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Biomedical subjects

R A Mitchell

Publications and source records attributed to R A Mitchell.

At least 73 records · Page 4Linked to original sources
PubMed1984

Modulation of pulmonary stretch receptors and airway resistance by parasympathetic efferents.

Recording from pulmonary stretch receptors in the intact cervical vagus nerve revealed a novel interaction between stretch receptors and smooth muscle in the lungs of anesthetized paralyzed cats. Firing rates of pulmonary stretch receptors were modulated in step with the inflation-deflation cycle of the mechanical respirator, as expected. Firing rates of most slowly adapting receptors, but not rapidly adapting receptors, were also strongly modulated in step with the phrenic nerve activity even when the respirator was turned off and the cat motionless. The modulation of some receptors' firing rates by the inspiratory motor output was as great as the change in firing-rate in response to a lung inflation of 20 ml of air (one tidal volume). Atropine blocked the inspiratory-related modulation of slowly adapting/receptor firing rates; it did not block the inflation-related modulation. Pulmonary resistance was modulated in step with the inspiratory activity on the phrenic nerve. Hyperventilation to neural apnea (no phrenic nerve activity) reduced pulmonary resistance to its lowest level, a level equal to that produced by an injection of isoproterenol or atropine. Hypoxia during hypocapnic apnea caused bursts of inspiratory activity on the phrenic nerve accompanied by one-to-one increases in airway resistance. We conclude that the intrathoracic airway smooth muscle contracts with each neural inspiration, that the modulation of the pulmonary stretch receptors is due to a mechanical interaction with the intrathoracic airway smooth muscle, and that through the mechanical link with airway smooth muscle, stretch receptor sensitivity depends on inspiratory output, a closed loop.

Afferent Pathways↗
PubMed1984

Short-chain fatty acids and encephalopathy of Reye's syndrome.

Plasma levels of six short-chain fatty acids (SCFA) were measured in 23 Reye's syndrome patients. In sequential measurements, only propionic acid correlated closely with neurologic severity. Although admission SCFA levels were slightly elevated, there were no significant differences between patients grouped by severity of encephalopathy. Admission SCFA did not predict neurologic outcome; also, they correlated poorly with admission blood ammonia, amino acid nitrogen, and lactate.

Coma↗
PubMed1983

Transmission in airway ganglia of ferrets: inhibition by norepinephrine.

We examined the possibility that norepinephrine inhibits transmission in parasympathetic ganglia of the ferret trachea. We impaled ganglion cells on recording microelectrodes and evoked postsynaptic action potentials by stimulating fiber tracts entering the ganglion. When norepinephrine was added to the recording bath, the action potentials were blocked. Phentolamine reversed this block. These results indicate that, by activating alpha-receptors, norepinephrine inhibits transmission in airway ganglia.

Animals↗
PubMed1982

Power spectral analysis of inspiratory nerve activity in the decerebrate cat.

To investigate the high frequency oscillations observed in the inspiratory activity of respiratory motor nerves of decerebrate cats, we applied a signal processing technique, power spectral analysis, to the electrical activity of the phrenic and recurrent laryngeal nerves. We found two peaks in the phrenic nerve power spectral densities, one at 88.1 +/- 6.4 Hz (mean +/- S.D.) and the other at 37.1 +/- 9.7 Hz, and two peaks for the recurrent laryngeal nerve, at 87.4 +/- 10.1 Hz and at 55.4 +/- 5.1 Hz. We identified 3 factors affecting the peaks. Anesthetics reduced or eliminated the 88 Hz peak and produced new low frequency peaks in the phrenic and recurrent laryngeal nerves. Increasing end-tidal CO2 decreased the bandwidth of the 88 Hz peak and increased its amplitude relative to that of the low frequency peak. Decreasing body temperature from 38 to 30 degrees C reduced the frequency of the 88 Hz peak by 5.0 Hz/degrees C. The power spectral density of the phrenic nerve activity differed from that of the recurrent laryngeal nerve activity because the single fibers in each nerve had different power spectral densities. About 70% of the fibers recorded in a nerve had power spectral densities similar to that of the whole nerve. A minority of the phrenic nerve fibers had the same low spectral peak as the recurrent laryngeal nerve, and conversely, a minority of the recurrent laryngeal fibers had the same low spectral peak as the phrenic nerve. Bilateral removal of the dorsal respiratory group eliminated the high frequency peak in the power spectral density of the phrenic nerve and the peripheral reflexes, but rhythmic bursts of inspiratory activity remained. From these findings we hypothesized that there are two central respiratory pattern generators in the brain stem with parallel pathways to the respiratory motoneurons.

Anesthesia, General↗
PubMed1981

The neural pathway involved in "efferent inhibition" of chemoreceptors in the cat carotid body.

