Daniel C. Shannon

Pneumograms in infants who subsequently died of sudden infant death syndrome

Victims of sudden infant death syndrome (SIDS) have occasionally been reported to have had prolonged apnea or an increased frequency of short apnea prior to their deaths. To examine the extent of these abnormalities, we compared pneumograms obtained in 17 infants who subsequently died of SIDS (10 with history of apnea) with those of 34 age- and sex-matched controls. The recordings were analyzed by a computer program that avoided observer bias. SIDS infants had significantly greater mean heart rate (P less than 0.05) and periodic breathing during quiet time (P less than 0.003) than control infants had. The apnea in SIDS infants tended to be more periodic than in control infants (P less than 0.002). In addition, the incidence of bradycardia was greater in SIDS (three infants) than in controls (none) (P less than 0.03). These differences suggest a disturbance of autonomic function prior to death in some victims of SIDS.

RET proto-oncogene is important for the development of respiratory CO2 sensitivity

Brain stem muscarinic cholinergic pathways are important in respiratory carbon dioxide (CO2) chemosensitivity. Defects in the muscarinic system have been reported in children with congenital/developmental disorders of respiratory control such as sudden infant death syndrome (SIDS) and congenital central hypoventilation syndrome (CCHS). This early onset of disease suggests a possible genetic basis. The muscarinic system is part of the autonomic nervous system which develops from the neural crest. Ret proto-oncogene is important for this development. Thus, a potential role for ret in the development of respiratory CO2 chemosensitivity was considered. Using plethysmography, we assessed the ventilatory response to inhaled CO2 in the unanesthetized offsprings of ret +/- mice. Fractional increases in minute ventilation during hypercapnia relative to isocapnia were 5.1 +/- 3.2, 3.0 +/- 1.6 and 1.4 +/- 0.8 for the ret +/+, ret +/- and ret +/- mice, respectively. The ret knockout mice have a depressed ventilatory response to inhaled CO2. Therefore, the ret gene is an important factor in the pathway of neuronal development which allow respiratory CO2 chemosensitivity.

Ventilatory responses to exercise in humans lacking ventilatory chemosensitivity.

1. In healthy humans during aerobic exercise ventilation increases and mean arterial PCO2 usually remains constant over a wide range of CO2 production. 2. Congenital central hypoventilation syndrome (CCHS) is associated with ineffective chemoreceptor regulation of breathing and severe hypoventilation during sleep (requiring mechanical ventilation) reflecting abnormalities in the brainstem respiratory complex or its chemoreceptor input. Such patients can have adequate spontaneous ventilation during resting wakefulness and participate in normal activities. 3. If children with CCHS have normal ventilatory responses to exercise then chemoreceptors are not necessary for this ventilatory response or the resultant control of Pa,CO2 during exercise. We studied five children with CCHS (aged 8‐17 years) with abnormally low ventilatory responses to steady‐state increased end‐tidal PCO2 (< 9 ml min‐1 kg‐1 mmHg‐1) and five age‐matched controls. 4. Depth and rate of breathing, end‐tidal PCO2, end‐tidal PO2, CO2 production, O2 utilization and heart rate were monitored during the following conditions: whilst subjects stood at rest; following the onset of treadmill exercise (4 m.p.h.); during steady‐state exercise (4 m.p.h.); during an incremental maximal exercise test; and during recovery from exercise. 5. There were no significant differences in the ventilatory responses between CCHS subjects and controls during the onset of treadmill exercise, in the dynamic response in achieving the steady‐state exercise, during steady‐state exercise, in the recovery from steady‐state exercise, or during incremental exercise (up to the point of presumed blood lactate accumulation, as indicated by gas exchange criteria). There was a very small mean increase in PCO2 in both groups during steady‐state exercise (controls 1.4 mmHg; CCHS 2.2 mmHg). 6. The only differences which emerged between groups were (i) slightly more variability in PCO2 in the CCHS group during steady‐state exercise, and (ii) the CCHS subjects did not hyperventilate, as the controls did, at exercise levels above the point of presumed blood lactate accumulation. 7. Breath‐by‐breath coefficient of variation of ventilation was significantly reduced in both groups during steady‐state exercise compared to rest. There were no differences between groups in either state. 8. We conclude that chemoreceptors are not necessary for an appropriate ventilatory response to aerobic exercise. Hence, other stimuli, such as afferent information from the exercising limbs or signals related to activation of the motor cortex, can increase alveolar ventilation in close proportion to CO2 production. 9. The lack of hyperventilatory response to blood lactate accumulation during heavy exercise provides good evidence that these CCHS patients have ineffective peripheral chemoreception.

A model of acoustic transmission in the respiratory system

A theoretical model of sound transmission from within the respiratory tract to the chest wall due to the motion of the walls of the large airways is developed. The vocal tract, trachea, and first five bronchial generations are represented over the frequency range from 100 to 600 Hz by an equivalent acoustic circuit. This circuit makes it possible to estimate the magnitude of airway wall motion in response to an acoustic perturbation at the month. The radiation of sound through the surrounding lung parenchyma is represented as a cylindrical wave in a homogeneous mixture of air bubbles in water. The effect of thermal losses associated with the polytropic compressions and expansions of these bubbles by the acoustic wave is included, and the chest wall is represented as a massive boundary to the wave propagation. The model estimates the magnitude of acceleration over the extrathoracic trachea and at three locations on the posterior chest wall in the same vertical plane. The predicted spectral characteristics of transmission are consistent with previous experimental observations.<<ETX>>

Whole Body Arginine Metabolism and Nitric Oxide Synthesis in Newborns with Persistent Pulmonary Hypertension

