Search PubMed⌕ Search

Biomedical subjects

N H Edelman

Publications and source records attributed to N H Edelman.

At least 55 records · Page 3Linked to original sources
PubMed1988

Central nervous system control of airway tone in guinea pigs: the role of histamine.

The central nervous system (CNS) plays an important role in the reflex control of bronchomotor tone, but the relevant neurotransmitters and neuromodulators have not been identified. In this study we have investigated the effect of histamine. Anesthetized male guinea pigs were prepared with a chronically implanted intracerebroventricular (icv) cannula and instrumented for the measurement of pulmonary resistance (RL), dynamic lung compliance (Cdyn), tidal volume (VT), respiratory rate (f), blood pressure (BP), and heart rate (HR). Administration of histamine (2-30 micrograms) icv caused a significant (P less than 0.05) reduction of Cdyn with no change in RL, VT, and f. At a dose of 100 micrograms icv, histamine caused an increase in RL (202 +/- 78%), a reduction of Cdyn (77 +/- 9%), an increase in f (181 +/- 64%), and a reduction of VT (53 +/- 18%). There were no changes in BP and HR after 100 micrograms of icv histamine. In contrast, intravenous administration of histamine (0.1-2 micrograms/kg) caused a dose-dependent decrease in Cdyn and increase in RL that was associated with tachypnea at each bronchoconstrictor dose. Intravenous histamine (2 micrograms/kg) produced a fall in BP and an increase in HR. The bronchoconstrictor responses to icv histamine were completely blocked by vagotomy and significantly reduced by atropine (0.1 mg/kg iv), whereas vagotomy and atropine did not block the bronchospasm due to intravenous histamine. Additional studies indicated that the pulmonary responses due to icv histamine (100 micrograms) were blocked by pretreatment with the H1-antagonist chlorpheniramine (1 and 10 micrograms, icv). These data indicate that histamine may serve a CNS neurotransmitter function in reflex bronchoconstriction in guinea pigs.

Airway Resistance↗
PubMed1988

Genioglossal and diaphragmatic EMG responses to hypoxia during sleep.

Activation of pharyngeal dilator muscles, such as the genioglossus, during hypoxia must be sufficient to overcome the increased subatmospheric pressure generated by the diaphragm. This is particularly important during sleep, when upper airway resistance is greater. We measured ventilatory, genioglossal (EMGgg) and diaphragmatic (EMGdi) electromyogram responses to isocapnic hypoxia during wakefulness (W), slow-wave sleep (SWS), and rapid eye movement (REM) sleep in seven chronically instrumented adult goats. We also compared the EMG responses to hypoxia to response to CO2 during W. delta EMGdi/delta SaO2 decreased progressively from W to SWS (p less than 0.05) to REM sleep (p less than 0.05 versus SWS), paralleling the corresponding ventilatory responses. EMGgg was activated only below an SaO2 threshold, similar during W (69.8 +/- 6.3%) and SWS (67.2 +/- 4.3%), beyond which there was a brisk linear increase. During REM sleep, arousal preceded activation of EMGgg in each animal, although SaO2 at arousal (61.3 +/- 4.4%) was less than the SaO2 threshold for EMGgg activation during W or SWS (p less than 0.05). Despite state-related differences in the individual muscle responses, simultaneous EMGgg and EMGdi during hypoxia or hypercapnia in W, and during hypoxia in SWS and REM sleep, were linked in a constant manner. This suggests common integration of central and peripheral chemoreceptor inputs. Furthermore, these relationships are unaffected by either SWS or REM sleep.

Animals↗
PubMed1987

Naloxone reduces ventilatory depression of brain hypoxia.

