Periods Of Hypoxemia Research Articles

Racial effects on Masimo pulse oximetry: a laboratory study

Recent publications have suggested that pulse oximeters exhibit reduced accuracy in dark-skinned patients during periods of hypoxemia. Masimo SET® (Signal Extraction Technology®) has been designed, calibrated, and validated using nearly equal numbers of dark and light skinned subjects, with the goal of eliminating differences between pulse oximetry saturation (SpO2) and arterial oxygen saturation (SaO2) values due to skin pigmentation. The accuracy concerns reported in dark-skinned patients led us to perform a retrospective analysis of healthy Black and White volunteers. Seventy-five subjects who self-identified as being racially Black or White underwent a desaturation protocol where SaO2 values were decreased from 100 to 70%, while simultaneous SpO2 values were recorded using Masimo RD SET® sensors. Statistical bias (mean difference) and precision (standard deviation of difference) were − 0.20 ± 1.40% for Black and − 0.05 ± 1.35% for White subjects. Plots of SpO2 versus SaO2 show no significant visible differences between races throughout the saturation range from 70 to 100%. Box plots grouped in 1% saturation bins, from 89–96%, and plotted against concomitant SaO2 values, show that occult hypoxemia (SaO2 < 88% when SpO2 = 92–96%) occurred in only 0.2% of White subject data pairs, but not in any Black subjects. There were no clinically significant differences in bias (mean difference of SpO2-SaO2) found between healthy Black and White subjects. Occult hypoxemia was rare and did not occur in Black subjects. Masimo RD SET® can be used with equal assurance in people with dark or light skin. These laboratory results were obtained in well-controlled experimental conditions in healthy volunteers—not reflecting actual clinical conditions/patients.

Automated closed-loop versus standard manual oxygen administration after major abdominal or thoracic surgery: an international multicentre randomised controlled study.

Hypoxaemia and hyperoxaemia may occur after surgery, with related complications. This multicentre randomised trial evaluated the impact of automated closed-loop oxygen administration after high-risk abdominal or thoracic surgeries in terms of optimising the oxygen saturation measured by pulse oximetry time within target range. After extubation, patients with an intermediate to high risk of post-operative pulmonary complications were randomised to "standard" or "automated" closed-loop oxygen administration. The primary outcome was the percentage of time within the oxygenation range, during a 3-day frame. The secondary outcomes were the time with hypoxaemia and hyperoxaemia under oxygen. Among the 200 patients, time within range was higher in the automated group, both initially (≤3 h; 91.4±13.7% versus 40.2±35.1% of time, difference +51.0% (95% CI -42.8-59.2%); p<0.0001) and during the 3-day period (94.0±11.3% versus 62.1±23.3% of time, difference +31.9% (95% CI 26.3-37.4%); p<0.0001). Periods of hypoxaemia were reduced in the automated group (≤3 days; 32.6±57.8 min (1.2±1.9%) versus 370.5±594.3 min (5.0±11.2%), difference -10.2% (95% CI -13.9--6.6%); p<0.0001), as well as hyperoxaemia under oxygen (≤3 days; 5.1±10.9 min (4.8±11.2%) versus 177.9±277.2 min (27.0±23.8%), difference -22.0% (95% CI -27.6--16.4%); p<0.0001). Kaplan-Meier analysis depicted a significant difference in terms of hypoxaemia (p=0.01) and severe hypoxaemia (p=0.0003) occurrence between groups in favour of the automated group. 25 patients experienced hypoxaemia for >10% of the entire monitoring time during the 3 days within the standard group, as compared to the automated group (p<0.0001). Automated closed-loop oxygen administration promotes greater time within the oxygenation target, as compared to standard manual administration, thus reducing the occurrence of hypoxaemia and hyperoxaemia.

