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Biomedical subjects

S T Chiang

Publications and source records attributed to S T Chiang.

At least 37 records · Page 2Linked to original sources

Improved computation of respiratory resistance as measured by transiently increased resistance.

The authors have previously described an automated system for measuring total respiratory resistance. The technique used by this system involves a transient, externally applied increase in resistance to breathing. The utility of this technique is limited by a number of assumptions and to free it from the constraints imposed by one of these assumptions a new method for analysing the data was developed. The paper describes the new method of analysis and presents data comparing the resulting Rrss with those computed using the old method.

Humans↗

Pharmacokinetic comparison of two triphasic oral contraceptive formulations containing levonorgestrel and ethinylestradiol.

The pharmacokinetics of levonorgestrel (LNG) and ethinylestradiol (EE2) were determined in 24 women (aged 21 to 35 years), following the administration of a single tablet from the second phase of two different triphasic preparations (Triphasil and Trinordiol. Each tablet contained 0.075 mg of LNG and 0.040 mg of EE2. The data were compared to the pharmacokinetics of LNG and EE2 obtained following the oral administration of a hydroalcoholic solution (standard) containing the same steroids and dose. The study consisted of a randomized design in which the three formulations were administered to each of the 24 subjects in a three-period crossover pattern. Blood samples were taken at frequent intervals after dosing. Serum levels of LNG and EE2 were measured by specific radioimmunoassays. The results show that both LNG and EE2 in the Triphasil and Trinordiol tablets are bioequivalent with respect to rate and extent of absorption. Furthermore, LNG, but not EE2, in both tablet formulations was bioequivalent to the solution dose. The serum concentration-time profiles for the three formulations showed that the range of mean peak levels was 2.3-2.8 ng/ml for LNG and 116-159 pg/ml for EE2. These levels were achieved within 2 hours in the majority of subjects. The ranges of mean values calculated for the areas under the curves were 15-16 ng.hr/ml for LNG and 1053-1390 pg.hr/ml for EE2. The ranges of mean values calculated for other pharmacokinetic parameters were: volume of distribution: LNG--1.6-1.8 L/kg, EE2--7.7-9.1 L/kg; clearance: LNG--84-88 ml/hr/kg, EE2--0.67-0.99 ml/hr/kg; half-life: LNG--13-15 hr, EE2--7-12 hrs.

Adult↗

Electrophysiological effects of dermorphin on locus coeruleus neurons of rat.

Intracellular recording was used to study the effects of dermorphin on neurons of the locus coeruleus in the rat, in a totally submerged brain slice preparation. Dermorphin caused the inhibition of spontaneous firing of all neurons of the locus coeruleus tested, with an IC50 of 7 nM. Based on the inhibition of spontaneous firing rate, dermorphin was 16.5 times more potent than morphine. Larger concentrations of dermorphin (30-100 nM) further hyperpolarized the neurons of the locus coeruleus and simultaneously caused a reduction in input resistance. These effects were antagonized by naloxone, with a dissociation equilibrium constant of 0.8 nM. The hyperpolarization of neurons of the locus coeruleus, caused by dermorphin, was reversed at a membrane potential of -112 mV in this preparation. Furthermore, this hyperpolarization was blocked by cesium chloride and barium chloride. Thus, these data suggest that dermorphin binds to mu-opioid receptors on the cell membrane of neurons of the locus coeruleus. This leads to opening of the inward-going rectification potassium channels, resulting in the observed hyperpolarization of the membrane.

Analgesics, Opioid↗

Responses of single phrenic motoneurons to altered ventilatory drives in anesthetized dogs.

We studied the effects of altered ventilatory drives on the activity of the whole phrenic nerve and single phrenic motoneurons in dogs anesthetized with alpha-chloralose and paralyzed with gallamine triethiodide. Single phrenic motoneurons were classified as either late-onset or early-onset motoneurons (LOM and EOM, respectively), depending on the time of onset of their activity during inspiration. Increase in ventilatory drive was induced by altering chemical drive with changes in arterial blood gases and also by altering the vagal afferent contribution to ventilatory drive. The latter was accomplished by inducing pulmonary gas embolism (PGE) during hyperoxia. Whole phrenic nerve activity was increased by both types of increase in ventilatory drive. In both cases, changes in the firing pattern of LOMs and EOMs were responsible for the increased phrenic output. The changes in post-PGE firing pattern of the LOMs generally consisted of a shift in the time of onset to an earlier point in inspiration and an increase in the number of spikes per inspiratory cycle. Vagotomy abolished the difference between the contributions of LOMs and EOMs to the phrenic response to PGE. Data from dogs studied while they were breathing spontaneously were qualitatively the same as those from the paralyzed animals, indicating no major role for phasic volume feedback in these responses. Our data regarding altered chemical drive are similar to those reported earlier in other species, whereas those regarding PGE demonstrate that vagally mediated increases in ventilatory drive affect both LOMs and EOMs, although LOMs are affected to a greater degree.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Right ventricular pressure and ventilatory responses to pulmonary gas embolism.