To assess whether endogenous opioids participate in respiratory depression due to brain hypoxia, we determined the ventilatory response to progressive carboxyhemoglobinemia (1% CO, 40% O2) before and after administration of naloxone (NLX, 0.1 mg/kg iv). Minute ventilation (VI) and ventral medullary surface pH (Vm pH) were measured in six anesthetized, peripherally chemodenervated cats. NLX consistently increased base-line hyperoxic VI from 618 +/- 99 to 729 +/- 126 ml/min (P less than 0.05). Although NLX did not alter the Vm pH response to CO [initial alkalosis, Vm pH +0.011 +/- 0.003 pH units, followed by acidosis, Vm pH -0.082 +/- 0.036 at carboxyhemoglobin (HbCO) 55%], NLX attenuated the amount of ventilatory depression; increasing HbCO to 55% decreased VI to 66 +/- 6% of base line before NLX and to 81 +/- 9% of base line after NLX (P less than 0.05). The difference in response after NLX was primarily the result of a linear increase in tidal volume (VT) with decreasing Vm pH (delta VT = 60.3 ml/-pH unit) which was absent before NLX. To assess whether the site of action of the endogenous opioid effect was the central chemosensors, the ventilatory and Vm pH response to progressive HbCO was determined in three additional cats before and after topical application of NLX (3 X 10(-4) M) to the ventral medullary surface. The effect of topical NLX was similar to systemic NLX; significant attenuation of the reduction in VI with increasing HbCO. We conclude that 1) endogenous opioids mediate a portion of the depression of ventilation due to acute brain hypoxia, and 2) this effect is probably at the central chemosensitive regions.

Administration, Topical↗
PubMed1987

NHLBI workshop summary. Respiratory disorders of sleep. Pathophysiology, clinical implications, and therapeutic approaches.

The extensive investigation into complex interactions of breathing and sleep have produced answers to numerous important questions, but it is clear that many of the most important questions in this area remain unanswered. Our understanding of the mechanisms through which sleep alters breathing and how disordered breathing can, in turn, effect sleep is rudimentary. Although a large body of recent work has done much to elucidate the factors that act to maintain the patency of the upper airway during sleep, our understanding of such mechanisms and the relative importance of structure and function in this context remains primitive. A better understanding of these issues will be critical in elucidating the pathophysiology of respiratory disorders of sleep. Although some progress has been made in this area, new insights will be critically important to the design of novel, potentially more effective approaches to treatment. Therapeutic decisions are greatly hampered by major uncertainties regarding respiratory disorders of sleep and the clinical significance of symptoms, signs, and laboratory findings, and their relationship to morbidity and mortality. It seems clear that new information regarding the pathophysiology and natural history of these disorders will be important in the development of new, more effective strategies for therapeutic intervention, and this together with rigorous, systematic evaluation of new and future therapeutic approaches will be critical to clinical progress in this field.

Airway Resistance↗
PubMed1987

Correlation between genioglossal and diaphragmatic responses to hypercapnia during sleep.

Oropharyngeal patency during sleep is dependent on the dilating force of the genioglossus, the main tongue protrusor muscle. We measured the ventilatory (Vl), diaphragmatic (EMGdi), and genioglossal (EMGgg) electromyographic responses to CO2 in awake and sleeping goats; delta Vl/delta PETCO2 decreased from awake (0.85 +/- 0.087 L/min/mm Hg) to NREM sleep (0.69 +/- 0.069) to REM sleep (0.57 +/- 0.078, p less than 0.005 versus awake). There were minimal decreases in delta EMGdi/delta PETCO2 and EMGdi at a PETCO2 of 55 mm Hg from awake to NREM, but a significant decrease in EMGdi at a PETCO2 of 55 mm Hg during REM sleep (p less than 0.025 versus NREM). Inspiratory EMGgg was only present above a PCO2 threshold, which was similar for each state (49.3 +/- 2.3 mm Hg PETCO2 awake, 48.8 +/- 2.4 during NREM, 49.5 +/- 2.5 during REM), and delta EMGgg/delta PETCO2 tended to be less during both sleep states compared with that while awake (p = 0.10). At any PCO2, inspiratory EMGgg was markedly inhibited during REM sleep when rapid eye movements were present (phasic REM). We conclude that there is disproportionate inhibition of the genioglossus relative to the diaphragm at low CO2 tensions and at any PCO2 during phasic REM sleep. This imbalance may predispose the upper airway to inspiratory occlusion during sleep.

Animals↗
PubMed1987

Obstructive sleep apnea following bilateral carotid body resection.