The effect of OSAHS on middle ear and inner ear vestibule function advances

Obstructive sleep apnea hypopnea syndrome(OSAHS) as a common frequentlyoccurring disease, it can cause repeated episodes of hypoxaemia and hypercapnia during sleep. With long period of hypoxaemia, obvious pathological changes and dysfunction emerged in heart，brain and lung then all kinds of clinical symptoms appear. Because of the middle ear and inner ear themselves anatomical characteristics and blood supply of regulating mechanism， they often has been damaged before the other important organ damage. As scholars have indepth study of the auditory system complications in patients with OSAHS, various influence of OSAHS on the middle ear，inner ear also gradually be known.This paper will review the effect of OSAHS on middle ear， inner ear and vestibule function, hope to have some application value for clinical work.

Hypoventilation in the Mdx Mouse Model of Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a fatal genetic disease caused by a lack of the structural protein dystrophin. Patients have severe muscle wasting and chronic respiratory insufficiency. Hypoventilation and sleep disordered breathing are both common features of the disease and are known to culminate in periods of hypoxaemia and hypercapnia. There is a paucity of information regarding the control of breathing in animal models of DMD. We measured ventilation, oxygen consumption (VO2) and carbon dioxide (VCO2) production in freely behaving mdx (dystrophin deficient; n=11) and wild‐type (WT; n=10) mice at 8 weeks of age. qRT‐PCR was used to examine inflammation and hypoxia associated gene expression in diaphragm muscle from WT and mdx mice. Minute ventilation (VE; whole‐body plethysmography) was significantly reduced in mdx mice compared with WT controls (30% reduction). There was no significant difference in VO2 and VCO2 when expressed in absolute terms. Carotid sinus nerve unitary discharge was significantly depressed during normoxia in mdx (n=6) compared with WT (n=6) ex vivo perfused preparations. NF‐kB and TNF‐α mRNA expression were both significantly increased in mdx diaphragm compared with WT. HIF‐1α was significantly increased, while HIF‐2α was significantly decreased in mdx diaphragm muscle. Young mdx mice hypoventilate during air breathing (decreased VE/VCO2), which likely relates to reduced carotid body discharge during normoxia. Mdx diaphragm muscle is in a pro‐inflammatory state and there is differential expression of hypoxia associated genes. We reveal that respiratory control is altered in the mdx mouse model of DMD at a young age.Support or Funding InformationFunded by the Department of Physiology, School of Medicine, University College Cork and Muscular Dystrophy Ireland.

Evidence of hypoxic tolerance in weak upper airway muscle from young mdx mice

Duchenne muscular dystrophy (DMD) is a genetic disease characterised by deficiency in the protein dystrophin. The respiratory system is weakened and patients suffer from sleep disordered breathing and hypoventilation culminating in periods of hypoxaemia. We examined the effects of an acute (6h) hypoxic stress on sternohyoid muscle function (representative pharyngeal dilator). 8 week old male, wild-type (WT; C57BL/10ScSnJ; n=18) and mdx (C57BL/10ScSn-Dmdmdx/J; n=16) mice were exposed to sustained hypoxia (FIO2=0.10) or normoxia. Muscle functional properties were examined ex vivo. Additional WT (n=5) and mdx (n=5) sternohyoid muscle was exposed to an anoxic challenge. Sternohyoid dysfunction was observed in mdx mice with significant reductions in force and power. Following exposure to the acute in vivo hypoxic stress, WT sternohyoid muscle showed evidence of functional impairment (reduced force, work and power). Conversely, mdx sternohyoid showed an apparent tolerance to the acute hypoxic stress. This tolerance was not maintained for mdx following a severe hypoxic stress. A dysfunctional upper airway muscle phenotype is present at 8 weeks of age in the mdx mouse, which may have implications for the control of airway patency in DMD. Hypoxic tolerance in mdx respiratory muscle is suggestive of adaptation to chronic hypoxia, which could be present due to respiratory morbidity. We speculate a role for hypoxia in mdx respiratory muscle morbidity.

Absence of inflammatory lung injury in rabbits challenged intravascularly with complement-derived chemotactic factors.

