Hypoxic Gas Mixture Research Articles

Diameter Changes of Retinal Arterioles During Acute Hypoxia In Vivo are Modified by the Inhibition of Nitric Oxide and Prostaglandin Synthesis

ABSTRACTPurpose: Inhibition of cyclooxygenase (COX) and nitric oxide synthesis (NOS) has previously been shown to modify hypoxia-induced relaxation of retinal arterioles in vitro. The purpose of the present study was to investigate whether these findings can be reproduced in vivo.Methods: Twenty healthy persons aged 20–55 years were examined. Using the dynamic vessels analyzer (DVA), the resting diameter and diameter changes during isometric exercise and flicker stimulation were studied before and during breathing of a hypoxic gas mixture. The examinations were carried out before and during intravenous infusion of the NOS-inhibitor l-NMMA, and were repeated on a second study day after topical administration of the COX-inhibitor diclofenac.Results: The resting diameter of retinal arterioles increased significantly during hypoxia and decreased significantly during l-NMMA infusion (p < 0.0001) which compensated for changes in the blood pressure. During hypoxia and l-NMMA infusion together contraction of retinal arterioles could not compensate for the increased blood pressure as assessed by a gain factor significantly lower than one (p = 0.002).The arteriolar contraction induced by isometric exercise was significantly reduced by diclofenac and flicker-induced dilatation of retinal arterioles was increased during l-NMMA infusion (p < 0.0001).Conclusion: Diameter changes of retinal vessels during acute hypoxia in vivo are modified by inhibiting NO and prostaglandin synthesis. The evidence points to possible new targets of intervention on the diameter regulation of retinal arterioles in diseases where retinal hypoxia is part of the disease pathogenesis.

Effects of hypoxia and hypercapnia on human HRV and respiratory sinus arrhythmia.

Hypercapnia increases minute ventilation (V’E) with little effect on heart rate (HR), whereas hypoxia may increase HR without affecting V’E. However, the effects of hypercapnia and hypoxia on both heart rate variability(HRV) and the clustering of heart beats during spontaneous breathing (respiratory sinus arrhythmia – RSA), are not clear. In this study, 10 human volunteers breathed room air (RA), hypercapnic (5% CO2) or hypoxic (10%O2) gas mixtures, each for 6 min, while resting supine. ECG, mean arterial pressure (MAP), ventilatory flow, inhaled and exhaled fractions of CO2 and O2, were recorded throughout. Both V’E and MAP increased with 5%CO2, with no change in HR. Hypoxia did not change ventilation but increased HR. High frequency components of HRV, and the relative proportion of heart beats occurring during inhalation increased with 5% CO2, but neither changed with 10% O2. Increased RSA concomitant with increased MAP suggests RSA – vagal dissociation with hypercapnia. Elevated heart rate with acute hypoxia with no change in either frequency components of HRV or the distribution of heart beats during ventilation, suggested that clustering of heart beats may not be a mechanism to improve ventilation-perfusion matching during hypoxia.

Inhibition of NO and COX products modifies the hypoxia‐induced dilatation of retinal vessels in vivo

AbstractPurpose Retinal hypoxia with consequent changes in blood perfusion is a central feature in common vision threatening diseases. The aim of this study was to examine the effects of inhibiting COX and NO‐synthesis on hypoxia‐induced relaxation of retinal vessels in humansMethods Twenty healthy persons aged 20‐55 years were examined on two days separated by 4‐7 days. The resting diameter and the diameter response to isometric exercise and flicker stimulation of retinal vessels were studied using the Dynamic Vessel Analyzer before and during breathing a hypoxic gas mixture and before and during intravenous infusion with the NOS inhibitor L‐NMMA and were repeated on a second day after topical administration of the COX‐inhibitor diclofenacResults The resting diameter of arterioles increased significantly during hypoxia and decreased significantly during L‐NMMA infusion (p&lt;0.0001) whereas no change in diameter was observed with the two applied together. When hypoxia and L‐NMMA were applied simultaneously, the gain factor was significantly lower than 1 (p=0.002) indicating that when diameter changes were corrected for changes in arterial blood pressure the blood flow increased, whereas this was not the case for either of the two interventions alone. Diclofenac significantly reduced contraction of retinal arterioles induced by isometric exercise (p=0.04) but not by the other interventions. Flicker‐induced dilatation of retinal arterioles was increased during L‐NMMA infusion (p&lt;0.0001) but not during the other interventionsConclusion Diameter changes of retinal vessels during hypoxia are influenced by NO and COX products. This may point to new treatment strategies for diseases characterized by retinal hypoxia and disturbances in retinal perfusion