A patient who had undergone bilateral carotid body resection five years earlier for palliation of chronic airflow obstruction was found to have severe obstructive sleep apnea. He presented with hypercapnic respiratory failure, which improved after tracheostomy. A physiologic mechanism is proposed to explain this association. Previously reported studies of anesthetized animals suggest that loss of peripheral chemoreceptor activity could selectively decrease neural output to the genioglossus, the main protrusor muscle of the tongue, predisposing the upper airway to inspiratory occlusion.

Carotid Body↗
PubMed1986

Correlation between ventilation and brain blood flow during hypoxic sleep.

Ventilation and brain blood flow (BBF) were simultaneously measured during carbon monoxide (CO) inhalation in awake and sleeping goats up to HbCO levels of 40%. Unilateral BBF, which was continuously measured with an electromagnetic flow probe placed around the internal maxillary artery, progressively increased with CO inhalation in the awake and both sleep stages. The increase in BBF with CO inhalation during rapid-eye-movement (REM) sleep (delta BBF/delta arterial O2 saturation = 1.34 +/- 0.27 ml X min-1 X %-1) was significantly greater than that manifested during wakefulness (0.87 +/- 0.14) or slow-wave sleep (0.92 +/- 0.13). Ventilation was depressed by CO inhalation during both sleep stages but was unchanged from base-line values in awake goats. In contrast to slow-wave (non-REM) sleep, the ventilatory depression of REM sleep was primarily due to a reduction in tidal volume. Since tidal volume is more closely linked to central chemoreceptor function, we believe that these data suggest a possible role of the increased cerebral perfusion during hypoxic REM sleep. Induction of relative tissue alkalosis at the vicinity of the medullary chemoreceptor may contribute to the ventilatory depression exhibited during this sleep period.

Animals↗
PubMed1986

The role of endogenous opioids in the ventilatory response to acute flow-resistive loads.

The ability of acute, short-term, inspiratory flow-resistive loading to generate endogenous opioids was studied in 6 unanesthetized goats. Endogenous opioid generation was assessed by measurement of immunoreactive beta-endorphin levels in the cisternal cerebrospinal fluid (CSF) after high (80 cm H2O/L/s) and moderate (50 cm H2O/L/s) resistive loading. The results show that CSF levels of beta-endorphin were significantly increased by both the high and moderate resistive loads (40 +/- 4 SEM pg/ml and 33.7 +/- 3.4 pg/ml, respectively) when compared with the same animals during unloaded control conditions (19.5 +/- 3.8 pg/ml). Both levels of loading also caused a significant progressive decline in tidal volume (to 82 +/- 8 and 89 +/- 8% of baseline tidal volume with the high and moderate loads, respectively). Naloxone administration (0.1 mg/kg) resulted in a transient but significant increase in tidal volume from the sixth through the twentieth minute (to 37 +/- 5 and 34 +/- 5% peak tidal volume increase with high and moderate loads, respectively). In addition, there was a significant correlation between the percent decline in tidal volume and mean inspiratory flow rate after loading and the level of beta-endorphin in the cisternal CSF. We conclude that relatively short-term, high-level, inspiratory flow-resistive loading results in elaboration of endogenous opioids within the central nervous system and that these opioids play a role in the progressive decline in tidal volume and mean inspiratory flow rate exhibited during these conditions.

Animals↗
PubMed1985

Effect of locus coeruleus stimulation on regional cerebral oxygen consumption in the cat.

Regional cerebral oxygen consumption was determined during stimulation of the intra-axial noradrenergic pathway to quantitate the metabolic effects of this manipulation on cerebral oxygen extraction, cerebral blood flow (CBF) and its regional distribution. Regional arterial and venous oxygen saturation were examined microspectrophotometrically. Regional CBF was examined using radioactively tagged microspheres (15 +/- 3 microns in diameter). Oxygen consumption was calculated as the regional product of CBF and oxygen extraction. Bipolar concentric electrodes were stereotaxically implanted bilaterally in the locus coeruleus of alpha-chloralose anesthetized, artificially respired adult mongrel cats. The control group was killed after hemodynamic and CBF measurements were taken. The experimental group was sacrificed after these same measurements were taken before and during 10 min of bilateral locus coeruleus stimulation. The cats' heads were simultaneously sawed in 3 places and quickly frozen in liquid nitrogen-cooled propane. Systolic blood pressure was significantly increased during treatment. The heterogeneity of venous oxygen saturation was significantly reduced by stimulation. Average CBF and oxygen consumption were significantly decreased to 57% and 59% of control, respectively. Oxygen consumption was significantly reduced in the hypothalamus from 1.5 +/- 0.3 to 0.9 +/- 0.3 ml O2/min/100 g and from 3.5 +/- 0.9 to 1.2 +/- 0.4 ml O2/min/100 g in the cerebellum by treatment. Changes in the neuronal and/or synthetic cerebral activity produced regional decreases in cerebral oxygen consumption and secondarily altered CBF. These changes are probably due to interaction of the intraparenchymal noradrenergic pathways with other systems or processes in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Ventral medullary pH and ventilatory responses to hyperperfusion and hypoxia.