This study was designed to test the hypothesis that changes in right ventricular pressure (PRV) are responsible in part for the altered breathing frequency (f) during pulmonary gas embolism (PGE). PGE was induced by infusing air into the femoral vein of alpha-chloralose anesthetized dogs. Respiratory flow pattern was recorded and analyzed in relation to PRV changes induced resulting from PGE. The rise of PRV, whether induced by PGE, by pulmonary artery occlusion, or by acute elevation of pulmonary arterial blood flow, was consistently associated with increased f. Breathing frequency rose principally through reduction of expiratory duration (TE). The inspiratory duration (TI) was shortened somewhat and the fractional inspiratory cycle, TI/(TE + TI), increased. The relationships between PRV and f were altered by changes of PRV resulting from the administration of histamine antagonist, by beta-adrenergic blockade, beta-adrenergic stimulation, and by changing pulmonary arterial blood flow. The responses did not occur after bilateral cervical vagotomy. These results demonstrate that f during PGE is partially regulated in response to changes in PRV and is mediated through the vagal afferent.

Adrenergic beta-Antagonists↗

Total respiratory resistance in chronic obstructive pulmonary disease.

Using a recently described automated system, we measured total respiratory resistance (Rrs) of 59 patients with obstructive lung disease during spontaneous tidal breathing. We also measured airway resistance (Raw) and various other indices of pulmonary function. The results demonstrate that this system gives values of Rrs which correlate well with other objective measures of the severity of obstructive lung disease. It can also be used to detect changes in resistance after inhalation of a bronchodilator. In 10 patients we measured Raw during tidal breathing and computed the total non-airway resistance (Rnaw) as the difference between Rrs and Raw. Rnaw made up a larger portion of Rrs than would be expected in these patients. These results could not be accounted for by differences in breathing frequency, and may instead have been caused by differences between the times in the ventilatory cycle at which Rrs and Raw were measured. We cannot exclude the possibility that Rnaw was abnormally elevated in these patients.

Adult↗

Measurements of components of resistance to breathing.

Total respiratory resistance (Rrs), pulmonary resistance (RL), and airway resistance (Raw) of 12 male patients with chronic obstructive lung disease were measured by the partial occlusion method, intraesophageal balloon technique, and body plethysmography, respectively. Chest wall resistance (Rew) and lung tissue resistance (Rti) were computed. Percentages of Rew/Rrs, RL/Rrs, Raw/Rrs, Rti/Rrs, Raw/RL, and Rti/RL were calculated. The magnitude of the components of resistance to breathing of this study and the data appearing in the literature are compared. Wide variation between the data reported by various authors was observed. The possible causes of these variations are discussed.

Aged↗

Activities of uterine muscles from rats in late pregnancy.

Although it has been reported that, in the uterine wall of rats at term, gap junctions between fibers of the same muscle layer are responsible for synchronized strong contractions, much less attention has been paid to the interaction between muscle layers. To learn about the relationship between the two uterine muscles of rats in late pregnancy, we developed a technique to do simultaneous monitoring of activities in two muscle layers. Using rectangular muscle strips, the electrical activity in one layer was measured with an intracellular microelectrode while the mechanical activity of the other layer was recorded through a force transducer. In some of the uterine wall strips prepared from animals on gestation day 15 and 16, interaction between longitudinal and circular muscle layers was observed. However, well coordinated activities of these two muscles did not occur until the morning of gestation day 21 and continued toward delivery. Usually, coordination presented as paired contractions, one in the circular muscle and the other in the longitudinal muscle. While these pairs of contractions appeared regularly, they also kept similar intervals. Sometimes, coordination presented as a continuous appearance of groups of three contractions, one in one layer and two in the other. Coordinating contractions of uterine muscles is considered to be beneficiary to the propelling of fetuses toward the cervix during parturition.

Action Potentials↗

Volume and pressure during transient added resistance.

