Search PubMed⌕ Search

Biomedical subjects

J Duffin

Publications and source records attributed to J Duffin.

At least 109 records · Page 6Linked to original sources

Ten-year experience with extracorporeal membrane oxygenation for severe respiratory failure.

In the last ten years, 17 patients with respiratory failure refractory to standard ventilator therapy have been treated with extracorporeal membrane oxygenation (ECMO) at the Toronto General Hospital. One patient was treated with ECMO twice. Four perfusions were veno-arterial, the remainder veno-venous. Perfusions ranged from 1 1/2 to 19 days, with a mean of six days. Ten patients died during treatment or soon after it was discontinued. Eight patients improved enough to allow resumption of standard ventilation, and four patients recovered sufficiently to have normal arterial blood gas levels on room air. Three are long-term survivors. Multiple surgical procedures have been performed successfully during use of ECMO including lung lavage, open lung biopsy and three lung transplants. Major complications include hemorrhagic diatheses and sepsis. The technique involves a substantial commitment of time and personnel but remains a tenable option for presumed reversible life-threatening respiratory failure.

Adolescent↗

Intracellular recordings from upper cervical inspiratory neurons in the cat.

Intracellular recordings were made from propriospinal, inspiratory neurons, at the lateral edge of lamina VII in the upper cervical cord of the cat. The membrane potentials were found to fluctuate with the central respiratory rhythm, as determined from a recording of the phrenic nerve discharge. Excitatory postsynaptic potentials occurred during the inspiratory phase, and inhibitory postsynaptic potentials were shown to occur in the expiratory phase by injecting chloride to reverse them. These recordings are the first demonstration that the upper cervical inspiratory neurons receive both excitation during inspiration and inhibition during expiration.

Animals↗

Excitation of upper cervical inspiratory neurons by inspiratory neurons of the nucleus tractus solitarius in the cat.

Experiments were conducted to investigate the connection from inspiratory neurons in the ventrolateral region of the nucleus tractus solitarius to the inspiratory neurons in the contralateral upper cervical (C1-C2) spinal cord. Microstimulation within the region usually produced long-latency (10 to 30 ms) synaptic activation of the upper cervical inspiratory neurons. Antidromic mapping of axons of the ventrolateral nucleus tractus solitarius in C1 demonstrated the existence of collateral arbors in the region of the upper cervical inspiratory neurons (7 of 15). Cross-correlation histograms showed the existence of short-term synchronization of firing for 12 of 74 pairs of ventrolateral nucleus tractus solitarius and upper cervical inspiratory neurons. Cross-correlation combined with antidromic activation showed that the short-term synchronization was due to a direct connection in two cases and a common input in one case. It was concluded that at least some ventrolateral nucleus tractus solitarius inspiratory neurons may directly excite upper cervical inspiratory neurons, probably via monosynaptic connections. Both groups of neurons may also share common inputs.

Afferent Pathways↗

Excitation of upper cervical inspiratory neurons by inspiratory neurons of the nucleus retroambigualis in the cat.

The experiments reported here examined inputs from inspiratory neurons of the nucleus retroambigualis to upper cervical inspiratory neurons. Antidromic mapping in contralateral C1 demonstrated the existence of axon collaterals for 9 of 19 nucleus retroambigualis axons tested (47%). Forty nucleus retroambigualis neurons were tested with antidromic mapping for a projection to the ipsilateral C1 segment; 9/40 (22%) had an ipsilateral axon (8 of these also projected contralaterally), and 2/40 (5%) had an axon collateral in ipsilateral C1. Cross-correlation histograms suggested monosynaptic excitation of an upper cervical inspiratory neuron by a contralateral nucleus retroambigualis neuron in 4/69 cases (6%) and common input to the pair in 2/69 cases (3%). Six of the 69 cross-correlograms were computed during antidromic activation of the nucleus retroambigualis neuron, and one of these six demonstrated direct excitation of the upper cervical inspiratory neuron by the retroambigualis neuron. We concluded that at least some upper cervical inspiratory neurons receive monosynaptic excitation from the contralateral, and possibly the ipsilateral, nucleus retroambigualis inspiratory neurons. These results, together with those published elsewhere for inputs from inspiratory neurons in the contralateral ventrolateral nucleus tractus solitarius, suggest that the rhythmic, inspiratory firing pattern of the upper cervical inspiratory neurons is due to excitatory inputs from these two inspiratory bulbospinal neuron populations.

Animals↗

The contribution of peripheral chemoreceptors to ventilation during heavy exercise.

