Diaphragm Electromyogram Research Articles

Clonidine induces upper airway closure in awake goats.

We examined the effects of the alpha(2)-adrenoceptor (alpha(2)-AR) agonist clonidine on pressure-flow relationships in the upper airway. Inspired and expired airflows, subglottic tracheal pressure (PTR), mask pressure and middle pharyngeal constrictor (MPC) and diaphragm electromyogram (EMG) activities were recorded in awake standing goats. Clonidine-induced central apneas were always associated with continuous tonic activation of the MPC. Subglottic PTR during expiration increased progressively in a dose-dependent manner after clonidine administration. In all cases, positive subglottic PTR was maintained throughout the duration of clonidine-induced apneas and was sufficient to retard or prevent expiratory flow during early and mid-expiration indicating complete airway closure. The effects of clonidine were reversed by selective alpha(2)-AR blockade with SKF-86466. Central apneas after spontaneous augmented breaths (sighs) were associated with continuous tonic activation of the MPC throughout the duration of the prolonged TE intervals. However, subglottic PTR during expiration was not significantly different from control breaths and there was no evidence of increased expiratory airway resistance or delayed expiratory flow. We conclude that continuous tonic activation of pharyngeal adductor muscles appears to be a constant feature of central apnea in the awake goat independent of the initiating cause of the apnea. However, our data suggest that MPC activation alone may not be sufficient to cause complete closure of the upper airway during central apnea.

A Respiratory Drive in Addition to the Increase in Co2 Production at Raised Body Temperature in Rats

Mammals that use the ventilatory system as the principal means of increasing heat loss, i.e. that pant, show two fundamental changes in the control of breathing at raised temperatures. First, alveolar ventilation increases by more than, rather than in proportion to, the increase in CO2 production. Second, hypocapnia no longer causes apnoea. Rats do not use the ventilatory system as the principal means of increasing heat loss, so we have investigated whether rats also show these two changes at raised temperatures. Breathing was detected from diaphragmatic electromyogram (EMG) activity. Anaesthesia and hyperoxia were used to minimise behavioural and hypoxic drives to ventilation and arterial PCO2 (Pa,CO2) was controlled using mechanical ventilation. At 36.6 +/- 0.1 >C, breathing was absent as long as Pa,CO2 was held below a threshold level of 32.9 +/- 0.7 mm Hg (n = 14) under steady-state conditions. When body temperature in rats was raised above 37 >C, both fundamental changes in the control of breathing became apparent. First, at 39 >C the mean Pa,CO2 level during spontaneous breathing (39.6 +/- 5.4 mm Hg, n = 4) fell by 3.9 +/- 1.4 mm Hg (P < 0.05, Student's paired t test). Second, at 39.9 +/- 0.1 >C breathing was present when mean Pa,CO2 levels were only 18.2 +/- 1.5 mm Hg (n = 14), the lowest mean Pa,CO2 level we could achieve with mechanical ventilation. We calculate, however, that at 39.9 >C, the drive to breathe from the increased CO2 production alone would not sustain breathing below a Pa,CO2 level of 27.8 +/- 1.4 mm Hg (n = 13). In rats at raised body temperatures therefore a respiratory drive exists that is in addition to that related to the increase in CO2 production.

Roles of periaqueductal gray and nucleus tractus solitarius in cardiorespiratory function in the rat brainstem

Periaqueductal gray (PAG) and nucleus tractus solitarius (NTS) are important centres for regulation of cardiorespiratory function in cats. We aimed to study the effects of specific PAG stimulation on cardiorespiratory parameters in the rat. Microinjection of D,L-homocysteic acid (DLH) into dorsolateral PAG of anaesthetised rats, led to: marked increases in respiratory frequency (RF) and amplitude of diaphragmatic electromyogram, decreases in inspiratory and expiratory durations, and increased blood pressure and heart rate. Following injection of propranolol (150 pmol, 30 nl), a beta-adrenergic antagonist, into the commissural subnucleus of NTS, the DLH-induced increase in RF was markedly attenuated. Inspiratory neurones (late I cells) in NTS were excited upon stimulation of PAG and their increased activity was accompanied by increased RF. The changes in activity of the late I cells in response to stimulation of dorsolateral PAG provide physiological evidence of a link, possibly noradrenergic, between the two nuclei and involvement of the NTS in control of respiratory functions orchestrated by the PAG.

