Respiratory activity of the rat posterior cricoarytenoid muscle

An anatomic and electrophysiological study of the rat posterior cricoarytenoid (PCA) muscle is described. The intramuscular nerve distribution of the PCA branch of the recurrent laryngeal nerve was demonstrated by a modified Sihler's stain. The nerve to the PCA was found to terminate in superior and inferior branches with a distribution that appeared to be confined to the PCA muscle. Electromyography (EMG) recordings of PCA muscle activity in anesthetized rats were obtained under stereotaxic control together with measurement of phrenic nerve discharge. A total of 151 recordings were made in 7 PCA muscles from 4 rats. Phasic inspiratory activity with a waveform similar to that of phrenic nerve discharge was found in 134 recordings, while a biphasic pattern with both inspiratory and post-inspiratory peaks was recorded from random sites within the PCA muscle on 17 occasions. The PCA EMG activity commenced 24.6 +/- 2.2 milliseconds (p < .0001) before phrenic nerve discharge. The results are in accord with findings of earlier studies that show that PCA muscle activity commences prior to inspiratory airflow and diaphragmatic muscle activity. The data suggest that PCA and diaphragm motoneurons share common or similar medullary pre-motoneurons. The earlier onset of PCA muscle activity may indicate a role for medullary pre-inspiratory neurons in initiating PCA activity.     

Diaphragm activation with intramuscular stimulation in dogs

We studied in 10 supine anesthetized dogs diaphragm contraction produced by electrical activation with intramuscular electrodes surgically implanted in the ventral surface of the diaphragm and compared this with activation of the ipsilateral phrenic nerve (C5, 6, and 7) before it entered the thorax. Repetitive 40-Hz pulse trains with supramaximal current stimulus were used after hyperventilation of the animals to apnea. A single intramuscular electrode within 1 to 2 cm of the site of phrenic nerve entry into the diaphragm produced a mean transdiaphragmatic pressure of 12.0 cm H2O +/- 0.97 SE and mean tidal volume of 0.27 L +/- 0.04 SE. Mean values observed with phrenic nerve stimulation were not statistically different, and both electrode systems produced equivalent outward abdominal motion and upper rib cage paradox, as monitored by inductive plethysmography. There was no difference in gas exchange during stimulation with a single hemidiaphragm electrode and mechanical ventilation compared at the same tidal volume and respiratory rate. Blockade of neuromuscular transmission with curare eliminated intramuscular and phrenic nerve stimulation proportionately, suggesting that activation of the diaphragm is dependent in both cases on the phrenic nerve. This technique does not entail manipulation of the phrenic nerve and may have clinical application as an alternative technique for diaphragm pacing.     

Ultrasound evaluation of piglet diaphragm function before and after fatigue

Clinically, a noninvasive measure of diaphragm function is needed. The purpose of this study is to determine whether ultrasonography can be used to 1) quantify diaphragm function and 2) identify fatigue in a piglet model. Five piglets were anesthetized with pentobarbital sodium and halothane and studied during the following conditions: 1) baseline (spontaneous breathing); 2) baseline + CO2 [inhaled CO2 to increase arterial PCO2 to 50-60 Torr (6.6-8 kPa)]; 3) fatigue + CO2 (fatigue induced with 30 min of phrenic nerve pacing); and 4) recovery + CO2 (recovery after 1 h of mechanical ventilation). Ultrasound measurements of the posterior diaphragm were made (inspiratory mean velocity) in the transverse plane. Images were obtained from the midline, just inferior to the xiphoid process, and perpendicular to the abdomen. M-mode measures were made of the right posterior hemidiaphragm in the plane just lateral to the inferior vena cava. Abdominal and esophageal pressures were measured and transdiaphragmatic pressure (Pdi) was calculated during spontaneous (Sp) and paced (Pace) breaths. Arterial blood gases were also measured. Pdi(Sp) and Pdi(Pace) during baseline + CO2 were 8 +/- 0.7 and 49 +/- 11 cmH2O, respectively, and decreased to 6 +/- 1.0 and 27 +/- 7 cmH2O, respectively, during fatigue + CO2. Mean inspiratory velocity also decreased from 13 +/- 2 to 8 +/- 1 cm/s during these conditions. All variables returned to baseline during recovery + CO2. Ultrasonography can be used to quantify diaphragm function and identify piglet diaphragm fatigue.     

