Start Of Hypoxia Research Articles

Detection of hypoxia by near-infrared spectroscopy and pulse oximetry: a comparative study.

.Significance: Pulse oximetry is widely used in clinical practice to monitor changes in arterial oxygen saturation (). However, decreases in can be delayed relative to the actual clinical event, and near-infrared spectroscopy (NIRS) may detect alterations in oxygenation earlier than pulse oximetry, as shown in previous cerebral oxygenation monitoring studies.Aim: We aim to compare the response of transcutaneous muscle NIRS measures of the tissue saturation index with pulse oximetry during hypoxia.Approach: Episodes of acute hypoxia were induced in nine anesthetized Yucatan miniature pigs. A standard pulse oximeter was attached to the ear of the animal, and a transcutaneous NIRS sensor was placed on the hind limb muscle. Hypoxia was induced by detaching the ventilator from the animal and reattaching it once the pulse oximeter reported 70% .Results: Twenty-four episodes of acute hypoxia were analyzed. Upon the start of hypoxia, the transcutaneous NIRS measures changed in , whereas the pulse oximetry measures changed in ().Conclusions: Transcutaneous muscle NIRS can detect the effects of hypoxia significantly sooner than pulse oximetry in the Yucatan miniature pig. A transcutaneous NIRS sensor may be used as an earlier detector of oxygen saturation changes in the clinical setting than the standard pulse oximeter.

0739 Cerebrovascular Response to Intermittent Hypoxia During Sleep in OSA Patients

Abstract Introduction Obstructive sleep apnea (OSA) is associated with increased risks of cerebrovascular accidents, but it remains unclear how OSA impacts the cerebral vasculature. Intermittent hypoxia is a hallmark feature of OSA and recurs throughout sleep. In awake humans, the cerebrovascular response to intermittent hypoxia has been well characterized, as an increase of blood perfusion that begins at least a few seconds after the start of hypoxia. Functional magnetic resonance imaging (fMRI) that measures the blood oxygen level dependent (BOLD) signal has revealed significant differences between the cerebrovascular responses in awake humans with and without OSA. However, intermittent hypoxia occurs primarily during sleep in OSA, yet the cerebrovascular response to intermittent hypoxia has not been studied during sleep. Methods Eight adult patients with severe OSA were recruited to this study. Each subject first underwent an acclimatization session in which they tried to sleep in the MRI scanner while listening to sound recordings of the fMRI. Each acclimatized subject then underwent an overnight study in which T2*-weighed BOLD fMRI of the whole brain was conducted for 1.5-3 hours in total (TE: 35 ms, TR: 2.0 s, 35 sagittal slices, 3.5 mm isotropic). Oxygen saturation (SaO2), chest movement, end-tidal carbon dioxide and scalp encephalography (EEG) were simultaneously recorded with the fMRI. After rigid-body motion correction and removal of artifacts, the temporal correlation between BOLD signal and the SaO2 signal was analyzed on a voxel-by-voxel basis. Results Four subjects (50%) were acclimatized to sleep in the MRI scanner and completed this study. In all subjects, the BOLD fMRI signal showed an initial decrease corresponding to the decrease of SaO2, followed by a delayed increase corresponding to the hyperperfusion, throughout the gray matter of cerebral cortex. The time course of BOLD fMRI signal was significantly advanced in time, by 2-4 seconds, in the visual cortex compared to the rest of cerebral cortex in all subjects. This phenomenon was also observed in some other brain regions, but not consistently across subjects. Conclusion This study is, to our knowledge, the first study of the cerebrovascular response to intermittent hypoxia during sleep in humans. In patients with OSA, we observed spatiotemporal heterogeneity of the cerebrovascular response, such that the response in the visual cortex was significantly advanced in time than other brain regions. This phenomenon has not been reported before, and future studies are needed to understand how this heterogeneity is associated with OSA. Support (If Any) AASM Foundation

Depression of hypoxic arousal response in adolescent mice following antenatal vasoactive intestinal polypeptide blockade.

