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Biomedical subjects

D T Frazier

Publications and source records attributed to D T Frazier.

At least 37 records · Page 2Linked to original sources
PubMed1991

Role of phrenic nerve afferents in the control of breathing.

A long-held belief is that respiratory-related reflexes mediated by afferents in the diaphragm are weak or absent. However, recent data suggest that diaphragmatic afferents are capable of altering ventilatory motor drive as well as influencing perception of added inspiratory loads in humans. This review describes the sensory elements of the diaphragm, their central projections, and their functional significance in the control of respiratory muscle activation. The reflexes elicited by electrical stimulation of phrenic nerve afferents and the contribution of diaphragmatic afferents in respiratory load compensation and perception are considered. There is growing evidence that phrenic nerve afferents are activated under a variety of conditions. However, the significance of this input to the central nervous system is yet to be discerned.

Afferent Pathways↗
PubMed1991

University of Kentucky science outreach program.

Institutions of higher learning and their faculty must make a significant commitment to participate in the revitalization of the science curriculum. An active science outreach program within colleges and universities can have a pronounced impact on science education at relatively little expense. This partnership requires time, energy, and the willingness to share one's dedication and enthusiasm for his/her vocation.

Curriculum↗
PubMed1990

Experience with a physiology workshop for high school and college teachers.

Science education in the United States at all academic levels is widely perceived to need direct assistance from professional scientists. The current dearth of quality applicants from this country to medical and graduate schools suggests that our existing undergraduate and high school science curriculum is failing to provide the necessary stimulus for gifted students to seek careers in the health sciences. Recognizing the need to become more directly helpful to high school and college science teachers, members of the faculty of the Department of Physiology and Biophysics at the University of Kentucky College of Medicine held a 5.5-day Physiology Summer Workshop during June, 1989. Participants included 25 college teachers from Kentucky and 5 other states plus 22 Kentucky high school teachers. The presence of the two levels of educators provided communication about curricular concerns that would be best addressed by mutual action and/or interaction. Each day's activities included morning lectures on selected aspects of organ system and cellular physiology, a series on integrative physiology, and afternoon laboratory sessions. The laboratory setting allowed the instructor to expand on principles covered in lecture as well as provided the opportunity for in-depth discussion. A selection of evening sessions was presented on 1) grants available for research projects, 2) obtaining funds for laboratory equipment, and 3) graduate education in physiology.

Capital Financing↗
PubMed1989

The stimulatory effect of nicotine on vagal pulmonary C-fibers in dogs.

Our recent studies suggested that a nicotine-induced stimulation of afferent vagal C-fibers in the lungs was involved in eliciting the immediate cardiorespiratory responses to inhaling cigarette smoke. To examine this possibility, afferent impulses were recorded from vagal pulmonary C-fibers in 16 anesthetized, open-chest and artificially ventilated dogs, before and after four separate doses of nicotine (2.5, 5, 10 and 20 micrograms/kg) were injected into the right atrium. The base-line activity did not change after injection of isotonic saline. In contrast, nicotine stimulated 24 of 29 C-fibers: a burst of discharge was evoked immediately (1-2 sec) after the injection and usually lasted 3-8 sec. The peak responses of these pulmonary C-fibers to nicotine injections showed a dose-dependent relationship. In 17 C-fibers tested, the responses evoked by right atrial injection of 10 micrograms/kg of nicotine were similar to those evoked by delivery into the lungs of a single breath of smoke generated from cigarette with a high-nicotine content. Based upon these results, we conclude that nicotine alone stimulates vagal pulmonary C-fibers in a dose-dependent manner and this stimulant action of nicotine may play a part in eliciting the immediate reflex cardiorespiratory responses to inhalation of cigarette smoke.

Afferent Pathways↗
PubMed1989

Stimulation of vagal pulmonary C-fibers by a single breath of cigarette smoke in dogs.

