Role Of Hypoxemia Research Articles

0700 Prospective and Cross-sectional Associations Between Sleep Apnea and Disease in a Phenome-wide Analysis of a Clinical Biobank

Abstract Introduction The potential contributions of sleep apnea (SA) to the risk of developing many diseases remain unidentified due to survey limits in cohort studies. We aimed to identify novel associations between common comorbidities in participants with SA compared to matched controls in a clinical biobank by leveraging electronic health record (EHR) information informed by natural language processing (NLP)-based phenotyping. We also investigated the relationship between polysomnography (PSG) statistics and these diseases. Methods The sample from the Mass General Brigham Biobank was comprised of 4,876 NLP-defined SA adult cases and 12,314 controls matched on age, biological sex, BMI, race/ethnicity, and healthcare utilization with a “data floor” of minimal EHR information. Prospective (>1 year post SA diagnosis) and cross-sectional analyses considered 527 merged PheCode groups of NLP-defined diseases with ≥1% prevalence. Sex-stratified analyses were also performed. Associations with case/control status were further analyzed using rank-normalized Apnea-hypopnea Index (AHI3p) and the percentage of sleep with hypoxemia <88% (Per88) in 4,544 participants, adjusting for age, biological sex, BMI, and race/ethnicity in a smaller single-night clinic sample (57% with AHI3p ≥15). Results In prospective analyses, 170 diseases had significant odds ratios (OR) when comparing participants with SA versus controls following Bonferroni adjustment (p < 3.3 × 10-5), 8 of which were confirmed using PSG. Lead associations included a broad range of pathophysiology (e.g. chronic pulmonary heart disease, tension headache, and chronic fatigue syndrome). Diseases with higher ORs in women compared to men included chronic pulmonary heart disease, chronic renal failure, congestive heart failure not otherwise specified (NOS), and gout (p for sex interaction ≤3.2 × 10-3). Significant associations with PSG traits included hypertensive heart disease, fluid overload, and heart failure NOS (p ≤7.8 × 10-5). 281 diseases significantly differed in cross-sectional analyses, 41 of which were confirmed using PSG. 37 of these 41 associated diseases had lower p-values for Per88 compared to the AHI3p. Conclusion Sleep apnea may contribute to disease risk across a broad range of pathophysiology, with increased sex-specific risks for multiple common comorbidities. Future work should investigate the specific role of hypoxemia in these associations. Support (If Any) NIH (K01-HL135405, R35-HL135818, U01-HG008685 and P30-AR070253).

Myocardial Fibrosis in Pediatric Patients With Ebstein's Anomaly.

Left ventricular dysfunction in Ebstein's anomaly (EA) is associated with higher mortality. The health of the left ventricular myocardium in children and adolescents with EA has not been investigated in detail. Patients with unrepaired EA who had undergone cardiac magnetic resonance imaging including T1 mapping were retrospectively reviewed. Patients were compared with age- and sex-matched controls. EA severity index was calculated using volumetric measurements at end diastole ([right atrial+atrialized right ventricular volumes]/[functional right ventricular+left atrial+left ventricular volumes]). Global circumferential and radial strain and as well as strain rate were examined using cardiac magnetic resonance feature tracking. Twelve EA patients and an equal number of controls were included. Functional and atrialized right ventricular end-diastolic volumes were 84±15 and 21±13 mL/m2, respectively. Late gadolinium enhancement, confined to the right ventricle, was found in 2 patients (16%). Left ventricular native T1 values and extracellular volume fractions were higher in patients compared with controls (1026±47 versus 956±40 ms, P=0.0004 and 28.5±3.4% versus 22.5±2.6%, P<0.001, respectively). Native T1 times correlated inversely with patients' age, body surface area, and O2 saturations (r=-0.63, -0.62, and -0.91, respectively; P=0.02, P=0.02, and P<0.0001, respectively). EA severity index ranged between 0.15 and 0.94 and correlated with T1 values (r=0.76, P=0.003). Native T1 correlated with global circumferential strain (r=0.58, P=0.04) but not ejection fraction (EF). EA patients had reduced maximum oxygen uptake (Vo2max). Vo2max correlated inversely with T1 values (r=-0.79, P=0.01). Children and adolescents with EA experience an abnormal degree of diffuse myocardial fibrosis. Its association with O2 saturation points toward a role of hypoxemia in the pathogenesis of fibrosis. Larger and prospective studies are needed to evaluate the value of T1 mapping for risk stratification and monitoring in EA.

