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J A Neubauer

Publications and source records attributed to J A Neubauer.

At least 37 records · Page 2Linked to original sources
PubMed1990

Cervical sympathetic and phrenic nerve responses to progressive brain hypoxia.

To determine if depression of central respiratory output during progressive brain hypoxia (PBH) can be generalized to other brain stem outputs, we examined the effect of PBH on the tonic (tSCS) and inspiratory-synchronous (iSCS) components of preganglionic superior cervical sympathetic (SCS) nerve activity. Peak phrenic and SCS activity were measured in nine anesthetized, paralyzed, peripherally chemodenervated, vagotomized cats. PBH was produced by inhalation of 0.5% CO in 40% O2 while blood pressure and end-tidal CO2 were maintained constant. A progressive reduction in arterial O2 content from 14.3 +/- 0.6 to 4.5 +/- 0.3 vol% caused a 79 +/- 7% depression of peak phrenic activity and an 84 +/- 10% reduction of iSCS activity, but tSCS activity increased 42 +/- 21%. During CO2 rebreathing, iSCS activity increased in parallel with peak phrenic activity while tSCS activity was unchanged. The slopes of the CO2 responses of both phrenic (6.3 +/- 1.2%max/mmHg) and iSCS (4.6 +/- 0.8%max/mmHg) activity were unaffected by PBH. In four of nine hypocapnic and three of nine hypoxic studies, inspiratory activity in the SCS nerve was observed even after completely silencing the phrenic neurogram.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Modulation of respiration during brain hypoxia.

This review is a summary of the effects of brain hypoxia on respiration with a particular emphasis on those studies relevant to understanding the cellular basis of these effects. Special attention is given to mechanisms that may be responsible for the respiratory depression that appears to be the primary sequela of brain hypoxia in animal models. Although a variety of potential mechanisms for hypoxic respiratory depression are considered, emphasis is placed on changes in the neuromodulator constituency of the respiratory neuron microenvironment during hypoxia as the primary cause of this phenomenon. Hypoxia is accompanied by a net increase in neuronal inhibition due to both decreased excitatory and increased inhibitory neuromodulator levels. A survey of hypoxia-tolerant cellular systems and organisms suggests that hypoxic respiratory depression may be a manifestation of the depression of cellular metabolism, which appears to be a major adaptation to limited oxygen availability in these systems.

Animals↗
PubMed1990

GABA antagonism reverses hypoxic respiratory depression in the cat.

We assessed the role of gamma-aminobutyric acid (GABA) as a potential causative agent of hypoxic respiratory depression by monitoring the response of the phrenic neurogram to systemic infusion of the GABA antagonist bicuculline (0.01 mg.kg-1.min-1) under control conditions and during isocapnic brain hypoxia produced by CO inhalation in separate groups of anesthetized, glomectomized, vagotomized, paralyzed, and ventilated cats with blood pressure held constant. The maximum effect of bicuculline in subseizure doses in control cats was to increase minute phrenic activity to 151 +/- 14% of preinfusion values. Infusion was continued until seizure activity was seen in the electroencephalogram. A 53% decrease of arterial O2 content resulted in a marked reduction of both peak phrenic amplitude and phrenic firing frequency to 16 and 64% of control values, respectively. Infusion of bicuculline while the level of hypoxia was maintained constant restored both peak phrenic amplitude and phrenic firing frequency to prehypoxic levels. The maximum effect of bicuculline was to increase minute phrenic activity to 123 +/- 13% of the prehypoxic value. These results suggest that although GABA has only a modest role in determining the output of the control phrenic neurogram, a significant portion of the phrenic depression that occurs during hypoxia can be attributed to inhibition of respiratory neurons by GABA.

Animals↗
PubMed1990

The role of vascular tone in the control of upper airway collapsibility.

Upper airway collapsibility may be influenced by both muscular and nonmuscular factors. Because mucosal blood volume (and therefore vascular tone) is an important determinant of nasal airway patency, vascular tone may be an important nonmuscular determinant of pharyngeal collapsibility. This hypothesis was tested in two experimental models. First, upper airway closing (CP) and opening (OP) pressures and static compliance were measured in nine anesthetized, sinoaortic-denervated, paralyzed cats with isolated upper airways. Vascular tone was decreased with either papaverine or sodium nitroprusside (NTP), and increased with phenylephrine (PE), whereas blood pressure and end-tidal CO2 were maintained constant. Vasodilation increased CP (control = -10.4 +/- 1.3, NTP = -7.3 +/- 1.2 cm H2O; p less than 0.05) and OP (control = -7.9 +/- 1.5, NTP = -3.3 +/- 1.8 cm H2O; p less than 0.05). In contrast, vasoconstriction tended to decrease CP (control = -10.7 +/- 1.5, PE = -11.7 +/- 1.4 cm H2O; p less than 0.09) and OP (control = -8.1 +/- 1.2, PE = -9.9 +/- 1.9 cm H2O; p less than 0.1). Thus, vasodilation increased and vasoconstriction tended to decrease upper airway collapsibility. Upper airway static compliance was unchanged during either drug infusion. In order to assess changes in pharyngeal cross-sectional area (CSA) that occurred during vasodilation, magnetic resonance imaging was utilized in seven cats. During vasodilation with NTP, pharyngeal CSA was reduced from 0.44 +/- 0.10 to 0.30 +/- 0.09 cm2 (p less than 0.05), and pharyngeal volume was reduced from 15.3 +/- 2.4 to 13.9 +/- 2.7 cm3 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1988

Linkage between brain blood flow and respiratory drive during rapid-eye-movement sleep.

