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Biomedical subjects

J A Hirsch

Publications and source records attributed to J A Hirsch.

At least 55 records · Page 3Linked to original sources
PubMed1984

Selective alteration of neurotransmitter release by low oxygen in vitro.

The potassium-stimulated release of acetylcholine, norepinephrine, serotonin, glutamate, and 4-aminobutyrate from superfused rat cortical slices was studied during hypoxia. A reduction in oxygen tensions from 603 +/- 6 to 22 +/- 2 mm Hg selectively altered the calcium-dependent efflux of these neurotransmitters, but did not change their calcium-independent release. The calcium-dependent release of [14C]acetylcholine decreased (39%), while that of glutamate increased (66%) and 4-aminobutyrate, [3H]norepinephrine, and [3H]serotonin were unaffected. Thus, low oxygen reveals variations in the calcium-dependent release mechanisms of several neurotransmitters. These differences may have important implications for pharmacological intervention of neurotransmitter release.

Acetylcholine↗
PubMed1984

Breathing pattern in humans: elevated CO2 or low O2 on positive airway pressure.

The purpose of this study was to determine effects on breathing pattern of pressure breathing alone and in combination with chemical stimulation. We analyzed ventilatory responses to elevated airway pressures (positive-pressure breathing, PPB) in subjects breathing air, 12% O2, or elevated CO2. Each subject sat in a body box and breathed via mouth-piece from a bag-in-box. Responses to PPB on air were increased minute ventilation (VI), tidal volume (VT), frequency (f), mean inspiratory (VT/TI) and expiratory (VT/TE) flows, decreased expiratory duration (TE) and end-tidal CO2. If end-tidal CO2 were held constant, VI, VT, and VT/TI increased less. Responses greater than predicted from summing responses to either stimulus alone were observed for VT, f, VT/TI, and VT/TE during 3 and 5% CO2 and for VT, f, and VT/TE during isocapnic hypoxia. Responses to other combined stimuli were sums of responses to the individual stimuli. Thus ventilatory responses to combined PPB and chemical stimuli cannot be predicted simply from summating responses to each independently imposed stimulus, suggesting that sensory information arises from and is integrated at multiple sites.

Adult↗
PubMed1984

Structure-activity relationship between guanidine alkyl derivatives and norepinephrine release: site(s) and mechanism(s) of action.

The effect of guanidine alkyl derivatives on the evoked release of [3H]norepinephrine [( 3H]NE) from spleen strips was examined. Guanidine, methyl guanidine and N,N-dimethyl guanidine all enhanced the field-stimulated release of [3H]NE 2- to 3-fold, whereas N,N'-dimethyl guanidine and propyl guanidine were without effect. The latter compound blocked the stimulatory effect of an equimolor concentration (4 mM) of guanidine. Guanidine enhanced moderately the field-stimulated release of [3H]NE from spleen strips pretreated with phenoxybenzamine. The efflux of [3H]NE from spleen slices induced by calcium ionophore A-23187 was not altered by guanidine incubation. The effect of guanidine on intracellular calcium movement was also tested by monitoring the effect of the drug on evoked secretion of ATP from human platelets. Guanidine did not modify this release. It is concluded that guanidine and its active structural derivatives augment [3H]NE release by increasing the influx of calcium through the voltage-sensitive calcium channels, but not by the mobilization of intracellular calcium pools. The biochemical basis for the action of the guanidinium cation is discussed.

Adenosine Triphosphate↗
PubMed1982

Effect of (+)- or (-)-enantiomers of fenfluramine or norfenfluramine on nutrient selection by rats.

The effects of the (+)- and (-)-enantiomers of fenfluramine and norfenfluramine on food choice and total food consumption by rats, have been examined. Animals were trained to select their food during an 8-h daily interval from two isocaloric-isocarbohydrate (40%) diets differing in protein contents (5 or 45% casein). Low doses of (+)-fenfluramine (1.25 or 1.65 mg kg-1) selectively reduced consumption of the 5%-protein diet during the hour after administration, thereby also reducing carbohydrate intake by a greater proportion than protein intake. Higher doses (2.5 or 4.0 mg kg-1) diminished consumption of both test diets to an equivalent extent. (+)-Norfenfluramine, although anorectic, did not modify the relative consumptions of carbohydrate and protein at any dose tested. These observations affirm that nutrient selection as well as total food consumption can be altered by drugs affecting particular neurotransmitters.

Animals↗
PubMed1982

Human breathing patterns on mouthpiece or face mask during air, CO2, or low O2.

Steady-state breathing patterns on mouthpiece and noseclip (MP) and face mask (MASK) during air and chemostimulated breathing were obtained from pneumotachometer flow. On air, all 10 subjects decreased frequency (f) and increased tidal volume (VT) on MP relative to that on MASK without changing ventilation (VE), mean inspiratory flow (VT/TI), or mean expiratory flow (VT/TE). On elevated CO2 and low O2, MP exaggerated the increase in VE, f, and VT/TE due to profoundly shortened TE. On elevated CO2, MASK exaggerated VT increase with little change in f. Increased VE and VT/TI were thus due to increased VT. During low O2 on MASK, both VT and f increased. During isocapnia, shortened TE accounted for increased f; during hypocapnia, increased f was related primarily to shortened TI. Thus the choice of a mouthpiece or face mask differentially alters breathing pattern on air and all components of ventilatory responses to chemostimuli. In addition, breathing apparatus effects are not a simple consequence of a shift from oronasal to oral breathing, since a noseclip under the mask did not change breathing pattern from that on mask alone.

