The reproducibility of tolerance to lower-body negative pressure and its quantification

The reproducibility of tolerance to lower-body negative pressure (LBNP) has not been assessed sufficiently. Furthermore, there has been confusion concerning the most appropriate index by which LBNP tolerance can be quantified. The purpose of this study was to assess the degree of reproducibility in pre-syncopal-symptom-limited LBNP (LBNP_tol), using an LBNP chamber. Twenty physically active subjects [median age (range) 21 (18–27) years] underwent three successive LBNP_tol tests with 72–120 h between each test. LBNP_tol was quantified using the LBNP tolerance index (LTI; ΔmmHg·min), cumulative stress index (CSI; mmHg·min), duration of negative pressure (DNP) and maximum magnitude of negative pressure (MNP). Heart rate (f _c), systolic (SBP) and diastolic (DBP) blood pressures from the three repeated tests were compared during a control period. The changes from control to maximum response (f _c, SBP, DBP) during LBNP were also compared, and percentage changes in estimated blood volume were measured. There were no statistical differences between any of these comparisons (P>0.05). LTI and CSI were greater in the third test when compared to the first two tests (P<0.05). The values for DNP and MNP were not statistically different between tests (P>0.05). Measures of LTI and CSI showed an acceptable level of reproducibility for the first two repeated tests. However, there was an increase in LBNP_tol on the third successive exposure to LBNP. These findings have shown that it is possible to achieve reproducible measures of tolerance to LBNP when using a custom-built chamber. This only applies to a test-retest procedure. Furthermore, these data also suggest that DNP and MNP do not adequately reflect the differences shown in LBNP tolerance when using LTI and CSI as measures. Electronic Publication     

Increased hypoxic ventilatory response during 8 weeks at 3800 m altitude

Acclimatization to chronic hypoxia (CH) increases ventilation (V(I)) and the isocapnic hypoxic ventilatory response (HVR) over 2-14 days but hypoxic desensitization blunts the HVR after years of CH. We tested for hypoxic desensitization during the first 2 months of CH by studying five normal subjects at sea level (SL) and for 8 weeks at 3800 m (CH, PI(O(2)) approximately 90 Torr). We measured the isocapnic HVR (Delta V(I)/Delta Sa(O(2)) and tested for hypoxic ventilatory decline (HVD) by stepping Sa(O(2)) to 80% after 14 min at 90%. The HVR increased significantly after 2 days and remained significantly elevated for 8 weeks of CH. HVD was similar at SL and during 8 weeks of CH. Hence, hypoxic desensitization of the HVR does not occur after only 8 weeks of hypoxia and the increased HVR during this time does not involve changes in HVD.     

A simple breathing circuit to maintain isocapnia during measurements of the hypoxic ventilatory response

We report the development and testing of a simple breathing circuit that maintains isocapnia in human subjects during hypoxic hyperpnea. In addition, the circuit permits rapid switching between two gas mixtures with different partial pressures of oxygen. Eleven volunteers breathed repeated cycles of exposure to air (2 min of 21% O(2), balance N(2)) and hypoxia (2 min of 8.3+/-0.1% O(2), balance N(2)). Hypoxia induced significant increases in minute ventilation, breathing frequency and tidal volume (P < 0.05) that were consistent over repeated cycles of hypoxia (P > 0.1, one-way ANOVA). The system successfully maintained isocapnia in all subjects, with an average change in end-tidal CO(2) of only -0.2 mmHg during hyperventilation in hypoxia (range 0.4 to -0.8 mmHg). This system may be suitable for repeated tests of the hypoxic ventilatory response (HVR) and may prove useful for exploring intra- and inter-individual variability of HVR in humans.     