Chronic Obstructive Pulmonary Disease and Semantic Language Abilities

Objective: The main aim of the present study is to evaluate the semantic language abilities of patients with Chronic Obstructive Pulmonary Disease (COPD) compared to normal group. Secondly to examine the role of hypoxemia, hypercapnia and pulmonary parameters on language scores. Method: We assessed 100 COPD patients with the use of a comprehensive battery of neurocognitive tests standardized for the Greek population, examining semantic language abilities, namely the Boston Naming Test (BNT), the Picture Peabody Vocabulary Test (PPVT) and the Controlled Oral Word Fluency Test (COWAT). Results: The results revealed that although the overall performance of our group of patients was within normal range, it was statistically significant lower compared to normal distribution on all semantic language tests. Moreover, we found that the percentile of COPD patients that performed in the deficient range was significantly higher compared to normal distribution. Further analysis of pulmonary parameters showed that Forced Expiratory Volume in 1 sec (FEV1, FEV1%), Forced Vital Capacity (FVC, FVC%) and FEV1/FVC were not correlated with patients’ performance on the language tests. Low Partial Pressure of Oxygen in blood oxygen levels (PaO2) was found to be able to predict the performance of patients on BNT, PPVT and semantic verbal fluency test. Abnormally elevated Partial Pressure of Carbon Dioxide (PCaO2) in blood were not found to be related to language dysfunctions. Conclusions: Our findings indicate that our group of COPD patients is more prone to present semantic language impairments compared to normal group while low blood oxygen levels were associated with reduced performance on BNT, PPVT and semantic verbal fluency tests.

Abstract WMP114: The Role of Hypoxemia and Hypercapnia as Risk Factors for Childhood Stroke

Background: Risk factors for childhood stroke differ significantly from those in adults. Obstructive Sleep Apnea (OSA) is an independent risk factor for adult stroke. Children with Sickle Cell Disease (SCD) have a higher prevalence of OSA than the general pediatric population, and nocturnal hypoxemia in these patients is independently predictive of future CNS events. Hypoxemia and hypercapnia secondary to OSA result in a pro-inflammatory and prothrombotic cascade associated with metabolic dysregulation and endothelial dysfunction. Hypothesis: We hypothesized that OSA, hypoxemia and/or hypercapnia are associated with an increased stroke risk in a pediatric population. Methods: Clinical and radiologic data of consented children seen in the stroke program from 1992-2014 with clinically indicated sleep study/polysomnography (PSG) were retrospectively reviewed and analyzed. Results: Thirty-one children (31/947; 14 male, mean age at PSG 8.4 years) were identified. Twenty-three children had arterial ischemic stroke (AIS) (mean age 7.6 years, SEM 0.99 years) and eight were non-stroke arteriopathy patients (mean age 10.5 years, SEM 1.16 years). Children diagnosed with AIS had significantly higher prevalence of OSA than children with no stroke (69% vs. 25%, p=0.0429) regardless of the timing of sleep study (11/15, 73.3% OSA post-stroke diagnosis and 5/8, 62.5% OSA pre-stroke diagnosis). AIS patients had significantly lower minimum SaO2 values overnight (83.19% vs. 94.56%, p=0.0072), and higher overnight mean end tidal (et) and transcutaneous (tc) CO2 levels (et CO2 42.78 vs. 41.75 mmHg, p=0.4940; tc CO2 42.08 vs. 39.67 mmHg, p=0.3544). Primary risk factors of AIS in children with clinically indicated PSG included 3 moyamoya (33% with OSA), 8 cardiac (63% with OSA), 5 SCD (83% with OSA), and 7 other (86% with OSA). Cardiac patients had the lowest nocturnal SaO2 and highest CO2 levels when compared to moyamoya, SCD and others. Conclusions: In our study, children with AIS were more likely to have OSA and nocturnal hypoxemia, highlighting these as potential risk factors for stroke in childhood. Future prospective studies are required to explore the relationship between stroke, hypoxemia and hypercapnia.