Late-gestation blockade of vasoactive intestinal polypeptide (VIP) activity in pregnant mice produces discrete morphological abnormalities in the somatosensory cortex of offspring. We investigated the functional implications of this lesion on the behavioural arousal response to moderate hypoxia. Pregnant mice received twice-daily injections of 200 microl saline (control), or saline + 50 microg VIP antagonist (anti-VIP) on embryonic days 17 and 18. Offspring were studied unrestrained at 6-7 weeks after birth, in a bias-flow whole-body plethysmograph during behavioural quiet sleep. Arousal was defined by movement (MVT) lasting > or =1 s. Hypoxic ventilatory (HVR) and arousal responses were measured during a 5 min exposure to 10 % O(2)-3 % CO(2) (hypoxia); peripheral chemoreflex drive was estimated by transient hyperoxia administered at rest and end-hypoxia (Dejours-type test). MVTs increased in all mice during hypoxia, but in anti-VIP mice: (a) MVT onset was delayed (174 +/- 90 vs. 108 +/- 59 s from the start of hypoxia, anti-VIP vs. control; P = 0.008); and (b) MVTs were less frequent, and total MVT time in hypoxia was less (8 +/- 7 vs. 15 +/- 9 %; P = 0.03). The HVR, and peripheral drive at rest and end-hypoxia were comparable in control and anti-VIP mice. In conclusion, a significant arousal deficit was evident in anti-VIP mice. This was not associated with obviously deranged peripheral or brainstem-mediated responses to hypoxia during sleep. This may signal a general deficit in the way hypoxic distress is monitored and processed, and arousal initiated and sustained in these mice.

Magnetic resonance imaging during cerebral hypoxia-ischemia: T2 increases in 2-week-old but not 4-week-old rats.

We investigated whether the changes detectable with magnetic resonance imaging techniques during and after an episode of cerebral hypoxia-ischemia differ in immature and older brain. Diffusion weighted (DW) and T2-weighted (T2W) images were repeatedly acquired before, during, and after an episode of cerebral hypoxia-ischemia (unilateral carotid artery occlusion plus hypoxia) in 2- and 4-wk-old rats lightly anesthetized with isoflurane. Areas of increased brightness were detected in DW images from both 2- and 4-wk-old rats by 10-20 min after the start of hypoxia. These hyperintense areas increased during hypoxia, comprising 60.8+/-4.9% and 30.5+/-2.7% of the brain image at the level of the thalamus in 2-wk-old and 4-wk-old animals, respectively (p < 0.003). Hyperintense areas (e.g. 27.0+/-8.3%) also appeared in T2W images during hypoxia-ischemia in 2-wk-old animals, but these did not occur in 4-wk-old animals (p < 0.02). This observation was reflected in T2, which increased during hypoxia-ischemia in the 2-wk-old but not the 4-wk-old group. By 60 min after the termination of hypoxia-ischemia in either age group, areas of hyperintensity resolved and then reappeared 24 h later on both DW and T2W images. Thus, irrespective of age, magnetic resonance imaging changes during transient hypoxia-ischemia generally recover with a delayed or secondary increase in DW and T2W hyperintensity hours later. Immature brain differs from older brain primarily with respect to some combination of hypoxic/ischemic cellular or biochemical changes, that are detectable as increases in T2 within 2-wk-old but not 4-wk-old animals.

Ventilatory and Pulmonary Vascular Responses to Acute Hypoxia Are Nonuniform in Healthy Man

The present study was undertaken to examine the pulmonary vascular and ventilatory responses to acute hypoxia in healthy individuals. Pulmonary hemodynamics and minute ventilation (VE) were serially measured during inhalation of 13% O2 for 15 min. There was a wide variability in the pulmonary vascular response to acute hypoxia, and a significant negative correlation between the initial increase in VE after the start of hypoxia (delta VE) and the percent increase in mean pulmonary arterial pressure (r = -0.646; p < 0.01). The fall in arterial oxygen tension significantly decreased in response to an increase in delta VE. These results support the view that a blunted ventilatory response to acute hypoxic stimulation enhances alveolar hypoxia, thereby favoring the constriction of pulmonary vasculature. Thus, our results suggest that the ventilatory response to acute hypoxia plays a significant role in the pulmonary vascular response to acute hypoxia.