Total respiratory resistance (Rrs) can be computed from measurements of flow before and during a brief period of added resistance. This "added resistance' method does not require measurement of total driving pressure (Pt). One of the assumptions of this method is that the change in Pt (delta Pt) is negligible during the time of increased resistance. To evaluate this assumption we measured both the volume exhaled during a brief imposition of an external resistor, and the total respiratory compliance (Crs) of 7 healthy volunteers. The mean volume exhaled was 18.6 ml, and the mean Crs was 88 ml/cm H2O. The volume exhaled divided by Crs gives the change in total static elastic recoil pressure (delta Pel, rs), which is one component of delta Pt. The mean delta Pel, rs was 0.22 cm H2O. Since the pressure exerted by contraction of inspiratory muscles (Pmus,I) opposes Pel, rs, we also estimated delta Pmus,I and subtracted it from delta Pel, rs to obtain delta Pt. The computed mean delta Pt during the time of added resistance was 0.045 cm H2O. This value is quite small in relation to Pt during a spontaneous expiration at rest. We also studied 13 subjects with Chronic Obstructive Pulmonary Disease and found no significant effect of transient added resistance on intraesophageal pressure. We conclude that the assumption of negligible delta Pt should not prevent the added resistance method from being very useful, particularly when simplicity of equipment and testing procedure are important.

Adult↗

Determination of total respiratory resistance in health and disease by added external resistance.

Previous studies have indicated that total respiratory resistance (Rrs) can be measured by addition of an external resistor. In an earlier study, the apparatus used to accomplish this included a multiperforated steel plate. In this study, we sought to improve the device. Details of this are given in this article. With this device, resistance was found to be reproducible over five consecutive days, and was sensitive to the increase in airway resistance induced by head and neck flexion. We also report on a comparison between this method and a commercially available device that works on the "interruptor" principle. There was no significant difference in either mean or variance of resistance between the two methods. The instrumentation required for the newly designed method is minimal, and its operation is simple. Furthermore, the measurement can be performed without invasive procedures during tidal breathing.

Adult↗

Acute effects of cigarette smoking on total respiratory resistance measured by partial airway occlusion.

Acute effects of inhalation of cigarette smoke on total respiratory resistance (Rrs) were studied by the partial airway occlusion method in five normal subjects. It was found that all five normal subjects were responders, though in two subjects the response was relatively weak. The results also demonstrated that the partial airway occlusion method is sensitive enough to detect the effects of cigarette smoking on Rrs. From the scatter of the individual data, it seems that the variation, or instability of response, is larger immediately after smoking compared with control. Since one of the subjects complained of dizziness when his resistance was not significantly increased, it is possible that systemic absorption of nicotine from inhalation of cigarette smoke is not necessarily related to increased Rrs.

Adult↗

Effect of chestwall removal on expiratory flow in dogs.

We studied the effect of chestwall removal on Flow-Volume (F-V) curves in anesthetized dogs, by applying suction at the airway opening. Pressure and volume ranges utilized were comparable to those by others in the past for studies of expiratory flow in canine models. It was found: 1) Expiratory flow became nil at residual volume (RV) in the intact animal. On the contrary, flow after chestwall removal continued below RV, until the lung reached its minimal volume (Vmin) which averaged 11 +/- 6% TLC or 50% RV. 2) At high lung volumes, flow, particularly peak flow of F-V curves, was greater before than after chestwall removal. Thus the chestwall has a bimodal effect on flow. At low lung volumes, particularly below RV, the chestwall inhibits expiratory flow, and chestwall removal always results in flow increase, such that the lung can empty until all airways are collapsed, down to a volume of about 50% RV. On the contrary, the chestwall facilitates expiratory flow at high lung volumes, particularly at peak flow. The bimodality of chestwall effect on expiratory flow is consistent with the well known directional reversal of chestwall elastic recoil as volume changes, being nil at chestwall resting volume (Vcwr), and directing inwards (thus helping expiration) above Vcwr, or outwards (thus inhibiting expiration) below this volume (12). In a hypothetical situation of no chestwall resistance, chestwall effect on flow would be nil at Vcwr. In our experimentation, we found that the volume where the chestwall had no effect on expiratory flow averaged 71% TLC, clearly higher than Vcwr (49% TLC). We attribute the difference to the chestwall resistance.

Animals↗

Effects of thyroidectomy and thyroxine replacement on the release of luteinizing hormone and gonadotropin-releasing hormone in vitro.