The Potential Association between Obstructive Sleep Apnea and Diabetic Retinopathy in Severe Obesity—The Role of Hypoxemia

BackgroundObstructive sleep apnea (OSA) is common in obese patients with type 2 diabetes mellitus (DM) and may contribute to diabetic microvascular complications.MethodsTo investigate the association between OSA, hypoxemia during sleep, and diabetic retinal complications in severe obesity. This was a prospective observational study of 93 obese patients mean (SD) age: 52(10) years; mean (SD) body mass index (BMI): 47.3(8.3) kg/m2) with DM undergoing retinal screening and respiratory monitoring during sleep. OSA was defined as apnea-hypopnea index (AHI) of ≥15 events/hour, resulting in two groups (OSA+ vs. OSA−).ResultsForty-six patients were OSA+: median (95% CI) AHI = 37(23–74)/hour and 47 were OSA–ve (AHI = 7(4–11)/hour). Both groups were similar for ethnicity, BMI, cardiovascular co-morbidities, diabetes duration, HbA1c, and insulin treatment (p>0.05). The OSA+ group was significantly more hypoxemic. There was no significant difference between OSA+ and OSA− groups for the presence of retinopathy (39% vs. 38%). More OSA+ subjects had maculopathy (22% vs. 13%), but this did not reach statistical significance. Logistic regression analyses showed that AHI was not significantly associated with the presence of retinopathy or maculopathy (p>0.05). Whilst minimum oxygen saturation was not significantly associated with retinopathy, it was an independent predictor for the presence of maculopathy OR = 0.79 (95% CI: 0.65–0.95; p<0.05), after adjustment.ConclusionsThe presence of OSA, as determined by AHI, was not associated with diabetic retinal complications. In contrast, severity of hypoxemia during sleep (minimum oxygen saturations) may be an important factor. The importance of hypoxia in the development of retinal complications in patients with OSA remains unclear and further studies assessing the pathogenesis of hypoxemia in patients with OSA and diabetic retinal disease are warranted.

COPD and cognitive impairment: the role of hypoxemia and oxygen therapy

several studies have shown an association between chronic obstructive pulmonary disease (COPD) and cognitive impairment. These studies have been limited by methodological issues such as diagnostic uncertainty, cross-sectional design, small sample size, or lack of appropriate referent group. This study aimed to elucidate the association between COPD and the risk of cognitive impairment compared to referent subjects without COPD. In patients with established COPD, we evaluated the impact of disease severity and impairment of respiratory physiology on cognitive impairment and the potential mitigating role of oxygen therapy. we used the Function, Living, Outcomes and Work (FLOW) cohort study of adults with COPD (n = 1202) and referent subjects matched by age, sex, and race (n = 302) to study the potential risk factors for cognitive impairment among subjects with COPD. Cognitive impairment was defined as a Mini-Mental State Exam score of <24 points. Disease severity was using Forced Expiratory Volume in one second (FEV(1)); the validated COPD Severity Score; and the BMI (Body Mass Index), Obstruction, Dyspnea, Exercise Capacity (BODE) Index. Multivariable analysis was used to control for confounding by age, sex, race, educational attainment, and cigarette smoking. COPD was associated with a substantive risk of cognitive impairment compared to referent subjects (odds ratio [OR] 2.42; 95% confidence interval [CI] 1.043-6.64). Among COPD patients, none of the COPD severity measures were associated with the risk of cognitive impairment (P > 0.20 in all cases). Low baseline oxygen saturation was related to increased risk of cognitive impairment (OR for oxygen saturation ≤88% (OR 5.45; 95% CI 1.014-29.2; P = 0.048). Conversely, regular use of supplemental oxygen therapy decreased the risk for cognitive impairment (OR 0.14; 95% CI 0.07-0.27; P < 0.0001). COPD is a major risk factor for cognitive impairment. Among patients with COPD, hypoxemia is a major contributor and regular use of home oxygen is protective. Health care providers should consider screening their COPD patients for cognitive impairment.

Downregulation of Akt/mammalian target of rapamycin pathway in skeletal muscle is associated with increased REDD1 expression in response to chronic hypoxia

Although it is well established that chronic hypoxia leads to an inexorable loss of skeletal muscle mass in healthy subjects, the underlying molecular mechanisms involved in this process are currently unknown. Skeletal muscle atrophy is also an important systemic consequence of chronic obstructive pulmonary disease (COPD), but the role of hypoxemia in this regulation is still debated. Our general aim was to determine the molecular mechanisms involved in the regulation of skeletal muscle mass after exposure to chronic hypoxia and to test the biological relevance of our findings into the clinical context of COPD. Expression of positive and negative regulators of skeletal muscle mass were explored 1) in the soleus muscle of rats exposed to severe hypoxia (6,300 m) for 3 wk and 2) in vastus lateralis muscle of nonhypoxemic and hypoxemic COPD patients. In rodents, we observed a marked inhibition of the mammalian target of rapamycin (mTOR) pathway together with a strong increase in regulated in development and DNA damage response 1 (REDD1) expression and in its association with 14-3-3, a mechanism known to downregulate the mTOR pathway. Importantly, REDD1 overexpression in vivo was sufficient to cause skeletal muscle fiber atrophy in normoxia. Finally, the comparative analysis of skeletal muscle in hypoxemic vs. nonhypoxemic COPD patients confirms that hypoxia causes an inhibition of the mTOR signaling pathway. We thus identify REDD1 as a negative regulator of skeletal muscle mass during chronic hypoxia. Translation of this fundamental knowledge into the clinical investigation of COPD shows the interest to develop therapeutic strategies aimed at inhibiting REDD1.

