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Biomedical subjects

D E Mayock

Publications and source records attributed to D E Mayock.

34 records · Page 2Linked to original sources

Ventilatory failure during loaded breathing: the role of central neural drive.

Minute ventilation (VE), arterial blood gases, diaphragmatic electromyogram (EMG) activity, centroid frequency (Fc) and peak inspiratory airway pressures (Paw) were measured in five unanesthetized tracheostomized infant monkeys during various intensities of inspiratory resistive loaded breathing (IRL) until either 1) ventilatory failure occurred (failed trial) or 2) normocapnia was sustained for 1 h (successful trial). During successful trials VE and arterial PCO2 (PaCO2) were sustained at base-line levels, and an increase in peak integrated diaphragmatic EMG activity and peak inspiratory Paw occurred. In contrast, during ventilatory failure runs, VE decreased and PaCO2 rose compared with their respective base-line values. The fall in VE occurred secondary to a significant decline in breathing frequency. Tidal volume was sustained at base-line levels during all trials (both successful and failed groups). Inspiratory Paw's and peak moving time average EMG were sustained at elevated levels during ventilatory failure runs, suggesting that the respiratory muscles did not fail as pressure generators. Furthermore, the EMG Fc did not change from base line during either successful or failed trials. These data suggest that peripheral muscle fatigue did not occur, although in the absence of a more direct test of muscle performance, i.e., a force-frequency curve, we cannot rule out the possibility that a component of peripheral failure contributed to our results. Ventilatory failure during severe IRL in the infant monkey was most clearly associated with an alteration in the respiratory center timing mechanism, i.e., such failure was a function of a decline in respiratory frequency.

Animals↗

Effect of hypercapnia and hypoxia on costal and crural diaphragm electromyograms in piglets.

We examined the separate effects of acute hypercapnia and acute hypoxia, on the electromyographic activity (EMG) of the costal and crural diaphragm in 6 anesthetized spontaneously breathing piglets (age 12-23 days, weight 3.00-4.37 kg). Bipolar wire electrodes were inserted into the anterior paratendinous costal diaphragm and the midportion of the crural diaphragm. EMG activity was quantified in arbitrary units (au) of peak moving time average while the animals breathed 50% O2/50% N2 (base-line) and after 30 min of either hypercapnia (12% CO2) or hypoxia (12% O2) exposure. After 30 min of hypercapnia, the peak moving time average EMG increased in both parts of the diaphragm with the increase in crural diaphragm EMG activity (from baseline: 20 +/- 2 au to 30 min 12% CO2: 83 +/- 20 au) not being significantly different from that observed in the costal diaphragm (from baseline: 21 +/- 2 au to 30 min 12% CO2: 72 +/- 20 au, p = 0.17). Similarly, the peak moving time average EMG increased in both parts of the diaphragm after 30 min of hypoxia with the increase in the crural diaphragm EMG activity (from baseline: 21 +/- 2 au to 30 min 12% O2: 28 +/- 6 au) not being significantly different from that observed in the costal diaphragm (from baseline: 21 +/- 1 au to 30 min 12% O2: 26 +/- 7 au, p = 0.51). These data indicate that the inspiratory EMG activity of the diaphragm is not differentially distributed between its costal and crural components during chemically stimulated breathing in piglets.

Animals↗

Effect of inspiratory resistive loading on costal and crural diaphragm electromyograms in piglets.

We examined the effect of inspiratory resistive loaded breathing (IRL) on the electromyographic (EMG) activity of the costal and crural diaphragm in nine anesthetized spontaneously breathing piglets (age 10-23 days, weight 2.8-4.4 kg). Bipolar wire electrodes were inserted into the anterior paratendinous costal diaphragm and the midportion of the crural diaphragm. EMG activity was quantified in arbitrary units (au) of peak moving time average while the animals breathed 50% O2/50% N2 (baseline) and during 30 min of IRL. Thirty min of IRL increased the peak moving time average of both parts of the diaphragm, with the increase in the crural EMG activity (from baseline: 22 +/- 2 to 30 min of IRL: 76 +/- 22 au) exceeding that of costal (from baseline: 23 +/- 2 to 30 min of IRL: 50 +/- 24 au), p less than 0.05. These results 1) suggest that the inspiratory EMG activity of the diaphragm can be differentially distributed between its costal and crural components and 2) document that crural inspiratory EMG activity undergoes greater augmentation under the condition of IRL than does the costal activity in piglets.

Animals↗

Response to resistive loading in the newborn piglet.