Морфологические аспекты радиопротекции в эксперименте

The problem of modification of the effects of ionizing radiation in morphological manifestations of authorities at different speeds update is relevant direction in recent years. The authors considered as modifiers - hypoxic gas mixture, normobaric oxygen and electromagnetic radiation. They are in certain conditions associated with ionizing radiation, as in the conditions of emergency situations, and in normal mode. The development of pathological process after exposure and outcome depend on the overall resistance and state systems of adaptation. Identify the most effective mechanisms of mobilization of protective forces and the restoration of the functional reserves of the organism as a whole, is a prospective task of modern radiobiology. Based on the study of literature data and the results of their research the authors concluded that the degree of modification was dependent on the sequence of application of modifiers and doses of ionizing radiation; the radioprotective effect was in direct correlation with tissue facilities body. The radioprotective effect was revealed by during previous combined and joint use of modified gas environment with high and low oxygen content and electromagnetic radiation. The authors believe that the use of these modifiers is promising in the field of safety.

Hand temperature responses to local cooling after a 10-day confinement to normobaric hypoxia with and without exercise.

The study examined the effects of a 10-day normobaric hypoxic confinement (FiO2: 0.14), with [hypoxic exercise training (HT); n = 8)] or without [hypoxic ambulatory (HA; n = 6)] exercise, on the hand temperature responses during and after local cold stress. Before and after the confinement, subjects immersed their right hand for 30 min in 8 °C water [cold water immersion (CWI)], followed by a 15-min spontaneous rewarming (RW), while breathing either room air (AIR), or a hypoxic gas mixture (HYPO). The hand temperature responses were monitored with thermocouples and infrared thermography. The confinement did not influence the hand temperature responses of the HA group during the AIR and HYPO CWI and the HYPO RW phases; but it impaired the AIR RW response (-1.3 °C; P = 0.05). After the confinement, the hand temperature responses were unaltered in the HT group throughout the AIR trial. However, the average hand temperature was increased during the HYPO CWI (+0.5 °C; P ≤ 0.05) and RW (+2.4 °C; P ≤ 0.001) phases. Accordingly, present findings suggest that prolonged exposure to normobaric hypoxia per se does not alter the hand temperature responses to local cooling; yet, it impairs the normoxic RW response. Conversely, the combined stimuli of continuous hypoxia and exercise enhance the finger cold-induced vasodilatation and hand RW responses, specifically, under hypoxic conditions.

Acute Effects of Normobaric Hypoxia on Hand-Temperature Responses During and After Local Cold Stress

The purpose was to investigate acute effects of normobaric hypoxia on hand-temperature responses during and after a cold-water hand immersion test. Fifteen males performed two right-hand immersion tests in 8°C water, during which they were inspiring either room air (Fio2: 0.21; AIR), or a hypoxic gas mixture (Fio2: 0.14; HYPO). The tests were conducted in a counterbalanced order and separated by a 1-hour interval. Throughout the 30-min cold-water immersion (CWI) and the 15-min spontaneous rewarming (RW) phases, finger-skin temperatures were measured continuously with thermocouple probes; infrared thermography was also employed during the RW phase to map all segments of the hand. During the CWI phase, the average skin temperature (Tavg) of the fingers did not differ between the conditions (AIR: 10.2 ± 0.5°C, HYPO: 10.0 ± 0.5°C; p = 0.67). However, Tavg was lower in the HYPO than the AIR RW phase (AIR: 24.5 ± 3.4°C; HYPO: 22.0 ± 3.8°C; p = 0.002); a response that was alike in all regions of the immersed hand. Accordingly, present findings suggest that acute exposure to normobaric hypoxia does not aggravate the cold-induced drop in hand temperature of normothermic males. Still, hypoxia markedly impairs the rewarming responses of the hand.