Abnormalitis in the distributions of ventilation-perfusion ratios and diffusing capacity-perfusion ratios in three types of chronic obstructive pulmonary disease

To assess whether diffusion-limited gas exchange plays a significant role in hypoxemia in various types of chronic obstructive pulmonary disease(COPD), we analyzed the distribution of ventilation-perfusion (VA/Q) ratios and of diffusing capacity-perfusion (G/Q) ratios. We compared VA/Q and G/Q distribution in patients with three basic types of COPD: emphysematous changes, bronchiolar involvement, and airway hypersecretion, which were classified based on symptoms and on findings of high-resolution CT. The results were that 1) hypoxemia was not caused by diffusion-limited gas exchange with low G/Q regions in any type of COPD, that 2) hypoxemia was not caused by inhomogeneities in VA/Q distribution, that 3) emphysematous changes and bronchiolar involvement were associated with high and low VA/Q regions, respectively, and that 4) either hypersecretion itself or related airway abnormalities may cause low VA/Q regions to form.

Elevated Burst Suppression Ratio: The Possible Role of Hypoxemia

To the Editor: We report a case characterized by the simultaneous occurrence of increased suppression ratio number (SR) and hypoxemia without a concomitant decrease in bispectral index (BIS). A 59-yr-old man was scheduled for tracheal granuloma removal by laser, using a rigid bronchoscopy. The patient’s history included two lobectomies for epidermoid carcinoma. Anesthesia induction was induced and maintained with infusions of propofol and remifentanil. A bolus of succinylcholine was injected to facilitate introduction of the bronchoscope. The lungs were mechanically ventilated through the lumen of the bronchoscope using a high frequency jet ventilator. Six minutes after the succinylcholine bolus, his Spo2 decreased dramatically below 80% despite ventilation with pure oxygen, and we also observed an increase of the SR. BIS was in the range of 40–60 and signal quality index was more than 75%. His mean arterial blood pressure was 80 mm Hg. The bronchoscope was withdrawn and replaced by an endotracheal tube; the lungs were mechanically ventilated using pure oxygen. High airway pressure and auscultation revealed bronchospasm. Spo2 improved after inhalation of a beta2-agonist and we observed a decrease of the SR (Fig. 1). The endotracheal tube was removed. The patient’s postoperative neurological examination was normal.Figure 1.: Acute decrease of Spo2 during rigid bronchoscopy. BIS, bispectral index; SR, burst suppression ratio; A, high frequency jet-ventilation; B, tracheal intubation; C to D, inhalation of beta2 agonist; E, recovery.In general, burst suppression patterns appear at BIS levels below 40. The effect of an increasing concentration of a volatile anesthetic on the electroencephalogram is a progressive slowing until burst suppression patterns occur. Our observation of an increased SR appearing while BIS was at an adequate anesthetic level could have been a coincidence, but we cannot exclude a relationship between SR and poor brain tolerance of hypoxemia. This hypothesis is supported by animal studies demonstrating that hypoxemia induces isoelectric electroencephalograms, oxygenation allowing the restoration of a baseline electroencephalogram (1), and a reduction in cerebral tissue damage (2). Ngai Liu, MD Thierry Chazot, MD Department of Anesthesiology Hôpital Foch Université Paris Ile-de-France Ouest Suresnes, France Catherine Mutter, MD Departments of Anesthesiology and Intensive Care Hôpital Hautepierre Strasbourg, France Marc Fischler, MD Department of Anesthesiology Hôpital Foch Université, Paris Ile-de-France Ouest Suresnes, France [email protected]

P3-48: Cardiac arrhythmias and obstructive sleep apnea syndrome: Role of hypoxemia

P3-48: Cardiac arrhythmias and obstructive sleep apnea syndrome: Role of hypoxemia

