Human investigations into the exercise pressor reflex

During exercise, neural input from skeletal muscles reflexly maintains or elevates blood pressure (BP) despite a maybe fivefold increase in vascular conductance. This exercise pressor reflex is illustrated by similar heart rate (HR) and BP responses to electrically induced and voluntary exercise. The importance of the exercise pressor reflex for tight cardiovascular regulation during dynamic exercise is supported by studies using pharmacological blockade of lower limb muscle afferent nerves. These experiments show attenuation of the increase in BP and cardiac output when exercise is performed with attenuated neural feedback. Additionally, there is no BP response to electrically induced exercise with paralysing epidural anaesthesia or when similar exercise is evoked in paraplegic patients. Furthermore, BP decreases when electrically induced exercise is carried out in tetraplegic patients. The lack of an increase in BP during exercise with paralysed legs manifests, although electrical stimulation of muscles enhances lactate release and reduces muscle glycogen. Thus, the exercise pressor reflex enhances sympathetic activity and maintains perfusion pressure by restraining abdominal blood flow, while brain, skin and muscle blood flow may also become affected because the reflex 'resets' arterial baroreceptor modulation of vascular conductance, making BP the primarily regulated cardiovascular variable during exercise.     

Renal vasoconstrictor responses to static exercise during orthostatic stress in humans: effects of the muscle mechano- and the baroreflexes

Renal circulatory adjustments to stress contribute to blood pressure and volume regulation. Both handgrip (HG) and disengagement of baroreflexes with lower body negative pressure (LBNP) can engage the sympathetic nervous system (SNS). However, the effect of simultaneous HG and LBNP on the renal circulation in humans is not known. Eighteen young healthy volunteers were studied. Beat-to-beat changes in renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres) and heart rate (ECG) were monitored during (a) 15 s HG at 30% maximum voluntary contraction (MVC); (b) LBNP at −10 and −30 mmHg (each level for 5 min); and (c) 15 s HG (at 30% MVC) during LBNP at both levels. Renal vascular resistance index (RVR units) was calculated by dividing MAP by RBV. The increases in RVR during HG alone (12 ± 6%) were not different from the responses noted during combined HG and LBNP (17 ± 6% at −10 mmHg and 25 ± 8% at −30 mmHg). These results suggest occlusion occurs between a neural circuit engaged during 15 s of HG (central command and/or the muscle mechanoreflex) and a circuit activated by LBNP. In additional experiments ( n = 6), similar non-algebraic summation of RVR was seen during 15 s involuntary biceps contractions (engages only muscle reflexes) and LBNP. With respect to RVR, neural occlusion occurs between baroreflexes and the muscle mechanoreflex. Muscle mechanoreflex mediated renal vasoconstriction during short bouts of HG is not influenced by baroreflex disengagement.     

Reduced arterial diameter during static exercise in humans

In eight subjects luminal diameter of the resting limb radial and dorsalis pedis arteries was determined by high-resolution ultrasound (20 MHz). This measurement was followed during rest and during 2 min of static handgrip or of one-leg knee extension at 30% of maximal voluntary contraction of another limb. Static exercise increased heart rate and mean arterial pressure, which were largest during one-leg knee extension. After exercise heart rate and mean arterial pressure returned to the resting level. No changes were recorded in arterial carbon dioxide tension, and the rate of perceived exertion was ? 15 units after both types of exercise. The dorsalis pedis arterial diameter was 1.50±0.20 mm (mean and SE) and the radial AD 2.45±0.12 mm. During both types of contractions the luminal diameters decreased ? 3.5% within the first 30 s (P< 0.05), and during one-leg knee extension they continued to decrease to a final exercise value 7.6±1.1% lower than at rest (P < 0.05). Thus, they became smaller than during the handgrip. After exercise resting values were reestablished. When the arterial diameter was expressed in relation to mean arterial pressure for the radial and dorsalis pedis artery was 22±3 and 28±3% lower during handgrip than the relation during rest, respectively. After one-leg knee extension both arteries reached 30±4% lower values. This study demonstrated arterial constriction in the resting limbs within the first 30 s of static exercise, and continued constriction during one-leg knee extension. These results support to the hypothesis that central command and/or muscle mechano- receptors influence arterial tone, and that the exercise pressor reflex becomes important with the involvement of a large muscle mass.     

