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Chronic Hypoxia (chronic + hypoxia)
Selected AbstractsChronic Hypoxia Induces Prolonged Angiogenesis in Skeletal Muscles of RatEXPERIMENTAL PHYSIOLOGY, Issue 3 2002D. Deveci Skeletal muscle capillarity and fibre cross-sectional area were investigated within and between diaphragm (Diaph), extensor digitorum longus (EDL), soleus (SOL) and tibialis anterior (TA) muscles of control and chronic hypoxic (12% O2 for 6 weeks) adult male Wistar rats (final body mass ,355 g). Cryostat sections were stained for alkaline phosphatase activity to depict all capillaries, and for succinic dehydrogenase to demonstrate regional differences in oxidative capacity within the muscles. Hypoxia-induced angiogenesis occurred in all muscles (P < 0.01), with capillary-to-fibre ratio (C:F) being higher in the more active and oxidative muscles, Diaph (27%) and SOL (26%), than phasically active and glycolytic muscles, TA (21%) and EDL (15%). Diaph, SOL and EDL maintained fibre size, and hence showed an increased capillary density (CD) and reduced intramuscular diffusion distance (DD), whereas TA showed fibre hypertrophy and maintained CD and DD compared to control muscles. The extent of angiogenesis among different regions of muscle varied so as to suggest that muscle fibre size has an additional influence on capillary growth during chronic systemic hypoxia, which is progressive over an extended period of systemic hypoxia. [source] Antioxidant and Vasodilatory Effects of Heme Oxygenase on Mesenteric Vasoreactivity Following Chronic HypoxiaMICROCIRCULATION, Issue 2 2009KAREN SWEAZEA ABSTRACT Objective: Chronic hypoxia (CH) results in impaired vasoconstriction associated with increased expression of heme oxygenase (HO). We hypothesized that enhanced HO activity minimizes reactive oxygen species (ROS) in arteries from CH rats, thereby normalizing endothelium-dependent vasodilation and concurrently produces carbon monoxide (CO), resulting in tonic vasodilation. Methods: ROS were quantified in mesenteric arteries from control and CH Sprague-Dawley rats. Reactivity to the endothelium-dependent vasodilator, acetylcholine (ACh), and the vasoconstrictor, phenylephrine (PE), were also assessed. Results: Basal ROS levels did not differ between groups and were similarly increased by HO inhibition. In contrast, catalase inhibition increased ROS in CH rats only. Vasodilatory responses to ACh were not different between groups. Combined inhibition of catalase and HO impaired PE-induced vasoconstriction in both groups. CH-induced impairment of vasoconstriction was reversed by either catalase or HO inhibition supporting the protective roles of the HO and catalase pathways following CH. Increased vascular smooth muscle calcium was observed with inhibition in the CH group, suggesting that catalase and HO-derived CO elicit reduced calcium influx, leading to the impaired vasoconstriction. Conclusions: Our data suggest that although the HO pathway is an important antioxidant influence, impaired vasoconstriction following CH appears to be due to effects of ROS and HO-derived CO. [source] Role of Vascular Heme Oxygenase in Reduced Myogenic Reactivity Following Chronic HypoxiaMICROCIRCULATION, Issue 2 2006JAY S. NAIK ABSTRACT Objective: Exposure to chronic hypoxia (CH) results in a persistent endothelium-dependent vascular smooth muscle hyperpolarization that diminishes vasoconstrictor reactivity. Experiments were performed to test the hypothesis that products of both cytochrome P450 epoxygenase (CYP) and heme oxygenase (HO) are required for the persistent diminished myogenic reactivity following CH. Methods: The authors examined myogenic responses of mesenteric arteries isolated from control and CH (48 h; PB = 380 mmHg) rats in the presence of a HO inhibitor (zinc protoporphyrin IX; ZnPPIX) or combined HO and CYP epoxygenase inhibition (sulfaphenazole). Arteries were isolated and cannulated and the vascular smooth muscle was loaded with the Ca2 + indicator Fura-2. Results: Control vessels maintained their internal