The diaphragmatic force generation and electromyographic response to long-term (1 h) inspiratory resistive loading was examined in the newborn piglet during the 3rd postnatal wk of life. Minute ventilation decreased to approximately 50% of baseline level within 5 min of imposition of a severe resistive load and remained at this level for the duration of loading. The decrease in ventilation was secondary to a fall in tidal volume at a constant frequency. There was a significant increase in central nervous system output to the diaphragm as manifested by integrated diaphragmatic electromyogram. Progressive augmentation of this index of central drive continued throughout the period of loading. Functional residual capacity fell significantly by 60 min of inspiratory resistive loading. This strategy should allow greater force generation by placing the diaphragm at a more optimal length-tension relationship. However, the force generating capability of the diaphragm was compromised as assessed by force-frequency curve analysis. These results suggest that the diaphragm of the neonatal piglet fatigues during prolonged inspiratory resistive loading.

Airway Resistance↗

Spectral analysis of diaphragmatic EMG during the neonatal biphasic hypoxic ventilatory response.

The newborn infant monkey consistently demonstrates a biphasic ventilatory response to hypoxemia. We have previously shown that the ventilatory depression during the late portion of this biphasic response is secondary to a decline in inspiratory volume that cannot be explained solely by central neural depression. We hypothesized that hypoxemia caused the diaphragm to fatigue, thereby accounting for the late ventilatory depression during the biphasic neonatal hypoxic response. Diaphragmatic fatigue has been reported to be associated with a decrease in the centroid frequency (Fc) of the electromyogram derived through frequency spectral analysis. Therefore, we analyzed the power spectral density of the diaphragmatic electromyogram recorded from percutaneously implanted crural diaphragmatic electrodes in five 2-day-old infant monkeys while they breathed room air and after 5 min exposure to two levels of hypoxemia during the late ventilatory depression. A fast Fourier transform of EKG free diaphragmatic electromyogram was used to compute the power spectral density and the Fc. The Fc during room air breathing was statistically equivalent to the Fc observed after five minutes exposure to 12% FiO2 (p = 0.79), and 8% FiO2 (p = 0.74) when ventilation was falling. In conclusion, our data demonstrate that changes in the centroid frequency are not present during the biphasic ventilatory decline that occurs with the hypoxic ventilatory response in newborn monkeys. Thus, diaphragmatic fatigue, as defined by a decline in Fc, does not occur during the neonatal biphasic hypoxic response.

Animals↗

Diaphragmatic muscle fiber type development in swine.

Diaphragmatic muscle fiber types were determined in the costal and crural segments of swine diaphragm at 4 postnatal ages (1 day, 1 month, 6 months, and between 3-6 yr of age). Fiber types were differentiated by enzyme histochemistry for adenosine triphosphatase and reduced nicotinamide adenine dinucleotide. A progressive increase in the number of type I fibers occurred in both costal and crural segments from birth to 6 months of age. The number of type IIA fibers decreased and type IIB fibers increased over the same time period. Type IIC fibers were present through 1 month of age, were rarely observed at 6 months, and were not found in older animals. Type I fibers were more numerous in the crural portion of the diaphragm. The cross-sectional area of all fiber types in both costal and crural segments increased significantly with age. No preferential fiber type growth was noted in either segment of the diaphragm. These data suggest that the pig diaphragmatic muscle is differentiated into its adult form by 6 months of postnatal age, but fiber cross-sectional area growth continues along with body growth.

Adenosine Triphosphatases↗

Role of endogenous opiates in hypoxic ventilatory response in the newborn primate.

The effects of opiate receptor antagonism by naltrexone hydrochloride on the biphasic hypoxic ventilatory response in the infant Macaca nemestrina have been investigated. Minute ventilation, tidal volume, and respiratory frequency were measured in six animals from timed gestations before and during inhalation of a hypoxic gas mixture. All studies were completed in non-rapid-eye-movement sleep. Arterial blood gases were obtained during each stimulus period. All animals demonstrated the typical biphasic ventilatory response to acute moderate-severe hypoxemia. After the administration of naltrexone hydrochloride to block opiate receptors, the animals still manifested a biphasic hypoxic response that was no different than that noted prior to drug administration. Naltrexone hydrochloride had no effect on room air resting ventilation in any of the animals. Our data suggest that endogenous opiates play no physiological role in the acute ventilatory response to moderate-severe hypoxia in the newborn subhuman primate.

Animals↗

Postnatal changes in transdiaphragmatic pressure in piglets.

We examined diaphragmatic force output in 25 anesthetized piglets ranging in postnatal age from 4 to 21 days (weight 1.3-4.0 kg) in order to determine whether the diaphragm produces greater force output with maturation for a given level of neural input. Transdiaphragmatic pressure (Pdi) served as our index of diaphragmatic force output and was measured during "supramaximal" transvenous phrenic nerve stimulation at 100 Hz in order to control neural drive. Mean Pdi was 53 +/- 17 cm H2O and ranged from a minimum of 29 cm H2O to a maximum of 83 cm H2O. A significant positive correlation between Pdi and postnatal age was observed (r = 0.79, p less than 0.001). In addition, positive correlations were noted between Pdi and total body weight (r = 0.73, p less than 0.001) and Pdi and diaphragmatic wet weight (r = 0.77, p less than 0.001). The voltage needed to stimulate the phrenic nerves "supramaximally" did not correlate with postnatal age (r = 0.02, p = 0.16). We conclude that a developmental pattern of increasing Pdi with increasing postnatal age, total body weight, and diaphragmatic wet weight exists in piglets and occurs within the context of a controlled level of neural drive.