Difference in acid-base state between venous and arterial blood during cardiopulmonary resuscitation

We investigated the acid-base condition of arterial and mixed venous blood during cardiopulmonary resuscitation in 16 critically ill patients who had arterial and pulmonary arterial catheters in place at the time of cardiac arrest. During cardiopulmonary resuscitation, the arterial blood pH averaged 7.41, whereas the average mixed venous blood pH was 7.15 (P less than 0.001). The mean arterial partial pressure of carbon dioxide (PCO2) was 32 mm Hg, whereas the mixed venous PCO2 was 74 mm Hg (P less than 0.001). In a subgroup of 13 patients in whom blood gases were measured before, as well as during, cardiac arrest, arterial pH, PCO2, and bicarbonate were not significantly changed during arrest. However, mixed venous blood demonstrated striking decreases in pH (P less than 0.001) and increases in PCO2 (P less than 0.004). We conclude that mixed venous blood most accurately reflects the acid-base state during cardiopulmonary resuscitation, especially the rapid increase in PCO2. Arterial blood does not reflect the marked reduction in mixed venous (and therefore tissue) pH, and thus arterial blood gases may fail as appropriate guides for acid-base management in this emergency.     

Quantification of radial arterial pulse characteristics change during exercise and recovery

It is physiologically important to understand the arterial pulse waveform characteristics change during exercise and recovery. However, there is a lack of a comprehensive investigation. This study aimed to provide scientific evidence on the arterial pulse characteristics change during exercise and recovery. Sixty-five healthy subjects were studied. The exercise loads were gradually increased from 0 to 125 W for female subjects and to 150 W for male subjects. Radial pulses were digitally recorded during exercise and 4-min recovery. Four parameters were extracted from the raw arterial pulse waveform, including the pulse amplitude, width, pulse peak and dicrotic notch time. Five parameters were extracted from the normalized radial pulse waveform, including the pulse peak and dicrotic notch position, pulse Area, Area₁ and Area₂ separated by notch point. With increasing loads during exercise, the raw pulse amplitude increased significantly with decreased pulse period, reduced peak and notch time. From the normalized pulses, the pulse Area, pulse Area₁ and Area₂ decreased, respectively, from 38 ± 4, 61 ± 5 and 23 ± 5 at rest to 34 ± 4, 52 ± 6 and 13 ± 5 at 150-W exercise load. During recovery, an opposite trend was observed. This study quantitatively demonstrated significant changes of radial pulse characteristics during different exercise loads and recovery phases.     

Relationship between ventilation and arterial potassium concentration during incremental exercise and recovery

Summary The purpose of this study was to compare the relationship of ventilation ( _E) with pH, arterial concentrations of potassium ([K⁺]_a), bicarbonate ([HCO₃ ^–]_a), lactate ([la]_a), and acid-base parameters which would affect hyperpnoea during exercise and recovery. To assess this relationship, ten healthy male subjects exercised with intensity increasing as a ramp function of 20 W · min^–1 until voluntary exhaustion and they were then allowed a 5-min recovery period. Breath-by-breath gas exchange data, [HCO₃ ^–]_a, pH, [1a]_a, [K⁺]_a and blood gases were determined during both exercise and recovery. Using a linear regression method, the _E/[K⁺]a relationship was analysed during both exercise and recovery. Several interesting results were obtained: a significant relationship between [K⁺]_a and _E was observed during recovery as well as during exercise; the _E at any given values of [K⁺]_a was significantly higher during recovery than during exercise and out of those factors affecting exercise hyperpnoea, only [K⁺]_a had a similar time-course to _E during recovery. Changes in [K⁺]a during recovery were shown to occur significantly faster than _E with an [K⁺]_a time constant of 70.0 s, SD 16.2 as opposed to 105.5 s, SD 10.0 for _E (P < 0.01). These results provided further evidence that [K⁺]_a might play an important role as a substance which can stimulate exercise hyperpnoea as has been suggested by other workers. The present study also showed that during recovery [K⁺]_a contributed significantly to the control of _E.     