Exercise- and hypoxia-induced blood flow through intrapulmonary arteriovenous anastomoses is reduced in older adults

Mean pulmonary arterial pressure (Ppa) during exercise is significantly higher in individuals aged ≥50 yr compared with their younger counterparts, but the reasons for this are unknown. Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) can be detected during exercise or while breathing hypoxic gas mixtures using saline contrast echocardiography in almost all healthy young individuals. It has been previously hypothesized that a lower degree of exercise-induced blood flow through IPAVA is associated with high Ppa during exercise. This association may suggest that individuals who are known to have high Ppa during exercise, such as those ≥50 yr of age, may have lower blood flow through IPAVA, but the presence and degree of exercise-induced blood flow through IPAVA has not been specifically studied in older populations. Using transthoracic saline contrast echocardiography, we investigated the potential effects of age on exercise-induced blood flow through IPAVA in a cross-section of subjects aged 19-72 yr. To verify our findings, we assessed the effects of age on hypoxia-induced blood flow through IPAVA. Age groups were ≤41 yr (younger, n = 16) and ≥50 yr (older, n = 14). Qualitatively measured exercise- and hypoxia-induced blood flow through IPAVA was significantly lower in older individuals compared with younger controls. Older individuals also had significantly higher pulmonary arterial systolic pressure and total pulmonary resistance (TPR) during exercise. Low blood flow through IPAVA was independently associated with high TPR. The reasons for the age-related decrease in blood flow through IPAVA are unknown.

Circulating N-terminal brain natriuretic peptide and cardiac function in response to acute systemic hypoxia in healthy humans.

BackgroundAs it remains unclear whether hypoxia of cardiomyocytes could trigger the release of brain natriuretic peptide (BNP) in humans, we investigated whether breathing normobaric hypoxic gas mixture increases the circulating NT-proBNP in healthy male subjects.MethodsTen healthy young men (age 29 ± 5 yrs, BMI 24.7 ± 2.8 kg/m2) breathed normobaric hypoxic gas mixture (11% O2/89% N2) for one hour. Venous blood samples were obtained immediately before, during, and 2 and 24 hours after hypoxic exposure. Cardiac function and flow velocity profile in the middle left anterior descending coronary artery (LAD) were measured by Doppler echocardiography.ResultsArterial oxygen saturation decreased steadily from baseline value of 99 ± 1% after the initiation hypoxia challenge and reached steady-state level of 73 ± 6% within 20–30 minutes. Cardiac output increased from 6.0 ± 1.2 to 8.1 ± 1.6 L/min and ejection fraction from 67 ± 4% to 75 ± 6% (both p < 0.001). Peak diastolic flow velocity in the LAD increased from 0.16 ± 0.04 to 0.28 ± 0.07 m/s, while its diameter remained unchanged. In the whole study group, NT-proBNP was similar to baseline (60 ± 32 pmol/ml) at all time points. However, at 24 h, concentration of NT-proBNP was higher (34 ± 18%) in five subjects and lower (17 ± 17%), p = 0.002 between the groups) in five subjects than at baseline.ConclusionIn conclusion, there is no consistent increase in circulating NT-proBNP in response to breathing severely hypoxic normobaric gas mixture in healthy humans, a possible reason being that the oxygen flux to cardiac myocytes does not decrease because of increased coronary blood flow. However, the divergent individual responses as well as responses in different cardiac diseases warrant further investigations.

