Search PubMed⌕ Search

Biomedical subjects

E C Fletcher

Publications and source records attributed to E C Fletcher.

At least 55 records · Page 3Linked to original sources
PubMed1993

Obstructive sleep apnea and the kidney.

Recent studies of obstructive sleep apnea and its comorbidity with other systemic diseases have stimulated interest in the relationship of apnea to renal disease and hypertension. Polysomnographic sleep studies in patients on dialysis who complain of day-time fatigue or sleepiness reveal significant apnea in up to 73% of those studied. Abnormalities in respiratory controller mechanisms from chronic hypocarbia, metabolic acidosis, and uremic toxins have been blamed for the occurrence of apnea in this setting. Proteinuria and sometimes nephrotic syndrome have been recognized in morbidly obese patients with sleep apnea syndrome. Renal biopsies of such patients have shown glomerulomegaly and focal segmental sclerosis. It is postulated that these lesions may result from increased glomerular filtration and blood flow. Elevated urine output, sodium and chloride excretion, and atrial natriuretic peptide have been well demonstrated in obstructive apnea patients and correct to control levels with treatment of the apnea. Both acute (with each apnea) and chronic daytime blood pressure elevation are frequently observed in sleep apnea patients, and occult sleep apnea is postulated as one possible cause of "primary" hypertension in middle-aged men. In younger patients, such hypertension seems to be more reversible with the elimination of apnea. In older patients, however, the cure of systemic hypertension cannot be guaranteed with the elimination of the apnea, and asymptomatic apnea patients tend not to tolerate the bother and discomfort of apnea treatment with nasal continuous positive airway pressure. Therefore, aside from a careful history regarding sleep symptomatology, polysomnographic studies of clinic populations with primary hypertension to search for apnea as a cause cannot be recommended.

Aged↗
PubMed1992

Carotid chemoreceptors, systemic blood pressure, and chronic episodic hypoxia mimicking sleep apnea.

We have described a rat model that responds to repetitive episodic hypoxia (12-s infusions of nitrogen into daytime sleeping chambers every 30 s, 7 h/day for 35 days) with an increase in diurnal systemic blood pressure. We hypothesized that afferent information from the peripheral chemoreceptors may be necessary to produce diurnal blood pressure elevation in this hypoxia model. Carotid body denervation (CBD) was accomplished by severing both carotid sinus nerves in two groups of male Wistar rats (250-375 g). Group 4 CBD rats were subjected to intermittent hypoxia for 35 days (3-5% nadir ambient O2) as described above, whereas group 5 CBD rats remained unhandled in their usual cages. Additional sham-operated controls included group 2 sham-"hypoxia" rats, which were housed in chambers identical to the hypoxia rats but supplied with compressed air instead of nitrogen, group 1 (not denervated) rats, which remained unhandled in their usual cages, and group 3 sham-operated rats, which were subjected to 35 days of intermittent hypoxia identical to group 4 CBD rats. Femoral arterial baseline and end-of-study blood pressures were measured in conscious rats. The group 3 rats exposed to episodic hypoxia displayed a 13-mmHg increase in mean blood pressure, whereas the other groups showed no significant change from baseline. Left ventricular hypertrophy was evident in all rats exposed to episodic hypoxia, but right ventricular hypertrophy was evident only in the group 4 rats. All CBD rats developed increased hematocrit and hemoglobin, while the group 3 rats (non-CBD, episodic hypoxia) did not. The baroreceptor reflex at baseline was not depressed in the CBD rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Repetitive, episodic hypoxia causes diurnal elevation of blood pressure in rats.