Inhalation of cigarette smoke into the lower airway via a tracheostomy evokes immediate apnea, bradycardia, and systemic hypotension in dogs. These responses can still be evoked when conduction in myelinated vagal fibers is blocked preferentially by cooling but are abolished by vagotomy, suggesting that they are mediated by afferent vagal C-fibers. To examine this possibility, we recorded impulses in pulmonary C-fibers in anesthetized, open-chest dogs and delivered 120 ml cigarette smoke to the lungs in a single ventilatory cycle. Pulmonary C-fibers were stimulated within 1 or 2 s of the delivery of smoke generated by high-nicotine cigarettes, activity increasing from 0.3 +/- 0.1 to a peak of 12.6 +/- 1.3 (SE) impulses/s, (n = 60); the evoked discharge usually lasted 3-5 s. Smoke generated by low-nicotine cigarettes evoked a milder stimulation in 33% of pulmonary C-fibers but did not significantly affect the overall firing frequency (peak activity = 2.2 +/- 1.1 impulses/s, n = 36). Hexamethonium (0.7-1.2 mg/kg iv) prevented C-fiber stimulation by high-nicotine cigarette smoke (n = 12) but not stimulation by right atrial injection of capsaicin. We conclude that pulmonary C-fibers are stimulated by a single breath of cigarette smoke and that nicotine is the constituent responsible.

Action Potentials↗
PubMed1988

Effect of diaphragm small-fiber afferent stimulation on ventilation in dogs.

Little is known regarding the role of diaphragm small-fiber afferents (groups III and IV) in the control of breathing. This study was designed to determine whether activation of these afferents with use of capsaicin affects phrenic efferent activity. Capsaicin injections into the phrenic artery were made in 10 alpha-chloralose-anesthetized dogs after each of the following procedures performed in succession: bilateral cervical vagotomy, C7 spinal cord transection, bilateral cervical dorsal rhizotomy. In six of these animals injections were also made after C2 spinal cord transection and removal of the cervical spinal cord. Injections made in the vagotomized animals were associated with apneusis followed by hyperpnea. C7 spinal transection eliminated the hyperpneic response, but the apneusis remained. Cervical dorsal rhizotomy or C2 spinal cord transection failed to abolish the apneusis in response to injection. No diaphragm response was obtained after removal of the cervical spinal cord. Experiments in three additional animals showed that capsaicin does not have a direct excitatory effect on the muscle cells of the crural diaphragm, nor does it potentiate the release of neurotransmitter in the diaphragm. The results of this study indicate that small-fiber afferents in the diaphragm have an excitatory effect on phrenic motoneurons. There is a segmental component to this reflex, since the response is observed after C2 spinal cord transection. The data also suggest that at least some of these afferents enter the spinal cord through the ventral roots.

Afferent Pathways↗
PubMed1987

Diaphragm afferent modulation of phrenic motor drive.

Experiments were performed in eight lightly anesthetized thiopental sodium (Pentothal) cats to examine whether diaphragmatic afferents can significantly alter the neural drive to the diaphragm when the animal is exposed to lower body negative pressure. Moving-time-averaged diaphragmatic electromyograms (EMGma) were recorded and compared before and during exposure to lower body negative pressure in each of three consecutive conditions: C7 spinalization, bilateral vagotomy, and cervical dorsal rhizotomy. Application of lower body negative pressure in C7-spinalized animals resulted in a decrease in inspiratory time and peak diaphragmatic activity compared with control levels. After bilateral vagotomy, EMGma activity was prolonged with the application of lower body negative pressure. However, there was no increase in peak EMGma activity. After transection of the cervical dorsal roots subserving the phrenic nerve, the prolongation of diaphragmatic activity negative was eliminated. Therefore, we conclude that the significant increase in duration of inspiration in response to application of lower body negative pressure in the C7-spinalized, bilaterally vagotomized cat is mediated by phrenic nerve afferents.

Afferent Pathways↗
PubMed1987

Role of bronchopulmonary C-fiber afferents in the apneic response to cigarette smoke.

The role of vagal bronchopulmonary C-fiber afferents in eliciting the immediate changes in breathing pattern after acute inhalation of cigarette smoke was assessed with a selective blockade of myelinated vagal afferents (innervating both stretch and irritant receptors) utilizing the method of differential cooling. In 15 of 17 chloralose-anesthetized dogs tested, spontaneous inhalation of cigarette smoke (19.7% avg conc, 500-700 ml vol) reproducibly caused the following immediate responses: apnea, bradycardia, and hypotension. These responses occurred within 1 to 2 breaths of smoke inhalation and were followed by a delayed hyperpnea. The apneic duration reached 326 +/- 33% (SE) (n = 15) of the mean base-line expiratory duration. Differential cold block of both vagi (coolant temperature 8.4 +/- 0.3 degrees C) abolished the reflex apnea induced by a positive-pressure (7-10 cmH2O) lung inflation but did not affect the apneic response to smoke inhalation (345 +/- 35%). The smoke-induced apnea was completely abolished by lowering the coolant temperature to -1.3 +/- 0.2 degrees C (n = 10) or by bilateral vagotomy (n = 5) and returned to the control level after both vagi were rewarmed. Based on these results, we suggest that the immediate apneic response to inhaled cigarette smoke is elicited by a stimulation of vagal C-fiber afferents in the lungs and airways.