Morphofunctional Changes in Thyroid Gland Induced by Normobaric Hypoxia in Young Rats

Effects of hypoxic gas mixture in different modes (HGM; 10% oxygen in nitrogen) on the morphometric changes in the functional activity of the thyroid parenchymatous tissue in 3-month-old rats were studied. Hypoxia-induced decrease in the average cross-sectional areas of a follicle and colloid, reduced follicle inner diameter, increased thyroid epithelium height, an increase in a number of thyrocytes in a follicle, resorption vacuoles and interfollicular islets, enhanced follicle-colloid index and decreased colloid accumulation index have been shown. Thus, dosed normobaric hypoxia intensifies functional activity and physiological regeneration processes in the thyroid gland of the young animals.

Assessment of Acute Mild Hypoxia on Retinal Oxygen Saturation Using Snapshot Retinal Oximetry

To study the effect of acute mild hypoxia on retinal oxygen saturation. Spectral retinal images were acquired under normoxic and hypoxic conditions for 10 healthy human volunteers (six male, four female, aged 25 ± 5 years [mean ± SD]) using a modified fundus camera fitted with an image-replicating imaging spectrometer (IRIS). Acute, mild hypoxia was induced by changing the oxygen saturation of inhaled air from 21% to 15% using a hypoxia generator with subjects breathing the hypoxic gas mixture for 10 minutes. Peripheral arterial oxygen saturation of the subjects was monitored using fingertip-pulse oximetry. Images were processed to calculate oxygen saturation, arteriovenous difference in oxygen saturation, and vessel diameter. Data are presented as mean ± SD and were analyzed using paired sample t-test with significance accepted at P < 0.05. The retinal arterial and venous oxygen saturation was 98.5% ± 1.6% and 70.7% ± 2.7% during normoxia. A reduction in the fraction of inspired oxygen resulted in a decline (P < 0.001) in both retinal-arterial and venous oxygen saturation to 90.3% ± 2.0% and 62.4% ± 2.2%, respectively. The arteriovenous oxygen saturation difference in normoxia (27.8% ± 2.9%) and hypoxia (27.9% ± 2.1%) did not change. Retinal arteriolar and venular diameters increased (P < 0.001) by 4% and 3%, respectively, under hypoxia. The acute inhalation of a hypoxic gas mixture resulted in a decline in both retinal-arterial and venous saturation, while arteriovenous oxygen difference was maintained with an accompanying significant increase in retinal vessel diameter. This may suggest an autoregulatory response to acute mild hypoxia.

Effectiveness of the combined effects of hypoxic gas mixture and electrical stimulation for the water-polo players` working ability correction

Аннотация В спортивной медицине давно известны и широко применяются недопинговые методы воз-действия, стимулирующие работоспособность спортсменов, например, нормобарическая и гипоба-рическая гипоксии, дыхание кислородно-гелиевыми смесями и др. Однако, практически никто не пробовал комплексно сочетать отдельные методы для коррекции работоспособности организма при подготовке спортсменов. Данные исследования были выполнены с целью подтверждения эф-фективности сочетанного воздействия гипоксической газовой смеси и электростимуляции на рабо-тоспособность ватерполистов. Полученные результаты говорят о том, что работоспособность ва-терполистов значительно увеличивается, одновременно улучшается и функциональное состояние спортсменов. Разработанная методика рекомендуется к использованию в подготовительный период тренировочного цикла. Курс воздействия – не менее 5 дней. Область применения – подготовка спортсменов на уровне высшего спортивного мастерства и спортивного совершенствования для участия в соревнованиях различного уровня, включая мировые первенства и Олимпийские игры. Ключевые слова

Tissue deoxygenation kinetics induced by prolonged hypoxic exposure in healthy humans at rest

