Exercise modulation of tumour perfusion and hypoxia to improve radiotherapy response in prostate cancer.

BACKGROUND: An increasing number of studies indicate that exercise plays an important role in the overall care of prostate cancer (PCa) patients before, during and after treatment. Historically, research has focused on exercise as a modulator of physical function, psychosocial well-being as well as a countermeasure to cancer- and treatment-related adverse effects. However, recent studies reveal that exercise may also directly influence tumour physiology that could beneficially affect the response to radiotherapy. METHODS: In this narrative review, we provide an overview of tumour vascular characteristics that limit the effect of radiation and establish a rationale for exercise as adjunct therapy during PCa radiotherapy. Further, we summarise the existing literature on exercise as a modulator of tumour perfusion and hypoxia and outline potential future research directions. RESULTS: Preclinical research has shown that exercise can reduce intratumoral hypoxia-a major limiting factor in radiotherapy-by improving tumour perfusion and vascularisation. In addition, preliminary evidence suggests that exercise training can improve radiotherapy treatment outcomes by increasing natural killer cell infiltration in a murine PCa model. CONCLUSIONS: Exercise is a potentially promising adjunct therapy for men with PCa undergoing radiotherapy that may increase its effectiveness. However, exercise-induced tumour radiosensitisation remains to be confirmed in preclinical and clinical trials, as does the optimal exercise prescription to elicit such effects.

Continuous positive airway pressure in children with severe pneumonia and hypoxaemia in Papua New Guinea: an evaluation of implementation.

AIM: To prospectively evaluate the use of bubble continuous positive airway pressure (CPAP) in children with very severe pneumonia and other acute lower respiratory infections, during its trial introduction in a low resource hospital in Papua New Guinea. METHODS: Prospective observational study of children treated with CPAP who had severe pneumonia and severe respiratory distress with hypoxaemia (SpO2 <90%). CPAP was driven by oxygen concentrators in which the fraction of inspired oxygen could be adjusted, and using low-resistance tubing and nasal oxygen prongs. RESULTS: A total of 64 children were commenced on CPAP: 29 (45.3%) survived and were discharged well, 35 (54.7%) died. Prior to commencing CPAP, the median SpO2 was 78% (IQR 53.3-86.8%), at one hour SpO2 was 92% (IQR 80-97.75%, n = 64), and at 84 hours (3½ days) 98% (IQR 93-98%, n = 29), in survivors at each of these time points. A higher SpO2 at one hour after commencement of CPAP predicted survival (p = 0.013), and human immunodeficiency virus infection was an independent predictors of death (p = 0.017). Technical and clinical problems encountered are described. CONCLUSION: Bubble CPAP improved oxygenation and reduced the severity of respiratory distress in some children with severe pneumonia; however, mortality was high reflecting high severity of illness and comorbidities. CPAP requires a quality system to be safe and effective.

Effect of dead space on breathing stability at exercise in hypoxia.

Recent studies have shown that normal subjects exhibit periodic breathing when submitted to concomitant environmental (hypoxia) and physiological (exercise) stresses. A mathematical model including mass balance equations confirmed the short period of ventilatory oscillations and pointed out an important role of dead space in the genesis of these phenomena. Ten healthy subjects performed mild exercise on a cycloergometer in different conditions: rest/exercise, normoxia/hypoxia and no added dead space/added dead space (aDS). Ventilatory oscillations (V˙E peak power) were augmented by exercise, hypoxia and aDS (P<0.001, P<0.001 and P<0.01, respectively) whereas V˙E period was only shortened by exercise (P<0.001), with an 11-s period. aDS also increased V˙E (P<0.001), tidal volume (VT, P<0.001), and slightly augmented PETCO2 (P<0.05) and the respiratory frequency (P<0.05). These results confirmed our previous model, showing an exacerbation of breathing instability by increasing dead space. This underlines opposite effects observed in heart failure patients and normal subjects, in which added dead space drastically reduced periodic breathing and sleep apneas. It also points out that alveolar ventilation remains very close to metabolic needs and is not affected by an added dead space. Clinical Trial reg. n°: NCT02201875.