A novel method for indirectly monitoring arterial pO2 during cardiopulmonary bypass

Arterial blood oxygen tension (P_aO₂) is a vital variable that has to be monitored during cardiopulmonary bypass (CPB). The aim of this study was to develop an alternative method for continuously P_aO₂ monitoring during CPB, based on measurements of exhaust-gas from an oxygenator. A total of 15 adult patients undergoing CPB (n = 81 samples) were included in a study in order to develop an appropriate algorithm for P_aO₂ estimation based on exhaust gas monitoring of the oxygen tension (P_exO₂). The acquired data was used as a basis for developing a statistical prediction algorithm designed for continuously estimating the P_aO₂-level based on exhaust gas data in combination with data from the surrounding medical equipment. A new instrument was developed in order to implement this P_aO₂ prediction algorithm and was tested on five patients (n = 39 samples). When the first sample was used for calibrating the instrument, the mean (SD) error was 8.7% (7.3%) with a 95% CI of 6.1–11.3%. Our results indicate that a pO₂-exhaust monitoring device with adequate precision is obtainable, but further studies are required.     

Effects of reduced frequency breathing on arterial hypoxemia during exercise

Summary It is uncertain that exercise with reduced frequency breathing (RFB) results in arterial hypoxemia. This study was designed to investigate whether RFB during exercise creates a true hypoxic condition in arterial blood by examining arterial oxygen saturation (SaO₂) directly. Six subjects performed ten 30 s periods of exercise on a Monark bicycle ergometer at a work rate of 210 W alternating with 30 s rest intervals. The breath was controlled to use 1 s each for inspiration and expiration, and two trials with different breathing patterns were used; a continuous breathing (CB) trial and an RFB trial consisting of four seconds of breath-holding at functional residual capacity (FRC). Alveolar oxygen pressure during exercise showed a slight but significant (p<0.05) reduction with RFB as compared to CB. However, a marked increase in alveolar-arterial pressure difference for oxygen (A-aDO₂) (p<0.05) with RFB over CB resulted in a marked (p<0.05) reduction in arterial oxygen pressure. Consequently, SaO₂ fell as low as 88.8% on average. Additional examination of RFB with breath-holding at total lung capacity showed no increases in A-aDO₂ in spite of the same amount of hypoventilation as compared with that at FRC. These results indicate that RFB during exercise can result in arterial hypoxemia if RFB is performed with breath-holding at FRC, this mechanism being closely related to the mechanical responses due to lung volume restriction.     

Thoracic sympathectomy and cardiopulmonary responses to exercise

The purpose was to study the effect of endoscopic thoracic sympathectomy (ETS) for palmar and/or axillary hyperhidrosis on physiological responses at rest, and during sub-maximal and maximal exercise in ten healthy patients (7 females and 3 males 18-40 years old) with idiopathic palmar and/or axillary hyperhidrosis. T2-T3 thoracoscopic sympathectomy was performed using a simplified one stage bilateral procedure. Physiological variables were recorded at rest and during sub-maximal (steady-state) and maximal treadmill exercise immediately prior to and 70 days (+/-7.5, SD) after bilateral ETS. Exercise performance capacity and peak VO(2) were not found to be different following bilateral ETS than prior to the ETS. However, heart rate was significantly reduced at rest (14%), at sub-maximal exercise (12.3%), and at peak exercise (5.7%), together with a significant increase in oxygen pulse (11.8, 12.7, and 7.8%, respectively). The rate pressure product (RPP) was also significantly reduced following the surgical procedure at all three study stages, while all other physiological variables measured remained unchanged. It is suggested that thoracic-sympathetic denervation affects the heart, sweating, and circulation of the respective denervated region but does not affect exercise performance or mechanical/physiologic efficiency, despite a significant reduction in heart rate (both at rest and during exercise). The latter was, most likely, fully compensated by an increase in stroke volume and less likely by an improved muscle O(2) extraction due to more efficient blood distribution, keeping the work-rate and oxygen uptake unaffected.     