RE: THE PREVALENCE OF HYPERTENSION, HYPERLIPIDEMIA, DIABETES MELLITUS AND DEPRESSION IN MEN WITH ERECTILE DYSFUNCTION

No AccessJournal of UrologyLetters to the Editor/Errata1 Mar 2005RE: THE PREVALENCE OF HYPERTENSION, HYPERLIPIDEMIA, DIABETES MELLITUS AND DEPRESSION IN MEN WITH ERECTILE DYSFUNCTIONis correction ofTHE PREVALENCE OF HYPERTENSION, HYPERLIPIDEMIA, DIABETES MELLITUS AND DEPRESSION IN MEN WITH ERECTILE DYSFUNCTION A.D. Seftel, P. Sun, and R. Swindle A.D. SeftelA.D. Seftel More articles by this author , P. SunP. Sun More articles by this author , and R. SwindleR. Swindle More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000156766.89773.10AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "RE: THE PREVALENCE OF HYPERTENSION, HYPERLIPIDEMIA, DIABETES MELLITUS AND DEPRESSION IN MEN WITH ERECTILE DYSFUNCTION." The Journal of Urology, 173(3), p. 1050 References 1 : Erectile dysfunction: an underdiagnosed condition associated with multiple risk factors. Curr Med Res Opin2004; 20: 603. Google Scholar 2 : Current and future strategies for preventing and managing erectile dysfunction following radical prostatectomy. Eur Urol2004; 45: 123. Google Scholar 3 : Cigarette smoking and erectile dysfunction. J R Soc Health1998; 118: 151. Google Scholar 4 : Is there a role of hypoxemia in penile fibrosis: a viewpoint presented to the Society for the Study of Impotence. Int J Impot Res1998; 10: 113. Google Scholar Departments of Urology and Clinical Biochemistry, Royal Free Hospital, London, United Kingdom (Lau)Department of Urology, Institute of Cancer Research, London, United Kingdom (Kommu)Department of Clinical Biochemistry, Royal Free Hospital, London, United Kingdom (Mikhailidis)Department of Urology, Royal Free Hospital, London, United Kingdom (Morgan)Department of Urology, Chase Farm Hospital, Enfield, United Kingdom (Mumtaz)© 2005 by American Urological Association, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology9 Nov 2018THE PREVALENCE OF HYPERTENSION, HYPERLIPIDEMIA, DIABETES MELLITUS AND DEPRESSION IN MEN WITH ERECTILE DYSFUNCTION Volume 173Issue 3March 2005Page: 1050 Advertisement Copyright & Permissions© 2005 by American Urological Association, Inc.MetricsAuthor Information A.D. Seftel More articles by this author P. Sun More articles by this author R. Swindle More articles by this author Expand All Advertisement PDF downloadLoading ...

Hypoxemia inducing endothelin-1 secretion in meconium aspiration in piglets.

According to our previous study, the secretion of endothelin-1 (ET-1) was induced after meconium aspiration in piglets. In order to determine the role of hypoxemia in the ET-1 secretion during meconium aspiration, 12 piglets were randomly assigned into 2 groups: the hyperoxia and the hypoxia group (6 animals/group). Instillation of meconium (20% in normal saline) was achieved via the endotracheal tube (3 mL/kg) in all these animals. The hyperoxia group was ventilated with 100% oxygen, whereas the hypoxia group was ventilated with only 40% of oxygen. The plasma ET-1 levels, arterial blood gases and hemodynamics were measured at the baseline, 60, 120, 180, and 240 minutes after meconium instillation. The result showed plasma ET-1 levels to be significantly higher in the hypoxia group than the hyperoxia group at 180 and 240 min, respectively (p <0.05 andp <0.01). Besides, the pulmonary arterial pressures were significantly higher in the hypoxia group after 60 min (p <0.05 at 60 min and p <0.01 after 120 min). These results suggested that hypoxemia may be the major factor for inducing ET-1 secretion in meconium aspiration syndrome.