Excitation of central and peripheral terminals of primary afferent neurons by capsaicin in vivo

In three groups of rats discharge activity was recorded (i) from the peripheral stump of the cut saphenous nerve (saphenous-receptor preparation); (ii) from the central stump of the cut L4 or L5 dorsal root (dorsal root preparation); or (iii) from the peripheral stump of the saphenous nerve segment cut at both ends (axon preparation) during slow intraarterial infusion of capsaicin (30-300 micrograms/kg/min for 5 min) into the carotid artery. Capsaicin produced excitation, i.e. an increase in frequency of action potentials in the same dose range (100-300 micrograms/kg/min) in both the saphenous-receptor and dorsal root preparations, while the axon preparations remained unresponsive. In the cat, close arterial injection of capsaicin (up to 20 micrograms) into a collateral branch of the saphenous artery failed to evoke discharges in the saphenous axon preparation, although similar injection of 4-aminopyridine (60 micrograms), a K+ channel blocking agent was readily effective. These results indicate that after systemic application of capsaicin the peripheral and central endings of primary afferent neurons are equally important sites for activation and are much more sensitive to capsaicin than the axons of the nerve trunk.     

Some pharmacodynamic and biochemical aspects of cefamandole

The pharmacodynamic and nephrotoxic effects of cefamandole were investigated. Cefamandole at concentrations of 512 and 1024 micrograms/ml bath caused complete relaxation in isolated guinea pig ileum and rabbit duodenum, respectively. Concentrations of 2048 and 4096 micrograms cefamandole/ml bath caused marked stimulation in force and frequency of rat uterine muscle in all stages of sex cycle. Cefamandole in all tested concentrations did not induce any response on isolated guinea pig tracheal chain or isolated rabbit aortic strip. Cefamandole in concentrations of 256 to 1024 micrograms/ml bath as well as 256 and 512 micrograms/ml cannula produced marked inhibition on isolated guinea pig auricles and rabbit heart, respectively. The effect of graded increased concentrations on isolated frog gastrocnemius muscle, frog rectus abdominis muscle and rat phrenic nerve hemidiaphragm was recorded. Cefamandole in a dose of 53.2 mg/kg b. wt. in anaesthetized dogs caused very marked hypotensive effects and decrease in rate of respiration. Single intramuscular injection of cefamandole in a therapeutic (23.3 mg/kg b. wt.) and double therapeutic (46.6 mg/kg.b. wt.) doses in rabbits had no effect on electrocardiographic parameters among a period of 8 hours after injection. Effects of cefamandole on serum and urine concentrations of creatinine, urea, sodium, potassium, calcium, glucose and protein as well as clearance tests were investigated in rats.     

Primary graft dysfunction after liver transplantation: from pathogenesis to prevention

Spontaneous bladder contractions (SBCs) in decerebrate, vagotomized, paralyzed, ventilated cats have been shown to decrease phrenic and hypoglossal inspiratory nerve activities, as well as the activities of other respiratory motor nerves. To determine whether vagal afferents from the lung influence the respiratory inhibition associated with SBCs, we recorded phrenic and hypoglossal nerve activities in decerebrate, paralyzed, vagally intact cats. The animals were ventilated by a servo-respirator, which inflated the lungs in accordance with integrated phrenic nerve activity. Maintained increases in end-expiratory lung volume were produced by the application of 2-10 cm H2O positive end-expiratory pressure (PEEP). SBCs were accompanied by decreases in both phrenic and hypoglossal peak integrated nerve activities, as well as by marked decreases in respiratory frequency. The reduction of respiratory frequency was greater with higher levels of PEEP, a few animals becoming apneic during SBCs. After bilateral vagotomy, SBCs continued to decrease phrenic and hypoglossal peak integrated nerve activities as previously reported, but the reduction of respiratory frequency was much less striking than when the vagi were intact. These results indicate that activity of vagal afferents from the lung augments the respiratory influence of SBCs. Furthermore, SBCs in vagally intact animals can induce periodic breathing.     