diameter in response to step increases in intraluminal pressure, whereas arteries from CH animals passively distended. ZnPPIX augmented myogenic reactivity and [Ca2 +] in arteries from CH animals. Combined administration of sulfaphenazole and ZnPPIX did not have an additional effect compared to ZnPPIX alone. Myogenic reactivity in control vessels was not altered by ZnPPIX or ZnPPIX + sulfaphenazole. Conclusions: HO appears to play a role in regulating myogenic reactivity following CH. Furthermore, these data suggest that products of HO and CYP are both required for the observed attenuation in vasoreactivity following CH. [source] Antioxidant and Vasodilatory Effects of Heme Oxygenase on Mesenteric Vasoreactivity Following Chronic HypoxiaMICROCIRCULATION, Issue 2 2009KAREN SWEAZEA ABSTRACT Objective: Chronic hypoxia (CH) results in impaired vasoconstriction associated with increased expression of heme oxygenase (HO). We hypothesized that enhanced HO activity minimizes reactive oxygen species (ROS) in arteries from CH rats, thereby normalizing endothelium-dependent vasodilation and concurrently produces carbon monoxide (CO), resulting in tonic vasodilation. Methods: ROS were quantified in mesenteric arteries from control and CH Sprague-Dawley rats. Reactivity to the endothelium-dependent vasodilator, acetylcholine (ACh), and the vasoconstrictor, phenylephrine (PE), were also assessed. Results: Basal ROS levels did not differ between groups and were similarly increased by HO inhibition. In contrast, catalase inhibition increased ROS in CH rats only. Vasodilatory responses to ACh were not different between groups. Combined inhibition of catalase and HO impaired PE-induced vasoconstriction in both groups. CH-induced impairment of vasoconstriction was reversed by either catalase or HO inhibition supporting the protective roles of the HO and catalase pathways following CH. Increased vascular smooth muscle calcium was observed with inhibition in the CH group, suggesting that catalase and HO-derived CO elicit reduced calcium influx, leading to the impaired vasoconstriction. Conclusions: Our data suggest that although the HO pathway is an important antioxidant influence, impaired vasoconstriction following CH appears to be due to effects of ROS and HO-derived CO. [source] Chronic hypoxia-induced morphological and neurochemical changes in the carotid bodyMICROSCOPY RESEARCH AND TECHNIQUE, Issue 3 2002Zun-Yi Wang Abstract The carotid body (CB) plays an important role in the control of ventilation. Type I cells in CB are considered to be the chemoreceptive element which detects the levels of PO2, PCO2, and [H+] in the arterial blood. These cells originate from the neural crest and appear to retain some neuronal properties. They are excitable and produce a number of neurochemicals. Some of these neurochemicals, such as dopamine and norepinephrine, are considered to be primarily inhibitory to CB function and others, such as adenosine triphosphate, acetylcholine, and endothelin, are thought to be primarily excitatory. Chronic hypoxia (CH) induces profound morphological as well as neurochemical changes in the CB. CH enlarges the size of CB and causes hypertrophy and mitosis of type I cells. Also, CH changes the vascular structure of CB, including inducing marked vasodilation and the growth of new blood vessels. Moreover, CH upregulates certain neurochemical systems within the CB, e.g., tyrosine hydroxylase and dopaminergic activity in type I cells. There is also evidence that CH induces neurochemical changes within the innervation of the CB, e.g., nitric oxide synthase. During CH the sensitivity of the CB chemoreceptors to hypoxia is increased but the mechanisms by which the many CH-induced structural and neurochemical changes affect the sensitivity of CB to hypoxia remains to be established. Microsc. Res. Tech. 59:168,177, 2002. © 2002 Wiley-Liss, Inc. [source] Evidence for surviving outer hair cell function in congenitally deaf ears,THE LARYNGOSCOPE, Issue 11 2003FRCS (London), FRCS (ORL-HNS), Peter A. Rea MA Abstract Objective/Hypothesis: The hypotheses of the study were that congenital hearing impairment in infants can result from the isolated loss of inner hair cells of the cochlea and that this is shown by the presence of abnormal positive summating potentials on round window electrocochleography. The objectives were to establish the proportion of infants with hearing loss affected, the nature of the cochlear lesion, and its etiology. And to highlight the important implications for otoacoustic emissions testing and universal neonatal screening. Study Design: A prospectively conducted consecutive cohort study with supplemental review of notes was performed. Methods: Four hundred sixty-four children underwent round window electrocochleography and auditory brainstem response testing under general anesthesia to assess suspected hearing loss. The presence of abnormal positive potentials was recorded. Otoacoustic emissions data were collected separately and retrospectively. Results: Three hundred forty-two children had significant bilateral congenital hearing loss. All results were from hearing-impaired children. Abnormal positive potentials were recorded in 73 of 342 children (21%). Eighty-three percent of children with otoacoustic emissions also had abnormal positive potentials, but only 14% of children without otoacoustic emissions had abnormal positive potentials (P < .001). In the neonatal intensive care unit setting, 43% of infants were found to have abnormal positive potentials, whereas only 10% had abnormal positive potentials if not in the neonatal intensive care unit setting (P < .001). Abnormal positive potentials were present in 63% of infants born before 30 weeks gestation and in 14% of infants born at term (P < .001). Abnormal positive potentials were identified in 57% of infants with documented hypoxia and 11% of children with no episodes (P < .001). Otoacoustic emissions were present in 48% of infants from the neonatal intensive care unit, despite their hearing loss. Conclusion: Both otoacoustic emissions and abnormal positive potentials may originate from outer hair cell activity following inner hair cell loss. This may occur in more than 40% of hearing-impaired children in the neonatal intensive care unit setting. Chronic hypoxia is the most likely cause. Otoacoustic emissions testing may not be a suitable screening tool for such infants. [source] Regulation of cerebral blood flow in mammals during chronic hypoxia: a matter of balanceEXPERIMENTAL PHYSIOLOGY, Issue 2 2010Philip N. Ainslie Respiratory-induced changes in the partial pressures of arterial carbon dioxide and oxygen play a major role in cerebral blood flow (CBF) regulation. Elevations in (hypercapnia) lead to vasodilatation and increases in CBF, whereas reductions in (hypocapnia) lead to vasoconstriction and decreases in CBF. A fall in (hypoxia) below a certain threshold (<40,45 mmHg) also produces cerebral vasodilatation. Upon initial exposure to hypoxia, CBF is elevated via a greater relative degree of hypoxia compared with hypocapnia. At this point, hypoxia-induced elevations in blood pressure and loss of cerebral autoregulation, stimulation of neuronal pathways, angiogenesis, release of adenosine, endothelium-derived NO and a variety of autocoids and cytokines are additional factors acting to increase CBF. Following 2,3 days, however, the process of ventilatory acclimatization results in a progressive rise in ventilation, which increases and reduces , collectively acting to attenuate the initial rise in CBF. Other factors acting to lower CBF include elevations in haematocrit, sympathetic nerve activity and local and endothelium-derived vasoconstrictors. Hypoxia-induced alterations of cerebrovascular reactivity, autoregulation and pulmonary vascular tone may also affect CBF. Thus, the extent of change in CBF during exposure to hypoxia is dependent on the balance between the myriad of vasodilators and constrictors derived from the endothelium, neuronal innervations and perfusion pressure. This review examines the extent and mechanisms by which hypoxia regulates CBF. Particular