Adult↗
PubMed1981

Respiratory sinus arrhythmia in humans: how breathing pattern modulates heart rate.

The relationship of respiratory sinus arrhythmia amplitude (RSA) to tidal volume and breathing frequency was quantified during voluntarily controlled tidal volume and breathing frequency and spontaneous quiet breathing. Seventeen seated subjects breathed via mouthpiece and nose-clip, maintaining constant tidal volumes at each of several breathing frequencies. Inspiratory breath hold was zero frequency. Log RSA was plotted vs. log frequency for each tidal volume. The large stable RSA for frequencies less than 6 cycles/min was called low-frequency intercept (LFI, 20 +/- 5 beats/min). Low-frequency intercept was inversely proportional to a subject's age only to 35 yr. At higher breathing frequencies above a characteristic corner frequency (fC, 7.2 +/- 1.5 cycles/min) RSA decreased with constant slope (roll-off; 21 +/- 3.4 dB/decade). The RSA-volume relationship was linear permitting normalization of RSA-frequency curves for tidal volume to yield one curve. Spontaneous breathing data points fell on this curve. Voluntarily coupling of heart rate to breathing frequency in integer ratios reduced breath-by-breath variability of RSA without changing mean RSA. In conclusion, low-frequency intercept, corner frequency, and roll-off characterize an individual's RSA-frequency relationship during both voluntarily controlled and spontaneous breathing.

Adult↗
PubMed1981

Volume, flow, and timing of each breath during negative airway pressure in humans.

We have analyzed the effects of 4-6 min of 5, 10 and 15 cmH2O continuous negative airway pressure breathing (NPB) on steady-state end-expiratory lung volume (delta VR) and breathing pattern. Fourteen healthy adults, seated in a full body box, breathed via a mouthpiece on a bag-in-box. Pressure in the body box was elevated to the desired pressure level. Inspiratory (TI) and expiratory (TE) durations, tidal volume (VT), minute ventilation (VI), mean inspiratory flow (VT/TI), and mean expiratory flow (VT/TE) were calculated from pneumotachometer recordings. The effects of NPB are decreases in delta VR, VT, and VT/TI and increases in VT/TE. The responses to NPB are an increase in breathing frequency, due to a shortened TE, and an increase in inspiratory activity. The decrease in delta VR and the increase in VT/TE are limited by an active retardation of expiratory flow. End-tidal CO2 and VI were not altered significantly during NPB, suggesting no alveolar hyperventilation. Thus multiple components of the human response to NPB are not all engaged at the same levels of NPB. The changes in the timing of respiratory events occur at -5 cmH2O, whereas VT compensation is not seen until -15 cmH2O.

Adult↗
PubMed1976

Effect of oxygen in graded concentrations upon tracheal mucous velocity. A study in anesthetized dogs.

Graded concentrations of oxygen were used to establish dose-duration relations for the effect of oxygen on tracheal mucous velocity and tracheobronchial histologic findings in the anesthetized dog. Observations of tracheal mucous velocity were made during 30-hour periods of breathing air (100-percent humidified and warmed to 38 degrees C) and oxygen mixtures (also 100-percent humidified and warmed to 38 degrees C). In animals breathing oxygen mixtures, the baseline tracheal mucous velocity was taken as the value while breathing room air at the experiment's start. No statistically significant differences in tracheal mucous velocity occurred during air breathing. Tracheal mucous velocity fell 45 percent from the baseline value after breathing 100-percent oxygen for two hours (P less than 0.01), fell 42 percent after 75-percent oxygen for nine hours (P less than 0.01) and fell 51 percent after 50-percent oxygen for 30 hours (P less than 0.001). Histologic examination of the trachea and major bronchi after six hours of 100-percent oxygen and 12 hours of 75-percent oxygen revealed signs of acute tracheobronchitis. Minor histologic alterations in the tracheobronchial tree occurred both in animals breathing air and 50-percent oxygen for 30 hours; therefore, histologic evidence of oxygen toxicity could not be established at 30 hours. These findings indicate that in the anesthetized dog, oxygen depresses mucous transport as a function of inspired oxygen concentration (FIO2) and that even FIO2 as low as 0.05 might be deleterious.

Acute Disease↗
PubMed1975

Tracheal mucous transport in Beagles after long-term exposure to 1 ppm sulfur dioxide.

Tracheal mucous velocity was determined in eight purebred beagle dogs exposed intermittently to 1 ppm sulfur dioxide for 12 months. Three control dogs were also studied. Teflon disks filmed at constant speed through a bronchofiberscope served as indicators of mucous motion. An average of 16 disks were analyzed in each dog. Although there was no significant difference in average velocity for controls and the SO-2-exposed animals, the frequency distribution curve of individual disk velocities in SO-2-exposed dogs revealed significant slowing. No significant differences in mechanics of breathing and gas exchange were found between the two groups. It appears that long-term exposure to low levels of SO-2 produces an impairment of mucociliary activity as one of the first signs of pulmonary dysfunction.

