Barbara Gothe

Sleep apnea considered as a control system instability.

In the present study a mathematical model of the chemical control of respiration is described which attempts to simulate periodic breathing during sleep. The model is an extension of an earlier model which has been shown to successfully reproduce the transient effects of CO2 inhalation on breathing, controlled changes in ventilation on arterial gas tension, and Cheyne-Stokes breathing. Included in the extended model are the effects of chemical stimuli during sleep on both chest wall and upper airway muscle activity. Data is presented indicating that simulations from the model reproduce reasonably well the essential features of the results obtained in eight subjects with periodic respiration during sleep when breathing room air, O2, or low concentrations of CO2. Simulations from the model and the experimental data suggest that periodic breathing during sleep results from unstable operation in the respiratory control system analogous to that seen during instabilities in physical control systems. The model indicates that obstructive as well as central apneas can be produced by control system instability. Furthermore, central apneas increase the likelihood of obstructive apneas while obstructive apneas tend to aggravate the control instability. The model results predict that the characteristics of the periodic breathing seen during sleep, such as apnea length, will depend on circulation time and the sensitivity of both upper airway and chest wall muscles to hypercapnia and hypoxia.

Familial 'sleep apnea plus' syndrome: Report of a family

We describe a familial disorder consisting of sleep apnea, anosmia, colorblindness, partial complex seizures, and cognitive dysfunction. The phenotypic expression of the syndrome suggests an autosomal dominant inheritance with incomplete penetrance.

Trimethoprim-sulfamethoxazole prophylaxis against urinary tract infection in the chronic spinal cord injury patient

Suppressive therapy with antibiotics has long been thought to decrease the number of complications from the neuropathic bladder in spinal cord injury patients, but it may also induce resistance to antibiotics which subsequently causes difficulties in treating symptomatic urinary tract infections. Forty-three chronic spinal cord injury patients were randomized to continue to receive daily trimethoprim-sulfamethoxazole (TMP-SMX) urinary tract prophylaxis versus discontinuing antibiotic prophylaxis. Patients were all at least 6 months after spinal cord injury. Patients were followed for a minimum of 3 months, with weekly catheter urine cultures. The difference in the colonization rate at onset and after 3 months (percent of cultures with asymptomatic bacteriuria) between the control and prophylaxis group was not statistically significant (P > 0.1). There was a significant decrease in the percentage of TMP-SMX resistant asymptomatic bacteriuria in the control group, 78.8%, compared to 94.1% in the suppressive group (P < 0.05). There was no significant difference in the number of symptomatic urinary tract infections following the withdrawal of suppressive therapy between the control group, 0.035/week, and the prophylaxis group, 0.043/week (P > 0.5). There was a larger percentage of TMP-SMX resistant symptomatic urinary tract infections in the treated group, 42.5% versus 37.5% in the control group, but the difference was not significant (P > 0.5). Irrespective of the method of bladder management, suppressive therapy with TMP-SMX did not reduce the incidence of symptomatic bacteriuria and did increase the percentage of cultures resistant to TMP-SMX in asymptomatic patients.

Factors affecting respiratory system stability

Periodic breathing (recurrent central apneas) occurs frequently during sleep. Periodic breathing can arise as a result of unstable behavior of the respiratory control system. A mathematical model of the respiratory control system was used to investigate, systematically, the effect of severity of disturbances to respiration and certain system parameters on periodic breathing occurring during sleep. The model consisted of multi-compartment representation of O2 and CO2 stores, a peripheral controller sensitive to O2 and CO2, and a central controller sensitive to CO2. The effects of hypoxia and hypercapnia on the upper airway muscles were not considered in the model. Episodes of hyperventilation or asphyxia were used to disturb the control system and explore the boundaries of stable breathing. Circulation time and metabolic rate were also varied. Simulations with the model produced the following findings: The number of central apneas associated with periodic breathing were greater as circulation time increased; controller gain increases also made the number of apneas greater, although periodic breathing occurs with lower controller gains as circulation time increases. At each level of circulation time there was a range of controller gain changes which caused little change in the number of apneas. There were more apneas with hypoxia; also the number of apneas increased with sleep-associated reductions in metabolic rate. The more rapidly resting PCO2 rose at sleep onset, the greater the likelihood of recurrent apneas. Finally, the more intense the disturbance, the more apneas there were.

INTERACTIVE EFFECTS OF CENTRAL AND OBSTRUCTIVE APNEA

Publisher Summary This chapter explores interactive effects of central and obstructive apnea. Irregularly recurring apneic periods lasting for more than ten seconds appear during sleep in one-third of normal individuals. The apneas are of two types: (1) central and (2) obstructive. Central apnea is characterized by an absence of airflow past the nose and mouth because of a cessation of respiratory efforts. In obstructive apnea, despite persistent respiratory effects, airflow ceases because of total upper airway obstruction. This study presents a mathematical model of the chemical control of breathing, which examines the hypotheses that instability in the negative feedback chemical control system, which regulates breathing, can result in central apnea during sleep. The results suggest that the model reasonably reproduces many of the features of the pattern of breathing seen in patients with recurrent sleep apnea and support the contention that obstructive and central apneas are interrelated and depend on variations in the effect of chemical drive on chest wall and upper airway muscles.

Mechanisms for Recurrent Apneas at Altitude

breathing is commonly interrupted by periods of apnea during sleep, particularly at altitude (39). These apneas have recently been classified into two types (5, 20, 28). Central apneas are those in which all respiratory activity disappears for a time; in obstructive apneas respiratory activity is continuous but airflow stops. Temporary failure of the central respiratory-pattern generator is believed to cause central apneas. Upper air blockade, on the other hand, is believed to cause obstructive apneas. Both types of apnea can be sporadic or recurrent. During sleep at sea level, apneas are most common in the very young and in the elderly and occur more frequently in males than in females (20, 28). Such apneas can be central, obstructive, or mixed (where apneas begin as central and continue during an obstructed phase), and all types can be observed in the same individual in a single night’s sleep (20, 28).

Sleep Apnea in Multiple Sclerosis

We performed polysomnography on eight randomly chosen male patients who met Posers criteria for definite multiple sclerosis (MS), to obtain an idea of the frequency and severity of sleep apnea (SA) in this population. Ages ranged from 27 to 67 years (mean, 50 years). The mean Kurtzkes disability score was 6.1. Only one complained of awakenings with shortness of breath. Otherwise, none had a history of sleep disorder or significant pulmonary disease. We found that two patients had an apnea index greater than 5, with oxygen desaturation to 60% in one. Two others had apnea indices less than 5, but had oxygen desaturation to 59% and 81% during the apneas. Two patients had apnea indices less than 5 without oxygen desaturation. The apneas were mainly central type, except in one who had a mixed central-obstructive pattern. These preliminary results suggest that SA in MS may be more frequent than suspected, and it can be associated to significant oxygen desaturation in some cases. The potential impact of SA in MS deserves further evaluation. Key Words: Sleep apnea—Multiple sclerosis—Automatic respiration—Central apneas—Apneas with central nervous system lesions.