ABSTRACT: Despite the potential relevance of the L-arginine-nitric oxide (NO) pathway in the pathophysiology of pulmonary hypertension, no in vivo studies of the kinetics of arginine and NO have been conducted previously in this population. The terminal guanidino N-atom of L-arginine is the precursor for NO, which is oxidized to the stable inorganic nitrogen oxides, nitrite (NO2-) and nitrate (NO3-). Thus, synthesized NO is detected in serum or urine as NO2- and NO3-. The purpose of this investigation was to compare studies of whole body arginine metabolism twice in nine patients with persistent pulmonary hypertension of the newborn (PPHN), using a primed constant i.v. infusion of L-[guanidino-15N2,5,52H2]arginine and L-[5,5,52H3]leucine, first during acute pulmonary vasoconstriction and again during convalescence, and thereby to characterize quantitative aspects of whole body arginine kinetics and NO production, as estimated from the rate of transfer of the 15N-guanidino-label of arginine to urinary nitrate (15NO3-). Arginine flux rates were 84.1 ± 8.6 μmol-kg.-1h-1 (mean ± SEM) during acute pulmonary hypertension and increased to 125 ± 13.2 (p < 0.05) during convalescence, whereas leucine fluxes were unchanged (168.5 ± 15 versus 178.8 ± 10.2 μmol.kg.-1h-1), and comparable to those reported in healthy newborns. During convalescence total urinary nitrate excreted increased by 66% (p < 0.05), urinary 15NO3- increased from 0.29 ± 0.07 to 0.74 ± 0.15 μmol.d-1 (p < 0.05), and the rate of plasma arginine conversion to NO increased from 10.3 ± 2.2 to 45.6 ± μmol.d-1 (p < 0.05). This study indicates a decreased plasma arginine utilization for whole body NO synthesis during the acute vasoconstrictive state of PPHN and suggests that arginine availability may become an important factor in NO formation.

Supercarbia in children: clinical course and outcome.

Supercarbia (Pco2 >150 torr) may result in a number of pathophysiologic conditions in experimental models and in humans. We report the clinical course and outcome after supercarbia secondary to hypoventilation in five children. Supercarbia resulted from severe airway obstruction in four children and central hypoventilation in one. Maximal PCO2 values ranged from 155 to 269 torr (mean 206). The time course to development of maximal PCO2 was between 35 min and 2 days. The pH ranged between 6.76 and 7.10 (mean 6.86). No patient was severely hypoxemic (Pao2 <55 torr) during the supercarbia period. Despite very high levels of PCO2 and low pH, the only pathophysiologic change found was temporary depression of neurologic function manifested by stupor or coma. Long-term follow-up of these patients has shown no serious adverse neurologic or developmental effects. (Crit Care Med 1990; 18:166)

Sudden infant death syndrome: abnormalities in short term fluctuations in heart rate and respiratory activity.

Summary: In order to test the hypothesis that a defect in cardiorespiratory regulation contributes to death of infants from sudden infant death syndrome (SIDS), we analyzed the power spectra of heart rate and respiratory activity during 256-sec epochs of quiet sleep. Data were obtained from pneumogram recordings performed for 12 h at night on eight infants who subsequently died from SIDS and 22 age-matched control infants. We computed the heart rate and respiratory power spectra from a single epoch on each infant using an algorithm developed for an 8085 microprocessor system dedicated to this investigation. There was no statistically significant difference between SIDS and controls based on mean respiratory and heart rates. Spectral analysis revealed enhancement of low frequency power in the 0.02 to 0.1 Hz band in the heart rate power spectrum in the SIDS group compared to control (p < 0.002) and dispersion in respiratory frequency as determined by the respiratory band width (p < 0.00001). These data suggest that a predisposition to SIDS manifests itself in an abnormal pattern of fluctuations in heart rate and respiratory activity.

Percutaneous catheterization of the radial artery in the critically ill neonate.

Percutaneous catheterization of the radial artery appears to be a simple and safe alternative to catheterization of the umbilical artery for monitoring critically ill neonates. This avoids the serious and potentially fatal complications associated with use of the umbilical arterial catheter, and it is also applicable to monitoring of neonates in whom the umbilical artery is no longer patent. We observed no serious sequelae in cannulation of the radial artery and think that the technique should be used more widely.

Sudden infant death syndrome and near sudden infant death syndrome: a review of the literature, 1964 to 1982.

During the past decade, investigators have begun to scientifically examine many of the theories that have been proposed to explain sudden infant death syndrome. The authors review the research in this area from 1964 to 1982.

Spectral characteristics of sound transmission in the human respiratory system

The amplitude of sound transmission from the mouth to a site overlaying the extrathoracic trachea and two sites on the right posterior chest wall over the 100-600-Hz frequency range was measured in eight healthy adult subjects. An acoustic driver and a rigid tube were used to introduce sound into the mouths of the subjects at resting lung volume, and the transmission measurements were performed using lightweight accelerometers. Similar spectral characteristics of acceleration were observed in all of the subjects showing peaks in the transmission. These characteristics included (1) two regions of increased transmission over the frequency range of the measurements, (2) a decrease in the magnitude of acceleration of the chest wall as compared to the tracheal site of roughly 20 dB at lower frequencies, and (3) a strong trend of decreasing acceleration of the chest wall with increasing frequency. These spectra agreed favorably with the predictions of a theoretical model of the acoustical properties of the respiratory system. The model suggests the primary structural determinants of a number of the observed characteristics including the importance of the lung parenchyma in sound attenuation.<<ETX>>