Release of thiamine and formation of a methylthiamine-like substance in the phrenic nerve-diaphragm preparation of the rat

An increased formation of a radioactive methylthiamine-like substance (MTLS) in the end plate region of the rat diaphragm muscle and a release of radioactivity chromatographed as thiamine into the bath medium after a subcutaneous injection of 35S-thiamine were found after stimulation of the phrenic nerve. There was also an increased formation of the radioactive methylthiamine-like substance in the denervated diaphragm preparation incubated with radioactive acetylcholine (ACh) in comparison with the innervated diaphragm.     

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Three patients with liver metastases receiving transarterial chemotherapy underwent embolization of extrahepatic collaterals to the liver under temporary balloon occlusion of the proper hepatic artery. Enhancement in the liver and tumors was observed at CT arteriography through the right inferior phrenic artery and was accentuated under balloon occlusion in all patients. A Cyanoacrylate-Lipiodol mixture was infused through the right inferior phrenic artery to occlude arterial communications with intrahepatic arteries. Better contrast agent distribution was obtained in all patients after embolization. It is suggested that this procedure can be effective for arterial redistribution against extrahepatic collaterals to the liver.     

Respiratory modulation of barareceptor and chemoreceptor reflexes affecting heart rate and cardiac vagal efferent nerve activity

1. Brief stimuli were delivered to the carotid chemoreceptors or baroreceptors in dogs anaesthetized with chloralose. Chemoreceptor stimulation was achieved by rapid retrograde injection of 0.2-0.5 ml. CO2 equilibrated saline through a cannula in the external carotid artery. Baroreceptor stimulation was achieved by forceful retrograde injection of 2-5 ml. air-equilibrated saline into the external carotid artery after first clamping the common carotid artery. 2. prompt decreases in heart rate were elicited by brief sudden chemoreceptor or baroreceptor stimuli when these were delivered during the expiratory phase of respiration. The stimuli did not modify the control heart rate pattern when delivered in the inspiratory phase of respiration. This respiratory modulation of reflex effectiveness persisted when the animals were completely paralysed and the phase of the respiratory cycle was monitored through a phrenic electroneurogram. 3. single cardiac vagal efferent nerve fibres were dissected from the cut central end of the right cervical vagus nerve. They were classified as cardiac efferents by their cardiac and respiratory rhythmicity, and by their increased activity in response to stimulation of a carotid sinus nerve or to mechanical elevation of the systemic arterial pressure. These efferent fibres increased their activity in response to brief chemoreceptor or baroreceptor stimuli delivered in expiration, but did not respond to stimuli delivered in inspiration. This respiratory modulation of both reflexes persisted after bilateral cervical vagotomy.     

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Laparoscopic mapping of the phrenic nerve motor points using test stimulation was conducted for the implant of epimysial electrodes for diaphragm pacing in dogs. Both visual assessment of muscle activation and measurements of recruitment were useful for identifying an implant location resulting in a mean electrode placement approximately 14 mm from the phrenic nerve motor points in 16 dogs. Postmortem analysis of the stimulus test site locations and corresponding recruitment curves suggested that the phrenic nerve motor points could be predicted during the laparoscopic procedure to within 4.5 mm of the anatomical motor point.     