focus will be given to the marked influence of hypoxia associated with exposure to high altitude and chronic lung disease. The associated implications of these hypoxia-induced integrative alterations for the regulation of CBF are discussed, and future avenues for research are proposed. [source] Arteriolar Remodeling Following Ischemic Injury Extends from Capillary to Large Arteriole in the MicrocirculationMICROCIRCULATION, Issue 5 2008Alexander M. Bailey ABSTRACT Objective: Skeletal muscle vasculature undergoes arteriogenesis to restore tissue perfusion and function following loss of blood flow. This process has been shown to occur in large vessels following ischemia, although recent studies suggest this may occur in the microcirculation as well. We tested the hypothesis that ischemia induces microvascular remodeling in the skeletal muscle microcirculation on the scale of capillary to sub-35 ,m diameter arterioles. Methods: Ligations of a feeding arteriole to the caudal-half of the spinotrapezius muscle were performed on C57BL/6 mice. At 5 days, microvascular remodeling responses were quantified using intravital and whole-mount confocal microscopy. Immunohistochemistry was performed to visualize vessels, incorporated leukocytes, and regions of hypoxia. Results: Ischemic tissue underwent localized microvascular remodeling characteristic of arteriogenesis, including pronounced vessel tortuosity. In patent microvessels (diameters 15,35 ,m), we observed increases in vascular density (38%), branching (90%) and collateral development (36.5%). The formation of new arterioles (diameters 6,35 ,m) increased by 24.3%, while chronic hypoxia was absent from all tissues. Conclusions: Ischemic injury induces arteriogenesis in skeletal muscle microcirculation. Furthermore, this surgical model enables en face analysis of microcirculatory adaptations with single-cell resolution and can provide investigators with morphometric data on a microscale that is difficult to achieve using other models. [source] Role of Vascular Heme Oxygenase in Reduced Myogenic Reactivity Following Chronic HypoxiaMICROCIRCULATION, Issue 2 2006JAY S. NAIK ABSTRACT Objective: Exposure to chronic hypoxia (CH) results in a persistent endothelium-dependent vascular smooth muscle hyperpolarization that diminishes vasoconstrictor reactivity. Experiments were performed to test the hypothesis that products of both cytochrome P450 epoxygenase (CYP) and heme oxygenase (HO) are required for the persistent diminished myogenic reactivity following CH. Methods: The authors examined myogenic responses of mesenteric arteries isolated from control and CH (48 h; PB = 380 mmHg) rats in the presence of a HO inhibitor (zinc protoporphyrin IX; ZnPPIX) or combined HO and CYP epoxygenase inhibition (sulfaphenazole). Arteries were isolated and cannulated and the vascular smooth muscle was loaded with the Ca2 + indicator Fura-2. Results: Control vessels maintained their internal diameter in response to step increases in intraluminal pressure, whereas arteries from CH animals passively distended. ZnPPIX augmented myogenic reactivity and [Ca2 +] in arteries from CH animals. Combined administration of sulfaphenazole and ZnPPIX did not have an additional effect compared to ZnPPIX alone. Myogenic reactivity in control vessels was not altered by ZnPPIX or ZnPPIX + sulfaphenazole. Conclusions: HO appears to play a role in regulating myogenic reactivity following CH. Furthermore, these data suggest that products of HO and CYP are both required for the observed attenuation in vasoreactivity following CH. [source] Blunted effect of the Kv channel inhibitor on pulmonary circulation in Tibetan sheep: A model for studying hypoxia and pulmonary artery pressure regulationRESPIROLOGY, Issue 1 2004Takeshi Ishizaki Objective: The aim of this study was to assess the effect of 4-aminopyridine, a Kv channel inhibitor, on the pulmonary circulation of Tibetan sheep. It has been reported that chronic hypoxia downregulates the 4-aminopyridine (4AP)-sensitive Kv channel (which governs the membrane potential (Em) of pulmonary vascular smooth muscle cells in pulmonary vessels) without a change in 4AP sensitivity. Methodology: Pulmonary haemodynamic indices and blood gas analyses were measured in six young male animals in an altitude chamber that was adjusted to simulated altitudes of 0 m, 2260 m, and 4500 m. Drip infusion of 4AP, 10 mg/h for 3 h, was started and continued during the study. Results: With the increase in altitude mean pulmonary artery pressure increased and mean Pao2 decreased. 