The role of a sudden increase in brain perfusion on ventral medullary surface pH (Vm pH) and minute ventilation (VI) was assessed in anesthetized peripherally chemo denervated cats. Acute hypertension (AH), produced by rapid inflation of an aortic balloon, and hypoxemia, produced with either inhalation of 1% CO (COHx) or inhalation of a hypoxic gas (HHx), were used to increase brain blood flow. In the AH group, increasing arterial blood pressure (from 122 +/- 3 to 180 +/- 5 mmHg) caused a rapid (less than 5 s) increase in Vm pH in every trial (n = 18). Associated with the mean peak increases in Vm pH (0.003 +/- 0.0004 pH units) were significant decrease in tidal volume (7-9%). In the COHx group, 17% HbCO caused a significant increase in Vm pH (0.003 +/- 0.0005 pH unit) and diminution of VI (9%). Further increases in HbCO caused a progressive ventral medullary acidosis and greater reductions in VI. The results from the HHX group were qualitatively similar to the COHx group; there was a biphasic response of Vm pH, i.e., an initial increase in Vm pH (0.008 +/- 0.001) followed by a steady decrease in Vm pH, with reductions in VI associated with both phases. We conclude that hyperperfusion, per se, produces an increase in Vm pH and a reduction in VI equivalent in magnitude to that predicted from the CO2 stimulus-response curve; the alkalotic shift in Vm pH and concomitant diminution in VI associated with mild hypoxia is probably related to an increase in ventral medullary perfusion; and the ventilatory depression associated with the medullary acidosis of moderate brain hypoxia must be attributed to another mechanism.

Acid-Base Equilibrium↗
PubMed1985

Opioids and breathing.

This review summarizes recent developments on the effects of opiate drugs and the various endogenous opioid peptides on breathing. These developments include demonstration of receptors and site-specific effects of application of opioids in the pons and medulla, demonstration of variable tolerance of respiratory responses in addicted individuals as well as their offspring, and demonstration of an endogenous opioid influence on breathing in early neonatal life and in certain physiological settings and disease states. The validity and limitations of using naloxone as a tool to uncover postulated endogenous opioid influences are also discussed as well as the potential problems imposed by the various settings in which this opiate antagonist drug is used. It is concluded that some parallelism exists between the role of endogenous opioids in pain modulation and their role in respiration especially in adults. Although more studies are needed especially with regard to defining specific effects of the various opioid receptors and ligands, it is felt that the effects of endogenous opioids on the control of breathing will probably be one of modulating the responses to drugs or nociceptive respiratory stimuli through inhibitory pathways.

Adult↗
PubMed1985

Nutritional emphysema in the rat. Influence of protein depletion and impaired lung growth.

Emphysema is produced by severe food restriction in rats and is postulated to result from depletion of lung connective tissue. We studied (1) whether total dietary protein depletion worsens nutritional emphysema, and (2) whether the reduced content of lung connective tissue in nutritional emphysema results from lack of accumulation caused by impaired lung growth or by a net loss from the lung. Lewis rats weighing 200 g were restricted to one third food intake with or without protein for 6 wk. Lungs were assessed by morphometry, pressure-volume (P-V) measurements, and content of collagen and elastin. Emphysema was found by morphometry (but not by P-V measurements) in food-restricted rats, and contrary to expectation, emphysema was less severe in those depleted of protein. Collagen and elastin content were reduced in emphysematous lungs; however, the levels were not below those found prior to nutritional intervention, suggesting that lack of growth, not depletion, accounts for the reduced content.