Acute hypoxic ventilatory response and exercise-induced arterial hypoxemia in men and women

Recent studies claim a higher prevalence of exercise-induced arterial hypoxemia (EIAH) in women relative to men and that diminished peripheral chemosensitivity is related to the degree of arterial desaturation during exercise in male endurance athletes. The purpose of this study was to determine the relationship between the acute ventilatory response to hypoxia (AHVR) and EIAH and the potential influence of gender in trained endurance cyclists and untrained individuals. Healthy untrained males (n = 9) and females (n = 9) and trained male (n = 11) and female (n = 10) cyclists performed an isocapnic AHVR test followed by an incremental cycle test to exhaustion. Oxyhemoglobin saturation (Sa(O(2)) was lower in trained men (91.4 +/- 0.9%) and women (91.3 +/- 0.9%) compared to their untrained counterparts (94.4 +/- 0.8% versus 94.3 +/- 0.7%) (P < 0.05). AHVR and maximal O(2) consumption were related for all subjects (r = -0.46), men (r = -0.45) and women (r = -0.53) (P < 0.05) but AHVR was unrelated to Sa(O(2)) for any groups (P > 0.05). We conclude that resting AHVR does not have a significant role in maintaining Sa(O(2)) during sea-level maximal cycle exercise in men or women.     

Protocol to measure acute cerebrovascular and ventilatory responses to isocapnic hypoxia in humans

This study describes a protocol to determine acute cerebrovascular and ventilatory (AHVR) responses to hypoxia. Thirteen subjects undertook a protocol twice, 5 days apart. The protocol started with 8 min of eucapnic euoxia (end-tidal P(CO2) (PET(CO2)= 1.5 Torr) above rest; end-tidal P(O2) (PET(O2)) = 88 Torr) followed by six descending 90 s hypoxic steps (PET(O2) = 75.2, 64.0, 57.0, 52.0, 48.2, 45.0 Torr). Then, PET(O2) was elevated to 300 Torr for 10 min while PET(O2) remained at eucapnia (5 min) then raised by 7.5 Torr (5 min). Peak blood flow velocity in the middle cerebral artery (MCA) and regional cerebral oxygen saturation (Sr(O2)) were measured with transcranial Doppler ultrasound and near-infrared spectroscopy, respectively, and indices of acute hypoxic sensitivity were calculated (AHR(CBF) and AHRSr(O2)). Values for AHR(CBF), AHRSr(O2) and AHVR were 0.43 cm s(-1) % desaturation(-1), 0.80% % desaturation(-1) and 1.24l min(-1) % desaturation(-1), respectively. Coefficients of variation for AHR(CBF), AHRSr(O2) and AHVR were small (range = 8.0-15.2%). This protocol appears suitable to quantify cerebrovascular and ventilatory responses to acute isocapnic hypoxia.     

The effects of sildenafil and acetazolamide on breathing efficiency and ventilatory control during hypoxic exercise

The reduced arterial oxygen tension at high altitude impairs the ability to work. Acetazolamide improves arterial oxygen saturation (SaO₂) by increasing ventilation but is associated with an increased work and cost of breathing. Depending on the settings, sildenafil can also increases SaO₂ possibly through a reduction in pulmonary hypertension and interstitial edema, which could improve ventilation–perfusion matching. The objective of this study is to determine the effects of acetazolamide and sildenafil on ventilatory control and breathing efficiency (V _E/VCO₂) during submaximal steady-state hypoxic exercise in healthy individuals. Following 18 h of hypoxic exposure in an altitude tent at an oxygen concentration of 12.5% (simulated altitude of 4,300 m), 15 participants performed 10 min of hypoxic exercise on a stationary bicycle at 40% of their sea level peak oxygen uptake (VO₂) while randomly receiving sildenafil 40 mg (SIL), acetazolamide 125 mg (ACZ) or a placebo (PLA). There was no difference in VO₂ during exercise between conditions while SaO₂ was greater with acetazolamide compared to both placebo and sildenafil. Acetazolamide increased ventilation (PLA 49.0 ± 3.2, SIL 47.7 ± 3.1, ACZ 52.1 ± 3.0 l/min) and reduced end-tidal CO₂ (P _ETCO₂) (PLA 32.1 ± 0.8, SIL 32.8 ± 0.9, ACZ 29.2 ± 0.7 mmHg) compared to placebo and sildenafil. Breathing was less efficient with acetazolamide (increased V _E/VCO₂) in comparison to placebo and sildenafil (PLA 41.5 ± 1.0, SIL 40.4 ± 1.3, ACZ 45.4 ± 1.0) while sildenafil did not change V _E/VCO₂ during hypoxic exercise. In conclusion, acetazolamide increased ventilation and reduced breathing efficiency while sildenafil did not affect breathing efficiency despite a trend toward a blunted ventilatory response, possibly due to a reduction in pulmonary hypertension and/or ventilatory drive, during submaximal hypoxic exercise in healthy individuals.     

