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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of sustained awake hypercapnia in the obstructive sleep apnea syndrome (OSA) is unknown. Recent work has implicated coexisting chronic airflow limitation (CAL) as an important contributing factor. We approached this question by studying consecutive patients with both OSA syndrome and severe CAL in detail and comparing those with and without retention of CO2 while awake. Of 28 patients with both severe OSA (mean NREM apnea index = 48 +/- 9, SEM) and severe CAL (mean FEV1 = 1.07 +/- 0.07 L), 14 had persistent awake hypercapnia (mean PaCO2 = 50 +/- 1 mm Hg), and 14 were normocapnic (mean PaCO2 = 40 +/- 1 mm Hg). When separated according to their PaCO2 level, there was no difference in the apnea indices in both non-rapid-eye-movement (NREM) sleep, or rapid-eye-movement (REM) sleep, although the hypercapnic group had lower average levels of oxyhemoglobin saturation in both NREM (SaO2 = 77 +/- 2% versus 85 +/- 3%, p less than 0.05) and REM (SaO2 = 60 +/- 4% versus 82 +/- 3%, p less than 0.001) sleep. The mean values for FEV1, VC, lung volumes, and diffusing capacity for CO measured while awake did not differ. The hypercapnic group had lower awake PaO2 levels (p less than 0.001), were heavier (p less than 0.05), had narrower upper airway size on CT scan measurements (p less than 0.01), and gave a history of much heavier alcohol intake (p less than 0.05). Our results demonstrate that some patients with severe OSA and severe CAL can maintain normal awake arterial CO2 levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Obstructive sleep apnea with severe chronic airflow limitation. Comparison of hypercapnic and eucapnic patients. 281 88

The electromyograms of the rectus abdominis, external oblique, and transversus abdominis muscles were recorded in eight lightly anesthetized, spontaneously breathing dogs. During quiet breathing in the supine posture seven animals invariably had a phasic expiratory activity in the transversus, whereas only two animals had invariable expiratory activity in the external oblique. An intermittent expiratory activity in the rectus was recorded in only one animal. The degree of activation, expressed as a percentage of the activity detected during breathing with 25 cm H2O positive end-expiratory pressure (PEEP), was also significantly greater (P less than 0.05) for the transversus (mean +/- SEM: 29.4 +/- 8.6%) than the external oblique (5.5 +/- 2.3%). Head up tilting and progressive hypercapnia elicited substantial increases in transversus and external oblique expiratory activity in all animals, whereas head down tilting caused marked decreases in expiratory activity. In each posture and at any given end-tidal CO2, however, the amount of transversus activity was larger than the amount of external oblique activity. The rectus was usually silent in all the conditions. Bilateral cervical vagotomy suppressed external oblique activity in most supine animals, and the muscle was no longer recruited by PEEP, head up tilting, or hypercapnia. In contrast, there was residual transversus expiratory activity in all supine animals (11.1 +/- 3.1%), as well as some expiratory recruitment during PEEP, head up tilting, and hypercapnia. These results indicate that: (1) the transversus is the primary abdominal muscle of expiration in the anesthetized dog; and (2) its behavior resembles that of the triangularis sterni, although it is more dependent on vagal afferent pathways. The present findings also strengthen the important fact that spontaneous quiet expiration in the dog is an active rather than passive process.
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PMID:Abdominal muscle use during breathing in the anesthetized dog. 295 99