This study was done to determine whether a pathway of efferent axons in the carotid sinus nerve is necessary for the phenomenon of "efferent inhibition" (inhibition induced in carotid body chemoreceptors by electrical stimulation of the carotid sinus nerve). Our approach was to eliminate efferent axons in the carotid sinus nerve of cats without destroying the sensory axons. This was achieved by cutting the ipsilateral glossopharyngeal and vagus nerves central to their sensory ganglia and/or by removing the nodose and superior cervical ganglia. In neurophysiological studies we found that the response of chemoreceptors in cats 10 days after surgery was the same as that in controls. chemoreceptor activity was decreased by electrical stimulation of the carotid sinus nerve and was increased by hypoxia and cyanide. In operated cats as in control animals, "efferent inhibition" was abolished by haloperidol and dihydroergotamine, drugs that block the inhibitory action of dopamine. Electron microscopic studies disclosed that the number of nerve endings in glomus cell/sheath cell complexes was not measurably different in control and experimental carotid bodies. By contrast, 10 days after the carotid sinus nerve was cut the number of nerve endings next to such ells was reduced by more than 99%. cutting the nerve roots and excising the ganglia eliminated most nerve endings on blood vessels: The number of noradrenergic-type nerve endings was reduced 99% and other types of nerve endings (presumptive cholinergic and peptidergic types) were reduced by more than 90%. Our experiments indicate that "efferent inhibition" is not abolished by operations that destroy inputs to blood vessels and to carotid boy glomus cells from (1) the nodose ganglion, (2) superior cervical ganglion, or from (3) neurons in the brain stem whose axons run in the glossopharyngeal or vagus nerves. We conclude that " efferent inhibition" may be caused by antidromic stimulation of sensory axons.

Animals↗
PubMed1981

Early identification of patients prone to develop adult respiratory distress syndrome.

Fifty-nine intubated nonhypoxic patients with clinical criteria associated with adult respiratory distress syndrome were studied. Clinical measurement were sought to identify patients before severe hypoxemia occurred. Etiologic factors, chest roentgenography, effective static compliance, intrapulmonary shunt and arterial blood gases on 40 and 100 percent inspired oxygen were analyzed. Pulmonary failure occurred in 22 patients, while 37 had minimal pulmonary difficulties. Comparison of these two groups revealed that only sequential arterial oxygen tensions accurately predicted pulmonary deterioration. A 40 percent arterial oxygen pressure below 100 torr and a 100 percent oxygen pressure below 350 torr indicated a 95 percent probability of pulmonary deterioration. When either determination was above these levels, the probability of pulmonary deterioration was 10 percent. The use of sequential arterial blood gases allows the selection of high risk patients for adult respiratory distress syndrome. This ensures that therapy is offered at the most beneficial time.

Bacterial Infections↗
PubMed1980

Comparison of cytosolic and mitochondrial hepatic enzyme alterations in Reye's syndrome.

The activities of nine enzymes in liver specimens obtained from four children who had died from Reye's syndrome were compared to the corresponding activities of a control group of four children who had died from unrelated causes. At the 95% significance level, the alterations could be classified into three groups. Five activities [lactate dehydrogenase, alanine aminotransferase, glucose 6-phosphatase, cytochrome oxidase, and malate dehydrogenase (mitochondrial plus cytosolic)] showed no change. Three enzymes [glutamate dehydrogenase, isocitrate dehydrogenase (NADP), and monoamine oxidase] were decreased. One activity (glucose 6-phosphate dehydrogenase) was increased. The malate dehydrogenase isozymes were resolved by electrophoresis, and the two bands were stained and measured. The ratio of cytosolic:mitochondrial enzyme was significantly greater in Reye's syndrome than in the control group. These results lend further support to the view that in Reye's syndrome the impairment of hepatic function is largely confined to the mitochondria. The lowered activity of monoamine oxidase means that the abnormalities extend to the outer mitochondrial membrane. Imbalances of the cytosolic:mitochondrial enzyme activities were evaluated in needle biopsy specimens from four other children under conditions where neurologic abnormalities were less severe. Two patients had elevated ratios of both glutamate:lactate dehydrogenase and cytosolic:mitochondrial malate dehydrogenase activities, and a third had only an abnormal malate dehydrogenase ratio. In contrast to these Reye's syndrome patients, a fourth case admitted with a provisional diagnosis of Reye's syndrome showed no abnormality in either ratio in stage IV coma.

Adolescent↗
PubMed1980

Neural regulation of respiration.

We would suggest that during the evolution of the mammalian respiratory neural networks the primitive centers in the cervical cord as well as the ventral respiratory group which evolved in fish have been preserved and are capable of functioning in the absence of the dorsal respiratory group generator which evolved with air breathing. We believe that these pattern generators are separate from the identified respiratory units that have so far been studied and that the apparent reciprocal inhibition observed in the identified cells results from synchronized excitatory and inhibitory inputs arising from the pattern generator itself. We believe that the model of such a system shown in Figure 3 is consistent with the observations cited in the previous section and inconsistent with models involving a single site for a pattern generator or interaction between various populations of known or identified respiratory units.