An association between chronic high blood pressure and obstructive sleep apnea has been described. We hypothesized that repetitive episodic hypoxia patterned after the hypoxia seen in sleep apnea could contribute to diurnal elevation of blood pressure. Using 12-second infusions of nitrogen into daytime sleeping chambers, four groups of male rats (250-375 g) were subjected to intermittent hypoxia (3-5% nadir ambient oxygen) every 30 seconds, 7 hours per day for up to 35 days. In one group, blood pressure was measured weekly by the tail-cuff method in conscious animals during 5 weeks of episodic hypoxia. In the other three groups, blood pressure was measured in conscious animals via femoral artery catheters at baseline and after 20, 30, or 35 days of exposure. Additional groups served as controls: two sham groups housed in identical "hypoxia" chambers received compressed air instead of nitrogen (35 days) while two other groups remained unhandled in their usual cages (35 days). Both groups challenged with 35 days episodic hypoxia showed significant increases in blood pressure compared with controls: the tail-cuff rats showed a 21 mm Hg increase in systolic pressure (p less than 0.05) and the intra-arterially measured rats a 13.7 mm Hg increase in mean arterial pressure (p less than 0.05). The 30-day exposed rats also showed a 5.7 mm Hg increase in mean pressure over baseline (p less than 0.05). Blood pressure did not change significantly from baseline in the control groups. Left ventricle-to-body weight ratio was higher in both 35-day exposed groups than in unhandled or sham controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Sympathetic denervation blocks blood pressure elevation in episodic hypoxia.

We have previously described a rat model that responds to repetitive episodic hypoxia (FiO2 nadir 3-5% for 12 seconds every 30 seconds for 7 hr/day for 35 days) with chronic increase in arterial blood pressure. The purpose of the current study was to determine if peripheral sympathetic nervous system denervation blocks this persistent blood pressure elevation. Chemical sympathetic denervation was achieved and maintained by three intraperitoneal injections (100 mg/kg 6-hydroxydopamine) on days 1, 3, and 27 of a 47-day experiment in two groups of rats. One denervated group was subjected to episodic hypoxia for 40 consecutive days beginning on day 7 and the other remained unhandled in their usual cages. A third group was injected with vehicle only and subjected to the same episodic hypoxia while a fourth group remained unhandled for 40 days. The vehicle-treated, episodic hypoxia-exposed group showed a 7.7 mm Hg increase in mean arterial blood pressure (conscious, unrestrained) over the 40-day period, whereas all other groups showed a decrease in mean arterial pressure. The left ventricle and septum/whole body weight ratio was higher in both episodic hypoxia-exposed groups at the end of the study. Plasma epinephrine in both groups administered 6-hydroxydopamine was higher on day 6 than in the vehicle-injected rats. Measurement of catecholamines in cardiac muscle homogenate confirmed denervation in 6-hydroxydopamine animals. These results indicate that the peripheral sympathetic nervous system is necessary for the persistent increase in blood pressure in response to repetitive episodic hypoxia.

Animals↗
PubMed1992

A double-blind trial of nocturnal supplemental oxygen for sleep desaturation in patients with chronic obstructive pulmonary disease and a daytime PaO2 above 60 mm Hg.

The efficacy of nasal oxygen during sleep was evaluated in patients with COPD, episodic rapid eye movement sleep desaturation, and a daytime PaO2 greater than 60 mm Hg. The double-blind, randomized 3-yr trial used nasal oxygen versus room air in two groups of nocturnal sleep desaturating subjects. The setting was the outpatient chest clinic of a Veterans Affairs Medical Center. There were 51 patients with moderate to severe COPD, daytime PaO2 greater than or equal to 60 mm Hg: 38 with proven REM sleep desaturation and 13 without desaturation. Nocturnal oxygen at 3 L/min was delivered by concentrator to 19 desaturating subjects, and room air at 3 L/min was delivered by defective concentrator to the remaining 19 desaturating subjects. There was no gas therapy for the 13 nondesaturating subjects. The nocturnal desaturator group who received supplemental oxygen during sleep over 36 months showed a significant downward trend in pulmonary artery pressure (-3.7 mm Hg) compared with desaturating patients treated with room air (+3.9 mm Hg). Nonvascular parameters of hypoxia, such as hemoglobin and red blood cell mass, did not differ between the sham- and oxygen-treated groups. Mortality was decidedly higher in the desaturating patients compared with non-desaturating subjects, but there was no significant difference between oxygen- and sham-treated desaturating subjects. We conclude that nasal supplemental oxygen used during sleep to reverse episodic desaturation in COPD patients whose daytime PaO2 is above 60 mm Hg has a beneficial effect in reducing pulmonary artery pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗
PubMed1992