4AP had no effect on the levels of mean PPA, mean pulmonary artery wedge pressure, cardiac output, and mean PaO2, mean PaCO2, and mean pH at any altitude but tended to alter heart rate and mean arterial pressure at altitudes of 2260 m and 4500 m. Conclusion: It is concluded that the 4AP-sensitive Kv channel does not play a role in pulmonary vascular tone in high-altitude active Tibetan sheep. Their pulmonary vascular oxygen sensing appears not to involve Kv channels. [source] On the mechanisms that limit oxygen uptake during exercise in acute and chronic hypoxia: role of muscle massTHE JOURNAL OF PHYSIOLOGY, Issue 2 2009José A. L. Calbet Peak aerobic power in humans () is markedly affected by inspired O2 tension (). The question to be answered in this study is what factor plays a major role in the limitation of muscle peak in hypoxia: arterial O2 partial pressure () or O2 content ()? Thus, cardiac output (dye dilution with Cardio-green), leg blood flow (thermodilution), intra-arterial blood pressure and femoral arterial-to-venous differences in blood gases were determined in nine lowlanders studied during incremental exercise using a large (two-legged cycle ergometer exercise: Bike) and a small (one-legged knee extension exercise: Knee) muscle mass in normoxia, acute hypoxia (AH) () and after 9 weeks of residence at 5260 m (CH). Reducing the size of the active muscle mass blunted by 62% the effect of hypoxia on in AH and abolished completely the effect of hypoxia on after altitude acclimatization. Acclimatization improved Bike peak exercise from 34 ± 1 in AH to 45 ± 1 mmHg in CH (P < 0.05) and Knee from 38 ± 1 to 55 ± 2 mmHg (P < 0.05). Peak cardiac output and leg blood flow were reduced in hypoxia only during Bike. Acute hypoxia resulted in reduction of systemic O2 delivery (46 and 21%) and leg O2 delivery (47 and 26%) during Bike and Knee, respectively, almost matching the corresponding reduction in . Altitude acclimatization restored fully peak systemic and leg O2 delivery in CH (2.69 ± 0.27 and 1.28 ± 0.11 l min,1, respectively) to sea level values (2.65 ± 0.15 and 1.16 ± 0.11 l min,1, respectively) during Knee, but not during Bike. During Knee in CH, leg oxygen delivery was similar to normoxia and, therefore, also in spite of a of 55 mmHg. Reducing the size of the active muscle mass improves pulmonary gas exchange during hypoxic exercise, attenuates the Bohr effect on oxygen uploading at the lungs and preserves sea level convective O2 transport to the active muscles. Thus, the altitude-acclimatized human has potentially a similar exercising capacity as at sea level when the exercise model allows for an adequate oxygen delivery (blood flow ×), with only a minor role of per se, when is more than 55 mmHg. [source] During hypoxic exercise some vasoconstriction is needed to match O2 delivery with O2 demand at the microcirculatory levelTHE JOURNAL OF PHYSIOLOGY, Issue 1 2008Carsten Lundby To test the hypothesis that the increased sympathetic tonus elicited by chronic hypoxia is needed to match O2 delivery with O2 demand at the microvascular level eight male subjects were investigated at 4559 m altitude during maximal exercise with and without infusion of ATP (80 ,g (kg body mass),1 min,1) into the right femoral artery. Compared to sea level peak leg vascular conductance was reduced by 39% at altitude. However, the infusion of ATP at altitude did not alter femoral vein blood flow (7.6 ± 1.0 versus 7.9 ± 1.0 l min,1) and femoral arterial oxygen delivery (1.2 ± 0.2 versus 1.3 ± 0.2 l min,1; control and ATP, respectively). Despite the