Heat stress attenuates the increase in arterial blood pressure during isometric handgrip exercise

The purpose of this study was to examine arterial blood pressure responses during isometric handgrip (IHG) exercise performed at increasing levels of heat stress. Ten male subjects performed 1 min of IHG exercise at 60 % of maximal voluntary contraction under no heat stress (NHS), moderate heat stress [MHS, 0.6 °C increase in esophageal temperature (T _es)] and high heat stress (HHS, 1.4 °C increase in T _es). For all conditions, IHG exercise significantly elevated mean arterial pressure (MAP) (NHS: 124 ± 6 vs. 90 ± 4 mmHg, MHS: 112 ± 6 vs. 89 ± 6 mmHg, HHS: 107 ± 7 vs. 91 ± 5 mmHg, P ≤ 0.05) and cardiac output (CO) (NHS: 9.0 ± 1.5 vs. 6.1 ± 0.6 L/min, MHS: 9.8 ± 1.8 vs. 7.6 ± 1.3 L/min, HHS: 10.0 ± 2.0 vs. 8.5 ± 1.9 L/min, P ≤ 0.05) relative to baseline, whereas no differences in total peripheral resistance (TPR) were observed (P > 0.05). However, the relative increases in MAP and CO were significantly reduced during MHS (MAP: 23 ± 6 mmHg, CO: 2.1 ± 0.9 L/min) and HHS (MAP: 16 ± 7 mmHg, CO: 1.5 ± 0.8 L/min) compared to NHS (34 ± 5 mmHg, CO: 2.9 ± 1.1 L/min, P ≤ 0.05). Furthermore, these elevations were significantly attenuated during HHS compared to MHS (P ≤ 0.05). Our findings show that heat stress attenuates the increase in arterial blood pressure during isometric handgrip exercise and this attenuation is cardiac output dependent, since TPR did not change during exercise for all heat stress conditions.     

Noninvasive assessment of cardiac output from arterial pressure profiles during exercise

The stroke volume of the left ventricle (SV) was assessed in nine young men (mean age 22.2, ranging from 20 to 25 years) during cycle ergometer upright exercise at exercise intensities from 60 to 150 W (about 20% to 80% of individual maximal aerobic power). The SV was calculated from noninvasive tracings of the arterial blood pressure, determined from photoplethysmograph records and compared to the SV determined simultaneously by pulsed Doppler echocardiography (PDE). Given the relationshipSV =A _s·Z ^–1 in whichA _S is the area underneath the systolic pressure profile (in millimetres of mercury and second), andZ (in millimetres of mercury and second per millilitre) is the apparent hydraulic impedance of the circulatory system, a prerequisite for the assessment of SV from the photoplethysmograph tracings is a knowledge of Z. The experimental value of Z (hereafter defined Z*) was calculated by dividing AS (from the finger photoplethysmograph) by SV as obtained by PDE. When the whole group of subjects was considered, Z* was not greatly affected by the exercise intensity: it amounted to 0.089 (SD 0.028;n = 36). The Z was also estimated independently of any parameter other than heart rate (HR), mean (MAP) and pulse (PP) arterial blood pressure obtained from the photoplethysmograph. A computerized statistical method allowed us to interpolate the experimental values ofZ*, HR, PP and MAP by the equationZ _m = a·(b + c·HR + d·PP + e·MAP)^–1, thus obtaining the coefficients a to e. The mean percentage error betweenZ _m (calculated from the coefficients obtained andZ _m was 21.8 (SD 14.3)%. However, it was observed that, in a given subject,Z* was significantly affected by the exercise intensity. Therefore, to improve the estimate ofZ a second algorithm was developed to update the experimental value ofZ determined initially at rest (Z _in). This updated value (Z _cor) ofZ was calculated asZ _cor =Z _in· [(f/(i + g·(HR/HR _in) + h·(PP/PP _in) + 1· (MAP/MAP _in], whereHR _in,PP _in,MAP _in,HR,PP,MAP are the above parameters at rest and during exercise, respectively. Also in this case, the coefficients f to 1 were determined by a computerized statistical method usingZ* as the experimental reference. The values ofZ _cor so obtained allowed us to calculate SV from arterial pulse contour analysis asSV _F =A _S·Z _cor/^–1. The mean percentage error between theSV _F obtained and the values simultaneously determined by PDE, was 10.0 (SD 8.7)%. It is concluded that the SV of the left ventricle, and hence cardiac output, can be determined during exercise from photoplethysmograph tracings with reasonable accuracy, provided that an initial estimate of SV at rest is made by means an independent high quality reference method.     