Animals↗
PubMed1975

Effects of topical and general anesthetic agents on tracheal mucous velocity of sheep.

Tracheal mucous velocity was estimated in eleven sheep by means of cine-bronchofiberscopic technique in which Teflon discs placed on the tracheal mucosa were filmed as markers. The procedure was done using a transnasal approach in conscious nonanesthetized sheep, and in the same sheep using topical and/or general anesthetic agents. The average mucous velocity in conscious sheep was 17.3 plus or minus 6.2 (SD) mm/min; in sheep anesthetized with intravenous pentobarbital or thioamylal, the average velocity was significantly depressed to 11.1 plus or minus 3.6 mm/min. No Significant differences in tracheal mucous velocity were found when 10 ml of 2 percent lidocaine was instilled into the tracheas of either conscious sheep or sheep under general anesthesia. Sheep as an animal model appear to be ideal in the study of the responses of tracheal mucous velocity to physical and chemical agents since they tolerate bronchofiberscopy quite well without the use of topical or general anesthetic agents. The basis for the depression of tracheal mucous velocity by barbiturates cannot be ascertained from the present study but the model should be useful for comparing different types of anesthetic agents.

Anesthesia, General↗
PubMed1975

Effects of dry air and subsequent humidification on tracheal mucous velocity in dogs.

The impairment of mucociliary transport by dry air breathing and the restoration of function with subsequent humidification of inspired air were investigated in anesthetized dogs. Tracheal mucous velocity was measured by a cinebronchofiberscopic technique. The breathing of dry air through an uncuffed endotracheal tube produced almost complete cessation of the flow of tracheal mucus after 3 h. Subsequent breathing of air at 38 degrees C with 100% relative humidity restored tracheal mucous velocity to control values by the end of and additional 3 h. Histologic examination of the trachea at the end of the 3-h dry air breathing period revealed focal areas of sloughing of the ciliated epithelium and submucosal inflammation. Although morphometry was not employed, the inflammatory changes appeared to have progressed during 3 h of breathing fully humidified air subsequent to the dry air breathing period. These findings were consistent with previous reports that the inflammatory response to injury of the tracheobronchial mucosa might be delayed and that the mucociliary transport system has a great deal of functional reserve. We found that an artificial heat and moisture exchanger placed on the proximal end of an endotracheal tube partially protects against the suppression of tracheal mucous velocity caused by dry air breathing.

Animals↗
PubMedDate not supplied

Application of bioelectric impedance methodology and prediction equations to determine the volume of distribution for ethanol.

In large-scale epidemiologic studies of drinking behavior there is a need for simple and reliable estimates of the body water compartment of subjects. This, in turn, provides an estimate of the volume of distribution of ingested ethanol and a better estimate of tissue exposure levels than the use of total body weight as the volume of distribution for alcohol. The volume of distribution for ethanol (total body water, TBW) was estimated in a racially mixed group of 276 alcoholics and 166 nonalcoholics (aged 20-59 years) by means of bioelectric impedance methodology (BIA) and by means of prediction equations based upon age, body weight, and height. Estimations of mean TBW from BIA were found to be only slightly higher (1-4%) than those provided by the prediction equations. TBW values generated from both prediction equations were also highly correlated with TBW values obtained by impedance methodology, with the highest correlations observed in females (particularly black) and in alcoholics (particularly female).

Adipose Tissue↗
PubMedDate not supplied

Gadolinium-enhanced fat-suppressed T1-weighted imaging of the head and neck: comparison of gradient and conventional SE sequences.

PURPOSE: The purpose of this study was to compare contrast-enhanced GRE and conventional SE (CSE) fat-suppressed T1-weighted techniques in the evaluation of head and neck lesions. A hybrid, opposed phase, frequency-selective, fat-suppressed fast multiplanar spoiled GRE (FMPSPGR) sequence was compared with a fat-suppressed CSE sequence. METHOD: Thirty-two patients with head and neck pathology were evaluated with both fat-suppressed CSE and FMPSPGR sequences. Regions of interest obtained by two viewers in consensus were used to establish contrast-to-noise (CNR) and signal-to-noise ratios for both sequences. Three neuroradiologists also independently reviewed the images for quality of fat suppression, lesion conspicuity, and potential pitfalls. RESULTS: The CNR of the FMPSPGR sequence was superior to that of the fat-suppressed CSE sequence. Subjectively, all three reviewers rated the FMPSPGR sequence as having fat suppression equal to or better than that in the CSE sequence in 94% of cases. Imaging times for the FMPSPGR sequence were 60-75% faster than those for the CSE sequence. CONCLUSION: Enhanced imaging of the head and neck region using an opposed phase, fat-suppressed GRE sequence results in improved fat suppression compared with the CSE technique, with substantial savings in imaging time.

Adult↗