Fructose metabolism and cell survival in freshly isolated rat hepatocytes incubated under hypoxic conditions: Proposals for potential clinical use

The protective effect of fructose with regard to hypoxia-induced cell injury was investigated. The addition of fructose (2 to 20 mmol/L) protected hepatocytes against hypoxia-mediated cell lysis in a concentration-dependent way. The intracellular ATP content was initially decreased as a result of fructose-1-phosphate formation, but it remained constant during the hypoxic incubation. Conversely, high initial ATP values observed at low fructose concentrations progressively declined. Cellular protection was observed only when fructose was added before (and not after) the start of hypoxia. In addition, a sufficient amount of fructose-1-phosphate rapidly accumulated before the induction of hypoxia, and the linear production of lactate, during hypoxic incubation, indicated that cells synthesized ATP continuously. The lack of cell protection by fructose added after the onset of the hypoxia may be explained by a lesser fructose-1-phosphate formation and a subsequently low accumulation leading to insufficient glycolytic ATP production. Under aerobic conditions, both glycolysis (lactate formation) and gluconeogenesis (glucose formation) were carried out in fructose-1-phosphate-loaded cells with the same initial rates, whereas under hypoxic conditions glycolysis was the main metabolic event. The fact that protein synthesis activity recovered faster during reoxygenation of previously hypoxic fructose-treated cells than in glucose-treated cells led us to hypothesize that in situ perfusion of liver with fructose, before its removal, would improve its metabolic capacity during the hypoxic cold preservation and subsequent transplantation.

Protective effects of a prostaglandin oligomer on rats exposed to hypoxia

To study the protective effecis of a prostaglandin E 1 oligomer against hypoxia, hypoxia was induced in artificially ventilated rats by replacing the air with 100% nitrogen under anesthesia. Parameters such as survival rate, blood pressure, electrocardiogram, blood lactate, glucose, pH, Po 2, Pco 2, intracellular adenosine triphosphate, and mitochondrial function were studied. A hypoxia time of 3.5 minutes reduced the survival rate to 50%. However, the prehypoxic administration of 6.0 mg/kg of MR-356, an oligomer synthesized from prostaglandin E 1, improved the survival rate to 90%. Similar beneficial effects were also observed when MR-356 was administered either 2 minutes after the start of hypoxia or 30 seconds before the cessation of hypoxia. Systemic parameters were not changed by the administration of the oligomer. The mechanism of action of the oligomer may be to protect membranes during hypoxic insult.

Failure of allopurinol to protect against cerebral injury when given after the start of hypoxia

One cause of ischemic brain injury is free radical formation during recirculation. Allopurinol inhibits xanthine oxidase, an important source of free oxygen radicals. It is known that allopurinol pre-treatment has a protective action during cerebral ischemia. In the present study we exposed slices from the rat hippocampus to 9 minutes of hypoxia to test whether it is sufficient that allopurinol is present in the tissue at the time of reoxygenation. Forty-six slices loaded with allopurinol (10(-5) M) prior to reoxygenation (during hypoxia) were compared to 34 control slices. The response of the pyramidal cell population to orthodromic stimulation was reduced in both groups and there was not a significant difference between the two groups.