Optimal level of pressure support ventilation for recovery from diaphragmatic fatigue in rabbits

To determine whether there is an optimal level of pressure support ventilation (PSV) for recovery from acute diaphragmatic fatigue. Prospective laboratory trial. Experimental laboratory. Twenty healthy adult New Zealand White rabbits. Diaphragmatic fatigue was induced with 50 Hz of phrenic nerve stimulation for 30 mins. Recovery was compared between inspiratory load + PSV of 0 cm H2O (L0), inspiratory load + PSV of 60 cm H2O (L60), inspiratory load + PSV of 80 cm H2O (L80), and PSV of 0 cm H2O without inspiratory load (SB) for 90 mins immediately after the end of the fatigue-inducing procedure. To add inspiratory load during the recovery phase, three pressure threshold valves, each having an opening pressure of -20 cm H2O, were used. After the fatigue-inducing procedure, diaphragmatic electromyogram and transdiaphragmatic pressure remained at baseline in both SB and L60, decreased in L80, and increased in L0. Recovery was assessed by abdominal cavity pressure (Pabd) generated by high-frequency (100 Hz) and low-frequency (20 Hz) stimulation. Pabd at 100 Hz recovered to baseline in L60 and SB but not in L0 and L80 (69.1%, 81.3%, 100.3%, and 100.7% of the baseline at 90 mins for L0, L80, L60, and SB, respectively). Pabd at 20 Hz did not differ among ventilatory settings. There is an optimal range of PSV assist level to improve recovery from diaphragmatic fatigue. Recovery was hampered not only by inadequate PSV but also by excessive PSV.

Quantification of the esophageal diaphragm electromyogram with magnetic phrenic nerve stimulation.

Measurement of the amplitude of the esophageal diaphragm compound muscle action potential (CMAP) could be useful for the diagnosis and monitoring of neuromuscular disease. However, quantification of the diaphragm CMAP has been hampered by difficulty in positioning the esophageal electrode at the diaphragm's electrically active center and many investigators report arbitrary units rather than voltage. To quantify the esophageal diaphragm CMAP we designed a multipair electrode which we evaluated during unilateral magnetic stimulation. The esophageal catheter consisted of four sequential electrode pairs. Overall the electrode spanned 17 cm and covered the entire electrically active region of the diaphragm. The diaphragm CMAP was simultaneously recorded from the four pairs at distances of 40, 39, 38, and 37 cm from the nose to the proximal electrode pair. Studies were undertaken in 10 normal subjects and 10 patients with diaphragm dysfunction. The amplitude of the CMAP (peak to peak) was defined as the average of five twitches recorded from the optimal pair of electrodes. The amplitude of the diaphragm CMAP elicited by unilateral maximal magnetic stimulation was 1.45 +/- 0.35 mV (mean +/- SD) for the right side and 1.68 +/- 0.47 mV for the left. When measured on different occasions the coefficient of variation (CV) was 8.6%. The amplitude of the CMAP measured from dysfunctional hemidiaphragms was much less than that measured from normal subjects. This study suggests that the diaphragm CMAP can be quantified using an appropriate esophageal electrode.

Differential effects of clonidine on upper airway abductor and adductor muscle activity in awake goats.