The purpose of this study was to determine, in man, the contribution of peripheral chemoreceptors to ventilation during constant-load, heavy exercise above anaerobic threshold at sea level, using hyperoxic suppression of peripheral chemoreceptor drive which was obtained by abrupt and surreptitious replacement of inspired air with 100% oxygen for a period of 20-30 sec during the exercise. There was a delay of at least 1 sec from the time of peripheral chemoreceptor blockade to the initial change in ventilation, suggesting the operation of a central neural reverberatory mechanism after the cessation of peripheral chemoreceptor drive. In contrast to Wasserman (1976), whose results indicated a 25% decrease in ventilation within two breaths, in the present study no significant drop was observed until some 4-6 breaths after the air-to-oxygen switch. Furthermore, the drop in ventilation, magnitude of which was of the order of 15%, was transient in 5 out of 8 subjects. In one subject, the ventilation increased following oxygen administration. It is concluded that the peripheral chemoreceptors are not the sole mediators of hyperventilation of heavy exercise above anaerobic threshold in man.

Acidosis↗

The effect of exercise on the central-chemoreceptor threshold in man.

1. The threshold of the central chemoreceptors was determined under resting and three exercise conditions in four volunteers. 2. The method used was the hyperoxic, Read rebreathing technique with prior hyperventilation. Plots of resting ventilation vs. carbon dioxide consisted of two straight-line segments of different slopes above and below a breakpoint which was taken as the central-chemoreceptor threshold at rest. 3. The threshold during exercise was determined from plots of exercise ventilation vs. carbon dioxide in a similar way, but the points for these plots were obtained in a different manner. They were obtained from a number of separate rebreathing experiments, so as to avoid the divergence between mouth and central-chemoreceptor carbon dioxide levels during rebreathing in exercise. 4. Exercise was started abruptly during rebreathing experiments similar to those at rest, at a particular level of carbon dioxide, and exercise ventilation was measured at the third breath. Each rebreathing experiment therefore provides one point for the exercise ventilation vs. carbon dioxide plot. 5. The results showed that the central-chemoreceptor threshold during exercise was not different from the resting threshold, and that the initial, fast component of exercise ventilation was independent of the chemical drive to breathe.

Adult↗

Monosynaptic excitation of thoracic motoneurones by inspiratory neurones of the nucleus tractus solitarius in the cat.

1. The connection between inspiratory neurones in the ventrolateral nucleus tractus solitarius (n.t.s.) and intercostal motoneurones was examined. 2. Descending axonal projections to contralateral T3-T5 spinal segments were found for 110 of 142 (77%) ventrolateral n.t.s. neurones examined. 3. Antidromic mapping was used to locate the axons of thirty-nine ventrolateral n.t.s. neurones in T4, and evidence for axon collaterals was found for thirty-two of forty-seven (68%) neurones examined. Axon collaterals were found in both T3 and T4 for four of nine neurones examined and in T3, T4 and T5 for two of three neurones examined. 4. Cross-correlation histograms were calculated for sixty-five ventrolateral n.t.s. neurones with the contralateral intercostal nerves. Peaks in the cross-correlograms were assessed for significance by calculating k, the ratio of the peak bin count to the mean bin count. Significant peaks (k ratios 1.07-1.24, mean 1.15) were found for twenty-eight (39%) cross-correlograms. Twelve of thirty-three (36%) were for the whole external intercostal nerve, ten of twenty-seven (37%) were for the whole internal intercostal nerve and six of eleven (54%) were for external intercostal nerve filaments. 5. Six of the cross-correlogram peaks were less than or equal to 1.2 ms in width at a level half-way between the peak and the mean bin count. The rest ranged from 2.0 to 4.6 ms (mean 3.0 ms). 6. Intracellular recordings from either internal or external intercostal motoneurones were made and averages of the intracellular potentials were computed using ventrolateral n.t.s. neurone spikes as triggers. 7. Thirty-two spike-triggered averages were computed for pairings between nineteen ventrolateral n.t.s. neurones and thirty-two intercostal motoneurones (twenty-five internal, seven external). Fast-rising, short-lasting depolarizations indicative of a monosynaptic e.p.s.p. were found for five ventrolateral n.t.s. neurones. 8. The characteristics of the cross-correlogram peaks were considered with respect to the e.p.s.p. shapes and it was concluded that the intercostal motoneurones receive a significant monosynaptic excitation from ventrolateral n.t.s. neurones.

Action Potentials↗

The effect of treadmill speed on ventilation at the start of exercise in man.

1. The change in ventilation at the start of exercise was determined during both hyperoxic rebreathing and air breathing in four volunteers. 2. In order to differentiate between the effects of limb-movement frequency and exercise load in terms of oxygen uptake, three treadmill exercises were tested: E1, at an oxygen uptake of 1 l/min on a level treadmill; E2, at 2 l/min on an inclined treadmill at the same speed as E1; E3, at 2 l/min on a level treadmill at a higher speed. All of the exercises were performed at a walking pace. 3. Prior to rebreathing, hyperventilation for 5 min to 20 mmHg was used to reduce carbon dioxide to below the central chemoreceptor threshold. From eleven to fourteen rebreathing experiments were done on each volunteer for each of the three exercises, with the treadmill started at carbon dioxide levels which ranged from 36 (below threshold) to 58 mmHg (above threshold). 4. Ten experiments were performed on each volunteer for each of the three exercises during air breathing, with the treadmill started after 5 min of rest. 5. In both the rebreathing experiments and the air breathing experiments it was found that the change in ventilation at the start of exercise was the same for exercises E1 and E2, and significantly greater for exercise E3. 6. It was concluded that the frequency of limb movement, rather than exercise load (oxygen consumption) is a determinant of the change in ventilation at the start of exercise.