Animals↗
PubMed1984

Nonuniform brain blood flow response to hypoxia in unanesthetized cats.

In seven unanesthetized cats, radiolabeled microspheres were used to determine regional brain blood flow (rBBF) to the medulla-pons (M-P), midbrain-thalamus (M-T), cerebellum (Cb), and cortex (Cx) during three conditions: 1) control [arterial O2 tension (PaO2) = 81 Torr, arterial CO2 tension (PaCO2) = 26 Torr]; 2) hypocapnic hypoxia (PaO2 = 39 Torr, PaCO2 = 22 Torr); and 3) isocapnic hypoxia (PaO2 = 47 Torr, PaCO2 = 26 Torr). Hypoxia increased blood flow significantly more in the caudal brain stem (M-P) than in the Cx (P less than 0.05) during both hypocapnic hypoxia (M-P/Cx: +33/ +17 ml X min-1 X 100 g-1) and isocapnic hypoxia (M-P/Cx: +13/ -2 ml X min-1 X 100 g-1). Since sympathetic innervation is greater anatomically to rostral than to caudal vessels, we examined the rBBF response to hypocapnic hypoxia in seven additional cats after unilateral superior cervical gangliectomy. All seven cats had a reduction in the cortical-to-caudal brain stem trend on the denervated side of the brain (M-P/Cx: +27/+28 ml X min-1 X 100 g-1) compared with the intact side of the brain (M-P/Cx: +34/+24 ml X min-1 X 100 g-1) owing to both increases in Cx and decreases in M-P flows. We conclude that in unanesthetized cats hypoxia causes a greater increase in the caudal brain stem compared with cortical blood flow, and this differential response is related to modulation by the sympathetic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Determinants of the ventilatory responses to hypoxia during sleep.

Disagreement exists on the effect of sleep on hypoxic ventilatory responses. We hypothesized that these differences were due to variabilities in methodology of inducing hypoxia, specifically, as they pertained to the PCO2 level during the studies. We therefore measured ventilatory responses to hypoxia with (eucapnic) and without (hypocapnic) added CO2 during wakefulness and sleep in 7 goats. Eucapnic responses to hypoxia were significantly decreased during both slow wave (SWS) and REM sleep. This decrease was not apparent when hypocapnia was allowed to occur. In 4 goats also provided with electromagnetic flow probes for brain blood flow (BBF) measurements, hypocapnia significantly attenuated the increase in BBF induced by hypoxia during both the awake and SWS stages. Concomitantly measured cerebral venous blood also showed lower oxygen tension during hypocapnia. We postulate that under hypocapnic conditions, the depressant effects of brain hypoxia may contribute to the obscuring of differences in hypoxic responses during wakefulness and sleep.

Animals↗
PubMed1984

Effect of naloxone on the respiratory responses to hypoxia in chronic obstructive pulmonary disease.

Ventilatory and airway occlusion pressure responses to hypoxia were measured in 7 subjects with chronic obstructive pulmonary disease (COPD). Paired responses were obtained after the administration of saline or naloxone and, on separate days, in 5 of the 7 subjects, after 2 saline injections. Naloxone increased (p less than 0.05) the mean inspiratory flow and the ventilatory and airway occlusion pressure responses to hypoxia when compared with the saline responses. Resting ventilation and tidal volume also increased, but not significantly. Involvement of endogenously generated opioid substances in the control of breathing of patients with COPD is further suggested by this study.

Humans↗
PubMed1984

Effect of naloxone on ventilatory control in parents of victims of sudden infant death syndrome.

To determine whether the decreased responses to CO2, hypoxia, and flow resistive loads in parents of sudden infant death syndrome (SIDS) victims are due to an effect of endogenous opioids, we tested response to these stimuli in 10 parents (5 couples) of such children after injection of saline placebo and after injection of naloxone hydrochloride (3 mg). The responses after saline were comparable to those of our previous study, i.e., lower than normal. Ventilatory response to CO2 and hypoxia, as well as airway occlusion pressure responses to flow resistive loading, were not significantly different after naloxone compared with saline. We concluded that increased endogenous opioids do not play a significant role in these subjects' reduced ventilatory drive.

Adult↗