Prone positioning as a bridge to recovery from refractory hypoxaemia following lung transplantation.

OBJECTIVES: Refractory hypoxaemia is the leading cause of mortality in the postoperative period after lung transplantation. The role of prone positioning as a rescue therapy in this setting has not been assessed. We evaluated its effects in lung transplant recipients presenting refractory hypoxaemia following the surgery. METHODS: Prospectively collected data from 131 consecutive adult patients undergoing lung transplantation between January 2013 and December 2014 were evaluated. Twenty-two patients received prone position therapy. Indications, associated complications, time to initiation and duration of the manoeuvre were analysed and the effects of prone position on gas exchange were evaluated. Finally, outcomes in this cohort were compared against the rest of lung transplant recipients. RESULTS: Prone positioning was more frequently implemented within the first 72 h (68.2%) and its main indication was primary graft dysfunction. The manoeuvre was maintained during a median of 21 h. After prone position, the pressure of arterial oxygen/fraction of inspired oxygen ratio significantly increased from 81.0 mmHg [interquartile range (IQR) 71.5-104.0] to 220.0 (IQR 160.0-288.0) (P < 0.001). No complications related with the technique were reported. Patients who underwent the manoeuvre had longer hospital stay [50.0 days (IQR 36.0-67.0) vs 30.0 (IQR 23.0-56.0), P = 0.006] than the rest of the population. No differences were found comparing either 1-year mortality (9.1% vs 15.6%; P = 0.740) or 1-year graft function [forced expiratory volume in 1 second of 70.0 (IQR 53.0-83.0) vs 68.0 (IQR 53.5-80.5), P = 0.469]. CONCLUSIONS: Prone positioning is safe and significantly improves gas exchange in patients with refractory hypoxaemia after lung transplantation. It should be considered as a possible treatment in these patients.

Tratamiento rehabilitador en el paciente infantouvenil con daño cerebral adquirido / Rehabilitation treatment in child and youth patients with acquired brain injury

El daño cerebral es una de las causas más frecuentes de muerte y discapacidad en la población infantojuvenil. La mejoría en la atención a los pacientes en el momento agudo y la evolución de la asistencia sanitaria han supuesto un aumento de la supervivencia de estos pacientes y también de las secuelas. Secuelas físicas, cognitivo-conductuales u orgánicas son frecuentes, y las segundas son unas de las más frecuentes y más limitantes en estos pacientes. El daño cerebral afecta al paciente, pero involucra a toda la familia por la discapacidad que implica y por la dependencia que conlleva. El equipo es multidisciplinar, y el médico rehabilitador hace las funciones de coordinación. La familia debe recibir asistencia desde el primer día y es parte importante en la evolución adecuada de los pacientes. El tratamiento debe ser individualizado y adaptado para cada paciente, y suele durar entre 6 y 18 meses (AU)

Brain injury is one of the most frequent causes of death and disability in the child and adolescent. The improvement in patient care in the acute moment and the evolution of health care has meant and increase in the survival of these patients and also of the sequelae. Physical, cognitive-behavioral or organic symptoms are usually. The second is being one of the most frequent and most limiting in these patients. The brain injury affects the patient but involves the whole family because of the disability and the dependence it entails. The team is multidisciplinary and the rehabilitation physician performs the coordination functions. The family should receive assistance from the first day and are an important part in the proper evolution of patients. The treatment must be individualized and adapted for each patient and usually last between 6 and 18 months (AU)

[INFLUENCE OF INTERMITTENT NORMOBARIC HYPOXIA ON CARDIOVASCULAR SYSTEM AND HEMODYNAMIC PARAMETERS OF CHILDREN LIVED AT RADIATION CONTAMINATED TERRITORIES.]

