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Biomedical subjects

M M Grunstein

Publications and source records attributed to M M Grunstein.

At least 73 records · Page 4Linked to original sources
PubMed1985

Effect of corticosteroids on bronchial responsiveness to methacholine in asthmatic children.

To elucidate the effects of corticosteroids on nonspecific bronchial reactivity in asthmatic children, inhaled challenges with methacholine were conducted in 10 atopic asthmatic subjects (9 to 15 yr of age) before and after consecutive week-long trials of daily orally administered placebo and prednisone (60 mg/day). Pharmacologic bronchial sensitivity was evaluated as the log dose of methacholine producing a 20% fall in FEV1 (PD20-FEV1). The week-long trial of placebo had no effect on either baseline lung function or PD20-FEV1. On the other hand, after the 1-wk course of prednisone: (1) both baseline FEV1 and FEF25-75 systematically improved in the patients who initially had (i.e., before prednisone) lower values, and (2) PD20-FEV1 significantly increased (p less than 0.001) in all the subjects studied. The magnitude of increase in PD20-FEV1 after prednisone was significantly inversely related (i.e., inverse hyperbola) to the initial degree of airway obstruction (i.e., FEV1) obtained prior to prednisone treatment. Moreover, whereas 6 of 10 patients only minimally changed their baseline FEV1 after prednisone, collectively for all the subjects, the percent increase in PD20-FEV1 after prednisone was directly related (correlation coefficient, 0.70; p less than 0.05) to the corresponding percent increase in baseline FEV1 after prednisone. These findings demonstrate that after a week-long course of high-dose prednisone therapy: (1) a significant reduction occurs in bronchial sensitivity to inhaled methacholine in the asthmatic child, and (2) the degree of diminution in airway sensitivity to methacholine is inversely related to the patient's baseline status of airway obstruction.

Adolescent↗
PubMed1985

Effects of impeded breathing on auditory brainstem responses in conscious man.

Auditory brainstem responses (ABR) recorded in two groups of 10 normal volunteers were compared under conditions of impeded and unimpeded breathing. Impedance to breathing was accomplished by adding inspiratory flow-resistive loads of varying magnitude. Loaded breathing selectively augmented the amplitude of ABR components generated in the vicinity of the pontomidbrain junction. Peak latencies and other peak amplitudes of the ABR were unaffected. These findings suggest that the ABR procedure may serve as a direct noninvasive approach to the assessment of brainstem respiratory functions in conscious humans.

Adult↗
PubMed1984

Mechanism of substance P-induced bronchoconstriction in maturing rabbit.

The maturational effects of substance P (SP) on airway function were quantitatively assessed in 30 anesthetized tracheotomized rabbits ranging in age from 2 to 29 days. Following paralysis, during mechanical ventilation with 100% O2 in a body plethysmograph, respiratory resistance (Rrs) and dynamic compliance (Cdyn) were continuously monitored. Noncumulative systemic infusions of SP (0.001-5.0 micrograms/g) produced dose-dependent decreases in pulmonary conductance (Grs), i.e., 1/Rrs, and Cdyn. The dose of SP producing a 50% decrease in Cdyn (PD50-Cdyn) significantly increased as a function of age indicating a diminution in airway sensitivity to SP. Bilateral cervical vagotomy and ganglionic blockade with hexamethonium had no effect on the airway response to SP. On the other hand, the response was significantly reduced following atropine sulfate infusion (2 mg/kg), suggesting a peripheral cholinergic contribution located distal to the airway parasympathetic ganglia. The magnitude of this cholinergic contribution increased as a function of age. Unlike atropine, antagonists to histamine and 5-hydroxytryptamine had no effect on the airway response to SP, however, the response was inhibited following infusion of the SP antagonist, D-Pro2,D-Trp7,9-SP. These findings indicate that the airway response to SP is age-related and mediated by binding of the agonist to airway smooth muscle coupled with an accelerated release of acetylcholine at the airway neuromuscular junction.

Age Factors↗
PubMed1984

Mechanisms of substance P-induced contraction of rabbit airway smooth muscle.