Effects of dietary magnesium on pulmonary vascular reactivity and chronic hypoxic pulmonary hypertension in rats

The effects of dietary magnesium (Mg) on pulmonary vascular reactivity and chronic hypoxic pulmonary hypertension were assessed in rats. The rats were fed high magnesium (H-Mg) diet or a regular diet for two months before the start of hypoxia, 10 +/- 0.5% O2 ventilation, 8 h/day, for 14 days running. The plasma level of Mg was significantly increased in the H-Mg group as compared to the controls. Mean pulmonary arterial pressure, pulmonary vascular reactivity to hypoxia and pulmonary vascular resistance were significantly lower in the rats fed H-Mg diet than in those fed regular diet. The weight ratios of the right ventricle to the ending body weight (RV/EBW) and to the left ventricle plus interventricular septum (RV/LV + S) in the rats fed H-Mg diet were remarkably lower as well. No difference was observed in blood viscosity and hematocrit between the H-Mg group and the hypoxic control. The above findings suggest that dietary Mg can attenuate basic pulmonary resistance and hypoxic pulmonary vasoconstriction, thereby preventing the development of chronic hypoxic pulmonary hypertension and right ventricular hypertrophy.

Direct evidence of changes in myofilament responsiveness to Ca2+ during hypoxia and reoxygenation in myocardium

In the presence of 1 microM ryanodine, muscles loaded with the calcium indicator aequorin were stimulated at 15-20 Hz to produce steady levels of force and intracellular Ca2+ concentrations [( Ca2+]i) at various extracellular Ca2+ concentration ([Ca2+]o). After 5, 10, and 15 min of hypoxia and 3 min of reoxygenation, tetani were initiated. Force vs. [Ca2+]i relation was shifted to the right 0.11, 0.18, and 0.24 pCa units, and maximal force was down 66, 48, and 37% after start of hypoxia. During reoxygenation, the relationship was shifted up by 26%. In skinned fiber preparations, an increase in inorganic phosphate ion concentration from 0 to 10 mM and 15 mM decreased maximal force development by 32 and 53%, respectively, and shifted the pCa-force curve to the right by 0.08 and 0.14 pCa. A decrease in pH from 7.1 to 6.8 shifted the pCa-force curve to the right by 0.20 pCa units without affecting maximal force. These changes indicate that during hypoxia, a decrease in the sensitivity of the myofilaments to Ca2+ and a depression of maximal Ca2(+)-activated force occur, whereas during reoxygenation, there is an increase in maximal Ca2(+)-activated force.

Cardiac function during long-term hypoxemia in fetal sheep.

To examine right ventricular function during long-term hypoxemia, we instrumented 12 fetal sheep with intravascular catheters and an electromagnetic flow probe on the pulmonary artery. In six cases, hypoxemia was induced by infusing N2 gas into the maternal trachea for 2 wk. Maternal arterial PO2 was less than 60 Torr, and fetal arterial PO2 was reduced from approximately 26 to approximately 19 Torr. Six cases served as nonhypoxic controls. We studied fetal cardiac function by increasing either preload with a volume infusion of 5% (wt/vol) dextrose or afterload by administering methoxamine (alpha-adrenergic agonist). In hypoxic animals, right ventricular output (QRV) and stroke volume (SV) were not affected on the first 2 days but fell 30% on day 3. Fetal arterial pressure (Pfa) increased 20%, hemoglobin concentration increased approximately 30%, and fetal heart rate (FHR) showed minimal changes. Within 2 wk, QRV recovered to normal values, whereas ventricular sensitivity to arterial pressure was reduced. We observed no change in plasma concentration of "cardiac enzymes" or differences in fetal growth between groups. In conclusion, during prolonged hypoxemia, right ventricular function showed a triphasic response (primary maintenance, secondary depression, and subsequent recovery), achieving a new steady state 2 wk after the start of hypoxia, characterized by decreased sensitivity to afterload, associated with polycythemia and hypertension.

Effect of dietary fish oil on lung lipid profile and hypoxic pulmonary hypertension.