This study aimed to investigate the effects of sustained hypoxic exposure on cerebral and muscle oxygenation and cardiorespiratory function at rest. Eleven healthy subjects inhaled a normobaric hypoxic (FiO2=0.12) or normoxic (FiO2=0.21) gas mixture for 4 h at rest, on two separated blinded sessions. Arterial oxygen saturation (SpO2), heart rate variability (HRV), end-tidal CO2 (EtCO2), and oxygenation of quadriceps muscle, prefrontal and motor cortices assessed by near-infrared spectroscopy (NIRS) were measured continuously during each session. Acute mountain sickness symptoms were evaluated at the end of each session. During a hypoxic session, SpO2 reduction (∼13%) plateaued after 20 min, while deoxygenation pattern took 30 to 40 min at the cerebral sites to plateau (+5.3±1.6 μMol of deoxygenated-hemoglobin). Deoxygenation was more pronounced in the cerebral cortex compared to the muscle (+2.1±2.3 μMol of deoxygenated-hemoglobin), and NIRS-derived tissue perfusion index showed distinct profiles between the muscle (hypoperfusion) and the brain (hyperperfusion) with prolonged hypoxia. Changes in tissue oxygenation were not associated with cardiorespiratory responses (e.g., HRV, EtCO2) and altitude sickness symptom appearance during hypoxic sessions. These data demonstrate that sustained hypoxia elicits time delay in changes between arterial and tissue (especially cerebral) oxygenation, as well as a tissue-specific sensitivity.

Retrograde blood flow in the inactive limb is enhanced during constant-load leg cycling in hypoxia

This study aimed to elucidate the effects of hypoxia on the pattern of oscillatory blood flow in the inactive limb during constant-load dynamic exercise. We hypothesised that retrograde blood flow in the brachial artery of the inactive limb would increase during constant-load leg cycling under hypoxic conditions. Three maximal exercise tests were conducted in eight healthy males on a semi-recumbent cycle ergometer while the subjects breathed a normoxic [inspired oxygen fraction (FIO2)=0.209] or two hypoxic gas mixtures (FIO2=0.155 and 0.120). Subjects then performed submaximal exercise at the same relative exercise intensity of 60% peak oxygen uptake under normoxic or the two hypoxic conditions for 30min. Brachial artery blood velocity and diameter were recorded simultaneously during submaximal exercise using Doppler ultrasonography. Antegrade blood flow gradually increased during exercise, with no significant differences among the three trials. Retrograde blood flow showed a biphasic response, with an initial increase followed by a gradual decrease during normoxic exercise. In contrast, retrograde blood flow significantly increased during moderate and severe hypoxic exercise, and remained elevated above normoxic conditions during exercise. At 30min of exercise, the magnitude of the change in retrograde blood flow during exercise was greater as the level of hypoxia increased (normoxia: -18.7±23.5mlmin(-1); moderate hypoxia: -39.3±21.4mlmin(-1); severe hypoxia: -64.0±36.3mlmin(-1)). These results indicate that moderate and severe hypoxia augment retrograde blood flow in the inactive limb during constant-load dynamic leg exercise.

AROMATIC AMINO ACIDS METABOLISM IN HUMANS EXPOSED TO EXPERIMENTAL SEVERE ACUTE SHORT-TERM NORMOBARIC HYPOXIA

In aviation, acute hypoxia is one of the most dangerous factors affecting humans, and developing new ways of increasing human hypoxic resistance in severe acute hypoxia remains important. In this work we have studied particular features of proteinogenous aromatic amino acids metabolism in volunteers breathing hypoxic gas mixture containing 9 % of O 2. We have shown that the healthy volunteers exposed to experimental hypoxia in postprandial state significantly decreased plasma levels of free tyrosine and phenylalanine in the early recovery period. We hypothesized that these amino acids being precursors for mediators and hormones (dopamine, epinephrine, norepinephrine) can play a significant role in increasing hypoxic resistance in humans.