The contractile effects of substance P (SP) were studied in isolated rabbit tracheal smooth muscle (TSM) segments in vitro. Noncumulative administration of SP produced dose-dependent increases in TSM tension. The mean (+/- SE) peak isometric tension (Tmax) with SP was 35.7 (+/- 6.2%) of the corresponding Tmax response to methacholine. The dose of agonist producing 50% of Tmax (ED50) was significantly lower for SP, averaging 1.8 (+/- 0.4) X 10(-7) M, vs. 1.7 (+/- 0.32) X 10(-6) M for methacholine. Blockade of both parasympathetic ganglia with hexamethonium (10(-4) M) and neural transmission with tetrodotoxin (1 microgram/ml) had no effect on the TSM response to SP. On the other hand, TSM contraction to an ED50 dose of SP was 1) augmented by a mean (+/- SE) of 470 (+/- 110%) following pretreatment with the cholinesterase inhibitor, neostigmine (10(-6) M);2) inhibited by a mean (+/- SE) of 35 (+/- 15%) with the cholinergic antagonist, atropine (10(-4) M); and 3) also inhibited by a mean (+/- SE) of 45 (+/- 11%) following inhibition of acetylcholine synthesis with hemicholinium-3 (10(-4) M). Antagonists to 5-hydroxytryptamine, alpha 1-adrenergic, and histamine receptor binding had no effect on TSM contraction with SP. In contrast, the SP antagonist, D-Pro2,D-Trp7,9-SP, markedly inhibited TSM contraction to SP. Our findings indicate that rabbit TSM is sensitive to SP and its contraction is in part mediated by a peripheral cholinergic action, likely involving the accelerated release of acetylcholine at the airway neuromuscular junction.

Animals↗
PubMed1984

Comparison of responsiveness to methacholine, histamine, and exercise in subgroups of asthmatic children.

Nonspecific bronchial reactivity, involving inhaled challenges with methacholine and histamine and treadmill exercise challenge, were compared in 2 groups of steroid-requiring asthmatic children (9 to 15 yr of age) distinguished on the basis of marked differences in their typical time course of clinical deterioration leading to in-hospital management. Group I patients (n = 8) had rapid clinical deterioration (occurring within 8 h from the onset of respiratory symptoms), whereas in Group II patients (n = 7), clinical deterioration occurred relatively slowly (i.e., exceeding 24 h from the onset of respiratory symptoms). Pharmacologic bronchial sensitivity was evaluated as the log dose of the agonist producing a 20% fall in FEV1 (PD20 X FEV1) and a 35% fall in specific conductance (PD35 X SGaw). Exercise-induced bronchospasm was evaluated in terms of the maximal decrease in FEV1 and SGaw after 6 min of steady-state treadmill exercise at 85% of the age-predicted maximal heart rate. Group I patients had near normal baseline FEV1 and SGaw, whereas in Group II patients, the baseline values of these parameters were significantly reduced (p less than 0.02). Group I was more sensitive to methacholine than was Group II, providing significantly lower mean values of PD20 X FEV1 (p less than 0.003) and PD35 X SGaw (p less than 0.001). On the other hand, the 2 groups were not significantly different with respect to their bronchial sensitivity to either histamine or exercise challenge. Thus, asthmatic children with marked differences in clinical presentation of bronchospasm may be further distinguished on the basis of methacholine sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

Respiratory response to intraesophageal acid infusion in asthmatic children during sleep.

Nocturnal asthma has been associated with nighttime gastroesophageal reflux (GER). To establish whether the presence of acid in the lower esophagus causes bronchoconstriction, nine children with nocturnal asthma and GER underwent intraesophageal acid-infusion challenges during sleep. The patients were divided into two groups on the basis of presence or absence of a positive Bernstein test for esophagitis. The test was considered positive if acid infusion produced symptoms of heartburn. On two occasions, at approximately midnight and 4 to 5 A.M., 30 ml of normal saline was infused over 15 min into the distal esophagus followed by a similar infusion of 0.1N HCl. Respiration was continuously monitored by inductance plethysmography along with clinical evaluation. The saline and midnight acid infusions had no effect in either patient group; however, with the 4 to 5 A.M. acid infusion, all the patients with a positive Bernstein test developed significant changes in their respiratory pattern indicative of bronchoconstriction as well as overt clinical wheezing. In the patients with a negative Bernstein test, the 4 to 5 A.M. acid infusion had no effect. It is concluded that during sleep the presence of acid in the lower esophagus can trigger bronchoconstriction in asthmatic children with a positive Bernstein test and that these children appear to be more susceptible to the bronchoconstrictive effects of intraesophageal acid at 4 to 5 A.M. than at midnight.

Adolescent↗
PubMed1982

Maturational effect of enkephalin on respiratory control in newborn rabbits.