The purpose of this study was to determine the extent to which alpha(2)-adrenoceptor (alpha(2)-AR) pathways affect the central motor output to upper airway muscles that regulate airflow. Electromyogram (EMG) measurements were made from posterior cricoarytenoid (PCA), cricothyroid (CT), thyroarytenoid (TA), and middle (MPC) and inferior (IPC) pharyngeal constrictor muscles in awake standing goats. Systemic administration of the alpha(2)-AR agonist clonidine induced a highly dysrhythmic pattern of ventilation in all animals that was characterized by alternating episodes of tachypnea and slow irregular breathing patterns, including prolonged and variable expiratory time intervals. Periods of apnea were commonly observed. Dysrhythmic ventilatory patterns induced by clonidine were associated with differential recruitment of upper airway muscles. alpha(2)-AR stimulation preferentially decreased the activity of the PCA, CT, and IPC muscles while increasing TA and MPC EMG activities. Clonidine-induced apneas were associated with continuous tonic activation of laryngeal (TA) and pharyngeal (MPC) adductors, leading to airway closure and arterial oxygen desaturation. Tonic activation of the TA and MPC muscles was interrupted only during the first inspiratory efforts after central apnea. Laryngeal abductor, diaphragm, and transversus abdominis EMG activities were completely silenced during apneic events. Ventilatory and EMG effects were reversed by selective alpha(2)-AR blockade with SKF-86466. The results demonstrate that alpha(2)-AR pathways are important modulators of central respiratory motor outputs to the upper airway muscles.

Sulfated cholecystokinin octapeptide in the rat: pontomedullary distribution and modulation of the respiratory pattern

We performed anatomical and physiological studies to determine the site and actions of sulfated cholecystokinin octapeptide (CCK8-S) on breathing. Peptide locations were determined by combined immunodetection of CCK8-S- containing synaptic varicosities and retrograde labeling of medullary neurons projecting to the ventral respiratory group. Retrogradely labeled neurons and CCK8-S immunolabeled varicosities overlapped within the nuclei of the solitary tract, ventral respiratory group, and the Kolliker-Fuse nucleus. Additional CCK8-S immunoreactive terminals were located in the rostroventrolateral medullary reticular nucleus, lateral paragigantocellular reticular nucleus, and the caudal pontine reticular nucleus. The respiratory effects of CCK8-S, which binds to CCK(A) and CCK(B) receptors, were examined by intravenous injection in adult rats and by bath application in the in vitro neonatal rat brainstem - spinal cord preparation. CCK8-S produced an increase in the mean amplitude of diaphragmatic electromyogram (EMG) of 28 +/- 35% (SD) and a decrease in mean respiratory interval of 13 +/- 4% in vivo. In vitro, CCK8-S significantly increased inspiratory duration and decreased respiratory interval, primarily by shortening expiratory duration. CCK8-unsulfated, a specific agonist for CCK(B) receptors, did not produce these effects. CCK8-S effects in the in vitro preparation were partially blocked by the CCK receptor antagonist lorglumide (final bath concentration 600 nM). These results suggest that CCK8-S modulates the respiratory rhythm via CCK(A) receptors within one or more medullary or pontine respiratory groups in both neonatal and adult rats.

Postinspiratory activity of costal and crural diaphragm.

Because the first stage of expiration or "postinspiration" is an active neurorespiratory event, we expect some persistence of diaphragm electromyogram (EMG) after the cessation of inspiratory airflow, as postinspiratory inspiratory activity (PIIA). The costal and crural segments of the mammalian diaphragm have different mechanical and proprioceptive characteristics, so postinspiratory activity of these two portions may be different. In six canines, we implanted chronically EMG electrodes and sonomicrometer transducers and then sampled EMG activity and length of costal and crural diaphragm segments at 4 kHz, 10.2 days after implantation during wakeful, resting breathing. Costal and crural EMG were reviewed on-screen, and duration of PIIA was calculated for each breath. Crural PIIA was present in nearly every breath, with mean duration 16% of expiratory time, compared with costal PIIA with duration -2. 6% of expiratory time (P < 0.002). A linear regression model of crural centroid frequency vs. length, which was computed during the active shortening of inspiration, did not accurately predict crural EMG centroid frequency values at equivalent length during the controlled relaxation of postinspiration. This difference in activation of crural diaphragm in inspiration and postinspiration is consistent with a different pattern of motor unit recruitment during PIIA.

Influence of central antitussive drugs on the cough motor pattern.