The correlation between brain blood flow (BBF) and respiratory neuromotor output, as reflected by diaphragmatic electromyogram (EMG) activity (EMGdi), was studied during wakefulness, rapid-eye-movement (REM) sleep, and non-REM sleep (NREM). Compared with the awake state, mean BBF increased by 4.7% during NREM and by 32.6% during REM (P less than 0.001). Also, surges of BBF during REM occurred during periods of intense phasic activity. EMGdi [peak and peak/inspiratory time (TI)] was highly variable within REM periods but fluctuated as a reciprocal function of simultaneously measured BBf (r = -0.49, P less than 0.001). Furthermore, mean EMGdipeak decreased from NREM to REM in a manner reciprocally related to the corresponding change in BBF (r = -0.77, P = 0.015). These findings suggest that a component of the reduction of respiratory neuromotor output during REM is attributable to increased BBF with consequent relative hypocapnia in the central chemoreceptor environment.

Animals↗
PubMed1988

Modulation by endogenous opioids of pulmonary vasoconstrictor response to acute lung injury.

The effects of endogenously generated opioids on distribution of pulmonary perfusion (as assessed by radiolabeled microspheres) and overall gas exchange in acute acid-induced lung injury were studied. In 14 anesthesized dogs, sufficient acid was given to one lung to double shunt fraction (Qs/Qt) from 14.2 +/- 0.8 to 32.4 +/- 2.6% (SE). This resulted in a significant decrease in Po2 from 495 +/- 9 to 136 +/- 21 Torr, cardiac output from 2.47 +/- 0.27 to 1.46 +/- 0.15 1/min, and blood pressure from 139 +/- 3 to 116 +/- 5 mmHg and a significant rise in pulmonary arterial pressure from 9.6 +/- 0.8 to 14.9 +/- 0.8 mmHg. After acid instillation, microsphere distribution to the injured lung segments decreased to 50% of the base-line value. At the same time, microsphere distribution in the normal segments increased to 160% of base line. In 7 of the 14 dogs the effects of naloxone (1 mg/kg) given after lung injury were compared with the other 7 animals that were given saline. Naloxone administration caused a significant redistribution of regional pulmonary perfusion such that microsphere distribution in the injured lung segments increased by a factor of 2 at 35 min compared with the animals given saline. Consistent with this finding, Qs/Qt in the naloxone group increased to 34.7 +/- 5.0% at 35 min, whereas that of the saline group decreased to 28.2 +/- 2.5%. The difference between the two groups was significant at 35 min. These changes occurred without further alterations in cardiac output, pulmonary arterial pressure, or systemic blood pressure in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

CO2 sensitivity of cat phrenic neurogram during hypoxic respiratory depression.

The CO2 response of the phrenic neurogram before and during CO-induced isocapnic brain hypoxia was studied in peripherally chemodenervated, vagotomized, paralyzed, ventilated cats with blood pressure held constant. During inhalation of 0.5% CO in 40% O2, arterial O2 content (CaO2) was reduced to 40% and minute phrenic activity to 38.4 +/- 9.4% (SE; n = 9) of prehypoxic levels, primarily due to depression of peak phrenic amplitude (PP). CO2 response, defined as the slope of the plot of PP vs. end-tidal PCO2 during CO2 rebreathing, was unaffected by phrenic depression even to the point of total suppression of phrenic activity in two cats. The effect of the tissue metabolic acidosis associated with hypoxia on phrenic CO2 sensitivity was assessed in a separate group of cats by blocking lactate formation during hypoxia with dichloroacetate (DCA). Preventing lactic acidosis during hypoxia did not affect the CO2 response of the phrenic activity during hypoxia. We conclude that 1) hypoxic depression does not limit the ability of central respiratory neurons to respond to CO2, and 2) the failure of DCA to affect the CO2 response of the phrenic neurogram suggests that brain intracellular lactic acidosis does not modify the phrenic response to hypercapnia.

Animals↗
PubMed1988

Role of brain lactic acidosis in hypoxic depression of respiration.