fact that with ATP mean arterial blood pressure decreased (106.9 ± 14.2 versus 83.3 ± 16.0 mmHg, P < 0.05), peak cardiac output remained unchanged. Arterial oxygen extraction fraction was reduced from 85.9 ± 5.3 to 72.0 ± 10.2% (P < 0.05), and the corresponding venous O2 content was increased from 25.5 ± 10.0 to 46.3 ± 18.5 ml l,1 (control and ATP, respectively, P < 0.05). With ATP, leg arterial,venous O2 difference was decreased (P < 0.05) from 139.3 ± 9.0 to 116.9 ± 8.4,1 and leg was 20% lower compared to the control trial (1.1 ± 0.2 versus 0.9 ± 0.1 l min,1) (P= 0.069). In summary, at altitude, some degree of vasoconstriction is needed to match O2 delivery with O2 demand. Peak cardiac output at altitude is not limited by excessive mean arterial pressure. Exercising leg is not limited by restricted vasodilatation in the altitude-acclimatized human. [source] Economy of locomotion in high-altitude Tibetan migrants exposed to normoxiaTHE JOURNAL OF PHYSIOLOGY, Issue 2 2005Claudio Marconi High-altitude Tibetans undergo a pattern of adaptations to chronic hypoxia characterized, among others, by a more efficient aerobic performance compared with acclimatized lowlanders. To test whether such changes may persist upon descent to moderate altitude, oxygen uptake of 17 male Tibetan natives lifelong residents at 3500,4500 m was assessed within 1 month upon migration to 1300 m. Exercise protocols were: 5 min treadmill walking at 6 km h,1 on increasing inclines from +5 to +15% and 5 min running at 10 km h,1 on a +5% grade. The data (mean ±s.e.m.) were compared with those obtained on Nepali lowlanders. When walking on +10, +12.5 and +15% inclines, net of Tibetans was 25.2 ± 0.7, 29.1 ± 1.1 and 31.3 ± 0.9 ml kg,1 min,1, respectively, i.e. 8, 10 and 13% less (P < 0.05) than that of Nepali. At the end of the heaviest load, blood lactate concentration was lower in Tibetans than in Nepali (6.0 ± 0.9 versus 8.9 ± 0.6 mm; P < 0.05). During running, of Tibetans was 35.1 ± 0.8 versus 39.3 ± 0.7 ml kg,1 min,1 (i.e. 11% less; P < 0.01). In conclusion, during submaximal walking and running at 1300 m, Tibetans are still characterized by lower aerobic energy expenditure than control subjects that is not accounted for by differences in mechanical power output and/or compensated for by anaerobic glycolysis. These findings indicate that chronic hypoxia induces metabolic adaptations whose underlying mechanisms still need to be elucidated, that persist for at least 1 month upon descent to moderate altitude. [source] Changes in ventral head width, a discriminating shape factor among African cichlids, can be induced by chronic hypoxiaBIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 3 2009HENDRIKUS A. RUTJES A massive enlargement of the gill surface proved to be an important factor in the hypoxia survival of young cichlids. Because the heads of cichlids are densely packed with structures related to both feeding and breathing, we hypothesized that the extra space needed for gill enlargement requires such large structural reorganizations that outer head shape is affected. We used a three-dimensional model to describe changes in the outer head shape of cichlids. Broods of cichlids of different phylogenetic lineages, habitats, and trophic specialization were split and raised at either 10% or 80,90% air saturation. Despite the above-mentioned differences between the species that were used, all hypoxia raised groups showed similar volume enlargements. Volume increases were most prominent in the ventral suspensorial and ventral opercular subcompartments. A relation with the enlarged gills of hypoxia raised fish is likely because the gills are mainly located in these compartments. The differences in ventral width correspond to those found in other studies comprising a wide variety of genotypic and phenotypic variations. The present study shows that such variation in the ventral width is conceivable by phenotypic plasticity alone. © 2009 The Linnean Society of London, Biological Journal of the Linnean Society, 2009, 98, 608,619. [source] | |||||||||||||