Animals↗
PubMed1980

Site of termination of primary afferents from the carotid body chemoreceptors.

The precise site of termination of primary afferents from the carotid chemoreceptors, has not been revealed as yet by anatomical or physiological studies. Identified units in the dorsal and ventral respiratory groups in the medulla can be evoked by chemoreceptor stimulation during inspiration, and inhibited by stimulation during expiration. Thus chemoreceptor input appears to be gated by an unidentified population of respiratory units before it reaches the recognized populations. For this as well as other reasons, we propose that chemoreceptor fibers terminate on a population of small interneurons that are the pattern generators for respiratory rhythmicity. At least two paired pattern generators exist, one pair associated with the dorsal respiratory group, and a second pair associated with the ventral respiratory group.

Afferent Pathways↗
PubMed1979

Early positive end-expiratory pressure in the adult respiratory distress syndrome.

This prospective study was designed to determine the effect of positive end-expiratory pressure (PEEP) instituted early in the course of adult respiratory distress syndrome (ARDS). Seventy-nine (7%) of 1,200 patients admitted to the surgical intensive care unit were selected because of a high probability that ARDS would develop, and were randomized into two treatment groups. Of the 79 patients, 45 were immediately treated with 5 cm H2O of end-expiratory pressure (early PEEP group), and 34 received PEEP only when severe hypoxemia developed (late PEEP group). The incidence of ARDS was significantly lower in the early PEEP group than in the late PEEP group (20% vs 53%; P less than .002). Fewer pulmonary deaths occurred in this group (11% vs 29%; P = .02), and there was less pulmonary morbidity. This study supports the efficacy of early low-level PEEP in the treatment of patients for whom there is a high probability that ARDS will develop.

Clinical Trials as Topic↗
PubMed1979

Appendicitis and aortofemoral graft infection.

A 59-year-old man who underwent successful aortofemoral bypass had acute appendicitis at an indeterminate time in the postoperative period. Thirteen months later, a pulsatile groin mass developed. After a complicated course, it was found that infection from appendicitis had extended to the body of the graft. This unusual cause of graft infection reaffirms the importance of careful closure of the retroperitoneum over an aortic anastomosis and suggests a relationship of other intra-abdominal inflammatory processes to graft infection.

Acute Disease↗
PubMed1979

Mechanism of the isoproterenol hyperpnea in the cat.

To clarify the role of peripheral chemoreceptors in the abrupt hyperpnea induced by isoproterenol injection, we measured, in anesthetized cats, the time course of VE, PETCO2, H.R. and B.P. following i.v. bolus injection of 0.5--2 microgram isoproterenol before and after bilateral section of the carotid sinus (csx), aortic (ax) and vagus (vx) nerves. We compared the hyperpneic response of isoproterenol to that of 100 microgram injections of NaCN (CN), a drug known to stimulate peripheral chemoreceptors, during air and 100% O2 breathing. The ventilatory response to isoproterenol persisted for over 90 s, whereas the CN response lasted only 30 s. Also 100% O2 markedly attenuated the CN hyperpnea but had little effect on the ventilatory response to isoproterenol. The maximum increase in ventilation in response to isoproterenol was reduced by approximately 1/3 by csx, 1/2 by combined csx and ax, and 2/3 by combined csx, ax and vx. The residual hyperpnea after csx, ax, and vs is delayed in time and lagged behind the increase in PETCO2. It is concluded that the peripheral chemoreceptors and possibly vagal afferents play a major role in the hyperpnea caused by isoproterenol, but in their absence central chemoreceptors respond to the increased PaCO2 induced by the elevated cardiac output to stimulate ventilation.

Animals↗
PubMed1979

Effects of dopamine, norepinephrine and 5-hydroxytryptamine on the carotid body of the dog.

The effects of bolus intracarotid (IC) infusions of dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT) on activity in single or few-fiber carotid chemoreceptor afferent nerve preparations were studied in pentobarbital anesthetized dogs. In addition, the effects of intravenous (IV) infusions of DA were also assessed. IC injections of DA (10 microgram) and (5-HT) (1 microgram) consistently produced a burst of intense activity followed by a period of inhibition. A similar effect was seen with IC NE (20--40 microgram) injections, but the burst of excitation occurred in only 45% of the injections. Inhibition of activity was seen in 88% of the IC NE injections. Low IC doses of all 3 amines produced inhibition of chemoreceptor afferent activity. High doses of DA IV (approximately 60 microgram/kg/))produced excitation followed by depression, while lower doses (approximately 21 microgram/kg) produced only inhibition. The excitatory effects of all 3 amines were blocked by d-tubocurarine (50--435 microgram/kg IV). Inhibitory effects of all 3 amines were blocked by dihydroergotamine (140--270 microgram/kg). The inhibitory effect produced by DA was specifically blocked by haloperidol (50--400 microgram/kg IV). We conclude that DA, NE and 5-HT can modulate carotid body activity by increasing or decreasing responses to physiologic stimuli.

Animals↗