The effect of intermittent normobaric hypoxia (INH) of sanogenic level on the state of the cardiovascular system in 120 children aged from 12 to 17 years was studied. Children were divided into 3 groups. The 1st control group consisted of 20 persons (practically healthy ones), the 2nd group, a group of comparison, included 50 persons, and there were 50 persons in the 3rd group - a main group. Examined patients of two studied groups received the standard therapy, and those of the 3rd group - the seances of intermittent, normobaric hypoxia additionally to standard therapy. Systolic arterial pressure was significantly decreased in the rest from 108,2±1,9 to 103,8±1,1 mm Hg in children of the main group. Comparing the heart rate, systolic arterial pressure and diastolic arterial pressure their statistically decreased values by 9,3 min(-1), 8,36 and 7,84 mm Hg were revealed at 10 minutes of orthostatic, respectively. Autonomic supplying the activity of cardiovascular system with normal type of reaction was 34 % higher than that of the comparison group. It indicates an the improvement in hemodynamics and an increase in adaptation capabilities of the autonomic nervous system.

Vacuum therapy in penile rehabilitation after radical prostatectomy: review of hemodynamic and antihypoxic evidence.

Generally, hypoxia is a normal physiological condition in the flaccid penis, which is interrupted by regular nocturnal erections in men with normal erectile function. [1] Lack of spontaneous and nocturnal erections after radical prostatectomy due to neuropraxia results in persistent hypoxia of cavernosal tissue, which leads to apoptosis and degeneration of cavernosal smooth muscle fibers. Therefore, overcoming hypoxia is believed to play a crucial role during neuropraxia. The use of a vacuum erectile device (VED) in penile rehabilitation is reportedly effective and may prevent loss of penile length. The corporal blood after VED use is increased and consists of both arterial and venous blood, as revealed by color Doppler sonography and blood gas analysis. A similar phenomenon was observed in negative pressure wound therapy (NPWT). However, NPWT employs a lower negative pressure than VED, and a hypoperfused zone, which increases in response to negative pressure adjacent to the wound edge, was observed. Nonetheless, questions regarding ideal subatmospheric pressure levels, modes of action, and therapeutic duration of VED remain unanswered. Moreover, it remains unclear whether a hypoperfused zone or PO 2 gradient appears in the penis during VED therapy. To optimize a clinical VED protocol in penile rehabilitation, further research on the mechanism of VED, especially real-time PO 2 measurements in different parts of the penis, should be performed.

Nocturnal hypoxia and functional outcome in stroke patients.

BACKGROUND: Sleep disorders and nocturnal hypoxia are common in patients with cerebrovascular disease. Sleep-disordered breathing is associated with a poor functional outcome in stroke patients. OBJECTIVE: We investigated the relationship between nocturnal hypoxia and functional outcome in the rehabilitation phase of stroke patients. METHODS: Thirty patients with stroke and 20 controls were included. Functional status was evaluated with the Functional Independence Measure (FIM). Pulse oximetry was performed overnight from 21.00  h to 07.00  h. Baseline awake oxygen saturation, nocturnal oxygen saturation, the lowest nocturnal oxygen saturation, and the >4% Oxygen Desaturation Index (ODI) were calculated. RESULTS: The mean oxygen saturation measurements were not significantly different among the groups (p >  0.05). There was no significant relationship between the FIM scores and the oxygen saturation measurements of the stroke patients (p >  0.05). The baseline oxygen saturation in patients with disease duration of 3 months or less was 94.67, and it was 96.56 (p = 0.016) in those with disease duration of more than 3 months. CONCLUSION: This study showed that nocturnal oxygen saturation was not associated with functional outcome in therehabilitation phase of stroke patients.

[OPTIMAL HYPERCAPNIC HYPOXIA CONDITIONS FOR INCREASING RESISTANCE TO ACUTE HYPOXIA].