The present study was conducted to determine the effects of administration of centrally active antitussive drugs on the cough motor pattern. Electromyograms of diaphragm and rectus abdominis muscles were recorded in anesthetized, spontaneously breathing cats. Cough was produced by mechanical stimulation of the intrathoracic trachea. Centrally acting drugs administered included codeine, morphine, dextromethorphan, baclofen, CP-99,994, and SR-48,968. Intravertebral artery administration of all drugs reduced cough number (number of coughs per stimulus trial) and rectus abdominis burst amplitude in a dose-dependent manner. Codeine, dextromethorphan, CP-99,994, SR-48,968, and baclofen had no effect on cough cycle timing (CTtot) or diaphragm amplitude during cough, even at doses that inhibited cough number by 80-90%. Morphine lengthened CTtot and inhibited diaphragm amplitude during cough, but these effects were not dose dependent. Only CP-99,994 altered the eupneic respiratory pattern. Central antitussive drugs primarily suppress cough by inhibition of expiratory motor drive and cough number. CTtot and inspiratory motor drive are relatively insensitive to the effects of these drugs. CTtot can be controlled independently from cough number.

Diaphragm electromyogram measured with unilateral magnetic stimulation.

The purpose of this study was to establish the phrenic nerve conduction time (PNCT) for magnetic stimulation and further assess the relatively new technique of anterior unilateral magnetic stimulation (UMS) of the phrenic nerves in evaluating the diaphragm electromyogram (EMG). An oesophageal electrode was used to record the diaphragm compound muscle action potential (CMAP) elicited by supramaximal percutaneous electrical phrenic nerve stimulation (ES) and UMS from eight normal subjects. The oesophageal electrode used for recording the CMAP was positioned at the level of the hiatus and 3 cm below. The diaphragm CMAP was also recorded from chest wall surface electrodes in five subjects. All of the phrenic nerves could be maximally stimulated with UMS. A clear plateau of the amplitude of the CMAP was achieved for the right and left phrenic nerves. The mean amplitudes of the CMAP recorded from the oesophageal electrode were, for the right side, 0.74+/-0.29 mV (mean+SD) for ES and 0.76+/-0.30 mV for UMS with maximal power output, and for the left side 0.88+/-0.33 mV for ES and 0.80+/-0.24 mV for UMS. PNCT measured by the oesophageal electrode with ES and UMS with maximal output were, for the right side, 7.0+/-0.8 ms and 6.9+/-0.8 ms, respectively, and for the left side 7.8+/-1.2 ms and 7.7+/-1.3 ms, respectively. However, the CMAP recorded from chest wall surface electrodes with UMS was unsuitable for the measurement of PNCT. The results suggest that unilateral magnetic stimulation of the phrenic nerves combined with an oesophageal electrode can be used to assess diaphragmatic electrical activity and measure the phrenic nerve conduction time.

Chronic intermittent hypoxia increases sympathetic responsiveness to hypoxia and hypercapnia

We sought to determine whether chronic exposure to intermittent hypoxia (CIH) increases sympathetic responsiveness to subsequent chemoreflex stimulation. Sprague-Dawley rats were exposed to 30 days of CIH: exposure chamber %O2 [fractional concentration of chamber O2 (FcO2)] nadir 6.5-7% with return to 21% each minute for 8 h/day during the diurnal sleep period (Exp group). Sham controls (SC group) were similarly handled but kept at 21% FcO2 and compared with unhandled controls (UC group). Rats were then anesthetized with urethan, and preganglionic cervical sympathetic activity (CSA), diaphragm electromyogram, arterial pressure, and electrocardiogram were recorded while the rats were spontaneously breathing 100% O2, room air, 10% O2, 12% CO2, and 10% O2-12% CO2. CSA and heart rate were also recorded during phenylephrine infusion to assess baroreceptor function. Mean arterial pressure was significantly greater in Exp than in SC and UC rats during all conditions (P < 0. 05). A vasopressor response to 10% O2-12% CO2 was observed only in Exp rats. CSA was greater in Exp than in SC and UC rats during 10% O2, 12% CO2, and 10% O2-12% CO2 but not during room-air exposure. A significant increase in CSA compared with room air was noted during 10% O2, 12% CO2, and 10% O2-12% CO2 in Exp but not in SC or UC rats. No differences in baroreceptor function were observed among groups. We conclude that CIH leads to increased sympathetic responsiveness to chemoreflex stimulation.