The role of lactic acidosis of progressive brain hypoxia (PBH) as both a central chemoreceptor stimulant and a general respiratory depressant was assessed by preventing lactate formation both locally and globally with dichloroacetate (DCA). Phrenic nerve activity (PN) and ventral medullary pH (Vm pH) responses to PBH (1% CO-40% O2-balance N2) were determined in anesthetized, paralyzed, peripherally chemodenervated, vagotomized cats while fraction of end-tidal CO2 (FETCO2) and mean arterial blood pressure (MABP) were maintained constant. Topical DCA near the central chemoreceptors prevented the progressive Vm acidosis of PBH and was associated with a slightly greater depression of PN for any given level of brain hypoxia [75 +/- 12% base-line mock cerebrospinal fluid compared with 63 +/- 11% base-line topical DCA at O2 content of arterial blood (CaO2) of 7.5 ml O2/dl]. Systemic DCA also prevented the progressive acidosis of PBH and significantly altered the profile of depression with PBH. Before DCA, PBH produced a progressive reduction in PN after reducing CaO2 by 20%. After DCA, PN was not significantly depressed until CaO2 was reduced to very low levels, whereupon there was a sharp decline in PN. Before DCA, reducing CaO2 to 6 ml O2/dl reduced PN by 41 +/- 16%, whereas after DCA there was no significant reduction in PN (4 +/- 5%). We conclude that 1) lactic acidosis near the central chemosensitive regions does produce a small stimulation of respiration during PBH but that 2) the overwhelming response to central lactic acidosis of PBH is respiratory depression.

Acidosis, Lactic↗
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

Reduction of chronic hypoxic pulmonary hypertension in the rat by an inhibitor of collagen production.

Chronic hypoxic pulmonary hypertension in the rat is associated with increased collagen and elastin in the pulmonary artery. We investigated whether excess vascular collagen contributes to chronic hypoxic pulmonary hypertension by administering the proline analogue cis-4-hydroxy-L-proline (cHyp), an agent relatively specific for inhibiting collagen production, to rats exposed to chronic hypoxia. Sprague-Dawley rats (weighting 200 g) were exposed to air or hypoxia (10% O2-90% N2) for 3 wk. Groups studied were: air-exposed injected with saline, air-exposed injected with cHyp, hypoxic injected with saline, and hypoxic injected with cHyp. At the end of 3 wk, we measured mean right ventricular pressure (RVP) of animals breathing room air and hydroxyproline and desmosine contents of the main pulmonary artery trunk. Hypoxia increased RVP from 13 +/- 1 to 27 +/- 1 mm Hg (p less than 0.05); cHyp partially prevented this increase since RVP was 17 +/- 1 mm Hg (p less than 0.05). There was no effect of cHyp on cardiac output. Hypoxia increased collagen from 0.9 +/- 0.1 to 2.0 +/- 0.3 mg/artery (p less than 0.05); cHyp completely prevented this increase since collagen was 1.0 +/- 0.2 mg/artery (p less than 0.05). Hypoxia increased elastin from 1.1 +/- 0.1 to 2.4 +/- 0.2 mg/artery (p less than 0.05); cHyp had no apparent effect since elastin was 2.1 +/- 0.1 mg/artery. Also, cHyp did not affect RVP or vascular collagen or elastin in air-breathing animals. The cHyp treatment prevented luminal narrowing and thickening of arteriolar walls by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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↗
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

Sleep, sleep apnea and the fibromyalgia syndrome.

A patient who presented with primary fibromyalgia syndrome (PFS) was found to have sleep apnea. Since frequent wakening and nonrestorative sleep are prominent clinical complaints in both disorders, we hypothesized an etiologic relationship. A subsequent clinical survey of 11 additional sleep apneics revealed that 3 (27%) fulfilled proposed criteria for PFS. This was significantly greater than local and literature reported studies of nonrheumatologic patients and was comparable to reported prevalence of fibromyalgia in rheumatologic referral populations. A blinded sleep physiology study of 7 patients with PFS revealed a significantly increased percentage of transitional sleep and increased frequency of miniarousals/h, but no significant evidence of occult sleep apnea compared to matched normal controls. The frequent arousals of sleep apnea may be associated with fibromyalgia in some patients but do not explain the sleep disorder of PFS.

Fibromyalgia↗
PubMed1986

Transdermal clonidine in mild hypertension. A randomized, double-blind, placebo-controlled trial.

In 30 patients with mild essential hypertension, clonidine hydrochloride was delivered from a skin patch reservoir designed to release medication at a constant rate for seven days. After a four-week washout period, patients were randomized (double-blind) into a clonidine- or a placebo-treated group. Clonidine or placebo was then given for five weeks, followed by a two-week washout period to assess withdrawal from treatment. Blood pressure was controlled in 11 of 15 clonidine-treated patients but in only four of 15 placebo-treated patients. The clonidine-treated group evidenced larger decreases in both systolic and diastolic blood pressures. In the clonidine-treated group, blood pressures and plasma clonidine levels were stable throughout a representative seven-day period. Besides mild skin irritation with both clonidine and placebo patches, few side effects were observed. After discontinuation of clonidine administration, plasma levels declined in a non-log linear manner. There was no rebound hypertension. The results suggest that clonidine delivered transdermally is safe and effective for control of mild essential hypertension.

Administration, Cutaneous↗
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↗
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↗