Animals↗

Proximal airway pressure monitoring in the neonatal ICU.

The static and dynamic responses of diaphragm-type pressure manometers currently used with manual ventilation in the neonatal ICU were determined at different pressures and frequencies. Using a precalibrated transducer attached to a closed-loop system, the manometer peak pressure was adjusted to 15, 20, 25, and 30 cm H2O, first for static measurements and then again while the frequency was increased from 20 to 200 breath/min in increments of 20. Most manometers with inlet flow-restricting devices built into the manometer or attached to the connection system in a ventilator significantly underestimated the delivered pressure as the peak inflation pressure and frequency were increased. In those manometers without inlet flow restrictors the correlation between transducer pressure and observed manometer pressure was close. Diaphragm-type pressure manometers with inlet flow-restricting devices may substantially underestimate the delivered proximal airway pressure when incorporated into neonatal manual ventilation equipment.

Humans↗

Group B streptococcal septicemia and delayed-onset congenital right-sided diaphragmatic hernia.

A case is reported of fulminant early-onset group B streptococcal septicemia and delayed-onset congenital right-sided diaphragmatic hernia in a neonate. The latter condition should be considered when early-onset group B streptococcal disease is followed by increasing respiratory distress, right-sided pleural effusion and partial or complete opacification of the right side of the thorax.

Blood↗

Dopamine and carotid body function in the newborn lamb.

The effect of dopamine on the acute ventilatory response to hypoxia was investigated in four newborn lambs studied on the 1st day of postnatal life and eight lambs studied between 7 and 12 days of age. Studies were accomplished during nonrapid-eye-movement sleep in unanesthetized tracheotomized animals. Changes in minute ventilation (VE/kg), tidal volume, and frequency induced by intravenous bolus injection of dopamine (10 micrograms/kg) or saline control were assessed while animals were breathing room air or N2, before and after carotid body denervation (CBD). Dopamine depressed resting ventilation at both postnatal ages. This effect was greater in the older animals. Dopamine blunted the hypoxia-induced increase in VE/kg at both ages. The magnitude of this depression did not vary with postnatal age. Dopamine induced cessation of respiratory effort at end expiration (apnea) during room air and N2 breathing significantly more often in the older animals. The effect of dopamine was mediated at the carotid body. CBD decreased ventilation by an increase in breath-to-breath interval in older animals, suggesting carotid sinus nerve afferent activity is more important during eucapnic respiration in older animals than in the immediate newborn period.

Animals↗

Hypoxic ventilatory response in the newborn monkey.

The hypoxic ventilatory response was determined in twelve unanesthetized newborn monkeys, Macaca nemestrina. Measurements of blood gases and ventilation were made during normoxia and hypoxia at the postnatal ages of 2, 7, and 21 days. Data were collected during quiet sleep. The infant monkey demonstrated a definite but transient hyperventilatory response following exposure to a FiO2 of 0.12 or 0.14 on the second day of life. Baseline ventilation increased 15% (Fi02=0.14) and 28% (Fi02=0.12) after 1 minute of hypoxia; p less than 0.05 in both instances. Return to baseline ventilation occurred between 3 and 5 minutes after hypoxic stimulus onset. This biphasic response to hypoxia converted to an adult-like, sustained hyperventilation during the ensuing three weeks of postnatal maturation. Episodes of periodic breathing and/or apnea were noted to occur during the induced hypoxemia. These data demonstrate that the infant subhuman primate has a ventilatory response to hypoxia that is similar to that of the human infant and is an excellent model for the study of the maturation of the respiratory control system.

Animals↗

Diaphragmatic pressures in piglets: transvenous versus direct phrenic nerve stimulation.

We examined transdiaphragmatic pressure (Pdi) generation during both direct (DPNS) and transvenous (TVPNS) modes of phrenic nerve stimulation in anesthetized piglets of varying postnatal age. Pdi measurements during TVPNS were not statistically different from those obtained during DPNS (p greater than 0.10). Furthermore, a good correlation (r = 0.98, p less than 0.001) was obtained when the mean Pdi measurements obtained by both methods were compared. We conclude that TVPNS can be used in lieu of DPNS to generate Pdi. Furthermore, our data suggest that this technique can be used to study the effects of various experimental manipulations on diaphragmatic force output within a developmental context.

Age Factors↗