Afferent Pathways↗
PubMed1987

A technique for recording from intact phrenic nerve afferents.

Recent evidence has suggested that phrenic nerve afferents can influence respiratory motor drive. This paper presents a technique whereby the activity of single phrenic nerve afferents can be recorded from uncut dorsal root filaments. Cervical dorsal roots 4, 5, and 6 were exposed by dorsal laminectomy in 10 anesthetized, spontaneously breathing cats. A stimulating electrode was placed on the right whole phrenic nerve low in the neck. The animal was then placed in a spinal suspension frame. Dissection of the dorsal root filaments was performed with probes made of fine tungsten wire. Single filaments were isolated intact from the dorsal root fascicles and placed across a tungsten electrode. Fiber classification was performed by determining conduction velocity. Monopolar recordings were made from a total of 38 fibers. Tonic activity was observed in 21, respiratory-related activity was evident in 15, and two fibers were silent but could be recruited by phrenic nerve stimulation. The conduction velocities ranged from 2.2 to 103 m/s. Approximately one-half of the fibers had conduction velocities of less than 20 m/s. This technique offers a way to record the activity of diaphragm afferents while maintaining the integrity of possible reflex pathways. Application of this method should prove helpful in elucidating the possible role of the various diaphragm afferents in the control of respiratory motor drive.

Action Potentials↗
PubMed1986

Effect of nicotine aerosol on slowly adapting receptors in the airways of the dog.

The response of slowly adapting airway stretch receptors to nicotine aerosol was studied in the paralyzed, artificially ventilated, anesthetized dog. Single-unit stretch receptor recordings were made from individual vagus nerve filaments placed on a pair of platinum hook electrodes. Administration of 2% nicotine aerosol for five consecutive breaths caused an increase in both the peak transpulmonary pressure (Ptp) and in the activity of the slowly adapting stretch receptors (SARs). The results suggest that tracheal SARs were more affected than those receptors located distal to the carina. Administration of nicotine aerosols following pretreatment with isoproterenol, a bronchodilator, failed to significantly increase Ptp and, concomitantly, the activity of SARs. Therefore, the stimulatory effect of nicotine on SARs appeared to involve primarily an indirect activation of SARs via nicotine-induced bronchoconstriction. It is suggested that the activation of SARs may be involved in the reported nicotine-dependent cigarette smoke-induced apnea.

Administration, Intranasal↗
PubMed1986

Inhibition of potentially lethal radiation damage repair in normal and neoplastic human cells by 3-aminobenzamide: an inhibitor of poly(ADP-ribosylation).

The effect of 3-aminobenzamide (3AB), an inhibitor of poly(ADP-ribose) synthetase, on potentially lethal damage repair (PLDR) was investigated in normal human fibroblasts and four human tumor cell lines from tumors with varying degrees of radiocurability. The tumor lines selected were: Ewing's sarcoma, a bone tumor considered radiocurable and, human lung adenocarcinoma, osteosarcoma, and melanoma, three tumors considered nonradiocurable. PLDR was measured by comparing cell survival when cells were irradiated in a density-inhibited state and replated at appropriate cell numbers at specified times following irradiation to cell survival when cells were replated immediately following irradiation. 3AB was added to cultures 2 hr prior to irradiation and removed at the time of replating. Different test radiation doses were used for the various cell lines to obtain equivalent levels of cell survival. In the absence of inhibitor, PLDR was similar in all cell lines tested. In the presence of 8 mM 3AB, differential inhibition of PLDR was observed. PLDR was almost completely inhibited in Ewing's sarcoma cells and partially inhibited in normal fibroblast cells and osteosarcoma cells. No inhibition of PLDR was observed in the lung adenocarcinoma or melanoma cells. Except for the osteosarcoma cells, inhibition of PLDR by 3AB correlated well with radiocurability.

Benzamides↗
PubMed1986

Effect of nicotine and acetylcholine on crustacean muscle membrane potential.