Systemic activation of the complement system results in the generation of chemotactic factors that have been suggested to play a role in the pathogenesis of inflammatory pulmonary diseases such as the adult respiratory distress syndrome. This led us to ask whether systemic complement activation by cobra venom factor (CVF) or intravascularly administered zymosan-activated rabbit plasma (ZAP) or rabbit C5a would result in lung injury. As had been described previously for CVF and ZAP, intravenously administered rabbit C5a also caused an acute neutropenia along with sequestration of neutrophils within the pulmonary vasculature. However, no significant lung inflammation as measured by neutrophil emigration or increased vascular permeability occurred with any of the three stimuli. Only when these agents were combined with anesthesia, surgical manipulation, and intubation did significant neutrophil emigration into alveoli occur, but again without any change in vascular permeability. After administration of ZAP, a decrease in dynamic compliance and an increase in pulmonary resistance as well as a transient period of hypoxemia occurred that was not observed after CVF or rabbit C5a treatment. Thus, our studies suggest that changes in lung function after ZAP instillation may not represent changes from complement activation alone in that they are not reproduced with CVF or rabbit C5a. We conclude that complement activation, as an isolated event, may be an insufficient insult in the lung to produce significant lung injury.

Clinical features of measles pneumonia in adults: usefulness of computed tomography

The clinical features, chest radiographs and computed tomographic (CT) images were evaluated in 11 cases with serologically proved adult measles complicated with pneumonia (10 were previously healthy and one had sarcoidosis). Pneumonia appeared during the rash period in all cases. Respiratory symptoms were cough (9/11), dyspnea (3/11), and hypoxemia (10/11). Pneumonia manifestations were detected in only 4 cases by chest radiograph; on the other hand, they were seen in all cases by CT scan and consisted of ground-glass opacities (73%), nodular opacities (64%) and consolidation (27%). CT seems to be a useful method to detect measles pneumonia if it is suspected. Measles pneumonia in previously healthy patients had a good prognosis, as the hypoxemia disappeared within 6 days in all cases. The sarcoidosis patient showed prolonged pneumonic shadows and period of hypoxemia. Measles pneumonia occurring in a host with cellular immunodeficiency may have a severe clinical course.

Acute Hypoxemia Increases Cardiovascular Baroreceptor Sensitivity in Humans

We postulated that acute hypoxemia increases susceptibility to orthostatic hypotension by increasing the sensitivity of cardiovascular baroreceptors. Hemodynamics were measured noninvasively in 17 healthy, normotensive subjects while being subjected to decreasing venous return by exposure to lower body negative pressure (LBNP) and breathing either a normobaric normoxic (21% O2) or normobaric hypoxic (12% O2) gas mixture. Hypoxia variably decreased hemoglobin saturation (in percent+/-SEM, from 99%+/-1% to 87%+/-2%, P<.01). Incremental increases in LBNP to -50 mm Hg significantly lowered systolic blood pressure (BP), pulse pressure (PP), forearm blood flow (FBF), and increased heart rate (HR). Hypoxia significantly increased baseline systolic BP, PP, and HR. The maximum change in HR in response to LBNP-induced reductions in PP increased during acute hypoxemia (maximum DeltaHR/DeltaPP, in +/-SEM) from 1.32+/-0.18 beats/min/mm Hg v 1.91+/-0.25 beats/min/mm Hg, P<.05. Those subjects who had the most hemoglobin desaturation during hypoxia, when compared to those subjects who desaturated minimally, had greater systolic BP at rest (128+/-3 mm Hg v 114+/-3 mm Hg, P=.05) and during LBNP (115+/-4 mm Hg v 100+/-1 mm Hg, P=.01). Acute hypoxia increased compensatory HR responses to LBNP-dependent reductions in BP. Those normotensive individuals with higher BP at rest and during LBNP developed greater degrees of hypoxia-induced hemoglobin desaturation. Patients with sleep apnea with periods of hypoxemia are prone to hypertension; more important, patients with higher BPs also demonstrate greater degrees of hypoxia-induced desaturation of oxyhemoglobin.