The present study was designed to determine the effect of changes in gases and pH in the blood on kinetics and passage to the cerebrospinal fluid (CSF) of phenytoin (DPH). Five groups of 6 rabbits were used, a control [with a mean partial pressure (Pa) of oxygen of 84 +/- 2 (SEM) mmHg, partial pressure of carbon dioxide (PaCO2) of 23 +/- 1 mmHg and pH = 7.512 +/- 0.018], a second group with hypercapnia (PaCO2 = 65 +/- 3 mmHg, pH = 7.244 +/- 0.008), a third group with hypoxemia (PaO2 = 48 +/- 2 mmHg), a fourth group with hypercapnia combined with hypoxemia (PaCO2 = 72 +/- 3 mmHg, PaO2 = 51 +/- 1 mmHg and pH = 7.252 +/- 0.008) and a fifth group with metabolic acidosis (pH = 7.232 +/- 0.011). All animals were conscious during the experiments following the administration of 10 mg/kg (i.v.) of phenytoin, hypoxemia decreased the clearance of phenytoin from 4.20 +/- 0.55 to 2.65 +/- 0.44 ml/min per kg (P less than 0.05) and consequently the area under the plasma concentration/time curve (AUC) for phenytoin increased (2575 +/- 319 to 4316 +/- 740 micrograms min/ml; P less than 0.05). Metabolic acidosis increased the volume of distribution of phenytoin from 780 +/- 70 to 1103 +/- 65 ml/kg (P less than 0.01). The protein binding of phenytoin was not affected by any of the experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of hypercapnia and/or hypoxemia and metabolic acidosis on kinetics and concentrations of phenytoin in the cerebrospinal fluid of conscious rabbits. 309 75

Regional (frontal, parietal, occipital, cortical, and basal ganglia) cerebral blood flow (rCBF) was examined at 1.5 and 3.5 MAC inspired isoflurane/O2 anesthesia in the rat using the radioactive microsphere technique to determine the effects of controlled hypotension with deep isoflurane anesthesia on rCBF and the response of rCBF to changes in PaCO2 when mean blood pressure (BP) was decreased to levels below the lower limit of the autoregulatory threshold. Four groups of six rats were studied with rCBF 1 determined at 1.5 MAC (mean BP 80-90 mm Hg) followed by two rCBF determinations at 3.5 MAC (mean BP 46-48 mm Hg). For CBF 1 the regional CO2 response was a 3.1-3.9% increase in rCBF/mm Hg increase in CO2. Regional cerebral blood flow (ml/g/min) ranged from 0.64 +/- 0.05-0.83 +/- 0.15 at PaCO2 of 19 mm Hg to 1.34 +/- 0.11-1.80 +/- 0.33 at PaCO2 of 41 mm Hg to 2.61 +/- 0.26-3.72 +/- 0.37 at PaCO2 of 59 mm Hg (mean +/- SEM). With controlled hypotension (CBF 2) rCBF was unchanged during normocarbia, increased 100% during hypocarbia, P less than 0.01 vs CBF 1 and decreased 30% during hypercarbia, P less than 0.01 vs CBF 1. For rCBF 3 measurements, the BP and inspired concentration of isoflurane were kept constant, while PaCO2 was increased in two and decreased in two of the four groups. Within-group comparisons between rCBF 2 and rCBF 3 results demonstrated loss of CO2 responsiveness of the rat cerebrovasculature in every region during controlled hypotension to below the autoregulatory threshold at 3.5 MAC isoflurane/O2 anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional cerebral blood flow and response to carbon dioxide during controlled hypotension with isoflurane anesthesia in the rat. 312 43

In patients with obstructive apnea, it was hypothesized that stimulation of the ventilatory system by hypercapnia during sleep would increase pharyngeal inspiratory muscle activity and thereby increase upper airway caliber. We predicted that this increase in caliber would decrease the number of apneas and sleep time spent apneic. In contrast, suppression of the ventilatory system activity with hyperoxia was predicted to decrease both inspiratory muscle activity and pharyngeal caliber and thereby increase the number of apneas and apnea time. In all 7 patients with symptomatic obstructive sleep apnea studied, 3 with upper airway narrowing obvious during wakefulness, inhalation of 3 to 6% CO2 preferentially stimulated upper airway inspiratory muscle tonic electrical activity relative to the activity of chest wall inspiratory muscles and diminished periodic breathing. Apnea time decreased from 60 +/- 2% (mean +/- SEM) of sleep time during ambient air inhalation to 12 +/- 3% during CO2 inhalation; 50% O2 had the reverse effect on inspiratory muscle tonic electrical activity and increased apnea time to 75 +/- 5% of sleep time. We conclude that manipulation of inspiratory muscle tonic activity and alteration of the pattern of breathing by CO2 and O2 inhalation lead to significant changes in the pattern of upper airway inspiratory collapse during sleep. We speculate that physiologic variables related to the control of upper airway inspiratory muscle function are instrumental in the pathophysiology of obstructive sleep apnea.
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PMID:Alteration in obstructive apnea pattern induced by changes in oxygen- and carbon-dioxide-inspired concentrations. 314 3