Adult↗

An electrophysiological investigation of propriospinal inspiratory neurons in the upper cervical cord of the cat.

This study was performed in order to describe the location, axonal projection and possible synaptic action of the inspiratory neurons recently described in the upper cervical cord. In 26 cats anaesthetized with Nembutal, extracellular recordings were made from 224 cervical inspiratory units which were found near the lateral border of lamina VII and formed a column extending from the caudal end of the nucleus retroambigualis at the C1 segment to the rostral half of the C3 segment. Most of the units (approximately 85%) could be excited antidromically from the thoracic cord. Antidromic mapping showed collateral branches to the C5 segment in the vicinity of the phrenic nucleus, occasionally crossing the midline. No synaptic connections with phrenic motoneurones could be revealed either by cross-correlation of the activity of the cervical units with the discharge of C5 phrenic root, or by spike-triggered averaging (STA) of the post-synaptic noise recorded intracellularly from phrenic motoneurons. Extensive branching was found in the examined T3-T5 segments with arborizations near the ipsilateral intercostal motor nuclei and often extending across the midline. Cross-correlation experiments did not show clear monosynaptic connections to the inspiratory intercostal motoneurons. Intracellular recording from intercostal motoneurons and STA resulted in a few (2 out of 37) small, probably disynaptic, e.p.s.p.s. It is concluded that the upper cervical neurons are involved in the control of phrenic and intercostal motoneurons, probably through a disynaptic pathway involving segmental interneurons.

Animals↗

Stabilization of intracellular recordings in the cat spinal cord using high-frequency ventilation.

Stabilization of intracellular recordings by a substantial reduction of respiratory motion may be accomplished by the use of high-frequency ventilation (600-800 breaths/min). The technique is a simple one and enables maintenance of relatively constant blood gas tensions. Although the improved stability was demonstrated in experiments performed on alpha motoneurones in the thoracic spinal cord, it is anticipated that a reduced respiratory movement should benefit recordings in other spinal and supraspinal sites.

Animals↗

Short-latency interactions among dorsomedial medullary inspiratory neurons in the cat.

Pairs of inspiratory neurons were recorded extracellularly with microelectrodes whose tips were close to one another (100 to 300 microns) in the ventrolateral region of the nucleus tractus solitarius. Each neuron was identified as an R beta or an R alpha type using lung volume manipulations. Those neuron pairs whose cross-correlation histograms indicated a positive interaction were tested for interneuronal connections by antidromic activation of one neuron of the pair combined with further cross-correlation. Three pairs of R alpha/R alpha, three pairs of R alpha/R beta, and three pairs of R beta/R alpha neurons were tested in this manner. One pair of R alpha/R alpha neurons and one pair of R beta/R beta neurons showed evidence of interneuronal interaction. We concluded that although the short-term synchronization in the firing patterns of these neurons was due mostly to common excitation of both neurons, interneuronal interactions were also responsible.

Animals↗

Cross-correlation of ventrolateral inspiratory neurons in the cat.

The ventrolateral region in the medulla of cats was explored with pairs of microelectrodes with tip separations from 100 to 300 micron such that extracellular potentials of pairs of near-neighboring neurons were recorded simultaneously. At least one neuron of each pair was antidromically activated from the spinal cord. Cross-correlation histograms were computed and showed the existence of short-term synchronization of firing for 8 of 20 neuron pairs (40%). The primary feature of the cross-correlation histograms was, typically, asymmetrical peaks on each side of time zero. The peaks were dissimilar, one low and broad, the other high and narrow, and occurred within a millisecond of time zero. Poststimulus histograms computed for one of the pair, during antidromic activation of the other, indicated a possible interaction between the neurons in one case but not in another. The results are suggestive of neuronal interactions among the late-firing inspiratory neurons of the nucleus retroambigualis but are not conclusive.

Animals↗

The medullary respiratory neurons: a review.

The medullary respiratory neurons involved in the generation of respiratory rhythm are reviewed. The subject is introduced by a brief description to the history of respiratory neurophysiology and of the pontine respiratory neurons. A detailed neurophysiological review is presented for the medullary respiratory neurons: their locations, morphology, firing patterns, afferent connections, axonal connections, and functional interrelations. The significance of the medullary respiratory neurons for rhythmogenesis is discussed.

Animals↗