Human adipose tissue blood flow during prolonged exercise II

Subcutaneous and perirenal adipose tissue blood flows (ATBF) were measured by the¹³³Xe washout method before, during and after 4 h exercise on a bicycle ergometer. The load corresponded to about 50% of max (i.e. about 1.7l/min). Subcutaneous and perirenal ATBF increased at an average to 3–400 and 700% of their initial control values respectively. In six of nine measuring sites ATBF remained increased in the hour following work. During work plasma glycerol concentrations increased 8 fold. The core temperature increased 0.9°C, skin temperature did not change significantly. During passive elevation of body temperature (core temperature +1.5°C; skin temperature +3°C) neither subcutaneous ATBF nor plasma glycerol concentrations changed significantly. It is concluded that the increase in subcutaneous ATBF during exercise is not a reaction to increased body temperature.     

Contribution of systemic arterial compliance and systemic vascular resistance to effective arterial elastance changes during exercise in humans

Background: Effective arterial elastance (Ea), an index of arterial load, increases with elevations in left ventricular elastance to maximize the efficiency of left ventricular stroke work during exercise. Systemic arterial compliance (C) and vascular resistance (R) are the primary components contributing to Ea, and R plays a greater role in determining Ea at rest. We hypothesized that the contribution of C to Ea increases during exercise to maintain an optimal balance between arterial load and ventricular elastance, and that the increase in Ea is due primarily to a reduction in C. Aim: The aim of this study was to investigate the contributions of C and R to Ea during exercise. Methods: Ea (0.9 × systolic blood pressure/stroke volume), C (stroke volume/pulse pressure), R (mean blood pressure/cardiac output), and cardiac cycle length (T) were measured at rest and during exercise of 40%, 60% and 80% maximal oxygen uptake (O_2max) using Doppler echocardiography in 45 healthy men. Results: Ea did not differ between rest and 40%O_2max, but it was greater at 60% and 80%O_2max. C markedly decreased during exercise in an exercise intensity‐dependent manner. The changes in R/T during exercise were small, whereas it decreased at 40%O_2max and gradually increased at 60% and 80%O_2max. Conclusions: The present results suggest that the contribution of systemic arterial compliance to effective arterial elastance increases during exercise. Therefore, we propose that the increase in arterial load during exercise is mainly driven by a reduction in systemic arterial compliance.     

Effects of angiotensin II on arterial pressure,renin and aldosterone during exercise

Summary To evaluate the effect of isotonic exercise on the response to angiotensin II, angiotensin II in saline solution was infused intravenously (7.5 ng · kg⁻¹ · min⁻¹) in seven normal sodium replete male volunteers before, during and after a graded uninterrupted exercise test on the bicycle ergometer until exhaustion. The subjects performed a similar exercise test on another day under randomized conditions when saline solution only was infused. At rest in recumbency angiotensin II infusion increased plasma angiotensin II from 17 to 162 pg · ml⁻¹ (P<0.001). When the tests with and without angiotensin II are compared, the difference in plasma angiotensin II throughout the experiment ranged from 86 to 145 pg · ml⁻¹. The difference in mean intra-arterial pressure averaged 17 mmHg at recumbent rest, 12 mmHg in the sitting position, 9 mmHg at 10% of peak work rate and declined progressively throughout the exercise test to become non-significant at the higher levels of activity. Plasma renin activity rose with increasing levels of activity but angiotensin II significantly reduced the increase. Plasma aldosterone, only measured at rest and at peak exercise, was higher during angiotensin II infusion; the difference in plasma aldosterone was significant at rest, but not at peak exercise. In conclusion, the exercise-induced elevation of angiotensin II does not appear to be an important factor in the increase of blood pressure. It is suggested that the vasodilating mechanisms in the working muscles and the vasoconstricting mechanisms in the non-working vascular beds are powerful and dominant during isotonic exercise and attenuate the opposing or additive vasoconstrictor effects of angiotensin II. The negative feedback effect of angiotensin II on renal renin secretion, however, is not inhibited by exercise.     