Sulfated cholecystokinin octapeptide in the rat: pontomedullary distribution and modulation of the respiratory pattern

We performed anatomical and physiological studies to determine the site and actions of sulfated cholecystokinin octapeptide (CCK8-S) on breathing. Peptide locations were determined by combined immunodetection of CCK8-S- containing synaptic varicosities and retrograde labeling of medullary neurons projecting to the ventral respiratory group. Retrogradely labeled neurons and CCK8-S immunolabeled varicosities overlapped within the nuclei of the solitary tract, ventral respiratory group, and the Kolliker-Fuse nucleus. Additional CCK8-S immunoreactive terminals were located in the rostroventrolateral medullary reticular nucleus, lateral paragigantocellular reticular nucleus, and the caudal pontine reticular nucleus. The respiratory effects of CCK8-S, which binds to CCK(A) and CCK(B) receptors, were examined by intravenous injection in adult rats and by bath application in the in vitro neonatal rat brainstem - spinal cord preparation. CCK8-S produced an increase in the mean amplitude of diaphragmatic electromyogram (EMG) of 28 +/- 35% (SD) and a decrease in mean respiratory interval of 13 +/- 4% in vivo. In vitro, CCK8-S significantly increased inspiratory duration and decreased respiratory interval, primarily by shortening expiratory duration. CCK8-unsulfated, a specific agonist for CCK(B) receptors, did not produce these effects. CCK8-S effects in the in vitro preparation were partially blocked by the CCK receptor antagonist lorglumide (final bath concentration 600 nM). These results suggest that CCK8-S modulates the respiratory rhythm via CCK(A) receptors within one or more medullary or pontine respiratory groups in both neonatal and adult rats.

Voluntary activation of the human diaphragm in health and disease.

Intersubject comparison of the crural diaphragm electromyogram, as measured by an esophageal electrode, requires a reliable means for normalizing the signal. The present study set out 1) to evaluate which voluntary respiratory maneuvers provide high and reproducible diaphragm electromyogram root-mean-square (RMS) values and 2) to determine the relative diaphragm activation and mechanical and ventilatory outputs during breathing at rest in healthy subjects (n = 5), in patients with severe chronic obstructive pulmonary disease (COPD, n = 5), and in restrictive patients with prior polio infection (PPI, n = 6). In all groups, mean voluntary maximal RMS values were higher during inspiration to total lung capacity than during sniff inhalation through the nose (P = 0.035, ANOVA). The RMS (percentage of voluntary maximal RMS) during quiet breathing was 8% in healthy subjects, 43% in COPD patients, and 45% in PPI patients. Despite the large difference in relative RMS (P = 0.012), there were no differences in mean transdiaphragmatic pressure (P = 0.977) and tidal volumes (P = 0.426). We conclude that voluntary maximal RMS is reliably obtained during an inspiration to total lung capacity but a sniff inhalation could be a useful complementary maneuver. Severe COPD and PPI patients breathing at rest are characterized by increased diaphragm activation with no change in diaphragm pressure generation.

Pulmonary vagal innervation is required to establish adequate alveolar ventilation in the newborn lamb.

To investigate the effects of bilateral intrathoracic vagotomy on the establishment of continuous breathing and effective gas exchange at birth, we studied 8 chronically instrumented, unanesthetized, sham-operated and 14 vagotomized newborn lambs after a spontaneous, unassisted vaginal delivery. Fetal lambs were instrumented in utero to record sleep states, diaphragmatic electromyogram, blood pressure, arterial pH, and blood-gas tensions. Six of eight sham-operated lambs established effective gas exchange within 10 min of birth, whereas 12 of 14 vagotomized animals developed respiratory acidosis and hypoxemia (P = 0.008). Breathing frequency in vagotomized newborns was significantly lower during the entire postnatal period compared with sham-operated newborns. Vagotomized subjects also remained hypothermic during the entire postnatal period (P < 0.05). Bronchoalveolar lavage indicated an increased minimum surface tension, whereas lung histology showed perivascular edema and partial atelectasis in the vagotomized group. We conclude that stimulation of breathing and effective gas exchange are critically dependent on intact vagal nerves during the transition from fetal to neonatal life.

Apneic threshold for CO2 in the anesthetized rat: fundamental properties under steady-state conditions.