Intraoperative jet ventilation during aortic coarctation repair in an infant

The patient was a 7-week-old, 1,930-g female triplet born at a gestational age of 32 and 3/7 weeks. The birth weight was 1,330 g. Immediately after birth, echocardiography revealed a large patent ductus arteriosus and an isolated short-segment aortic coarctation. Past surgical history included a colostomy shortly after birth for imperforate anus. Additional neonatal issues included ventilatory support for 2 to 3 days, grade I intraventricular hemorrhage, and occasional episodes of apnea and bradycardia. At 7 weeks of age and a weight of 1,930 g, elective repair of the coarctation and ligation of the patent ductus arteriosus were planned. An arterial blood gas obtained while breathing room air, 24 hours before coming to the operating room, revealed pH 7.38, PaCO2 49 mmHg, PaO2 86 mmHg, and bicarbonate 28.1 mEq/L with an oxygen saturation of 96%. The preoperative chest x-ray was negative for pulmonary infiltrates. For the case, an Ohmeda 210 SE anesthesia machine (Madison, WI) was used. The infant was held nil per os for 6 hours, and intravenous fluids of 5% dextrose in 1/2 normal saline were administered at a maintenance rate of 8 mL/h. After transport to the operating room, standard ASA monitors plus a transcutaneous CO2 monitor (TCM-3; Radiometer, Copenhagen, Denmark) were placed. The pulse oximeter probe was placed around the right hand. Glycopyrrolate (0.05 mg) was administered intravenously. Anesthetic induction consisted of fentanyl (incremental doses to a total of 10 g/kg) followed by neuromuscular blockade with cisatracurium to facilitate tracheal intubation with a 3.0-mm endotracheal tube (ETT). An audible airleak was noted at 18 cmH2O. The ETT was taped at 8 cm at the alveolar ridge. A right radial arterial catheter and a second peripheral intravenous catheter were placed. The patient was positioned in the right lateral decubitus position and prepared for surgery. The patient tolerated surgical incision without changes in her hemodynamic status. Anesthesia was supplemented as needed with isoflurane (expired concentration 0.2%-0.3%) and intermittent doses of cisatracurium administered to provide ongoing neuromuscular blockade. Initial ventilatory management included positive-pressure ventilation with a fraction of inspired oxygen concentration (FIO2) of 1.0, rate of 34 breaths/min, inspiratory-to-expiratory ratio of 1:2, and a peak inflating pressure (PIP) of 26 cmH2O, which provided adequate chest excursion. The oxygen saturation measured by pulse oximetry was 100%, and the transcutaneous CO2 was 32 to 36 mmHg. During surgical manipulation of the lung on the operative side to obtain surgical visualization of the coarctation, there were frequent episodes of oxygen desaturation into the 60% to 70% range, which resolved with discontinuation of lung retraction. During this time, the transcutaneous CO2 increased to 64 mmHg. Repeat arterial blood gas analysis revealed a pH of 7.23 and a PaCO2 of 62 mmHg. There were persistent episodes of oxygen desaturation despite hand ventilation with a PIP up to 36 to 38 cmH2O, several variations of surgical retractor placement, and assurance of correct ETT placement without inadvertent mainstem intubation. Because of the inability of the surgeon to gain appropriate visualization of the aorta without significant oxygen desaturation, HFJV was started using the Bunnell Life Pulse High-Frequency Ventilator (Bunnell Inc, Salt Lake City, UT) with initial settings of PIP of 30 cmH2O, rate of 420 breaths/min, inspiratory time of 0.02 seconds, and F IO2 of 1.0. Repeat arterial blood gas analysis revealed a pH of 7.57, a PaCO2 of 26 mmHg, PaO2 of 382 mmHg, and a bicarbonate of 24.4 mEq/L with an oxygen saturation of 100%. There were no further oxygen desaturations during lung retraction/compression. Aortic cross-clamp time was 14 minutes, and the aortic coarctation was repaired without difficulty. ABG analysis after release of the cross-clamp revealed a pH of 7.53, a PaCO2 of 26 mmHg, a PaO2 of 460 mmHg, and a bicarbonate of 22 mEq/L. After closure of the thoracotomy, the patient was returned to conventional mechanical ventilation without consequence. The infant’s trachea was extubated on the first postoperative day. The remainder of the postoperative course was unremarkable. DISCUSSION Thoracic surgical procedures may require alterations in ventilatory management to allow for adequate visualization. In the majority of cases, this is accomplished by using techniques of one-lung ventilation or merely retraction/compression of the lung to avoid interference with surgical visualization. Although, in most circumstances, these techniques are well tolerated without periods of hypoxemia; in rare instances, patients may not tolerate these alterations in respiratory mechanics. In the authors’ patient, retraction or compression of the lung on the operative side resulted in hypoxemia and hypercarbia, which necessitated re-expansion of the lung to allow for adequate ventilation and oxygenation. When several different maneuvers of conventional ventilation failed, HFJV provided adequate ventilation and oxygenation without impairing surgical visualization. In such circumstances, before using HFJV, appropriate maneuvers to rule out mainstem intubation are indicated as well as discontinuation of agents that interfere with hypoxic pulmonary vasoconstriction.