Survival in COPD patients with a daytime PaO2 greater than 60 mm Hg with and without nocturnal oxyhemoglobin desaturation.

There have been few studies examining the relationship between NOD and mortality in patients with COPD and none examining this relationship in those patients with a daytime PaO2 greater than 60 mm Hg. Is NOD related to early death, and if so, should nocturnal supplemental oxygen be considered as therapy for altering survival? We examined survival in 169 COPD subjects. Two definitions were used to classify subjects as NOD and non-NOD, one considering episodic desaturation associated mainly with REM sleep (definition 1) and one considering greater than 30 percent of time in bed spent below an SaO2 of 90 percent (definition 2) to be significant. Survival corrected for age was significantly better in non-NOD subjects. However, when stratified for supplemental oxygen use, survival remained better only in subjects separated by definition 1. There was a trend toward increased survival in 35 oxygen-treated vs 38 non-oxygen-treated NOD subjects (definition 1), but this difference was not statistically significant.

Circadian Rhythm↗
PubMed1992

Lactate kinetics in severe COPD. Implications of an abnormal aminopyrine breath test.

The ability of the 13C aminopyrine breath test (APBT) to reflect hepatocellular metabolic capacity and therefore to predict lactate removal following incremental exercise in male COPD patients was evaluated. Two previous patients with COPD who had histories of heavy alcohol intake but no overt liver disease showed prolonged lactate elevation following exercise. The possibility of subclinical hepatic disease affecting lactate removal was considered. No patient in the present study had clinical evidence of liver disease. Four of 9 patients had an abnormal APBT (mean 5.0% cumulative dose 13CO2 excreted over 2 h). Patients with a normal APBT (group 1) and with an abnormal APBT (group 2) were compared. The groups did not differ in age or severity of lung disease. An incremental exercise test was performed and lactate samples were collected before, during, and for 90 min following exercise. Exercise parameters (work rate, duration, VO2max, VEmax, and peak lactate) did not differ between groups. Comparing group 1 with group 2 mean values, the time to recover to resting lactate values (Trecov 45 vs 76 min, respectively, p less than 0.005) and the time required for lactate level to return to the normal range (Tnorm 35 vs 65 min, respectively, p less than 0.005) were statistically different. Furthermore, the 2-h excretion of 13CO2 was inversely correlated with both Trecov (r = -0.76, p less than 0.05) and Tnorm (r = -0.79, p less than 0.05). We conclude that subclinical derangement of hepatocellular capacity, as determined by APBT, may adversely affect lactate removal following exercise.

Aminopyrine↗
PubMed1991

"Near miss" death in obstructive sleep apnea: a critical care syndrome.