Pulmonary Hypertension and Cardiac Function in Adult Cystic Fibrosis: Role of Hypoxemia

To determine (1) the prevalence of pulmonary hypertension and cardiac dysfunction in adult cystic fibrosis (CF) patients with severe lung disease, (2) the relationship between these cardiovascular abnormalities and hypoxemia, and (3) the impact of subclinical pulmonary hypertension on survival. Single-blind, cross-sectional study. Ambulatory clinic of the Adult CF program at a tertiary-level hospital. Clinically stable patients with severe lung disease (FEV1 < 40% of predicted normal value) who were not receiving supplemental oxygen. A second cohort of patients in stable condition with less severe lung disease (FEV1 40 to 65% predicted) was also recruited to enable multivariate analysis for the determinants of pulmonary hypertension. Eighteen patients with severe lung disease (FEV1 28 +/- 7% of predicted normal value) were initially studied. Each patient had overnight polysomnography, pulmonary function tests, and Doppler echocardiography. Arterial oxygen saturation (SaO2) was reduced during wakefulness (87.1 +/- 6.1%) and fell during sleep (84.0 +/- 6.6%) while transcutaneous PCO2 was normal during wakefulness (41.1 +/- 6.9 mm Hg) and increased during sleep (46.6 +/- 4.7 mm Hg). Left ventricular size, systolic function, and diastolic function were normal except in one patient who had had a previous silent myocardial infarction due to coronary artery disease. Qualitative assessment of right ventricular function was normal in all patients. Pulmonary artery systolic pressure (PASP) was increased (> 35 mm Hg) in seven patients without clinical evidence of cor pulmonale. Regression analysis was performed by combining these data with data from an additional 15 CF patients with moderately severe lung disease (FEV1 56.3 +/- 8.9% predicted normal) who were recruited to a modified study protocol that included overnight oximetry, pulmonary function tests, and Doppler echocardiography. None of these patients had evidence of hypoxemia and only three had mild elevation of PASP (36, 37, and 39 mm Hg). Linear regression analysis revealed that PASP was significantly correlated with FEV1 (r = -0.44; p = 0.013), and SaO2 during wakefulness (r =-0.60; p = 0.0003), during sleep (r = -0.56; p = 0.0008), and after 6 min of exercise (r = -0.75; p < 0.0001). Multivariate analysis revealed that awake SaO2 was a significantly better predictor of PASP than FEV1 (p = 0.0104). Clinical follow-up of the original cohort for up to 5 years revealed that mortality was significantly higher in those with pulmonary hypertension than those without pulmonary hypertension (p = 0.0129). In adult CF patients with severe stable lung disease, left and right ventricular function is well maintained in the absence of significant coronary artery disease; pulmonary hypertension develops in a significant proportion of patients and is strongly correlated with oxygen status, independent of lung function; and subclinical pulmonary hypertension is associated with an increased mortality.

Mechanisms of acute cardiovascular response to periodic apneas in sedated pigs.

This study was designed to evaluate the importance of sympathoadrenal activation in the acute cardiovascular response to apneas and the role of hypoxemia in this response. In addition, we evaluated the contribution of the vagus nerve to apnea responses after chemical sympathectomy. In six pigs preinstrumented with an electromagnetic flow probe and five nonpreinstrumented pigs, effects of periodic nonobstructive apneas were tested under the following six conditions: room air breathing, 100% O2 supplementation, both repeated after administration of hexamethonium (Hex), and both repeated again after bilateral vagotomy in addition to Hex. With room air apneas, during the apnea cycle, there were increases in mean arterial pressure (MAP; from baseline of 108 +/- 4 to 124 +/- 6 Torr, P < 0.01), plasma norepinephrine (from 681 +/- 99 to 1,825 +/- 578 pg/ml, P < 0.05), and epinephrine (from 191 +/- 67 to 1,245 +/- 685 pg/ml, P < 0.05) but decreases in cardiac output (CO; from 3.3 +/- 0.6 to 2.4 +/- 0.3 l/min, P < 0.01) and cervical sympathetic nerve activity. With O2 supplementation relative to baseline, apneas were associated with small increases in MAP (from 112 +/- 4 to 118 +/- 3 Torr, P < 0.01) and norepinephrine (from 675 +/- 97 to 861 +/- 170 pg/ml, P < 0.05). After Hex, apneas with room air were associated with small increases in MAP (from 103 +/- 6 to 109 +/- 6 Torr, P < 0.05) and epinephrine (from 136 +/- 45 to 666 +/- 467 pg/ml, P < 0.05) and decreases in CO (from 3.6 +/- 0.4 to 3.2 +/- 0. 5 l/min, P < 0.05). After Hex, apneas with O2 supplementation were associated with decreased MAP (from 107 +/- 5 to 100 +/- 5 Torr, P < 0.05) and no other changes. After vagotomy + Hex, with room air and O2 supplementation, apneas were associated with decreased MAP (from 98 +/- 6 to 76 +/- 7 and from 103 +/- 7 to 95 +/- 6 Torr, respectively, both P < 0.01) but increased CO [from 2.7 +/- 0.3 to 3. 2 +/- 0.4 l/min (P < 0.05) and from 2.4 +/- 0.2 to 2.7 +/- 0.2 l/min (P < 0.01), respectively]. We conclude that sympathoadrenal activation is the major pressor mechanism during apneas. Cervical sympathetic nerve activity does not reflect overall sympathoadrenal activity during apneas. Hypoxemia is an important but not the sole trigger factor for sympathoadrenal activation. There is an important vagally mediated reflex that contributes to the pressor response to apneas.