Acute Hypoxemia Does Not Increase the Oxidative Stress in Resting and Contracting Muscle in Humans

In healthy humans sustaining static handgrip at 60% of maximal voluntary contraction (MVC) until exhaustion, we measured the venous blood concentration of reduced ascorbic acid (RAA) and thiobarbituric acid reactive substances (TBARS), respectively, used as markers of the post-exercise oxidative stress and lipid peroxidation. Measurements were conducted in normoxemia, then during a 30-min period of hypoxemia (PaO 2 =56 mmHg) produced by inhalation of an hypoxic gas mixture. Compared to normoxemia, hypoxemia did not significantly modify the resting concentrations of TBARS and RAA, and did not affect the consumption of ascorbic acid after 60% MVC but suppressed the post-exercise TBARS increase. We conclude that acute hypoxemia does not modify the production of oxygen free radicals after strenuous static efforts and even seems to attenuate the lipid peroxidation.

Hypoxemia near mid-gestation has long-term effects on fetal brain development.

We tested the hypotheses that an episode of hypoxemia near mid-gestation in fetal sheep has long-term effects on brain development and that the extent and type of damage is related to the stage of development within a particular brain structure at the time of the hypoxemia. Fetal sheep (n = 8) were made hypoxemic at 90 +/- 2 days (term approximately 147 days) by restricting the maternal blood supply to the placenta for 12 hours (h) using a vascular clamp so as to reduce fetal arterial O2 saturation by 50%-60%. Fetuses were killed 35 days later and the brains analysed histologically and immunohistochemically. Age-matched fetuses (n = 8) were used as controls. Gross brain damage was observed in only 1 fetus, the most acidemic during the period of hypoxemia. There was a reduction of 12% (p < 0.05) in the cross-sectional area of the cerebral cortex in hypoxemic fetuses compared with controls. In lobule 6 of the cerebella of hypoxemic fetuses, significant reductions were seen in (a) the volume density of Purkinje cells (33%), (b) the width of the molecular layer (13%), (c) the area of the inner granule cell layer (13%), (d) the area of the white matter (18%), and (e) the total cross-sectional area (15%). There were also significant reductions in the area of arborization of Purkinje cell dendritic trees (50%), in the branching density (25%), and in the number of dendritic spines (31%). In the ventral hippocampi of hypoxemic fetuses, there was a 36% reduction (p < 0.05) in the volume density of CA1 pyramidal cells and a 50% increase (p < 0.05%) in the number of astrocytes. We conclude that an episode of hypoxemia near mid-gestation reduces neuronal numbers in the hippocampus and cerebellum and probably also in the cerebral cortex. The growth of neural processes in a particular region will be significantly retarded if the hypoxemia occurs at an early stage of the growth of neural processes (e.g. cerebellum) but not if development is well advanced at the time of the insult (e.g. hippocampus). Damage is sustained in the white matter of the cerebral hemispheres if the insult is particularly severe. Together, these deficits could affect neural connectivity and impair postnatal brain function.