Pontine GABAergic pathways: role and plasticity in the hypoxic ventilatory response

The hypoxic ventilatory response (HVR) was compared before and after uni- and bi-lateral injections of bicuculline, a GABA(A) receptor antagonist, into the ventrolateral (vl) pons and before and after conditioning animals to chronic sustained hypoxia (CSH). The HVR was assessed by recording phrenic nerve activity (PNA) during and after brief exposures to hypoxia (8% O(2) and 92% N(2) for 45s). Inspiratory (T(I)) and expiratory (T(E)) durations were averaged before hypoxia, at the peak breathing frequency during hypoxia, before the end of hypoxia, immediately after hypoxia, and 60s after hypoxia. Blocking GABA(A) receptors in the vl pons prolonged T(E) during, but not after hypoxia. After CSH induced by 14 days in a hypobaric chamber (0.5atm), the HVR was attenuated compared to that in the naive animals. This plasticity of HVR was associated with selective induction of alpha6 and delta GABA(A) receptor subunit mRNAs specifically in the pons compared to the medulla. These physiological and molecular results illustrate the importance of pontine GABAergic pathways in shaping the response to hypoxia.     

The effect of ventilation on spectral analysis of heart rate and blood pressure variability during exercise

Heart rate variability (HRV) and systolic blood pressure variability (BPV) during incremental exercise at 50, 75, and 100% of previously determined ventilatory threshold (VT) were compared to that of resting controlled breathing (CB) in 12 healthy subjects. CB was matched with exercise-associated respiratory rate, tidal volume, and end-tidal CO(2) for all stages of exercise. Power in the low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, >0.15-0.4 Hz) for HRV and BPV were calculated, using time-frequency domain analysis, from beat-to-beat ECG and non-invasive radial artery blood pressure, respectively. During CB absolute and normalized power in the LF and HF of HRV and BPV were not significantly changed from baseline to maximal breathing. Conversely, during exercise HRV, LF and HF power significantly decreased from baseline to 100% VT while BPV, LF and HF power significantly increased for the same period. These findings suggest that the increases in ventilation associated with incremental exercise do not significantly affect spectral analysis of cardiovascular autonomic modulation in healthy subjects.     

Anterior cingulate activity correlates with blood pressure during stress

The anterior cingulate cortex presumptively regulates blood pressure reactions to behavioral stressors. There is little evidence in humans, however, that stressor-evoked changes in blood pressure correlate with concurrent changes in anterior cingulate activity. Using fMRI, we tested whether changes in mean arterial blood pressure correlate with ongoing changes in blood oxygen level dependent (BOLD) activation in 9 women and 11 men who completed a stressful Stroop color-word interference task. Higher mean arterial pressure during the Stroop task correlated with greater BOLD activation in two regions of the cingulate cortex (perigenual and mid-anterior) and in other networked brain regions, including the insula, thalamus, and periaqueductal gray. These results support the hypothesis that the anterior cingulate cortex regulates blood pressure reactions to behavioral stressors in humans.     