Our previous experiments have shown that thromboxane A2 is a strong contractor of cerebral arterial smooth muscle strips. The objective of these experiments was to determine if U 46619, a stable thromboxane A2 mimetic, affects the cerebral microcirculation in vivo. Pial arteriole diameter in rabbits and rats was measured with a microscope using the closed cranial window technique. Topical application of 10(-11) to 10(-6) M U 46619 induced dose-dependent arteriole vasoconstriction in both species. In rabbits and rats the maximum vasoconstriction was 9.7 +/- 1.3% (mean +/- SEM) and 14.0 +/- 0.5%, respectively. In rats, 10(-7) and 10(-6) M U 46619 induced intravascular platelet aggregation accompanied by a further decrease in diameter and transient occlusion of the arterioles and venules. U 46619 had no significant effect on rabbit pial arterioles that were predilated by hypercapnia or hypercapnia plus hypoxia. Our data suggest that in animals with a normal vasculature, thromboxane A2 may be a moderate constrictor of cerebral arterioles and that this constrictor effect is prevented by hypercapnia and hypoxia.
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PMID:Effect of the thromboxane A2 mimetic U 46619 on pial arterioles of rabbits and rats. 360 7

We studied the effect of systemic hypoxemia and hypercarbia on the bronchial blood flow in open-chested, anesthetized dogs. The pulmonary artery and vein of the left lower lobe (LLL) were isolated with cannulas and connected to reservoirs set at atmospheric pressure relative to the base of the LLL. That fraction of the bronchial arterial flow (Qbr) to the LLL, which flowed through the bronchopulmonary anastomoses into these reservoirs, was continuously measured. The LLL was inflated continuously with 6% CO2 and air at a constant alveolar pressure of 10 cm H2O. Systemic arterial O2 tension (PaO2) and arterial CO2 tension (PaCO2) were varied by separately ventilating the right lung through a bifurcated endotracheal tube. A 10-min period was allowed for stabilization after each change in experimental condition. Anastomotic Qbr was measured for 5 min during each experiment. In separate animals, similar studies were performed before and 30 min after intravenously administered indomethacin (6 mg/kg body weight). During normoxic conditions when PaO2 was 79 +/- 8 torr (mean +/- SEM), the mean anastomotic Qbr was 5.7 +/- 2.0 ml/min (n = 9). This flow increased to 8.3 +/- 2.5 ml/min (p less than 0.05) during hypoxemic conditions (PaO2, 38 +/- 3). The anastomotic Qbr increased from 5.8 +/- 1 to 9.0 +/- 2 ml/min (p less than 0.005) when PaCO2 was increased from 23 +/- 1 to 47 +/- 2 torr (n = 11). Pretreatment with intravenously administered indomethacin blocked both the hypoxemia-induced (n = 4) and hypercarbia-induced (n = 4) increases in anastomotic Qbr. We conclude that both hypoxemia and hypercarbia increased the anastomotic Qbr through a mechanism involving cyclooxygenase products of arachidonic acid.
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PMID:Hypoxia and hypercarbia increase bronchial blood flow through bronchopulmonary anastomoses in anesthetized dogs. 372 66