The effects of thyroidectomy and thyroxine (T4) replacement on the release of luteinizing hormone (LH) and gonadotropin-releasing hormone (GnRH) in ovariectomized (Ovx) rats were studied. Immediately after ovariectomy, rats were thyroidectomized (Tx) or sham-Tx. The Ovx-Tx rats were injected subcutaneously with either saline or T4 (2 micrograms/100 g body weight) daily for 30 days before sacrifice. Sham-Tx rats were treated with saline only. Twenty hours after the last injection, the blood sample was obtained by decapitation. The excised anterior pituitary gland (AP) was bisected and incubated in vitro with or without 0.1, 0.5, 2.5, and 50 ng GnRH at 37 degrees C for 4 h. The mediobasal hypothalamus (MBH) was bisected and incubated with or without the AP of Ovx donor rat in vitro. Concentrations of LH and GnRH in the medium and that of LH in the serum were measured by radioimmunoassay. LH in the serum of Tx rats was higher than that in the serum of sham-Tx and Tx-T4 rats. Thyroidectomy resulted in an increase of LH release by Ovx rat AP, stimulated with or without 0.1 and 50 ng GnRH, as well as in an increase of immunoreactive GnRH release from MBH of Ovx rats in vitro. After a 4-hour incubation with donor APs, the LH in the medium containing MBH obtained from Tx rats was significantly higher than that obtained from sham-Tx and Tx-T4 rats. LH concentrations, in both sera and media, as well as GnRH concentration in the media of euthyroid and T4-replaced Tx groups were nonsignificantly different. These results suggest that T4 is inhibitory to the basal and GnRH-stimulated LH release as well as to the release of GnRH in the absence of ovarian hormones.

Animals↗

The coordination of contractions of circular and longitudinal muscle layers of rat uterus in late pregnancy and during delivery.

Although it is well known that, in visceral smooth muscle, gap junctions between muscle fibers of the same muscle layer are responsible for synchronized strong contractions, much less attention has been paid to the interaction of muscle layers. An L-shaped preparation of the myometrium composed of circular and longitudinal muscle layers was adapted to study the relationship between the activities of these two muscle layers of pregnant rats. After careful separation, each of the two arms of the preparation would consist of only one muscle layer, while both layers remained connected at the angle of the L. Thus, contractions of both muscle layers could be monitored simultaneously and their relationship could be investigated. It was found that coordination of the contractions of longitudinal and circular muscles appeared in the morning of gestation day 21 and continued toward delivery. The coordination was expressed as a special sequence of the contractions of the two muscle layers which occurred repetitively for an hour or longer. In most of the cases, pacemaker was located in the longitudinal layer. Dissociation of one of the arms would make both arms contract independently. A few specimens from animals in their early third trimester also showed interaction of the muscle layers. Nevertheless, the correlation was not as strong as that in specimens prepared from animals close to term.

Animals↗

Studies on resistance to breathing.

Some aspects of resistance to breathing are reviewed in this article. The importance in medicine of the determination of resistance to breathing is emphasized. Estimation of respiratory resistance in clinical practice by spirometry is mentioned. Clinically useful methods for determination of resistance to breathing reported in the literature are reviewed. The body plethysmograph, an instrument specially designed to measure airway resistance and currently used in clinical medicine, is complicated and expensive. A newly designed instrument for measuring total respiratory resistance by partial airway occlusion is strongly recommended. A comparison of the two methods, body plethysmography and partial airway occlusion, has been made. The theory of the partial airway occlusion method is also briefly described. Factors affecting respiratory resistance are analyzed. The relationship between the size of dead space and the magnitude of respiratory resistance is also discussed.

Airway Resistance↗

Effects of intrapleural pressure on phrenic nerve activity.

In order to evaluate the effect of changing respiratory mechanics on the relation between respiratory mechanical output and phrenic activity, we simultaneously measured ventilatory output from the trace of pneumotachograph and changes in phrenic nerve activity before and after pneumothorax in alpha-chloralose anesthetized dogs. After pneumothorax, the dynamic lung compliance, inspiratory duration and tidal volume were decreased significantly, whereas the integrated peak amplitude and the rate of rise of phrenic neural output were increased substantially. The difference between respiratory mechanical output and phrenic activity was also significant (p less than 0.05). As shown from the results, the increase of phrenic response to pneumothorax may be mediated through intrapulmonary receptors along the vagal afferent rather than through the changes in chemical drive.

Animals↗