Accuracy of noninvasive oxyhemoglobin saturation, end-tidal carbon dioxide concentration, and blood pressure monitoring during experimentally induced hypoxemia, hypotension, or hypertension in anesthetized dogs

SUMMARY Objective To determine reliability of noninvasive methods of arterial oxyhemoglobin saturation (SpO2), end-tidal CO2 concentration (PEtCO2 and blood pressure (BP) determination during periods of hypoxemia and systemic arterial BP perturbations. Animals 7 healthy, conditioned dogs weighing 19 to 22 kg. Procedure 3 pulse oximeters, 2 capnometers, and 2 oscillometric BP monitors were used to measure oxygen-carrying capacity of the blood, heart rate, ventilatory status and arterial BP changes during hypoxemia, and altered arterial BP. Pulse oximeter-derived SpO2 and PEtCO2 were determined during rapidly induced plateaus of hypoxia (decreased fractional inspired oxygen concentration [FiO2) and altered systemic arterial BP. A lead-II ECG was used to monitor heart rate. Results Pulse oximetry provided an accurate assessment of fractional oxyhemoglobin saturation (SaO2) at SpO2 &gt; 70%. As SaO2 decreased from 70%, the magnitude of the SpO2 error increased (20% error at SpO2 &lt; 30%). The PEtCO2 was accurate at PaCO2, ranging from 30 to 55 ± 5 mm of Hg under all experimental conditions. When PaCO2 was &gt; 55 mm of Hg, both capnometers produced values that were as much as 20 mm of Hg less than the corresponding PaCO2. Mean BP was least dependent on pulse wave quality, consistently underestimating mean arterial BP by approximately 10 mm of Hg. Conclusions and Clinical Relevance The pulse oximeters tested provided an accurate estimation of SaO2 at SpO2 &gt; 70%. A PEtCO2 value &gt; 55 mm of Hg may represent hypercapnia that is more profound than indicated. Systolic BP determinations were most accurate during hypotensive states and least accurate during hypertension. Diastolic BP measurements were generally more accurate during hypertension than normotension. Accuracy is not appreciably affected by hypotension resulting from vasodilation or blood loss. The tendency to underestimate systemic arterial BP should not interfere with trend detection during unstable clinical conditions. (Am J Vet Res 1998;59:205–212)

Role of nitric oxide in the regulation of cerebral blood flow in the ovine foetus.

1. Our aim was to determine the role of nitric oxide (NO) in regulating cerebral blood flow (CBF) in foetal sheep under conditions of both hypoxaemia and normoxaemia. 2. Aseptic surgery was performed on 11 pregnant sheep at 125 +/- 1.1 days of gestational age (g.a.) when foetal vascular catheters were implanted for the measurement of CBF using coloured microspheres. Additionally, each ewe was prepared for one of two procedures for inducing foetal hypoxaemia; either an adjustable clamp was placed around the maternal common internal iliac artery to reduce uterine blood flow, or a catheter was implanted into the maternal trachea for insufflation of N2. At 131 +/- 0.3 days g.a., in control foetuses (n = 5), CBF and cerebral vascular resistance (CVR) were measured under basal (normoxaemic) conditions and after 3h of hypoxaemia. In other foetuses (n = 6) CBF and CVR were measured under basal conditions and after 3 h of hypoxaemia; in these foetuses NO synthesis was inhibited with N-nitro-L-arginine (NOLA) between 2-3 h of hypoxaemia. 3. In the hypoxaemia experiments foetal SaO2 and PaO2 were reduced (P < 0.05) in both control and NOLA-treated foetuses, from normoxaemic values of 69.5 +/- 2.1% and 23.8 +/- 1.0 mmHg, respectively, to 29.3 +/- 1.0% and 14.6 +/- 0.4 mmHg during the period of hypoxaemia. In control foetuses, CBF (mL/min) was increased by 82.7% during hypoxaemia; in NOLA-treated foetuses CBF increased by 55.3%, which was less (P < 0.05) than in control foetuses. In control foetuses CVR (mmHg)/ mL/min) was reduced by 43.5% during hypoxaemia, whereas in NOLA-treated foetuses there was no significant change. 4. In five of the 11 foetuses, the role of NO in regulating CBF under basal (normoxaemic) conditions was determined at 132 +/- 0.3 days g.a. Cerebral blood flow and CVR did not significantly change from basal values after NOLA-treatment. 5. We conclude that in foetal sheep NO plays an important role in regulating cerebral vascular tone and hence CBF during hypoxaemia, but its contribution during normoxaemia is less apparent.

Nitric oxide in the developing kidney.