Is there a role of hypoxemia in penile fibrosis

Is there a role of hypoxemia in penile fibrosis

Is there a role of hypoxemia in penile fibrosis: a viewpoint presented to the Society for the Study of Impotence.

During erection, oxygen tension changes in the corpus cavernosum penis from 25-40 mm Hg in the flaccid state to 90-100 mm Hg in the erect state. The relationship between corpus cavernosum trabecular structure and erectile function is dependent on a critical balance of smooth muscle to connective tissue for successful veno-occlusion. In this article, the potential role for transforming growth factor beta(1) (TGF-beta(1)) and prostaglandin E (PGE) in maintaining a functional smooth muscle/connective tissue balance are discussed as well as the importance of oxygen tension in the synthesis of these factors. Correlations between animal models of disease as well as clinical reports are presented in support of a role for hypoxemia in penile fibrosis. A case is presented for a biological basis of nocturnal penile tumescence in the preservation of potency and an overall hypothesis for the molecular pathology of erectile dysfunction is proposed.

Role of hypoxemia and hypercapnia in acute cardiovascular response to periodic apneas in sedated pigs

The effects of hypoxemia and hypercapnia in acute cardiovascular response to periodic non-obstructive apneas were explored in seven preinstrumented, sedated paralyzed and ventilated pigs under three conditions: room air breathing (RA), O 2 supplementation (O2), and supplementation with O 2 and CO 2 (CO2). EEG monitoring showed no arousal under any conditions. RA apneas increased mean arterial pressure (MAP, from baseline 95.9±4.5 to late apnea 124.4±7.8 Torr, P<0.01), left ventricular end-diastolic pressure, end-diastolic and end-systolic myocardial fiber lengths and systemic vascular resistance, but decreased cardiac output (CO, 3.09±0.34–2.37±0.26 L/min, P<0.01), heart rate (HR, 115.1±7.5–102.0±7.8 bpm, P<0.01), and stroke volume (SV, 29.6±0.7–21.1±1.8 ml, P<0.01). O2 apneas produced similar decreases in HR (114.0±11.8–105.4±8.7 bpm, P<0.05) as with RA apneas, but smaller increases in MAP (94.5±1.8–103.4±2.8 Torr, P<0.01) and in the variables of pre- and after-load. CO and SV remained unchanged with O2 apneas. CO2 was associated with higher MAP, CO, and HR at baseline relative to RA, but similar cardiovascular response during apneas in direction and magnitude to those of O2 apneas. We conclude that in this model hypoxemia is a major but not the sole determinant of the pressor response during apneas. Hypercapnia cannot explain the pressor response seen when hypoxemia is abolished. The HR fall during apneas is independent of hypoxemia, hypercapnia and the pressor response.

Role of hypoxemia in sleep apnea-induced sympathoexcitation

The importance of hypoxemia in determining sympathoexcitation during obstructive sleep apnea was examined by comparing changes in efferent sympathetic nerve activity (SNA) during spontaneous obstructive apneas with hypoxemia alone of similar magnitude and duration induced by 1–4 breaths of 100% nitrogen in six patients with obstructive sleep apnea and with spontaneous apneas while breathing 100% oxygen (apnea without hypoxemia) in three patients. In addition, eight control subjects were studied during induced hypoxemia. The magnitude of sympathoexcitation during spontaneous apneas (103 ± 15%) was more than twice that observed during induced hypoxemia (47 ± 14%) during episodes in which the nadir of oxygen desaturation (78 ± 2 and 75 ± 2%, respectively) and duration of hypoxemia (27 ± 3 and 33 ± 3 s, respectively) were the same ( P > 0.20). Similarly, in three patients SNA increased 115% during normoxic spontaneous obstructive apneas, but increased only 43% during hyperoxic spontaneous obstructive apneas in which oyxgen saturation did not decrease significantly. Sympathetic neural responses to induced hypoxemia in control subjects (17 ± 7%) were significantly less than that of the sleep apnea patients. We conclude that hypoxemia contributes importantly, but is not the sole determinant of the sympathoexcitation provoked during episodes of obstructive sleep apnea.