We have investigated the effect of nicotine and acetylcholine on the resting membrane potential of the crayfish extensor muscle in order to determine whether crustacean muscle can be activated by cholinergic compounds. Intracellular recordings from individual deep extensor abdominal muscle cells were made using standard glass microelectrode techniques. The resting membrane potential was measured before and after treatment with glutamate, nicotine, and acetylcholine. Glutamate, which is a known activator of crayfish muscle, was used to determine whether the muscle cell preparation was viable and capable of responding to any of the test substances. Our results confirm that application of glutamate is associated with a depolarization of the muscle membrane. However, muscle cells showed no depolarization after treatment with nicotine (50 microM) or acetylcholine (66 microM). These results argue against the notion that increases in muscle tension may be responsible for the increased receptor organ discharge observed in the presence of nicotine. Rather, it supports the hypothesis that nicotine is acting directly on the mechanoreceptor membrane to change its sensitivity.

Acetylcholine↗
PubMed1985

Response of abdominal muscle to graded mechanical loads.

Abdominal muscle electromyograms were monitored in response to graded mechanical loads added to either inspiration or expiration in anesthetized cats. The surgical preparation, the apparatus, and the levels of loads applied (resistive, tracheal occlusion, and continuous positive pressure) were matched with those employed in our previous study on medullary expiratory neurons [Baker et al, 1979]. Although expiratory neuron firing was significantly increased by each of three graded levels of expiratory resistive loads, abdominal muscles were activated in only about 50% of the animals exposed to the highest-level resistive load. The smaller resistive loads failed to elicit any discernible abdominal muscle activity. These findings suggest that the lower motor neurons have a higher threshold for activation than the medullary neurons. Recruitment of medullary expiratory neurons and integration of synaptic input at the spinal level must play important roles in the response to expiratory loading. Abdominal muscles did not respond to mechanical loading during inspiration. Bilateral cervical vagotomy eliminated the abdominal muscle responses to expiratory loads.

Abdominal Muscles↗
PubMed1985

Static lung compliance during the development of the bullfrog, Rana catesbeiana.

The static compliance of excised lungs was measured during the metamorphic development of the bullfrog, Rana catesbeiana. Absolute static compliance of excised lungs increased with developmental stage from 0.02(+/- 0.01 SD) ml/cm H2O at Taylor-Kollros (TK) stage III to 34.67(+/- 15.00 SD) ml/cm H2O for adults. When static lung compliance was standardized by dividing by the lung volume at 4 cm H2O transmural pressure (approximately maximal capacity), lung compliance was relatively constant during early development and increased at the onset of metamorphic climax (TK stage XX). Although the absolute lung compliances of developing tadpoles are small, the volume-specific compliances are three to four times greater than those of some mammals. The compliance-independent index of hysteresis also increased during development from 0.0008(+/- 0.0006 SD) cm at TK stage V to 1.36(+/- 1.21 SD) cm for adults suggesting increases in pulmonary structural complexity and/or an increase in the production and secretion of a pulmonary surfactant-like substance. These developmental changes in pulmonary compliance and hysteresis mirror the increasing utility of the lung for gas exchange during the metamorphosis of the bullfrog.

Animals↗
PubMed1985

Influence of nicotine in cigarette smoke on acute ventilatory responses in awake dogs.

To determine whether the acute ventilatory responses to inhaled cigarette smoke are affected by a difference in nicotine level, control cigarettes (low-nicotine research cigarettes) were laced with nicotine to generate an increase of 330% (mean) in nicotine content with little or no change in the levels of other smoke constituents. Acute ventilatory responses to both control and nicotine-laced cigarettes were determined and compared in six awake chronic dogs. Spontaneous inhalation of nicotine-laced cigarette smoke (10% concn, 750 ml vol) via a tracheostomy tube caused distinct and consistent changes in breathing pattern on the first or second breath of inhaled smoke: an apnea in three dogs, an augmented inspiration in two dogs, and rapid shallow breathing in one dog. No significant change in breathing pattern was found immediately following inhalation of control cigarette smoke. Both types of cigarettes caused a delayed hyperpnea. However, the increase in minute ventilation induced by nicotine-laced cigarettes (from a base line of 2.8 to a peak of 25.7 l/min) was significantly greater than that by control cigarettes (from 2.9 to 5.5 l/min). Results of this study suggest that nicotine is responsible for the elicitation of both the immediate and delayed ventilatory responses to inhaled cigarette smoke generated under our experimental conditions.

Animals↗