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Although studies have examined the susceptibility and pattern of injury induced by infusion of free radical-generating solutions into a number of vital organs, no such investigation has been performed for the diaphragm. The purpose of the present study was to examine the susceptibility of the diaphragm to damage by a free radical-generating solution (iron-ADP complexes). Studies were performed using an in situ canine diaphragmatic strip preparation in which the phrenic artery supplying the strip was cannulated and perfused with blood from the ipsilateral femoral artery. Four groups of studies were performed: (1) a group in which saline was infused into the arterial supply of the diaphragm for 15 min; (2) a group in which a solution of iron-ADP was infused; (3) a group in which both iron-ADP and superoxide dismutase (SOD), a free radical scavenger, were infused; and (4) a group given iron-ADP and denatured SOD. Strip tension and blood flow were monitored during electrically induced diaphragmatic contractions for 15 min before intraphrenic infusions, during the period of infusions, and for 90 min after cessation of infusions. We found that diaphragm tension did not change over time in saline-treated control animals but fell significantly in animals in which iron-ADP was infused. The effects of iron-ADP were largely prevented by concomitant administration of active SOD, but not by denatured SOD. On average, at 90 min after cessation of infusions, tension had fallen to 82 +/- 6, 41 +/- 8, 63 +/- 4, and 28 +/- 9% of its initial value in saline, iron-ADP, iron-ADP/SOD, and iron-ADP/denatured SOD groups, respectively (p < 0.001 for comparison of the four groups, with saline and iron-ADP/SOD groups different from the other two groups). Diaphragm blood flow did not change significantly in any group. These data suggest that free radical-mediated diaphragmatic injury can result in a marked reduction in diaphragm contractility.     

Power spectral analysis of electromyographic and systemic arterial pressure signals during fentanyl-induced muscular rigidity in the rat

We have measured electromyographic (EMG) and systemic arterial pressure (SAP) signals during fentanyl-induced muscular rigidity in adult male Sprague-Dawley rats anaesthetized initially with ketamine 120 mg kg-1 i.p. during controlled ventilation. Fentanyl 100 micrograms kg-1 i.v. induced significant increase in EMG activity, recorded from the sacrococcygeus dorsi lateralis muscle. Power spectral analysis revealed that this was produced by an increase in the root mean square and a decrease in the mean power frequency values of the signals, signifying recruitment and synchronous activation of motor units. Together with transient hypotension and bradycardia, power spectral analysis of the SAP signals demonstrated a reduced but maintained power density of the frequency components that represent respiratory, baroreceptor and vasomotor activities. All these effects were only demonstrated unequivocally in rats maintained by i.v. infusion of ketamine until 10 min before the administration of fentanyl. We conclude that analysis of the temporal alterations in the spectral components of the EMG and SAP signals in rats during mechanical ventilation provides a sensitive method of measuring fentanyl-induced muscular rigidity and the accompanying alterations in haemodynamic variables.     

Transient respiratory augmentation elicited by acute head-down tilt in the anesthetized cat

Acute head-down tilt (AHDT, -30 degrees) in humans induces a transient ventilatory augmentation for 1-2 min accompanied by a high venous return. However, the mechanisms underlying this respiratory response remain obscure because of limitations of experiments carried out in human subjects. The present study was undertaken to determine whether AHDT-induced respiratory augmentation exists in the anesthetized, paralyzed, and ventilated cat and, if so, whether this response depends on 1) the cerebellum, 2) the carotid sinus (CS) and/or vagal afferents, and 3) elevation of central venous return. The integrated phrenic neurogram, arterial blood pressure, central venous pressure (CVP), and end-tidal PCO2 were recorded before, during, and after AHDT. The results showed that AHDT produced a transient ( approximately 2 min) enhancement of minute phrenic activity (approximately 30%) primarily via an increase in peak integrated phrenic neurogram amplitude associated with a remarkable elevation of CVP (approximately 3 min). Cerebellectomy, CS denervation, bilateral vagotomy, or clamping CVP did not affect the presence of the AHDT-induced minute phrenic activity response. These findings demonstrate that the anesthetized cat is a suitable model for investigating the mechanisms involved in AHDT-induced respiratory augmentation. Preliminary studies suggest that this response does not require the cerebellum, CS/vagal afferents, or an associated rise in central venous return.     