OBJECTIVE: The objective of this study was to alert critical care physicians to the syndrome of obstructive sleep apnea with respiratory failure ("near miss" death) and to elucidate characteristics that might allow earlier recognition and treatment of such patients. DESIGN: We examined clinical and laboratory characteristics of eight patients with obstructive sleep apnea presenting to the ICU with respiratory failure. These characteristics were compared with those of eight stable apnea patients of similar severity but without a history of presentation with respiratory failure. SETTING: Medical ICU and pulmonary outpatient clinic at the Houston Veterans Administration Medical Center, a teaching hospital affiliated with Baylor College of Medicine. PATIENTS: Eight patients with obstructive sleep apnea who presented in, or developed, acute respiratory failure requiring tracheal intubation and mechanical ventilation were matched to eight stable obstructive sleep apnea outpatients from the chest clinic. MEASUREMENTS AND MAIN RESULTS: The records of these 16 patients were reviewed and multiple characteristics that might predict these obstructive sleep apnea patients prone to respiratory failure and death (called the "near miss" death group; n = 8) were examined. The mean age of the near miss group was 57 yrs. All eight patients presented with respiratory acidosis (mean pH 7.22), hypercarbia (mean PaCO2 82 torr [10.9 kPa]), and hypoxemia (mean PaO2 45 torr [6.0 kPa]). Six of the eight patients had concomitant chronic obstructive pulmonary disease as determined by clinical characteristics and spirometry. Predisposing factors included facial trauma, lower respiratory tract infections or bronchospasm, and use of pain medication. All but one of the near miss subjects had awake hypercarbia (mean PaCO2 49 torr [6.5 kPa]) and hypoxemia (mean PaO2 58 torr [7.7 kPa]) during periods of clinical stability while only two controls had concomitant chronic obstructive pulmonary disease and none had hypercarbia. The prevalence of a history of wheezing and prior hospitalization for "respiratory problems" were greater in the near miss group. Once cured of apnea, no patient presented with recurrence of respiratory failure in follow-up ranging from 6 to 80 months, and cor pulmonale recurred in only one patient during subsequent onset of central apneas. CONCLUSION: Patients with obstructive sleep apnea who have concomitant chronic obstructive pulmonary disease or hypercarbia and hypoxemia are more prone to develop severe respiratory failure and probable death than those patients with apnea alone. The current study shows that recurrent respiratory failure and presumably mortality from this acute complication can be reversed with effective treatment of the obstructive apnea.

Acute Disease↗
PubMed1991

Rate of oxyhemoglobin desaturation in obstructive versus nonobstructive apnea.

Preapneic thoracic gas volume (Vtg), arterial saturation (SaO2), and mixed venous oxygen saturation (SvO2), have been shown to influence the rate of SaO2 fall (dSaO2/dt) during apnea. We asked the following question: does tissue oxygen consumption (tVO2) affect the dSaO2/dt during apnea? We attempted to answer this question by comparing dSaO2/dt during obstructive apneas (high tVO2) with dSaO2/dt during nonobstructive apneas (low tVO2) in six adult baboons. Fiberoptic central venous and arterial catheters were used for continuous monitoring of SvO2, SaO2, and cardiac output. A sapphire-bearing turbine monitored minute ventilation and airflow cessation. A Respitrace and esophageal pressures were used to assess relative differences in Vtg. Obstructive apneas (30, 45, and 60-s) were created by clamping an indwelling cuffed endotracheal tube at end-expiration. Nonobstructive apneas were created by paralyzing the animals with atracurium and interrupting ventilation for periods equivalent to those of the obstructed apneas. The ventilator was adjusted to duplicate the respiratory rate, tidal volume, and relative Vtg of the spontaneously breathing animal. Mean tVO2 during spontaneous breathing was 110 ml/min (Fick method) and decreased to 90 ml/min during paralysis (p less than 0.05). The dSaO2/dt for the three apnea durations (mean, all animals), obstructive versus nonobstructed were: 0.85 and 0.74%/s (n = 6), 0.87 and 0.75%/s (n = 6), and 0.60 and 0.48%/s (n = 4), respectively. The dSaO2/dt was significantly lower during the nonobstructive apneas. We conclude that differences in VO2 during apnea may affect the dSaO2/dt and that for the same duration apnea, central apneas may show less desaturation than obstructive apneas where vigorous muscular efforts at overcoming obstruction are common.

Animals↗
PubMed1991

The effect of positive reinforcement on hourly compliance in nasal continuous positive airway pressure users with obstructive sleep apnea.