The respiratory responses to systemic infusion of the opioid peptide, [D-Ala2, D-Leu5]enkephalin (ENK) were determined in 39 unanesthetized tracheotomized rabbits (age range 1-20 days). At all ages, ventilation (VE), measured in a body plethysmograph, was depressed after ENK infusion in association with a decrease in CO2 elimination (VCO2) and body temperature. The degree of VE depression varied inversely with increasing age and was directly related to changes in mean inspiratory flow (i.e., VT/TI) while the ratio of inspiratory to total breath duration (TI/TT) was unaltered, except in rabbits under about 1 wk of age. Maturational differences in the VE response to ENK were related to age-dependent variation in the stability of the central inspiratory activity, which was manifested as periodic breathing with apnea in rabbits under about 5 days of age. Since the initial inspiratory volume-time profile was little affected by ENK and vagal afferent influence on respiration was not diminished, the depression in VE could be explained by an inhibition of the central inspiratory "off-switch" threshold and delay in central inspiratory "on-switching." All effects of ENK were reversed by the opiate antagonist, naloxone.

Animals↗
PubMed1982

The relationship of gastroesophageal reflux to nocturnal wheezing in children with asthma.

Gastroesophageal reflux (GER) has been reported in a high percentage of children with asthma. To investigate the relationship between GER and nocturnal asthma (NA), 25 pediatric patients with histories of NA were studied prospectively with three to 13 weeks of in-patient observation to document NA and quantitative day-time and night-time wheezing frequency. Two distinct groups of patients were identified: 17 patients with predominant day-time asthma (DA) and eight with prominent NA. All were studied with overnight esophageal pH recordings to detect GER during sleep while also monitoring clinical status. A reflux score (RS) was calculated to quantitate the severity of GER. Sixteen of 25 patients (64%) had abnormal GER, including all eight patients with NA. A significant positive correlation was found between the RS and the percentage of nights with wheezing, while age, serum theophylline level and pulmonary function at the time of study did not correlate with RS. The NA group also had significantly higher RS than the DA group. Three of the eight NA patients had the onset of clinical wheezing during an episode of GER. We conclude that there is a significant association between NA and GER independent of age, lung function and theophylline levels and that GER may induce NA in a subpopulation of patients with reactive airways.

Asthma↗
PubMed1981

Effect of naloxone on ventilation in newborn rabbits.

Endorphins have been isolated from amniotic fluid and cord blood of mammals. To determine if these agents influence ventilation after birth, we measured ventilation (VE), tidal volume, inspiratory time, and respiratory frequency (f) in 19 rabbit pups before and after administration of naloxone (NLX), an endorphin antagonist. Tracheostomy and carotid artery cannulation were performed under light ether anesthesia. After 30-90 min for recovery the pups were placed in a body plethysmograph. Rectal temperature was kept at 37 +/- 0.5 degrees C. After 15 min of control measurements we infused saline, which had no respiratory effect. NLX (4 microgram/g) was then infused and measurements continued for 30 min. In 6 of 7 pups less than or equal to 4 days old, VE increased to 140-180% of control values and remained elevated for the remainder of the study period. Increased VE was due solely to increased f. By contrast, only 1 of 12 pups greater than or equal to 5 days old responded in this fashion. This difference was significant (P less than 0.005). Arterial blood gases were measured before and after NLX in 10 pups. In those pups who increased their ventilation after NLX, arterial CO2 tension fell and pH rose above pre-NLX values (P less than 0.05) for both variables). Blood gases of the group whose ventilation was uneffected remained unchanged. These results indicate that early in postnatal life endorphins probably modulate central respiratory drive in rabbits but that these agents become less important with maturation.

Age Factors↗
PubMed1981

Respiratory control during hypoxia in newborn rabbits: implied action of endorphins.

The mechanism of ventilatory depression during hypoxia in the neonate is unknown. Since endorphins depress ventilation and their actions are antagonized by naloxone, we tested the effect of naloxone on respiration during acute hypoxia in newborn rabbits. In 27 tracheotomized unanesthetized pups, ranging in age from 1 to 15 days, ventilation (VE) was measured in a body plethysmograph. At all ages, inhalation of 5% O2 initially increased VE; thereafter VE became depressed in association with a decrease in CO2 elimination (VCO2). The time constant of VE depression increased with age. During ventilatory and VCO2 depression, saline infusion had no effect. Infusion of naloxone (4 micrograms/g body wt), however, abruptly stimulated both VE and VCO2. Since naloxone acts by competitive blockade of opiate (endorphin) receptors, these data provide evidence that 1) depression in respiration and metabolism during hypoxia is related to the action of endorphins, 2) the degree of endorphin influence decreases with age, and 3) naloxone is effective in reversing hypoxic respiratory depression provided apnea is not established.

Aging↗
PubMed1980

Effects of hypoxia on respiratory control in neonates at high altitude.