Reflex vascular responses to alterations in abdominal arterial pressure and flow in anaesthetized dogs

The existence of abdominal arterial baroreceptors has long been controversial. Previously difficulties have been encountered in localizing a stimulus to abdominal arteries without affecting reflexogenic areas elsewhere. In these experiments, using anaesthetized dogs, the abdomen was vascularly isolated at the level of the diaphragm, perfused through the aorta, and drained from the inferior vena cava to a reservoir. Changes in abdominal arterial pressure were effected by changing the perfusion pump speed. During this procedure the flow back to the animal from the venous outflow reservoir was held constant. Increases and decreases in abdominal arterial pressure resulted, respectively, in decreases and increases in perfusion pressure to a vascularly isolated hind-limb and in some dogs also a forelimb. Responses were significantly larger when carotid sinus pressure was high (120-180 mmHg) than when it was low (60 mmHg). Responses were still obtained after cutting vagus, phrenic and splanchnic nerves, but were abolished by spinal cord lesion at T12. These experiments provide evidence for the existence of abdominal arterial baroreceptors. The afferent pathway for the reflex vasodilatation appears to run in the spinal cord.     

Effects of carotid Body chemoreceptor stimulation by 5-HT on phrenic nerve activity and ventilation in the rabbit

Effects of carotid body chemoreceptor stimulation by 5-hydroxytryptamine (5-HT) on the phrenic nerve activity and ventilation were studied by injecting it into the external carotid artery of the rabbits. 5-HT induced an immediate and transient increase of ventilatory rate which became more pronounced with increasing the dose, but it was accompanied by decreases in integrated phrenic nerve activity and tidal volume. The excitatory response was followed by an inhibition in 35% of the experiments. The 5-HT-induced excitation was unaffected by pretreatment with atropine and mecamylamine, but it was completely blocked by tetrodotoxin (TTX) which failed to inhibit the excitation induced by NaCN. Prior administration of atropine abolished the inhibitory effect of 5-HT and the ventilatory excitation induced by baroreceptor stimulation. It may be suggested that the excitation induced by 5-HT results from stimulation of chemoreceptor nerve endings, whereas the inhibition is probably due to its action on baroreceptor nerve endings.     

Origin of tonic electrical activity patterns in the diaphragm of the fetal lamb

The respiratory pattern generator in fetal and postnatal life activates the phrenic nucleus and diaphragm muscle with phasic bursts of activity. In the fetus, diaphragmatic activity is also characterized by tonic activity patterns of unknown origin. We have examined whether such activity is diaphragmatic, or radiated from nearby ribcage muscles, by placing two sets of electrodes side-by-side in the costal portion of the diaphragm in five fetuses. The rationale for this approach is that if tonic activity, radiates to the diaphragm it should be recorded by both sets of electrodes and there should be no delay between the action potentials from each set of electrodes. Of 24 single tonic units identified, 15 were recorded from only one of the two sets of electrodes in the diaphragm. In the 9 tonic units recorded from both sets of electrodes, there was a time delay between the appearance of the action potentials in the two recordings (mean +/- S.E.M. 1.6 +/- 0.2 ms). This is the expected conduction delay along the muscle fibres separating the two electrodes. Since tonic diaphragmatic activity persisted in fetuses with the spinal cord transected rostral or caudal to the phrenic nucleus, we conclude that the spinal cord alone is sufficient to produce the tonic activity recorded from the fetal diaphragm but that the brain may also generate such activity.     