Previous reports have described compliance with nasal continuous positive airway pressure (nCPAP) for the treatment of obstructive sleep apnea (OSA) only in terms of the number of patients able to use it beyond their initial trial night or those continuing after some home use. Because of a possible difference between the level of compliance (mean number of hours of use per 24 h) needed for symptomatic relief of OSA versus cardiovascular improvement, the level of hourly compliance in chronic nCPAP users may be important. The first part of this study prospectively examines compliance in a stable population of OSA patients already using nCPAP for 6 months to 2 yr. The second part is a prospective randomized, crossover study examining the effect of weekly (three times) then monthly (twice) positive reinforcement on hourly compliance of new nCPAP users for 3 months versus no reinforcement for 3 months. Positive reinforcement consisted of telephone discussions with the patients about the severity or complications of OSA, benefits of nCPAP, and suggestions about minimizing side effects. Using self-assessment scales, each patient reported the perceived level of improvement from the untreated to the treated condition and the prevalence and severity of side effects from the nCPAP therapy. The level of compliance in stable, chronic nCPAP users with OSA was 6.1 +/- 2.2 h/24 h (n = 9). For the new nCPAP users during the nonreinforced period, the mean compliance was 6.0 +/- 2.8 h/24 h; that during the reinforcement period was 6.0 +/- 2.7 h/24 h (NS). There was no significant correlation between perceived improvement in OSA symptoms or between the perceived side effects of nCPAP versus hourly compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1991

Evolution of nocturnal oxyhemoglobin desaturation in patients with chronic obstructive pulmonary disease and a daytime PaO2 above 60 mm Hg.

We studied 31 clinically stable chronic obstructive pulmonary disease (COPD) patients with a PaO2 greater than or equal to 60 mm Hg using polysomnographic sleep study at baseline (between 1983 and 1986) and at a mean follow-up time of 42.5 months to examine the evolution of rapid-eye-movement (REM) sleep nocturnal oxyhemoglobin desaturation (NOD). Arterial blood gases and spirometry measured at baseline and follow-up were compared with mean nocturnal SaO2 and to other REM sleep SaO2 parameters. We postulated that the onset of NOD would be seen most frequently in those patients with marked derangements of lung mechanics and greater longitudinal deterioration in arterial blood gases. Eight of the subjects developed REM-NOD on follow-up polysomnography. The appearance of REM-NOD was not related, or only minimally so, to initial PaO2, PaCO2, or mean nocturnal SaO2. Upon follow-up, however, the onset of NOD was always associated with deterioration of daytime PaO2 and PaCO2, mainly in those patients with the most severe baseline derangement of spirometry (lung mechanics). On the other hand, one group showed equivalent deterioration in daytime PaO2 and a stable PaCO2 but had less severely deranged baseline mechanics and demonstrated a fall in mean nocturnal SaO2 only. The findings in this latter group indicate that the development of NOD is not purely a result of decreasing daytime PaO2. We conclude that the onset of REM-NOD is mainly related to a severe derangement of lung mechanics with deterioration of resting awake gas exchange (progressive hypoxemia, hypercarbia, and worsening airflow).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Effect of cardiac output reduction on rate of desaturation in obstructive apnea.