The study was focused on finding an optimal length of hypercapnia-hypoxia sessions of training resistance to acute hypoxia and looking for benefits from reoxygenation intervals and intermittent training over daytime. It turned out that 3 days of a 5-minute hypercapnia-hypoxia session per day improved resistance to acute hypoxia explicitly and that a 30-minute session increased resistance to the highest rate. Two training sessions per day are no better than one session. Hypercapnia-hypoxia training with reoxygenation intervals are the least effective in comparison to the other modes of training.

Decúbito prono: una técnica para mejorar la hipoxemia del síndrome de distrés respiratorio agudo / Prone position: a technique to improve the hypoxemia in acute respiratory distress syndrome

El síndrome de distrés respiratorio agudo (SDRA) representa una complicación respiratoria grave que suelen presentar pacientes ingresados en las Unidades de Cuidados Intensivos (UCI) y se asocia con una alta incidencia y mortalidad, de ahí la importancia del rápido diagnóstico y tratamiento. La posición de decúbito prono (DP) mejora notablemente la oxigenación y la redistribución pulmonar de los pacientes con SDRA. Sin embargo, la utilización del DP en las UCI implica algunos cambios en el tratamiento diario y requiere la protocolización de la actuación antes, durante y después de la maniobra, así como su seguimiento para evitar las posibles complicaciones. En este trabajo, a partir de la revisión bibliografía y teniendo en cuenta la experiencia propia y la forma de trabajar en este hospital, se describe el potencial beneficio de esta técnica, cómo realizarla adecuadamente, las indicaciones y contraindicaciones, las complicaciones potenciales y las intervenciones enfermeras para prevenirlas o detectarlas precozmente

Acute Respiratory Distress Syndrome (ARDS) represents a severe respiratory complication often shown by patients hospitalized in Intensive Care Units (ICUs), and it is associated with high incidence and mortality; hence the importance of its fast diagnosis and treatment. The prone position leads to a noticeable improvement in oxygenation and pulmonary redistribution of patients with ARDS. However, the use of the prone position at ICUs involves certain changes in daily treatment, and requires the protocolization of the action before, during and after the manoeuvre, as well as its follow-up in order to prevent any potential complications. Based on a bibliographic review and taking into account our own experience and the way we work in this hospital, this article describes the potential benefits of this technique, how to perform it adequately, its indications and contraindications, potential complications, and nursing interventions for prevention or early detection

Exercise limitation in IPF patients: a randomized trial of pulmonary rehabilitation.

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) have severely limited exercise capacity due to dyspnea, hypoxemia, and abnormal lung mechanics. This pilot study was designed to determine whether pulmonary rehabilitation were efficacious in improving the 6-min walk test (6-MWT) distance, exercise oxygen uptake, respiratory muscle strength [maximum inspiratory pressure (MIP)], and dyspnea in patients with IPF. Underlying physiological mechanisms and effects of the intervention were investigated. METHODS: Subjects were randomly assigned to a 3-month pulmonary rehabilitation program (n = 11) or to a control group (n = 10). All subjects initially underwent the 6-MWT and constant load exercise gas exchange studies. RESULTS: Subjects in the rehabilitation group increased treadmill exercise [metabolic equivalent of task-minutes] over the first 14 sessions. Beneficial effects on physical function resulted in those who completed rehabilitation. Subjects who completed the program increased cycle ergometer time and maintained exercise oxygen consumption (exercise VO(2)) at the baseline level over 3 months, while the control group suffered a significant decrease in exercise VO(2). Rehabilitation subjects also increased their MIP. Plasma lactate doubled and brain natriuretic peptide levels increased significantly after exercise, as did the plasma amino acids glutamic acid, arginine, histidine, and methionine. These changes were associated with significant decreases in arterial oxygen saturation and increases in 15-F(2t)-isoprostanes after exercise. CONCLUSIONS: Pulmonary rehabilitation effectively maintained exercise oxygen uptake over 3 months and lengthened constant load exercise time in patients with moderately severe IPF. Exercise endurance on cycle ergometry testing was limited by dyspnea and severe hypoxemia associated with systemic oxidant stress.