The effects of intra-arterial and intraportal injections of vasopressin on the simultaneously perfused hepatic arterial and portal venous vascular beds of the dog

The hepatic arterial and hepatic portal venous vascular beds of the chloralose-urethane anesthetized dog were perfused simultaneously in situ. Vasopressin (10 mU = 1 unit) was injected in graded increasing doses into the hepatic artery and into the portal vein. Both intra-arterial and intraportal vasopressin elicited both hepatic arterial vasoconstriction and hepatic venous dilation; the delay in onset of both hepatic vascular effects was significantly shorter than that for any succeeding systemic effects (a rise in systemic arterial pressure and fall in heart rate), showing that they were not attributable to recirculation or to arterial baroreceptor reflexes. Injections of vasopressin into the inferior vena cava at the level of the hepatic veins consistently produced smaller hepatic vascular effects than either intra-arterial or intraportal injections of the same doses. The results are discussed in the context of the therapeutic role of vasopressin in controlling gastrointestinal bleeding and portal hypertension.     

Diaphragmatic electromyogram and respiratory pattern after unilateral and bilateral partial denervation of the diaphragm in the cat

In the present study we investigated the mechanism of early respiratory compensation of partial paralysis of the sternal and lateral diaphragm due to an unilateral or bilateral section of the C5 rootlet of the phrenic nerves in anesthetized cats. Compensatory effects were evaluated from the recordings of the bilateral diaphragmatic EMGs, neural respiratory pattern and ventilation. The results of the study demonstrate that successive C5 denervation of the diaphragm caused a decrease in the ipsilateral diaphragmatic EMG. Bilateral C5 section evoked an up to 10 percent decrease in minute ventilation. The compensation of the unilateral and then bilateral partial impairment of the muscle function was achieved always by an increase in the neuromuscular projection to the currently contralateral diaphragm. Neural mechanisms of compensation involve a general increase in the respiratory drive, expressed mostly as an increase in the frequency of breathing. The contribution of afferent respiratory muscles to these mechanisms is likely.     

Neural respiratory responses to cortically induced seizures in cats

Seizure activity can lead to profound respiratory stimulation in spontaneously breathing animals with intact respiratory feedback mechanisms (Paydarfar et al., Am. J. Physiol. 260, R934, 1991). The present study was designed to test the hypothesis that peripheral respiratory feedback mechanisms are not important for the genesis of seizure-induced hyperpnea. Studies were performed in 16 anesthetized, vagotomized, glomectomized cats whose end-tidal PCO2 (PETCO2) was kept constant. Integrated phrenic nerve activity was used to represent respiration. Seizures were induced by injection of penicillin into the parietal cortex and electrocorticographic (ECoG) and biceps femoris nerve activities, arterial pressure, airway PCO2 and brain temperature were recorded continuously. Progressive seizure activity was associated with progressive increases of respiratory frequency and peak phrenic activity, despite constancy of PETCO2 and brain temperature. Patterns of entrainment were identified among ECoG spikes, biceps femoris nerve and phrenic nerve activities. Phrenic nerve activity became highly irregular during generalized ictal seizures and ceased to respond to changes of PETCO2. Acute intercollicular decerebration in all experiments resulted in normalization of respiratory rhythm even while ictal ECoG activity continued. We conclude that stimulation of breathing during seizures occurs in the absence of respiratory feedback mechanisms. The findings suggest that an important cause of the respiratory response is a feedforward mechanism, whereby activation of subcortical structures above medulla and pons results in stimulation of breathing.     

Experimental muscle pain does not cause long-lasting increases in resting electromyographic activity

The mutual links between muscle pain and resting electromyographic (EMG) activity are still controversial. This study described effects of experimental muscle pain on resting EMG activity in a jaw-closing muscle and a leg muscle. Pain was induced by injections of hypertonic saline into the muscles in 10 subjects. Injections of isotonic saline served as a control. The pain intensity was scored on visual analog scales (VAS) and surface and intramuscular wire EMGs were obtained from the resting muscles before, during, and after saline injections. EMG activity was analyzed in 30-s intervals and demonstrated, in both muscles, significant increases 30-60 s after injection of hypertonic saline, but not after injection of isotonic saline. In contrast to the transient increase in EMG activity, the pain sensation lasted up to 600 s after injection of hypertonic saline. It was concluded that acute muscle pain is unable to maintain longer-lasting resting muscle hyperactivity.