Experiments were performed to measure the apneic threshold for CO2 and its fundamental properties in anesthetized rats under steady-state conditions. Breathing was detected from diaphragmatic electromyogram activity. Mechanical hyperventilation resulted in apnea once arterial PCO2 (PaCO2) had fallen far enough. Apnea was not a reflex response to lung inflation because it did not occur immediately, was not prevented by vagotomy, and was reversed by raising PaCO2 without changing mechanical hyperventilation. The apneic threshold was measured by hyperventilating rats mechanically with O2 until apnea had occurred and then raising PaCO2 at constant hyperventilation until breathing reappeared. The mean PaCO2 level of the apneic threshold in 42 rats was 32.8 +/- 0.4 Torr. The level of the threshold did not depend on the volume at which the lungs were inflated. The level of the threshold, under steady-state conditions, was the same when approached from hypocapnia as from eupnea. The level of the threshold could be raised by 9 Torr by chronic elevation of the eupneic PaCO2 level by 18 Torr.

Response of breathing pattern to flow and pressure in the upper airway of rats

The effects of upper airway (UAW) flows and pressures on breathing pattern and respiratory muscle activities were studied in anesthetized rats breathing through a tracheostomy. A steady flow (∼1000 ml/kg/min) of cold dry air, or cold wet air, or warm wet air was passed through the UAW, in the expiratory direction for approximately 20 sec (20–40 sec). In other trials positive or negative pressure was applied to the isolated UAW for a similar duration. There was a marked prolongation of the expiratory duration and decreases in peak inspiratory flow, tidal volume, and peak diaphragm electromyogram (EMG) activity in response to cold dry airflow. The responses to cold wet air were reduced but still significant. Warm wet air had no effect on breathing. These responses show that UAW cooling and drying depress breathing in the rat and that cooling itself could cause the inhibition of breathing. Negative pressure induced substantial increases in genioglossus and laryngeal inspiratory activity while positive pressure caused a decrease in genioglossus activity. Positive pressure also increased expiratory time while negative pressure increased inspiratory time. These results confirm the functional role of the UAW dilating muscles in preventing UAW from collapse in rats.

Effects of pressure-support ventilation on recovery from acute diaphragmatic fatigue in rabbits.

To examine the effects of pressure-support ventilation on recovery from acute diaphragmatic fatigue. Prospective laboratory trial. Experimental laboratory. Twenty-one healthy, adult New Zealand white rabbits. Diaphragmatic fatigue was induced with 50-Hz phrenic nerve stimulation for 30 mins. Recovery was compared between pressure-support ventilation 0 cm H2O (SB), 10 cm H2O (P10), and 20 cm H2O (P20) for 90 mins immediately after the end of the fatigue inducing procedure. After the fatigue-inducing procedure, pressure-support ventilation reduced transdiaphragmatic pressure and integrated diaphragmatic electromyogram both at P20 and P10, but not in SB. Recovery was assessed by airway occlusion pressure (Poccl) generated by high- (100 Hz) and low- (20 Hz) frequency phrenic nerve stimulation. Poccl at 100 Hz was lower in P10 and P20 than in SB (74.6 +/- 6.2 [SEM] %, 66.9 +/- 3.3%, and 94.8 +/- 3.6% of the baseline at 90 mins for P10, P20, and SB, respectively), while those at 20 Hz showed no differences between the three groups. Recovery from acute diaphragmatic fatigue might be disturbed with pressure-support ventilation.

High-frequency oscillation and centroid frequency of diaphragm EMG during inspiratory loading

Power spectra were derived from the diaphragm electromyogram (EMG) in anesthetized rabbits subjected to inspiratory resistive loading (IRL) with airway pressure swings of 40–60 cm H 2O for 20 min to 2 h. Shifts in the centroid frequencies of the power spectra were found to be associated with the appearance of power spectral peaks in the range of 105–140 Hz, termed high-frequency oscillation, or HFO. Such peaks have been described before in phrenic nerve activity and in the diaphragm EMG. However, these peaks have not previously been connected with the shifts in centroid frequency seen during loaded breathing. Although such changes in frequency content have been taken to indicate fatigue in the diaphragm, we find that HFO can also cause a shift in centroid frequency during loaded breathing, an effect whose relation to fatigue has yet to be established.