Effect of intermittent hypoxia and exercise on blood rheology and oxygen transport in trained rats.

Intermittent hypobaric hypoxia (IHH) exposure, accompanied or not with active recovery, can help to skeletal muscle repair. However, the erythropoietic response elicited can disturb blood rheology and thus alter the oxygen delivery to tissues. Male Sprague-Dawley rats were studied in two basal states: untrained and trained and compared with early (1-3 days) and late (7-14 days) stages of damage recovery in three groups of trained rats that had suffered skeletal muscle injury: Control, passive recovery rats; HYP, rats exposed to IHH after muscle damage; and EHYP, trained rats that performed light aerobic exercise sessions in addition to IHH. Hematocrit, RBC count and hemoglobin were only elevated in the late stage of recovery in HYP (13%; 14% and 8%) and EHYP (18%; 13% and 15%) groups. Blood viscosity increased about double for EHYP rats. It is concluded that intermittent exposure to hypobaric hypoxia in combination with light aerobic exercise in normoxia has an erythropoietic effect, but also provides advantageous hemorheological conditions for the perfusion of damaged muscle.

The evidence base for oxygen for chronic refractory breathlessness: issues, gaps, and a future work plan.

Breathlessness or "shortness of breath," medically termed dyspnea, is a common and distressing symptom featuring strongly in advanced lung, cardiac, and neuromuscular diseases; its prevalence and intensity increase as death approaches. However, despite the increasing understanding in the genesis of breathlessness, as well as an increasing portfolio of treatment options, breathlessness is still difficult to manage and engenders helplessness in caregivers and health care professionals and fear for patients. Although hypoxemia does not appear to be the dominant driver for breathlessness in advanced disease, the belief that oxygen is important for the relief of acute, chronic, and acute-on-chronic shortness of breath is firmly embedded in the minds of patients, caregivers, and health care professionals. This article presents current understanding of the use of oxygen for treating refractory breathlessness in advanced disease. The objective is to highlight what is still unknown, set a research agenda to resolve these questions, and highlight methodological issues for consideration in planned studies.

Supplementation of essential amino acids may reduce the occurrence of infections in rehabilitation patients with brain injury.

BACKGROUND: To investigate whether supplementation with oral essential amino acids (EAAs) may reduce the occurrence of nosocomial infection among patients with brain injury (BI: stroke, trauma, anoxic coma). METHODS: Patients (n = 125; 77 men, 48 women; mean age 63 ± 15 years) with stroke (68.8%), subarachnoid hemorrhage (17.6%), traumatic BI (7.2%), and anoxic BI (6.4%) 88 ± 15 days after the index event. Patients were randomly assigned to 2 months of oral EAAs (n = 63; 8 g/d) or placebo (n = 62). RESULTS: Over the first month of rehabilitation, there were 60 infections in the whole population of 125 patients (48%); however, the rate was 23.2% lower in the EAA group (23 episodes/63 patients; 36.5%) than in the placebo group (37 episodes/62 patients; 59.7%) (P < .01). The types of infection were similarly distributed between the 2 groups. Serum levels of prealbumin <20 mg/dL and C-reactive protein (CRP) >0.3 mg/dL were the best predictors of future infection (prealbumin: odds ratio [OR] = 4.17, confidence interval [CI] 1.84-9.45, P < .001; CRP: OR = 3.8, CI 1.71-8.44, P < .001). CONCLUSION: Supplementary EAAs may reduce the occurrence of nosocomial infections in rehabilitation patients with BI. Prealbumin and CRP are the best predictors of future infections.