The nadir of SaO2 during an obstructive apnea is dependent upon the apnea's duration and the rate of fall of saturation (dSaO2/dt). We postulated that a low Q, such as in patients with congestive heart failure with sleep apnea, or a reduction in Q, as seen in some humans during obstructive sleep apnea, might steepen dSaO2/dt. The mechanism postulated was lowering of SvO2 with increased pulmonary capillary blood oxygen uptake and faster depletion of alveolar oxygen. This study examines dSaO2/dt following the onset of apnea in eight spontaneously breathing adult baboons. Nonrepetitive obstructive apneas (30, 45, and 60 seconds) were created by clamping an indwelling cuffed endotracheal tube at the end of expiration. Following baseline measurements, the animals were given a bolus of a rapid-acting beta-adrenergic blocker followed by continuous infusion to reduce cardiac output and to limit the cardiovascular response to obstructive asphyxia. Fiberoptic catheters were used for continuous monitoring of SaO2, SvO2, and cardiac output. Esophageal pressure and relative thoracic gas volume (Respitrace) were monitored to insure equivalence of lung volume at the onset of apnea. Beta-adrenergic blockade reduced resting Q by a mean of 25 percent. The blocked vs unblocked dSaO2/dt was 0.73 vs 0.72 percent/s, 0.76 vs 0.73 percent/s, and 0.70 vs 0.71 percent/s for 30-second, 45-second, and 60-second apneas, respectively. Thus, mean dSaO2/dt for all durations of apneas was unaffected by beta-adrenergic blockade. We concluded that dSaO2/dt is not influenced by limited Q preceding or induced by obstructive asphyxia.

Adrenergic beta-Antagonists↗
PubMed1990

Chronic lung disease in the sleep apnea syndrome.

Several well controlled epidemiologic and hemodynamic studies suggest that about 20% of sleep apnea syndrome (SAS) patients will have chronic obstructive pulmonary disease (COPD), and the majority of these patients (with combined diseases) will have pulmonary hypertension. Indeed it has been suggested that only patients with underlying hypoxemia, such as that from COPD, will develop right heart failure in the OSA setting. Experience shows that apnea/COPD patients will have severe hypersomnolence associated with the OSA, cough and dyspnea with the airways disease, and edema and plethora related to chronic hypoxemia. Many patients present with respiratory failure and are diagnosed at the time of initial intubation and mechanical ventilation. Episodic nocturnal hypoxemia may be worsened by a steeper rate of desaturation due to lower alveolar and blood oxygen stores, and longer apneas perhaps contributed to by depressed chemosensitivity. Daytime hypoxemia may also add to the severe hemodynamic disturbances. Since COPD cannot be cured, aggressive treatment of SAS is critical. Past studies have shown that tracheostomy or nasal CPAP in this setting not only leads to resolution of episodic nocturnal desaturation but may lead to rapid improvement in daytime oxygenation in many patients. Pulmonary hypertension and other measures of cardiopulmonary function improve when apnea is cured. Elimination of the SAS may disclose nonapneic REM related desaturation that could require supplemental oxygen therapy in addition to tracheostomy or nasal CPAP. Pulmonary function testing in SAS patients with smoking histories, followed by aggressive treatment of SAS, is recommended.

Humans↗
PubMed1990

Atelectasis affects the rate of arterial desaturation during obstructive apnea.

Chronic hemodynamic disturbances are more profound in patients with obstructive sleep apnea when underlying lung disease with abnormal gas exchange (low arterial PO2) is present. Previous studies suggest that pulmonary gas exchange could influence the rate of fall of arterial oxygen saturation (dSaO2/dt) in obstructive sleep apnea. We postulated that abnormal gas exchange in the form of atelectasis would steepen dSaO2/dt and thereby lower nadir arterial oxyhemoglobin saturation (SaO2) for the same duration of apnea. Apneas were created by clamping an indwelling cuffed endotracheal tube at end expiration in eight spontaneously breathing adult baboons. Apneas of the same duration were then repeated during temporary endobronchial occlusion of one lobe of the lung. SaO2 and mixed venous O2 saturation were continuously monitored, and cardiac output was calculated. Worsening of pulmonary gas exchange during atelectasis was documented by an increase in calculated venous admixture from 10.5 +/- 0.8 to 25.0 +/- 0.7% (P less than 0.001). The dSaO2/dt was independent of apnea duration at 30, 45, and 60 s. During endobronchial occlusion, apnea dSaO2/dt increased 20%, and nadir SaO2 was significantly lower. Possible mechanisms for steepening of dSaO2/dt during atelectasis are discussed.

Animals↗