Recovery from the lethal effects of saxitoxin: a therapeutic window for4-aminopyridine (4-AP)

We have shown that saxitoxin (STX) induced lethality can be reversed by 4-AP when it is administered at the time of respiratory arrest [Benton, B. J., Spriggs, D. L., Capacio, B. R. and Chang, F.-C. T. (1995) 4-Aminopyridine antagonizes the lethal effects of saxitoxin (STX) and tetrodotoxin (TTX). International Society of Toxicology, 5th Pan American Symposium on Animal, Plant and Microbial Toxins, Frederick, MD. July/August 1995, p. 217]. The purpose of this study was to determine whether 4-AP's efficacy could be enhanced further when administered at different times relative to STX intoxication. The animals used in this study were chronically instrumented for concurrent recordings of diaphragm electromyogram (DEMG), neck skeletal muscle electromyogram, Lead II electrocardiogram, and electrocorticogram (ECoG). There were five groups of unanesthetized guinea pigs. The first group served as 4-AP controls and received a 2 mg/kg i.m. dose of 4-AP. The four remaining groups were given a lethal dose of STX (5 μg/kg i.m.); the second group, STX controls, received no 4-AP; the third group, the 4-AP treatment group, received 4-AP immediately following cardiorespiratory collapse; the fourth group was the 4-AP/STX co-administration group and 4-AP was given concurrently with STX; and the fifth group was the 4-AP pretreatment group in which 4-AP was given 10 min before STX. At the point of STX-induced cardiorespiratory collapse, the guinea pigs were ventilated and given an i.p. injection of sodium bicarbonate. Results showed that 4-AP prevented cardiorespiratory collapse in 3/7 animals in the 4-AP pretreatment group. Also, 4-AP in conjunction with artificial ventilation and sodium bicarbonate accelerated recovery from STX-induced cardiorespiratory collapse in all the treatment groups compared to the STX controls.

Vagal Denervation Decreases the Large Surfactant Aggregates and mRNAs for SP-A and SP-B. 1951

We have previously shown that fetal lambs which have undergone intrathoracic vagal denervation have increased surface tension and develop respiratory failure at birth. However, the mechanism of surfactant dysfunction remains unknown. To quantify the relative roles of surfactant synthesis, release and activity, we studied 15 chronically instrumented unanesthetized newborn lambs; eight of 15 fetuses underwent intrathoracic vagal denervation whereas seven were sham-operated. Each fetus was instrumented to record heart rate, blood pressure, diaphragmatic electromyogram, arterial pH, and blood gas tensions between 131-133 d gestation (term=147±2 d) and studied at 142-143 d after spontaneous vaginal delivery. Various cardiorespiratory variables were recorded immediately after birth and the animals were sacrificed at 1 hr of age. Surfactant associated proteins (SP-A, -B and -C) mRNAs were analyzed in the right middle lobe whereas bronchoalveolar lavage(BAL) was performed on the remaining lungs to determine total and various phospholipid (PL) species, large aggregates (LA), small aggregates (SA) and plasma proteins. Recovery of BAL was similar in both groups (91±1 vrs 90±2%). Total phospholipids were also similar in the sham-operated and vagotomized animals. However, LA (mg/kg) in sham group (23±4.24) were significantly higher than in the vagotomized group (10±1.9; p=0.01). Also, the LA as a percentage of total PL was significantly higher in the sham operated animals (52±6 vrs. 25±8, respectively, p=0.009). The percentage of phosphatidylcholine (n=9) was similar in both groups, however, phosphatidylinositol (PI) was higher (p=0.02) and phosphatidylglycerol (PG) was lower (p=0.05) in the vagotomized group. Northern blot analysis showed decreased mRNA levels of SP-A and SP-B, whereas no significant differences were observed for SP-C. We conclude that vagally denervated animals have an increased proportion of SA, an inactive form of surfactant, decreased LA, and delayed surfactant maturation as indicated by the PI and PG ratios, and decreased expression of surfactant apoproteins mRNAs. These changes in surfactant system may play a role in respiratory failure in vagally denervated newborn lambs.