Hypoxic ventilatory response during rest and exercise after a Himalayan expedition

Hypoxic ventilatory response (HVR) was examined before and after acclimatization to high altitude. Transient hyperoxic switches according to Dejours's technique were used to examine the contribution of HVR to the hyperpnoea of increasing exercise intensities. Ten mountaineers were exposed to hypoxia (oxygen fraction in inspired gas,F ₁O₂ = 0.11, 79 mmHg) before the expedition and after return from altitude (56 days, 30 days at 4900 m or higher). After 25-min breathing hypoxic gas, the subjects performed a maximal cycle ergometer test (increments 50 W per 5 min). Respired gases and ventilation were analysed breath-by-breath, partial pressure of oxygen (PO₂) and oxygen saturation (SO₂) were measured in capillary blood. The HVR was tested by switching two breaths to anF ₁O₂ of 1.0. The nadir of after the switch was measured (decrease in ventilation, D ). The HVR was expressed as the D at a PO₂ of 40 mmHg (D ) and the D versus decrease ofSO₂ (D /[100 −SO₂]). The HVR estimated by D increased from 19.9 to 28.01 · min⁻¹ (median,P = 0.013). The HVR expressed as D /(100 −SO₂) at rest was no different before and after acclimatization (0.89 and 0.86 l · min⁻¹ · %⁻¹, respectively) and during exercise it did not change before the expedition (0.831 · min⁻¹ %⁻¹). However, D /(100 −SO₂) increased significantly with exercise intensity after the expedition (1.61 l · min⁻¹ · %⁻¹ at 200 W). The changes of D versusSO₂ as well as of D versus were steeper after the expedition than before. In summary, after return from 30 day at high altitude, an increased HVR was observed. The augmentation of HVR was evident at higher exercise intensities and we suggest that this reflects a change in sensitivity of the peripheral chemoreflex loop.     

兔急性颅内高压时,颅内压及血压对眼内压的影响

本文以颅内压、血压与眼内压之间的病理生理为基础,应用通经分析方法,分析实验兔急性颅内压增高时,眼内压上升的机理。结果提示急性颅内高压时,不仅颅内高压本身直接引起眼内压上升,同时,颅内高压所导致的血压增高亦可间接地促使眼内压上升。     

Changes of elastic properties of central arteries during acute static exercise and lower body negative pressure

The aim of this investigation was to determine the acute effects of isometric fatiguing handgrip (IFHG) and lower body negative pressure (LBNP) on indices of central arterial stiffness. Thirteen subjects were studied. Renal blood velocity (Duplex Ultrasound) and blood pressure (Finapres) were monitored during IFHG and LBNP at −30 and −50 mmHg. Radial pulse-wave forms were recorded by applanation tonometry. Central aortic waveforms and other hemodynamic parameters were assessed using the Sphygmocor software. Renal vascular resistance index (RVRI; mean BP/renal blood velocity) was used as index of sympathetic nervous system (SNS) engagement. RVRI increased during both IFHG and LBNP indicating that SNS was engaged; however, BP increased only during the IFHG. Pulse-wave analysis showed that during the IFHG protocol the transit time of the pulse wave decreased and the peripheral pulse pressure/nonaugmented central pulse pressure ratio increased from baseline. Both of these measurements suggest an increase in central large artery stiffness. During LBNP no changes in the indices of central stiffness were noted, in spite of a similar level of sympathetic system engagement. Heart rate increased during both protocols, whereas augmentation index increased during the IFHG protocol and decreased during the LBNP. Our major conclusion was that blood pressure rather than sympathetic activity seems to play the major role in modulating the elastic properties of the central arteries. The decrease in augmentation index during the LBNP protocol can be attributed to the increased heart rate, given that there is a negative correlation between these two parameters.     