Hypoxic hepatitis in patients with cardiac failure

Hypoxic (HH) commonly called ischemic hepatitis or refers to a sharp but transient increase in serum activity of one or both of the aminotransferases (AST and/or ALT) of at least 20 times the upper limit of normal following circulatory failure. The definition of the syndrome in patients with previously healthy livers was reviewed by Gibson & Dudley in 1984 (I). HH is characterized by a rapid fall in transaminases if the causing condition is treated successfully. HH has been described in cardiogenic shock, after hemorrhage, and with sepsis, postoperative hypotension and pulmonary embolism, although the cause of appears to be irrelevant for the development of the syndrome. The patlaophysiological mechanisms of HH are still not well known. Most published papers describe patients with diseases and consider the relative contributions of HH (hepatic ischemia, hypoxia and congestion) to be relevant. Hepatic injury of HH may thus occur as a result of a reduction in liver blood flow followed by ischemia. Another study, however, showed that there was a higher incidence of passive venous congestion and hypoxemia in patients who developed HH, compared with patients with cardiogenic shock who did not develop HH (2). The role of hypoxemia is controversial since it has been reported that hyperbaric oxygen does not prevent hepatic necrosis in experimental models of shock (3). Further contributing factors may be the simultaneous administration of different drugs (e.g., vasoconstrictor inotropes which may impair hepatic blood flow by splanchnic vasoconstriction, or cardiodepressing drugs like calcium channel blockers or anti-arrhythmic agents) (4,5), It might be useful to summarize briefly the wide spectrum of hepatic complications due to heart failure syndromes. Chronic heart failure, which may exacerbate to acute heart failure (2), can cause cardiac with the typical nutmeg appearance, but the more common finding and the first step which normally occurs in cirrhosis is simple congestive hepatomegaly (6). This disorder is usually recognized by elevated serum transaminases, high bilirubin levels, up to 20 mg/dl, due to an increase in both direct and indirect fractions, and jaundice. The serum transaminases may be increased I0to 15-fold and serum alkaline phosphatase is increased. When the prothrombin time is substantially prolonged, congestive hepatopathy is usually severe and the prognosis poor. The development of end-stage cirrhosis will produce all of the findings associated with chronic liver failure, including hypoalbuminemia, hypoglycemia, ascites, and hepatic coma. Hepatic disorders due to acute failure can be caused by sudden low output syndromes or may arise also as a consequence of aggravation of chronic heart failure. In one study (2), the onset of HH was usually preceded by an acute complicaton, e.g., arrhythmia, provoking a sudden decrease in output. Fig. 1 and 2 depict the histological correlates of two typical hypoxic states in the liver. In the article by Henrion and coworkers, published in this issue of the journal (7), the authors present for the first time a prospective study on the incidence of HH in a European coronary care unit and measure the effective hepatic blood flow in patients with low output and HH, using the method of galactose clearance at low concentration. In this setting, low output was defined clinically by: I) Existence of disease (chronic or acute); 2) Cutaneous signs of circulatory failure; and 3) Intravenous inotropic treatment with dobutamine. Shock (defined in Henrion's paper as a fall of systolic blood

Histamine and exercise-induced hypoxemia in highly trained athletes.

To determine whether exercise-induced hypoxemia in extreme athletes results from an increase in histamine level during maximal incremental exercise, seven young athletes [YA; age 22.2 +/- 1.23 (SE) yr] and seven master athletes (MA; age 66.2 +/- 2.94 yr), all of whom were known to develop exercise-induced hypoxemia, were compared with age-matched control groups (young controls and older controls, respectively). During maximal incremental exercise, blood samples for arterial blood gas analysis and for plasma and total histamine were drawn at rest and at 50, 75, and 100% of maximal O2 uptake. The percentage of histamine released (%H) was calculated from plasma and total histamine samples. In all athletes (MA and YA groups), exercise induced an increase in %H with a concomitant decrease in arterial PO2 (PaO2); in control groups there was no change in either histamine levels or PaO2. When the data for the YA and MA groups were combined, a correlation was observed between the increase in %H and the drop in PaO2. Nevertheless, further studies are required to establish whether histamine plays a causative role in hypoxemia or is a response to injury.