Sleep desaturation and its relationship to lung function, exercise and quality of life in LAM.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is characterised by progressive airway obstruction and hypoxaemia in young women. Although sleep may trigger hypoxaemia in patients with airway obstruction, it has not been previously investigated in patients with LAM. METHODS: Consecutive women with lung biopsy proven LAM and absence of hypoxaemia while awake were evaluated with pulmonary function test, echocardiography, 6-min walk test, overnight full polysomnography, and Short Form 36 health-related quality-of-life questionnaire. RESULTS: Twenty-five patients with (mean±SD) age 45±10 years, SpO(2) awake 95%±2, forced expiratory volume in the first second (median-interquartile) FEV(1)(% predicted) 77 (47-90) and carbonic monoxide diffusion capacity, DL(CO) (%) 55 (34-74) were evaluated. Six-minute walk test distance and minimum SpO(2) (median-interquartile) were, respectively, 447m (411-503) and 90% (82-94). Median-interquartile apnoea-hypopnoea index was in the normal range 2 (1-5). Fourteen patients (56%) had nocturnal hypoxaemia (10% total sleep time with SpO(2) <90%), and the median sleep time spent with SpO(2) <90% was 136 (13-201)min. Sleep time spent with SpO(2) <90% correlated with the residual volume/total lung capacity ratio (r(s)=0.5, p: 0.02), DL(CO) (r(s)=-0.7, p: 0.001), FEV(1) (r(s)=-0.6, p: 0.002). Multivariate linear regression model showed that RV/TLC ratio was the most important functional variable related to sleep hypoxaemia. CONCLUSION: Significant hypoxaemia during sleep is common in LAM patients with normal SpO(2) while awake, especially among those with some degree of hyperinflation in lung function tests.

Can patent foramen ovale affect rehabilitation? The uncommon association of platypnea-orthodeoxia syndrome and stroke.

Platypnea-orthodeoxia is a rare syndrome characterized by dyspnea and deoxygenation induced by a change to a sitting or standing from a recumbent position. It is the result of posturally accentuated intracardiac or pulmonary right-to-left shunt leading to arterial oxygen desaturation. Only few cases of platypnea-orthodeoxia syndrome are reported in the literature and the association between stroke and platypnea-orthodeoxia syndrome with evidence of patent foramen ovale is extremely rare. We describe the case of a 67-year-old female admitted to our Rehabilitation Unit for disabling basilar stroke due to paradoxical embolism from patent foramen ovale that during the first days of rehabilitation showed signs and symptoms of platypnea-orthodeoxia syndrome. To remove a life-threatening condition for the patient and in order to develop the normal rehabilitation project, that was stopped by the platypnea-orthodeoxia syndrome, the patient fastly underwent to percutaneous closure of patent foramen ovale. The stabilization of oxygen arterial saturation with postural changes and the disappearance of symptoms of POS allowed to develop the rehabilitation project with progressive neurological improvement.

Effect of respiratory muscle training on maximum aerobic power in normoxia and hypoxia.

To assess the effects of respiratory muscle training (RMT) on maximum oxygen uptake (VO2max) in normoxia and hypoxia, 9 healthy males (age 24 +/- 4 years; stature 1.75 +/- 0.08 m; body mass 72 +/- 9 kg; mean +/- SD) performed on different days maximal incremental tests on a cycle ergometer in normoxia and normobaric hypoxia (FIO2=0.11), before and after 8 weeks of RMT (5 days/week). During each test, gas exchange variables were measured breath-by-breath by a metabolimeter. After RMT, no changes in cardiorespiratory and metabolic variables were detected at maximal exercise in normoxia. On the contrary, in hypoxia expired and alveolar ventilation (V(E(and V(A), respectively) at maximal exercise were significantly higher than pre-training condition (+12 and +13%, respectively; P < 0.05). Accordingly, alveolar O2 partial pressure (PAO2) after RMT significantly increased by approximately 10%. Nevertheless, arterial PO2 and VO2max did not change with respect to pre-training condition. In conclusion, RMT improved respiratory function but did not have any effect on VO2max, neither under normoxic nor hypoxic condition. In hypoxia, the significant increase in V(E) and V(A) at maximum exercise after training lead to higher alveolar but not arterial PO2 values, revealing an increased A-a gradient. This result, according to the theoretical models of VO2max limitation, seems to contradict the lack of VO2max increase in hypoxia, suggesting a possible role of increased ventilation-perfusion mismatch.