模拟急进高原过程对清醒和麻醉状态大鼠血压和呼吸的影响

目的:为了全面地反映急进高原过程中机体的一些真实改变,本实验通过动态监测清醒和麻醉2种不同状态下大鼠血流动力学指标,旨在探讨清醒和麻醉状态大鼠在急性缺氧时血流动力学的差异,并以此进一步探讨其可能的机制。方法:实验将SD大鼠随机分为麻醉组、清醒组、5 000 m麻醉对照(A-5000-control)组、5 000m麻醉氨基胍(A-5000-AG)组、5 000 m清醒对照(C-5000-control)组和5 000 m清醒氨基胍(C-5000-AG)组。麻醉组和清醒组大鼠在低压氧舱从2 260 m开始,以2 m/s模拟急进高原5 000 m过程;其余4组均在模拟5 000 m海拔条件下进行。实验期间通过Power Lab生理记录仪实时、动态地监测整个过程中大鼠的系统动脉压(system arterial pressure,Psa)、中心静脉压(central venous pressure,CVP)、心率(heart rate,HR)和呼吸频率(breathing rate,BR)。结果:清醒组大鼠的HR和BR明显高于麻醉组,但MAP明显低于麻醉组。随着海拔的逐渐升高,清醒组和麻醉组大鼠均出现平均动脉压(mean arterial pressure,MAP)降低,且清醒组大鼠降低更为显著。另外,在5 000 m时,清醒组大鼠HR明显降低,而整个过程中2组大鼠的BR均无明显改变。静脉注射诱导型一氧化氮合酶(inducible nitric oxide synthase,i NOS)抑制剂氨基胍后,C-5000-AG组和A-5000-AG组大鼠动脉血压均明显升高,而HR和BR未见明显变化。结论:在急进高原过程中,血压和心率会明显下降,而呼吸频率变化不大。该现象可能的机制为:急性缺氧早期机体启动自我保护机制,活化i NOS,大量产生并释放NO,使血管舒张,可调节肺通气、引起血压下降;达到海拔5 000 m左右甚至更早时,机体可能出现失代偿,使心率减慢,引起血压进一步降低。由于受麻醉药物戊巴比妥钠的影响,麻醉状态的大鼠血压下降出现得较为迟缓,而清醒大鼠对急进高原性低氧反应迅速,能够更真实全面地反映急进高原过程中低氧引起的血流动力学改变。     

正常和低氧时尼群地平对家兔肺动脉压影响及其机理探讨

本文在正常及低氧(吸10%O_2气体)情况下给家兔侧脑室及耳静脉注入尼群地平,观察平均肺动脉压(P_(Pa))的改变并探讨其作用机理。结果:正常时侧脑室及耳静脉注入尼群地平后P_(Pa)分别增高0.22±0.13kPa和0.28±0.24kPa;低氧时给药则P_(Pa)分别增高0.06±0.19kPa和0.14±0.09kPa,其中侧脑室给药后P_(Pa)的变化幅度与正常组相比明显减小(P<0.05)。通过预先给予阿托品、纳络酮或切断颈部迷走神经后重复上述给药表明,尼群地平增高肺动脉压的作用主要不是由Ach介导的,其中枢作用可能与中枢的阿片受体有关,主要传出途径是迷走神经。结果提示尼群地平可增高正常及缺氧时的肺动脉压,临床对缺氧性肺高压患者应慎用。     

Shifting hemodynamics of blood pressure control during prolonged mental stress

The present study examined the hemodynamics underlying blood pressure elevations for evidence of a shift in the control of blood pressure during prolonged mental stress. Mean arterial pressure (MAP), cardiac output (CO), and total peripheral resistance (TPR) were measured at rest, during a 28-min mental arithmetic stress task, and during recovery, in 30 young healthy men and women. The stress task elicited a sustained increase in MAP: CO rose during the first half of the task but returned to baseline levels during the last quarter of the task, whereas TPR increased as the task progressed. When participants' hemodynamic reactions were classified as cardiac, vascular, or neither, there were more cardiac reactors early relative to late in the task, whereas there were more vascular reactors late relative to early. Thus, the sustained pressor response was initially supported mainly by cardiac mechanisms but subsequently by predominantly vascular mechanisms.     

