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Biomedical subjects

H E Ward

Publications and source records attributed to H E Ward.

27 records · Page 2Linked to original sources
PubMed1983

High-frequency oscillations via the pleural surface: an alternative mode of ventilation?

We applied high-frequency oscillatory ventilation (HFOV) of low amplitude to the pleural surface of the isolated rat lung (IPL) perfused at 10 ml X min-1 with Krebs bicarbonate containing 4.5% albumin (hematocrit 34%). Lung volume was held constant by a continuous positive airways pressure (CPAP) of 5 cmH2O. Varying CPAP from 2 to 15 cmH2O did not affect O2 uptake. Tidal volume (VT) was estimated with an impedance pneumograph, and it bore a direct linear relationship to the amplitude of both the loudspeaker input signal and the pressure change in the chamber up to 30 Hz; VT was inversely proportional to the frequency (f). However, at a constant loudspeaker input of 10 V, minute expired ventilation (VE) remained constant (mean 104 ml X min-1) as f increased from 5 to 30 Hz. Hemoglobin saturation increased by more than 80% during HFOV of 5-40 Hz and amplitude of 10 V, the maximum O2 uptake being 14.6 ml O2 per 100 ml perfusate. Whereas dead space was approximately 335 microliters, a VT of less than 40 microliters could effect normal O2 uptake, suggesting that bulk flow is playing only a minor role in gas exchange. HFOV for 60 min (CPAP 5 cmH2O) did not affect the amount of alveolar surfactant compared with conventional ventilation at the same mean airway pressure. We conclude that normal O2 uptake can be maintained by applying HFOV to the pleural surface of the IPL held at constant volume.

Animals↗
PubMed1982

Assessment of beta-adrenoceptor antagonists in asthmatic patients.

1 Bronchial smooth muscle, skeletal muscle and cardiac beta-adrenoceptor antagonism have been compared in twelve asthmatic patients after three beta-adrenoceptor antagonists at two dose levels. The non-selective antagonist propranolol (40 and 160 mg), the non-selective antagonist with partial agonist activity pindolol (5 and 20 mg) and the beta 1-selective antagonist atenolol (50 and 200 mg) were studied on separate occasions. 2 Six placebo days were used in this double-blind crossover study to allow interpretation of individual as well as group results. 3 Bronchial smooth muscle effects were assessed by resting spirometry, histamine inhalation test and spirometric response to inhaled fenoterol. Skeletal muscle effects were assessed by resting tremor and fenoterol induced tremor. 4 Cardiac beta-adrenoceptor antagonism was assessed by measuring the effect on resting heart rate and on maximum heart rate in a standard exercise test. 5 Pindolol tended to cause least change from placebo in resting spirometry, caused significant tremor response, inhibited the fenoterol airway response, and tended to protect against inhaled histamine. 6 Atenolol 60 mg was the only drug to allow a fenoterol airway response similar to placebo. Atenolol increased the inhaled histamine responsiveness. 7 Propranolol 160 mg caused the most reduction in spirometry but also tended to cause the maximum reduction in exercise heart rate. Propranolol caused increased inhaled histamine responsiveness. 8 Initial sensitivity to inhaled histamine did not necessarily predict significant reduction in an asthmatics' spirometry by a beta-adrenoceptor antagonist. The effect of a beta-adrenoceptor antagonist on histamine responsiveness does not correspond to its effect on inhaled beta 2-adrenoceptor agonist responsiveness.

Adrenergic beta-Antagonists↗
PubMed1982

Reversible ventilation and perfusion abnormalities in unilateral obstructed lung.

An intraluminal carcinoid tumor obstructing the left mainstem bronchus produced hypoxemia through alteration in ventilation/perfusion matching. Studies of regional lung function using 133-xenon (133Xe) and a multiprobe computerized instrumentation system documented a reduction of perfusion to 22 percent and ventilation to 6 percent of the total. There was negligible washout of intravenously injected 133Xe from the left lung consistent with air trapping. Four days after left mainstem bronchial sleeve resection, perfusion, ventilation and washout of injected xenon had significantly improved and by four months postresection, all measurements were virtually normal, although complete restoration of perfusion in relation to ventilation was delayed. Regional lung function studied with a multiprobe system in this patient provided a clinical model for the study of ventilation and perfusion inter-relationships in large airway obstruction and demonstrated that a prolonged time may be required for return of perfusion to normal.

Adult↗
PubMed1981

Synthesis and preliminary pharmacology of an internal standard for assay of neostigmine.

The synthesis of the diethyl analog of neostigmine, its preliminary pharmacology, and its use as an internal standard for the GLC assay of neostigmine are described. Both the diethyl analog and neostigmine undergo thermal demethylation in the injection port. The column selected produced satisfactory resolution and short retention times for neostigmine and the diethyl analog. The diethyl analog apparently possesses acetylcholinesterase-inhibiting properties, as evidenced by potentiation of the contractile response to acetylcholine in the ileum. In addition, acetylcholine levels in the brain were elevated slightly. Water solutions of the diethyl analog appeared to lose biological activity with time. the diethyl analog appears to be suitable for use as an internal standard for the GLC assay of neostigmine.

Acetylcholine↗
PubMedDate not supplied

Effects of prenatal stress on defensive withdrawal behavior and corticotropin releasing factor systems in rat brain.

Exposure of pregnant rats to stress results in offspring that exhibit abnormally fearful behavior and have elevated neuroendocrine responses to novelty and aversive stimuli. This study examined the effects of prenatal stress on plasma corticosterone, adrenal weight, defensive withdrawal behavior, and the density of receptors for corticotropin releasing factor (CRF) in the amygdala. Pregnant Sprague-Dawley rats were stressed by daily handling and saline injection (s.c., 0.9%, 0.1 mL) during the last week of gestation. Male offspring were studied at adulthood (60-120 days of age). Adrenal hypertrophy and increased plasma corticosterone were observed in the prenatally stressed offspring. Defensive withdrawal, an ethological measure of the conflict between exploratory behavior and retreat, was quantified in naive offspring, and in offspring exposed to restraint stress (2 h). Restraint stress increased defensive withdrawal in both control and prenatally stressed offspring. Both naive and restraint-stressed prenatally stressed offspring exhibited increased defensive withdrawal compared to control offspring. There was a significant interaction between prenatal stress and restraint stress, suggesting increased vulnerability of prenatally stressed offspring. The effects of restraint in the defensive withdrawal test were reduced by intracerebroventricular administration of the CRF antagonists, alpha-helical CRF9-41 (20 microg every hour) or D-phe(12), Nle(21, 38), C(alpha)-MeLeu(37)]-CRF((12-41)) (5 microg every hour) during the restraint period. The difference between control and prenatally stressed offspring was abolished by the CRF antagonists, suggesting that increased activation of CRF receptors may be a factor in the behavioral abnormalities of prenatally stressed rats. Measurement of CRF receptors in amygdala revealed a 2.5-fold increase in binding in prenatally stressed offspring. In light of previous work from this laboratory demonstrating increased content and release of CRF in amygdala from prenatally stressed offspring, the present study suggests that the increased fearfulness of prenatally stressed rats may be a consequence of increased activity of CRFergic systems in the amygdala.

Adrenal Glands↗