The respiratory responses to acute hypoxia were investigated in 21 newborn infants in Leadville, CO. Time-related changes in pulmonary ventilation (VE) described four distinct phases to the hypoxic response characterized by an abrupt initial decrease (phase I), a transient subsequent increase (phase II) and decrease (phase III), and a further transient decrease upon termination of the hypoxic challenge (phase IV). Based on the degree of respiratory stimulation during phase II, the subjects were divided into two groups, "responders" and "nonresponders." In both groups in VE were attributed to variation in tidal volume (VT), inspiratory duration (TI), and breath duration being little affected. The latter indicated an absence of vagal volume-related modulation of respiratory pattern. In all subjects, a fixed linear function described the relationship between the mean inspiratory flows at 0.3 s after inspiratory onset (i.e., V0.3/0.3) ant at end inspiration (i.e., VT/TI). Thus, changes in respiratory output with hypoxia are attributed to variations in both the "gain" and "shape" of the inspiratory drive.

Adaptation, Physiological↗
PubMed1977

Effect of SO2 on control of breathing in anesthetized cats.

In seven anesthetized tracheotomized cats we studied the acute respiratory effects of SO2 inhalation at different steady-state levels of arterial CO2 tension (Paco2). During room air breathing, SO2 (0.05%) addition caused a progressive reduction in tidal volume (VT) and increases in both respiratory frequency (f) and pulmonary resistance (RL). Atropine sulfate abolished the bronchoconstriction response to SO2 and thus permitted the study of the influence of SO2 on VT and f in the absence of constricted airways. Despite marked reductions in the VT VS. PaCO2 relationships with SO2 exposure after atropine, the relationship between pulmonary ventilation (VE) and PaCO2 was not signifcantly altered. This was the case since SO2 caused solely a reduction in inspiratory duration (Ti), affecting neither the mean rate of rise of inspiratory activity (i.e., VT/Ti) nor the relationship between Ti and breath duration. Thus, airways irritation with SO2 produced rapid, shallow breathing characterized by a shortening of inspiratory and total respiratory cycle times with no change in the rate of development of inspiratory activity. The findings suggest an influence exclusively concerned with the timing of inspiration. Perhaps premature onset of inspiratory activity accounts for the observed effects.

Animals↗
PubMed1975

Regulation of frequency and depth of breathing during expiratory threshold loading in cats.

In six spontaneously breathing anesthetized cats, intermittently subjected to inspiratory elastic loads, we have studied the relationships between tidal volume (VT) and the durations of inspiration (Ti) and breath duration (Ttot) obtained during spontaneous ventilation from resting lung volume (FRCc) and from elevated end-expiratory levels. The latter was elevated by submerging the expiratory breathing line into a column of water, representing the addition of an expiratory threshold load (ETL). The VT vs. Ti relationships obtained at different end-expiratory levels were similar, indicating that during ETL the vagal mechanism regulating Ti responds only to lung volume changes above the new end-expiratory level and is independent of the absolute end-expiratory lung volume. Single vagal fiber recordings suggest that this effect on Ti control may be explained on the basis of adaptation occurring at the level of the pulmonary stretch receptors. The control of Ttot, on the other hand, was found to depend both on the Ti of the preceding breath (phasic component) and on a separate vagal mechanism specifically affecting the duration of expiration (Te) in response to changes in the absolute end-expiratory lung volume. The latter mechanism is functionally inoperative at FRCc.

Animals↗
PubMed1975

Control of depth and frequency of breathing during baroreceptor stimulation in cats.

In 10 tracheotomized anesthetized cats during steady-state inhalation of various concentrations of CO2 and O2, the acute respiratory response to baroreceptor stimulation produced by transient inflation of a balloon placed in the descending aorta was studied. The latter induced a sudden rise in mean arterial pressure, ranging from 62 to 95 mmHg. At all PACO2 levels above 30 mmHg, elevation in arterial pressure was accompanied by an immediate drop in tidal volume (VT) and prolongation of the durations of inspiration (Ti) and total breath (Ttot). Breaths obtained during baroreceptor stimulation fell along the same VT vs. Ti and VT vs. Ttot relationships obtained in the normotensive state, suggesting that the lung volume-related vagal control of Ti and Ttot is unaffected by changes in arterial pressure. Since, for a given change in arterial pressure, a constant reduction in VT was obtained at all PACO2 levels above 30 mmHg, it can be concluded that the interaction between PACO2 and arterial pressure is additive. In three cats, at PACO2 levels below 30 mmHg, aortic obstruction resulted in brief periods of apnea. Following apnea, the control of Ti and Ttot was transiently offset, describing hysteresis pathways on the VT vs. Ti and VT vs. Ttot relationships.

Abdominal Muscles↗