Cardiovascular Reactivity in Borderline Hypertensives during Behavioural and Orthostatic Stress

Blood pressure and heart rate were measured in 16 borderline hypertensive and 10 normotensive subjects during mental arithmetic and reaction time tests, on standing, and during the pre-test period and instructions preceding these tests. The reliability of responses was assessed on 3 consecutive days. Increases in systolic blood pressure and heart rate during mental arithmetic instructions, increases in systolic blood pressure during the mental arithmetic test, and increases in diastolic blood pressure on standing were greater in borderline hypertensives. These differences persisted throughout the 3 experimental sessions. Apart from stress ratings for the reaction time test, other behavioural measures, including number of mental arithmetic mistakes and reaction times, did not differ between normotensives and borderline hypertensives. The possibility that the parasympathetic nervous system exerts a restraining influence on sympathetic overactivity in borderline hypertension was discussed.     

Dexamethasone’s influence on tyrosine hydroxylase activity in the chemoreflex pathway and on the hypoxic ventilatory response

 Catecholamines have been implicated in neuromodulation of peripheral chemosensitivity and central respiratory mechanisms. Because glucocorticoids can affect catecholamine metabolism in the carotid body and brainstem, this study explored the possibility that, in rats, dexamethasone or adrenalectomy affects catecholamine biosynthesis in carotid body chemoreceptors and the medullary areas (A2C2, A5, A6, A7) involved in the chemoreflex pathway and the hypoxic ventilatory response (HVR). One dexamethasone injection (1 mg/kg body wt.) stimulated tyrosine hydroxylase activity in the carotid body and had no effect in brainstem catecholamine areas, while HVR was reduced. Chronic dexamethasone (1 mg/kg body wt. daily for 10 days) had a stimulatory influence on tyrosine hydroxylase activity in the carotid body and an inhibitory effect on A2C2, A5 and A7 cell groups. Breathing pattern, but not HVR, was altered. Adrenalectomy elicited an increase in tyrosine hydroxylase activity in A2C2, which was accompanied by a decreased respiratory frequency in hypoxia. The data show that glucocorticoids have differential effects on catecholamine biosynthesis in peripheral and central structures involved in the chemoreflex pathway. Depending on the treatment, the neurochemical changes were accompanied by alterations of HVR or the breathing pattern, which are consistent with a neuromodulating influence of catecholamines on peripheral chemosensory inputs or the central respiratory network. Received: 25 September 1997 / Received after revision: 9 December 1997 / Accepted: 16 December 1997     

Maintenance of ventilatory control by CO2 in the rat during growth and aging

The long-term adjustment of ventilation and blood gases throughout life was studied in halothane anaesthetized male Wistar rats of various ages (1.5–20 months). Basal metabolic rate (O₂ consumption, CO₂ production), ventilation and ventilatory response to CO₂ changed significantly during growth and aging, whereas arterial partial pressure of CO₂ (P _aCO₂) and pH remained unchanged. Changes in the rate of CO₂ production were associated with proportional changes in alveolar ventilation and in the sensitivity of the ventilatory control system to a CO₂ stimulus at various ages. Ventilatory equivalent (ratio of alveolar ventilation to CO₂ production) and the slope of the CO₂/ventilation response line normalized for CO₂ production were maintained constant throughout life, despite significant changes in the breathing pattern. These findings suggest that P _aCO₂ homeostasis is maintained by ventilatory regulation coupled tightly with CO₂ production throughout life.     

The blood pressure response during isometric exercise in fast and slow twitch skeletal muscle in the cat

Summary The blood pressure response during fatiguing isometric contractions was examined in a slow twitch muscle (the soleus) and a mixed muscle (the medial gastrocnemius) of the cat. The results of these experiments showed that electrical stimulation of the ventral roots of the spinal cord which carried the efferent innervation to the soleus muscle failed to result in a blood pressure response during isometric exercise. Further, although stimulation of the fast twitch motor units in the medial gastrocnemius muscle was associated with a potent pressor response to isometric exercise, stimulation of the slow twitch motor units was associated with a markedly reduced response throughout the duration of the exercise. These findings infer that the pressor response to isometric exercise may be a function of the fast twitch motor units in the muscle.