The mechanisms responsible for the development of chronic hypercapnia in patients with obstructive sleep apnea (OSA) are not well defined. Therefore, we tested the hypothesis that diffuse airway obstruction may be involved by studying 50 patients with a well-documented OSA syndrome. Seven patients had daytime hypercapnia with a mean PaCO2 of 51 +/- 2 (SEM) mm Hg, compared to a PaCO2 of 35 +/- 1 in the other 43 patients. There were no differences between the 2 groups in the number or duration of nocturnal obstructive events. In contrast, the hypercapnic patients were significantly heavier than the normocapnic patients (body weight, 189 +/- 11 versus 148 +/- 6% of ideal; p less than 0.005) and had evidence of diffuse airway obstruction, as indicated by an increased residual volume and a reduction in all expiratory flow rates. When the hypercapnic patients were compared with a weight-matched group of 9 normocapnic patients (body weight, 196 +/- 8% of ideal), there were still no differences in nocturnal obstructive events, but the differences in tests of airway mechanics persisted. Multiple regression analysis of PaCO2 against several anthropometric, respiratory physiologic, and polysomnographic variables revealed that only 2 variables (expiratory reserve volume and FEV1/FVC), both of which are influenced by airway mechanics, were significantly correlated with PaCO2 (multiple r = 0.78; p = 0.0001). The findings suggest that OSA alone does not produce daytime hypercapnia even in obese patients, and that the presence of diffuse airway obstruction is an important predisposing factor to the development of chronic CO2 retention in such patients.
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PMID:Role of diffuse airway obstruction in the hypercapnia of obstructive sleep apnea. 377 88

The purpose of this study was to determine the effect of sympathetic nerve stimulation on regional cerebral blood flow during the first 3 wk of postnatal development in piglets. Forty-one piglets ranging in age from 2 to 24 days were studied while anesthetized with 30% N2O, paralyzed and mechanically ventilated (PaCO2 = 35-40 mm Hg). Regional cerebral blood flow was measured with tracer microspheres (15 +/- micron) during electrical stimulation (15 Hz, 15 V, 3 ms) of the right cervical sympathetic trunk. Sympathetic stimulation decreased blood flow to the ipsilateral cerebrum (gray and white matter) (-15 +/- 2%), hippocampus (-9 +/- 2%), choroid plexus (-50 +/- 5%), and masseter muscle (-93 +/- 2%) compared to the contralateral side where blood flow to these regions was 74 +/- 4, 45 +/- 2, 258 +/- 26, and 24 +/- 4 ml/min/100 g, respectively (mean +/- SEM; p less than or equal to 0.05). The magnitude of the reduction in cerebral blood flow was not dependent on postnatal age as no significant differences were noted when the piglets were grouped according to age. Hypercapnia (PaCO2 = 64 +/- 5 mm Hg) increased blood flow 2- to 4-fold above control in all brain regions except the choroid plexus. The effect of sympathetic nerve stimulation was augmented during hypercapnia where blood flow to the ipsilateral cerebrum, hippocampus, and caudate nucleus was decreased by -34 +/- 4, -23 +/- 5, and -16 +/- 3%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of sympathetic nerve stimulation on cerebral blood flow in newborn piglets. 394 23

Recent studies have shown that the antiemetic neuroleptic drug, prochlorperazine, is a potent stimulant of the ventilatory response to hypoxia. To investigate whether or not this effect persisted in the presence of central depression of ventilatory drive, the effects on ventilatory control of morphine with and without prochlorperazine were studied in 12 normal humans. Measurement of resting ventilation and the ventilatory responses to progressive hypercapnia and to transient asphyxia were made before and 15 min after morphine (0.15 mg/kg) given intravenously. Prochlorperazine (12.5 mg) was then administered intravenously to 6 study subjects and saline to 6 control subjects. After a further 10 min, resting ventilation and chemoreceptor function were remeasured. After the administration of morphine, resting ventilation, the ventilatory response to hypercapnia, and the ventilatory response to asphyxia were all significantly decreased (p less than 0.01 in each case; mean effect in control and study group were, respectively, -16 and -17%, -50 and -32%, -46 and -55%). Administration of saline produced no significant additional changes in the 6 control subjects. By contrast, administration of prochlorperazine to the 6 study subjects markedly increased the ventilatory response to asphyxia to levels significantly greater than postmorphine values (p less than 0.005; 2.38 +/- 0.22 L . min-1 . % Sao2 versus 0.80 +/- 0.14 L . min-1; mean +/- SEM). Resting ventilation and ventilatory response to hypercapnia were not significantly affected by prochlorperazine. These results were not explained by differences in end-tidal PCO2 at which hypercapnic hypoxic tests were performed. It is concluded that prochlorperazine reverses the depression of the ventilatory response to asphyxia caused by morphine.
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PMID:The effects of combined morphine and prochlorperazine on ventilatory control in humans. 396 24


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