artery pressure during early exercise in chronic obstructive pulmonary disease patients

The causes of both exertional pulmonary hypertension and pulmonary hypertension in general in chronic obstructive pulmonary disease (COPD) remain to be elucidated. To further understand the pathophysiology in COPD patients, it may be important to recognize the existence of exertional pulmonary hypertension and to determine the severity of exertional hypoxemia. However, little is known about their relationship. To investigate whether the severity of exertional hypoxemia, as evaluated by the Deltaartery oxygen tension/Deltaoxygen consumption (PaO(2)-slope) correlates with the mean pulmonary artery pressure (Ppa), cardiopulmonary exercise testing with haemodynamics was done in 10 patients with moderate to very severe COPD. The PaO(2)-slope was significantly correlated with the mean Ppa from 25% to 40% of the maximum Watts (Wmax), and was most significant at 30% Wmax (r = -0.904, P<0.0001). In this phase, all parameters, except for the mean Ppa and the mixed venous oxygen tension, were not markedly changed from resting levels. At 30% Wmax, the mean Ppa (mean, 27 mmHg) with no or mild hypoxemia was also significantly correlated with the Deltaartery oxygen saturation/Deltaoxygen consumption (SpO(2)-slope) (r = -0.789, P = 0.004). On stepwise multiple regression analysis, the PaO(2)-slope was the most significant predictor of mean Ppa at 30% Wmax. In conclusion, the PaO(2)-slope and the SpO(2)-slope reflect Ppa during the early exercise phase. Thus, assessment of these parameters could be useful to evaluate the cardiopulmonary haemodynamic pathophysiology of COPD patients.     

Arterial concentration of 99mTc-sestamibi at rest, during peak exercise and after dipyridamole infusion

Tracers for myocardial perfusion imaging during stress should not only have high cardiac uptake but they should also have a fast blood clearance to prevent myocardial tracer uptake after the ischaemic stimulus. The present study characterize the early phase of the arterial (99m)Tc-sestamibi (MIBI) time-activity curve after venous bolus injection at rest, during peak exercise and after dipyridamole infusion. We included 11 patients undergoing angioplasty for one-vessel disease (rest study) and 20 patients evaluated for the detection of haemodynamic significant coronary stenoses by (99m)Tc-sestamibi single photon emission computed tomography (SPECT) using either bicycle exercise testing (10 patients) or standard dipyridamole testing (10 patients). Arterial blood samples of 1 ml were taken from the left femoral artery (rest study) or the right radial artery (exercise and dipyridamole studies) every 5 s during the first 5 min postinjection. In the exercise and the dipyridamole studies blood sampling were extended to include blood samples every 5 min 5-30 min postinjection. Peak MIBI concentration was lower and decrease in concentration slower after tracer injection during exercise than during dipyridamole stress testing. This may cause an underestimation of perfusion defects during exercise because of MIBI uptake after the ischaemic stimulus. The implications of the study not only refer to the choice of stress modality when using MIBI. This study also underlines the importance of considering early blood clearance in addition to regional myocardial tracerkinetic aspects such as myocardial extraction fraction when new tracers are introduced.     

Effects of oxygen supplementation on cerebral oxygenation during exercise in chronic obstructive pulmonary disease patients not entitled to long-term oxygen therapy

Background: The rate of change (Δ) in cerebral oxygenation (COx) during exercise is influenced by blood flow and arterial O₂ content (CaO₂). It is currently unclear whether ΔCOx would (i) be impaired during exercise in patients with chronic obstructive pulmonary disease (COPD) who do not fulfil the current criteria for long‐term O₂ therapy but present with exercise‐induced hypoxaemia and (ii) improve with hyperoxia (FIO₂ = 0·4) in this specific sub‐population. Methods: A total of 20 non‐hypercapnic men (FEV₁ = 47·2 ± 11·5% pred) underwent incremental cycle ergometer exercise tests under normoxia and hyperoxia with ΔCOx (fold‐changes from unloaded exercise in O₂Hb) being determined by near‐infrared spectroscopy. Pulse oximetry assessed oxyhaemoglobin saturation (SpO₂), and impedance cardiography estimated changes in cardiac output (ΔQT). Results: Peak work rate and ΔCOx in normoxia were lower in eight O₂‘desaturators’ compared with 12 ‘non‐desaturators’ (P<0·05). Area under ΔCOx during sub‐maximal exercise was closely related to SpO₂ decrements in ‘desaturators’ (r = 0·92, P<0·01). These patients showed the largest improvement in peak exercise capacity with hyperoxia (P<0·05). Despite a trend to lower sub‐maximal ΔQT and mean arterial pressure with active intervention, ΔCOx was significantly improved only in this group (0·57 ± 0·20 versus 2·09 ± 0·42 for ‘non‐desaturators’ and ‘desaturators’, respectively; P<0·05). Conclusions: ΔCOx was impaired in non‐hypoxaemic patients with COPD who desaturated during exercise. Hyperoxic breathing was able to correct for these abnormalities, an effect related to enhanced CaO₂ rather than improved central haemodynamics. This indicates that O₂ supplementation ameliorates exercise COx in patients with COPD who are not currently entitled to ambulatory O₂ therapy.