Although nitric oxide (NO) has a well-established role in regulating renal function in the adult, recent studies point to perhaps an even more critical role for NO in maintaining basal renal blood flow (RBF) and glomerular filtration rate (GFR) in the developing kidney. The immature kidney has enhanced renal hemodynamic and functional responses to stimulation and inhibition of NO synthesis when compared with the adult, and these increased responses are not mediated by prostaglandins. Increased intrarenal activity of NO in the developing kidney counter-regulates the highly activated renin angiotensin system by modulating the angiotensin II-mediated vasoconstriction of the developing renal vasculature, the angiotensin II effects on GFR, as well as renin release. Localization studies demonstrate that NO acts on neonatal RBF and stabilization of GFR through an intrarenal distribution of the synthesizing enzyme, nitric oxide synthase, that is different from that of the adult. The developing kidney is dependent on NO to maintain RBF and GFR during periods of hypoxemia, protecting against renal injury, such as acute renal failure. In summary, NO is vital in the developing kidney to maintain normal physiological function and to protect the immature kidney during pathophysiological stress.

The effect on the heart of hypoxaemia in patients with severe coronary artery disease.

The aim of the study was to examine the effect of spontaneous nocturnal hypoxaemia on myocardial ischaemia in patients with severe coronary artery disease. This was a prospective study of continuously measured oxygen saturation and ECG overnight in patients prior to coronary artery bypass graft surgery. Fifteen patients with angiographically proved coronary artery disease were studied between October 1992 and September 1993. All patients had episodes of hypoxaemia with oxygen saturation < 94% and eight of the 15 patients had episodes where oxygen saturation < 85%. An episode was defined as a period of hypoxaemia not less than 2.5 min in duration, the longest total duration of hypoxaemia in one patient being 355 min. Twelve of the 15 patients showed a drop in ST segment of 1 mm or more lasting from 5-700 min. The hypoxaemic and ischaemic episodes apparently occurred at random. No causal relationship could be shown between hypoxaemia and ischaemia.

REGULATION OF WHOLE BLOOD POLYMORPHONUCLEAR LEUKOCYTE PHAGOCYTOSIS FOLLOWING HYPOXEMIA AND HYPOXEMIA/REOXYGENATION

Phagocytosis of whole blood polymorphonuclear leukocytes (PMN) was evaluated following periods of hypoxemia or hypoxemia/reoxygenation. Hypoxemia (O2 saturation 5-20%) significantly increased the percentage of PMN positive for phagocytosis. This effect required mobilization of intracellular Ca2+ stores and was accompanied by a significant increase in CD16, CD32w, and CD35 expression assayed using FITC-labeled Mabs. PMA (10 ng/ml) increased CD32w expression while protein kinase C inhibitors H-7 and staurosporine but not the protein kinase A inhibitor H-9 reversed the effect of hypoxemia on phagocytosis and receptor expression. Further, genistein (tyronsine kinase inhibition) reversed hypoxemia-induced increases in phagocytosis (ID50-50 microM). Reoxygenation (O2 saturation 97-99%) reduced the percentage of PMN positive for phagocytosis back to baseline values without affecting mean channel fluorescence. Reoxygenation reduced CD32w and CD16 expression with kinetics assays demonstrating concordance between reduced phagocytosis and CD32w and CD16 expression. Reoxygenation-induced decreases in CD32w and CD16 expression were prevented if whole blood PMN were incubated with either NaN3 (10 mM), dimethyl sulfoxide (DMSO) (10 mM), or taurine (15 mM) prior to reoxygenation. These results demonstrated that hypoxemia and hypoxemia/reoxygenation recruit and suppress distinct populations of whole blood PMN for phagocytosis. Intracellular kinase activation and Ca2+ mobilization are required for hypoxemia-induced increases in phagocytosis. Reoxygenation reduces whole blood PMN phagocytosis via an oxident-derived reduction of surface CD16 and CD32w expression.