Морфофункціональні зміни щитоподібної залози молодих щурів за умов нормобаричної гіпоксії

We investigated the influence of hypoxic gas mixture (the different modes) on the morphometric indexes of thyroid gland functional activity in 3-mounth rats. It was shown a decrease in the size of follicles of middle area and the colloid and an increase in the amount of thyrocytes in a follicle, resorption vacuoles and interfollicular epithelium after exposure to hypoxic gas mixture (10% oxygen). We also detected an increase in a follicle-colloid index and a decrease in the colloid accumulation index. Thus, a dosed normobaric hypoxia intensifies the functional activity and physiological regeneration processes of thyroid gland in the young animals.

Inflammatory response to acute hypoxia in humans

BackgroundIn animal studies hypoxia is known to cause an inflammatory response, inducing multiple transcription factors and activating molecular processes at the cellular level. However, it is not known whether acute hypoxia causes similar inflammatory effects in humans, although such an assumption is commonly made. MethodsThe effects of acute hypoxic exposure were studied in 12 healthy adults: Each subject was studied on 2 different days. Group 1 (mean age 33 ± 5.5 years; 2 females, 4 males) was exposed either to a hypoxic gas mixture or room air for 30 min and Group 2 (mean age 26.5 ± 7.5 years; 3 females, 3 males) for 60 min. Measurements of circulating adhesion molecules (AMs), Clara cell secretory protein (CC16), hypoxia inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and C reactive protein (hsCRP) were made at baseline and at intervals following exposure for 240 min. ResultsNo significant changes were seen in circulating AMs, CC16, TNF-α, IL-6 or hsCRP, although both HIF-1α and VEGF levels increased significantly (p < 0.05) after hypoxic exposure. ConclusionsAcute hypoxic exposure in normal man does not induce a measurable change in inflammatory or epithelial biomarkers, in contrast to studies at the cellular level in animals. However, acute hypoxic exposure does induce the expression of HIF-1α and VEGF. These results indicate that in humans acute hypoxic exposure for up to 60 min does not induce a generalized inflammatory response, indicating that the human response to hypoxia is more complex than inferred from animal/cellular studies.

Quantification of hypoxia‐induced blood flow through intrapulmonary arteriovenous anastomoses in healthy humans at rest

Breathing hypoxic gas mixtures has been shown to increase blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA) in healthy humans, as detected by saline contrast echocardiography. Although this method cannot quantify QIPAVA, Technetium‐99m‐labeled macroaggregated albumin (99mTc‐MAA) and quantitative whole body planar scanning has previously been used to quantify QIPAVA at rest and during exercise. We hypothesized that breathing 12% O2 would increase QIPAVA compared to breathing room air. We studied 4 male subjects while they breathed room air for 30 minutes on one day and 12% O2 for 30 minutes on another day in a randomized order, separated by &gt;;6 days. In the final minute, 99mTc‐MAA, filtered through a 20μm filter (median size MAA = 35.3μm), was injected and subjects immediately underwent whole body quantitative planar scanning. A venous blood sample was drawn at the end of the scan to quantify the free 99mTc that became unbound during the scan. QIPAVA significantly increased from 0.1% at rest breathing room air to 1.5% (range: 1.1–1.9%) while breathing 12% O2. These data suggest that breathing 12% O2 increases QIPAVA in healthy humans. If QIPAVA is acting as a source of shunt, as we have previously suggested, then QIPAVA may play a role in the development of arterial hypoxemia that develops at altitude.