Differential mobilization of leucocyte and lymphocyte subpopulations into the circulation during endurance exercise

Summary A total of 14 healthy subjects [means (SD): 27.6 (3.8) years; body mass 77.8 (6.6) kg; height 183 (6) cm] performed endurance exercise to exhaustion at 100% of the individual anaerobic threshold (Th_an) on a cycle ergometer (mean workload 207 (55) W; lactate concentrations 3.4 (1.2) mmol · l^–1; duration 83.8 (22.2) min, including 5 min at 50% of individual Th_an). Leucocyte subpopulations were measured by flow cytometry and catecholamines by radioimmunological methods. Blood samples were taken before and several times during exercise. Values were corrected for plasma volume changes and analysed using ANOVA for repeated measures. During the first 10 min of exercise, of all cell subpopulations the natural killer cells (CD3^–CD16/CD56+) increased the most (229%). Also CD3^÷CD16/CD56+ (84%), CD8^÷CD45RO^– (69%) cells, eosinophils (36%) and monocytes (62%) increased rapidly during thattime.CD3⁺, CD3⁺HLA-DR⁺, CD4⁺CD45RO⁺, CD4⁺CD45RO^–, CD8⁺CD45RO^÷ and CD19⁺ cells either did not increase or increased only slightly during exercise. Adrenaline and noradrenaline increased nearly linearly by 36% and 77% respectively at 10 min exercise. The increase of natural killer cells and heart rates between rest and 10 min of exercise correlated significantly (r=0.576,P=0.031). We conclude that natural killer cells, cytotoxic, non-MHC-restricted T-cells, monocytes and eosinophils are mobilized rapidly during the first minutes of endurance exercise. Both catecholamines and increased blood flow are likely to contribute this effect.     

Leg exchange of amino acids during exercise in patients with arterial insufficiency

Intermittent claudication is associated with adaptation in muscle metabolism. This study has evaluated the metabolism of amino acids at rest and during non-steady state exercise in patients with arterial insufficiency of at least six months duration in comparison with matched control individuals. The exchange of amino acids were measured during two periods of acute exercise; one initial exercise period with a standardized work load and exercise time and a second exercise period which continued until further exercise was impossible due to pain in the patients and exhaustion in the controls. The maximum blood flow was reduced by 40% in the patients but the maximum oxygen uptake per unit power developed was almost the same in patients and controls. The patients had significantly lower concentrations of glutamine, lysine and taurine at rest compared with the controls. The exchange of amino acids across the resting leg did not differ between the two groups. Exercise increased the efflux of amino acids in both patients and controls. The efflux of glutamine (896 +/- 205 vs. 48 +/- 359 nmol/100 ml/min/watt) was higher in the patients compared to the controls at the first exercise period with inverse changes in the opposite direction of asparagine (149 +/- 105 vs. 799 +/- 121 and 27 +/- 70 vs. 633 +/- 334 nmol/100 ml/min/watt at the first and second exercise, respectively. Alanine release did not differ between the groups. The complementary patterns of glutamine and asparagine during hypoxic exercise in the patients may reflect the fact that these amino acids share a common carrier system. The similarity in the efflux of non-metabolized amino acids, such as methionine, phenylalanine, tyrosine and 3-methylhistidine, indicated that muscle hypoxia in claudication patients did not promote net degradation of either globular or myofibrillar proteins, although exercise increased the efflux of 3-methylhistidine three- to fourfold in both patients and control individuals (from 1 +/- 0.4 to 4 +/- 1.8 and from 0 +/- 0.7 to 6 +/- 2.5 nmol/100 ml/min/watt, respectively). The exercise-induced alterations in leg exchange of amino acids were restored within 10-20 min following exercise regardless of hypoxia. The results demonstrate that patients with arterial insufficiency have altered intermediary metabolism of amino acids during exercise. However, muscle hypoxia in such patients does not seem to promote a negative protein balance or induce serious alterations in cell membrane integrity.