Inhibition of Fetal Breathing: A Pilot Study

Fetal breathing occurs sporadically and is inhibited during periods of hypoxemia, when blood, returning from the placenta, is mainly taking the shortcut through the ductus venosus. The hypothesis tested is that this inhibition might be caused by an expansion of the ductus venosus. Such expansion is pronounced during fetal life but ceases to occur after birth. Regular breathing of newborn lambs was recorded, and it was noted how the breathing was affected when blood, with the aid of a roller pump, was infused from the umbilical arteries into the umbilical veins. Nine lambs were examined, and for a maximal period of 2 min blood was infused into the umbilical veins at a rate of 50-150 mL/min. During 12 infusions, breathing temporarily came to a complete stop; in 30 cases, respiration was only partially inhibited; and in five cases, it was not affected. it is concluded that a very clear breathing inhibition may be obtained with an infusion of blood into the umbilical vein. It is speculated that expansion of the ductus venosus may trigger the inhibition and that the reason the effect varies may have to do with the fact that blood entering the body through the umbilical veins may predominantly take one of two routes: the ductus venosus or the hepatic vessels.

Effect of Hypoxemia and Hypovolemia on Retinal and Choroidal Blood Flow in the Newborn Piglet

The effect of hypoxemia and/or hypovolemia on ocular blood flow was studied in paralyzed and mechanically ventilated newborn piglets with the isotope-labelled microsphere method. Twenty-six piglets were studied in four different groups. One group of piglets (n = 6) was made hypoxemic by breathing 10% O2, a second group (n = 7) and a third group (n = 7) were studied during hypoxemia (10% O2), followed by hypovolemia (bleeding 20 and 30% of estimated blood volume, respectively). A fourth group of piglets (n = 6) was made hypovolemic by bleeding 20% of estimated blood volume. Hypoxemia resulted in a 2- to 3-fold increase in retinal blood flow (RBF), while hypovolemia did not change RBF, not even when preceded by a period of hypoxemia. In the case of choroidal blood flow (ChBF), the increase caused by hypoxemia was only 10-40%. Although ChBF decreased significantly during hypovolemia, no significant correlation between mean arterial blood pressure and ChBF was found. The results indicate that autoregulation is normally seen in RBF, but probably not in ChBF. However, during hypoxemia autoregulation was found neither in RBF nor in ChBF.

HYPOXEMIA DURING ORAL FEEDING OF CHILDREN WITH SEVERE CEREBRAL PALSY

Oral feeding of children with severe dysphagia and multiple disabilities may result in hypoxemia. Pulse oximetry was used to monitor hemoglobin saturation (SpO2) during oral feeding of five children with multiple disabilities who were referred because of food refusal or coughing and fatigue during feeding. Modified barium videofluoroscopic swallow studies demonstrated deglutition abnormalities. SpO2 values were within the normal range at rest, but routine, upright oral feeding resulted in significant degrees of hypoxemia. The pharyngeal stage of deglutition was abnormal in all five children. In three, the periods of hypoxemia were dependent on food texture. Awareness of meal-time hypoxemia contributed to the decision to use gastrostomy-tube feedings for the other two children. Pulse oximetry during oral feeding should be considered for all children with severe dysphagia and multiple disabilities.

Sympathoadrenal responses during hypoglycemia, hyperinsulinemia, and hypoxemia in the ovine fetus

Interrelations of sympathoadrenal function and changes in glucose and insulin homeostasis were studied in chronically cannulated late gestation fetal sheep. Catecholamine secretory rates (based on direct adrenal sampling) and plasma concentrations were determined in the fetus during 2 h of insulin-induced hypoglycemia, during a period of hypoxemia, and during hyperinsulinemia per se (i.e., without hypoglycemia). Fetal insulin infusion (5-10 mU.kg-1.min-1) resulted in hypoglycemia and a significant rise in secretion of epinephrine but not of norepinephrine. By contrast, fetal hypoxemia caused a prompt and significant increase in adrenal secretion of both norepinephrine and epinephrine. Changes in peripheral plasma catecholamine levels were usually, but not always, qualitatively similar to those in adrenal secretion; the latter was a far more sensitive indicator of adrenal function. Hyperinsulinemia per se caused no change in adrenal secretory rates or plasma concentrations of catecholamines. Nevertheless, insulin infusion caused a fetal tachycardia even in the absence of hypoglycemia and hypoxemia, suggesting either a direct effect on the heart or stimulation of sympathetic nerves.