Effects of Intermittent Normobaric Hypoxia on the CNS Functions and Cerebral Circulation in Children with Cerebral Palsy

We studied the effects of intermittent normobaric hypoxia (INH) on the CNS functions and cerebral circulation recovery in children with cerebral palsy (CP). Altogether, 87 patients (from 8.5 months to 12 years old) with CP were examined and received the course of complex treatment. Clinico-neurophysiological examination was performed before the treatment and immediately after termination of the therapeutic course. Patients were divided into two randomized groups according to age, sex and clinical manifestations of CP. The comparison group included 34 children who received the course of the generally accepted complex therapy (medicamental treatment, massage, Bobat-therapy, Vojta-therapy at al). The main group included 53 patients who, in addition to the same therapy, were exposed to INH using an individual apparatus for artificial mountain air, Borey-M, made in the Scientific Medico-Engineering Center NORT (Ukrainian National Academy of Sciences, Kyiv). Children of the main group were exposured to the dosed normobaric intermittent hypoxia at sanogenetic level once per day. For this purpose, we used a normobaric hypoxic gas mixture (12% O2 + 88% N2). Each cycle included a 15-min-long episode of breathing with the gas mixture alternated by a 5-min-long episode of breathing with an ambient atmospheric air. The number of hypoxic cycles was gradually increased (from one to three). The entire course of treatment included 10 sessions, on average. After complex therapy, the stable positive effects on the motor status were observed in 94% of patients of the main group (exposed to INH) and in 74% of patients of the comparison group (unexposed to INH). EEG examination showed positive dynamics in patients of both the main group (70%) and in children of the comparison group (56%). Doppler examination showed that brain hemodynamics was normalized in 85% of patients of the main group and in 59% of children in the comparison group. In the course of ophthalmoscopic examination, positive changes in the state of the eye fundus were found more expressed in children of the main group, compared to those in patients of the comparison group (32% and 12% of patients, respectively).

Rho-Kinase Inhibition Attenuates Acute Hypoxic Fetoplacental Vasoconstriction in the Rat

The vessels on the fetal side of the placenta differ from most other vascular beds except the lungs in that they respond to acute hypoxia by vasoconstriction. An essential role of calcium influx in the mechanism of this hypoxic fetoplacental vasoconstriction (HFPV) has been shown previously. That finding does not, however, exclude the possible involvement of other mechanisms of vascular tone regulation. In this study we tested the hypothesis that Rho-kinase-mediated calcium sensitization is involved in HFPV. We used a model of isolated rat placenta dually perfused (from both the maternal and fetal side) with Krebs salt solution saturated with normoxic and hypoxic gas mixture respectively at constant flow rate. Rho-kinase pathway was inhibited by fasudil (10 microM). We found that fasudil reduced basal normoxic fetoplacental vascular resistance and completely prevented HFPV. This suggests that the activity of Rho-kinase signaling pathway is essential for HFPV.

Effect of hypoxia on the dynamic response of hyperaemia in the contracting human calf muscle

Although systemic hypoxia increases the muscle hyperaemic response during 'steady-state' exercise, its effect on the dynamic characteristics of this response is not clear. In the present study, we first established that hypoxia increases the steady-state hyperaemic response at low workloads during calf exercise. To study dynamic aspects of this response, eight subjects performed eight exercise trials while breathing a normoxic (fractional inspired O(2) = 0.2094) or hypoxic gas mixture (fractional inspired O(2) = 0.105). Subjects performed intermittent contractions (1 s) of the calf muscle at 20% maximal voluntary contraction, and the leg blood flow (LBF), leg vascular conductance (LVC) and EMG activities of the triceps surae muscles were measured during each contraction-relaxation period (3 s). The LBF and LVC responses were averaged for each subject and fitted using a four-phase, exponential growth and decay function. Hypoxia evoked significant increases in the change in LBF (15%) and LVC (23%) from the start to the end of exercise, as well as the amplitude of the rapid growth phase of LBF and LVC (21%). Similar, but non-significant, effects on the amplitude of the slow growth phase of LBF (P = 0.08) and LVC (P = 0.10) were observed. By contrast, hypoxia had no effect on temporal parameters of these growth phases, parameters defining the decay phases or EMG activities. These results suggest that the effect of hypoxia on exercise hyperaemia is targeted at the rapid and perhaps the slow growth phase of the response, and is not mediated by a change in the level of muscle activation.