The effects of dietary polyunsaturated fats on chronic hypoxic pulmonary hypertension were assessed in rats fed fish oil, corn oil, or a lower fat, "high-carbohydrate" diet (regular) beginning 1 mo before the start of hypoxia (0.4 atm, n = 30 for each). Mean pulmonary arterial pressures were lower in the chronically hypoxic rats fed fish oil (19.7 +/- 1.8 mm Hg) than in the rats fed corn oil (25.3 +/- 1.6 mm Hg) or regular diets (27.5 +/- 1.5 mm Hg, P less than 0.05). The fish oil diet increased lung eicosapentaenoic acid 50-fold and depleted lung arachidonic acid 60% (P less than 0.0001 for each). Lung thromboxane B2 and 6-ketoprostaglandin F1 alpha levels were lower, and platelet aggregation, in response to collagen, was reduced in rats fed fish oil. Chronically hypoxic rats fed fish oil had lower mortality rates than the other hypoxic rats. They also had lower blood viscosity, as well as less right ventricular hypertrophy and less peripheral extension of vascular smooth muscle to intra-acinar pulmonary arteries (P less than 0.05 for each). The mechanism by which dietary fish oil decreases pulmonary hypertension and vascular remodeling during chronic hypoxia remains uncertain. The finding that a fish oil diet can reduce the hemodynamic and morphological sequelae of chronic hypoxia may have therapeutic significance.

Differential actions on rabbit nodal, atrial, Purkinje cell and ventricular potentials of melperone, a bradycardic agent delaying repolarization: effects of hypoxia.

1 Melperone, a butyrophenone tranquillizer, caused bradycardia in vivo and in vitro. 2 Although Melperone had alpha-adrenoceptor antagonist activity in the pithed rat, it was not a beta-adrenoceptor antagonist, nor was it a cholinoceptor agonist. 3 The bradycardic action could be attributed almost entirely to a prolongation by Melperone of action potential duration (APD) in sinus node cells, with little effect on the slow diastolic depolarization. 4 APD was prolonged by Melperone in atrial and ventricular muscle, and most of all in the bundle of His, but only moderately in the terminal Purkinje cells. 5 In all cardiac tissues depolarized by fast inward current. Melperone caused a dose-related reduction in the maximum rate of depolarization and conduction velocity. On desheathed frog nerve Melperone had a local anaesthetic potency equal to that of procaine. 6 There was no negative inotropic effect in cardiac muscle, nor interference with A-V nodal conduction, from which it was inferred that Melperone did not restrict slow inward current. 7 Melperone did not reduce hypoxic shortening of APD relative to the initial value at the start of hypoxia, but because APD was already lengthened by Melperone in normoxic conditions, APD90 during hypoxia remained close to normal values. There was no protection against hypoxic depression of contractions. 8 It was concluded that Melperone had class 1 and class 3 antiarrythmic actions and merited trial as an antiarrhythmic drug.

Dynamic characteristics of the cardiovascular autonomic effects during severe arterial hypoxia in the unanesthetized rabbit.

The reflex autonomic effects due to inhalation of low concentrations of oxygen (Pao 2 30 mm Hg) were assessed in unanesthetized rabbits from the differences in responses between groups of normal and autonomically "deefferented" rabbits and those with selective effector block. Changes due to autonomic effects were estimated for heart rate, total and regional (portal, renal, muscle, and cutaneous) peripheral resistance, and the rate of epinephrine secretion. The autonomic effects could be described by an early component having a time course similar to the initial vagal effects, where the maximum change occurred soon after the start of hypoxia and then declined to 37% of this value in 5 minutes, and a late component similar to the neural effects in muscle, starting 5 minutes after the start of hypoxia and rising slowly to 63% of the maximum in 15 minutes. Four autonomic effector patterns involving different combinations of early and late components were distinguished: (1) vasoconstriction in the portal and renal beds followed the time course of the sum of early and late components; (2) inhibition of cutaneous constrictor tone was the mirror image of the above response; (3) the biphasic sympathoadrenal effect on heart rate was the sum of a negative early and positive late component; (4) the neural constrictor effect in muscle and the rate of epinephrine secretion had only a late component. The early effects resulted in reduction in cardiac output and major redistribution of peripheral blood flow, probably due to chemoreceptor stimulation. During the late phase, cardiac output rose and blood flow was redistributed further, probably mainly through baroreceptor mechanisms.