[Automatic control and safety concepts for extracorporeal lung support]. / Regelungs- und Sicherheitskonzepte für extrakorporale Systeme zur Lungenunterstützung.

In some cases of severe acute respiratory distress syndrome, hypoxemia occurs despite optimized conservative therapy; however, extracorporeal membrane oxygenation (ECMO) can assure sufficient gas exchange. To increase safety and reliability of devices, the oxygenator design was optimized integrating new plasma-resistant composite membranes and new blood pumps are used with longer durability and reduced blood cell damage. Another approach is the use of an arterio-venous pumpless extracorporeal lung assist (pECLA) using an oxygenator with reduced pressure drop to simplify management and to avoid pump-related complications. First attempts were made to integrate basic control and safety concepts in ECMO circuits, but this does not seem to be sufficient to overcome the specific problems of ECMO (long-term use and limited supervision of the intensive care unit). The integration of sophisticated automated control and safety concepts in combination with revised ECMO circuits could allow a more reliable application of ECMO of the intensive care unit without continuous observation by a perfusionist. Easier intra- and interhospital transfer of patients with running ECMO would be another advantage.

Pulmonary vascular response to air-breathing exercise in humans following an 8-h exposure to hypoxia.

This study is concerned with the pulmonary vasculature in euoxia after preconditioning with 8h of hypoxia. The particular question we ask is whether the pulmonary vasculature will dilate normally with exercise or retain some degree of vasoconstriction, as has previously been reported in studies involving longer exposures to the hypoxia of high altitude. Ten subjects were studied on two separate days. On one day, subjects were exposed to 8h of isocapnic hypoxia (end-tidal P(O)(2) 55Torr) and on the other day to 8h of euoxia as a control. Before and after each exposure, subjects undertook 20min of exercise at an intensity to elevate heart rate (HR) by approximately 30bpm. During this period, Doppler echocardiography was used to assess the maximum pressure gradient during systole across the tricuspid valve (DeltaP(max)) as an index of pulmonary arterial pressure. Following 8-h hypoxia, but not control, DeltaP(max) increased by approximately 2mmHg with the subjects breathing air at rest (ANOVA, P<0.02). Under control conditions, exercise at approximately 30 bpm above resting HR increased DeltaP(max) by 9.9+/-1.3mmHg (mean+/-SE). Following 8-h hypoxia, but not control, this sensitivity of DeltaP(max) to exercise increased by approximately 35% to 13.4+/-2.1mmHg (P<0.05). We conclude that prior conditioning with 8h of hypoxia impairs the ability of the pulmonary vasculature to dilate normally during exercise.

Respiratory control during air-breathing exercise in humans following an 8 h exposure to hypoxia.

Hypoxic exposure lasting a few hours results in an elevation of ventilation and a lowering of end-tidal P(CO2) (P(ET(CO2))) that persists on return to breathing air. We sought to determine whether this increment in ventilation is fixed (hypothesis 1), or whether it increases in proportion to the rise in metabolic rate associated with exercise (hypothesis 2). Ten subjects were studied on two separate days. On 1 day, subjects were exposed to 8h of isocapnic hypoxia (end-tidal P(O2) 55 Torr) and on the other day to 8 h of euoxia as a control. Before and 30 min after each exposure, subjects undertook an incremental exercise test. The best fit of a model for the variation in P(ET(CO2)) with metabolic rate gave a residual squared error that was approximately 20-fold less for hypothesis 2 than for hypothesis 1 (p<0.005, F-ratio test). We conclude that the alterations in respiratory control induced during early ventilatory acclimatization to hypoxia better reflect those associated with hypothesis 2 rather than hypothesis 1.