Herbert S. Harned

Respiratory Suppression and Swallowing from Introduction of Fluids into the Laryngeal Region of the Lamb

Summary: Introduction of 0.9% NaCl or undiluted fetal tracheal fluid into the laryngeal region produced no suppression of breathing in lambs during the perinatal period. As NaCl or tracheal fluid solutions were increasingly diluted with water, progressively greater respiratory suppression associated with rapid swallowing was observed. Introduction of amniotic fluid was associated with variable suppression of respiration. The swallowing induced by the dilute solutions was as rapid as two swallows per sec. Lambs 3 months of age swallowed when water was introduced into the laryngeal region, but were able to alternate swallows between breaths without suppression of breathing.Speculation: The suppression of breathing by presence of certain fluids in the laryngeal region may have important clinical implications. At birth, aspiration of amniotic fluid into the laryngeal area could seriously suppress breathing under certain conditions. In the pre-term or newly born infant, introduction of fluids with low osmolality into the laryngeal region might initiate this detrimental reflex more strongly than in older children. Finally, the aggravated response where life-threatening apnea develops from presence of small amounts of fluid in the laryngeal region might occur especially in neonatal disease states predisposing to apneic episodes. Under such conditions, swallowing could clear the liquid from the laryngeal region so that this area would be free of fluid at subsequent postmortem examination. Death from apnea could occur as terminal hypoxia supervenes, leaving little evidence for the pathologist to define the cause of death.

Initiation of breathing by cold stimulation: Effects of change in ambient temperature on respiratory activity of the full-term fetal lamb

The effects on breathing were studied in the submerged, exteriorized, full-term lamb during alteration of its ambient temperature. Slow cooling from an environmental temperature of 40° C. to 27° C. resulted in rhythmic breathing in 32 consecutive experiments. Rewarming of the water temperature invariably caused respiratory activity to cease. Monitoring of brachial arterial blood gas values and of umbilical venous blood flow revealed no significant changes in these parameters during the cooling or rewarming challenges.

Respiration and the Respiratory System

While the fetus is undergoing development of its own respiratory tract and the intricate neural, muscular, and circulatory structures necessary for initiating respiration at birth, it must entirely depend on its mother for the supply of oxygen and release of carbon dioxide, and for the maintenance of a metabolic environment compatible with its well-being. The dramatic substitution of its own respiratory system for that of the placenta is the primary event that occurs at birth, and the failure to perform this respiratory transition is the major cause of death or morbidity in the perinatal period. To visualize the primary significance of this change at birth, it is essential to understand the respiratory state of the fetus in utero. To aid in this understanding, the development of the placenta and its function as a respiratory organ will be emphasized in this section, as well as the development of the fetus’s own respiratory system.

Respiratory effects of division of the carotid sinus nerve in the lamb soon after the initiation of breathing.

Extract: Increased activity of the carotid chemoreceptors from hypoxia and hypercarbia, induced by occlusion of the umbilical cord, has importance in initiating effective respiration of the term lamb. The state of hypoxia and hypercarbia continuing after birth should also evoke strong stimulation from the carotid glomi. The present experiments measure the effects on ventilation resulting from interruption of carotid chemoreceptor stimulation to the respiratory center by division of each carotid sinus nerve of the lamb during the newborn period.Ewes were given spinal anesthesia and each lamb was partly removed from the uterus to permit an operative approach through the neck. The carotid sinus nerves were exposed and tagged with loose threads to facilitate division of the nerve at a later stage. The lamb was then delivered, its umbilical cord clamped, and its inspiratory volume measured by pneumotachometric techniques.Each of the seven lambs studied was permitted to establish respiration before its first carotid sinus nerve was divided. The time intervals between birth and division of the first nerves varied from 5.5 to 38.5 minutes after birth. The second nerves were divided several minutes later when respiration had recovered from the effects of division of the first nerve. A significant fall in ventilation was observed within 50 seconds after division of each carotid sinus nerve. Improved ventilation began to occur in some animals 150 seconds later, and occurred in all animals within several minutes after division of each nerve. Levels of PO2, pH and PCO2 in carotid artery blood before nerve division revealed hypoxia, hypercarbia and acidosis; this aberrant state became worse during the period of diminished ventilation. The minimal changes in heart rate and blood pressure resulting from interruption of baroreceptor fibers were insufficient to influence respiration.Speculation: When viewed in conjunction with experiments performed in lambs immediately at birth and with those performed in older newborn lambs, these experiments reveal a continuum of physiologic activity of the carotid chemoreceptors which is important in the establishment and regulation of breathing. The consistent recovery of ventilation after the initial depression produced by division of the second carotid sinus nerve indicates that under these conditions, chemical regulatory mechanisms other than those of the carotid glomi are important in the lamb. The only peripheral chemoreceptors known to be active in the newborn are those in the carotid bodies. Accordingly, some central chemosensor mechanisms must be invoked to explain the recovery of respiration.

Ultrasound detection and quantitation of left to right aortopulmonary shunt flow in a canine model.

To test the sensitivity and accuracy of pulsed Doppler ultrasonography to detect and quantitate left to right aortopulmonary shunt flow, an arterial allograft aortopulmonary anastomosis was constructed in nine adult mongrel dogs. Cardiac output and allograft flow were measured as the diameter of the allograft was varied. Piezoelectric crystals attached to the carotid artery and proximal descending aorta were energized with 20 MHz pulsed Doppler signals. Negative Doppler shift and negative Doppler shift/positive Doppler shift were calculated for seven dogs. All dogs exhibited negative Doppler shift in the carotid artery at zero allograft flow; five of the seven dogs exhibited a similar pattern in the descending aorta. Increasing negative Doppler shift was measured in all dogs from both sites as the allograft flow increased. Excellent linear correlation existed between allograft flow and negative Doppler shift and negative Doppler shift/positive Doppler shift for each dog from both sampling sites. However, marked interanimal variation in the slopes of the linear regression lines existed, making the composite linear correlation very poor. Detection of small left to right aortopulmonary shunting and single measurements to quantitate accurately left to right aortopulmonary shunting introduce errors due to intersubject variation. However, these results suggest that serial ultrasound measurements made over a short time can accurately predict changes in left to right aortopulmonary shunting.

69 NORTH CAROLINA PERINATAL TELECOMMUNICATIONS NETWORK: AN INNOVATIVE APPROACH TO INTERNURSERY COMMUNICATIONS

Transport of high risk mothers and infants has been shown to reduce neonatal morbidity and mortality. However, lack of information regarding availability of neonatal facilities at any center often causes excessive time delay before instituting a patient transfer. To address this communication problem we have designed a computer-based system which collects and disseminates referral information throughout a statewide network of ten perinatal centers. The system consists of a centrally-based microcomputer and auto-dial modem which interfaces through public telephone lines to a computer terminal (CRT) located in each center. At each center, the ability to accept maternal and neonatal transfers is assessed by the obstetrical and pediatric staff and entered into the CRT. Referral mechanisms and phone numbers as well as specific information regarding available facilities at each center are also displayed on the CRT. Every two hours the central computer sequentially interrogates each CRT and updates the entire system. Data regarding every center are continuously displayed on each CRT throughout the network. This system has the following advantages over manual systems: 1) information is always current; 2) complete data is available at each perinatal center throughout the state; 3) practitioner referral patterns are not affected; 4) reduced cost; and 5) automatic data compilation for long-term regional planning.

1351 CENTRAL NEURAL MATURATION OF THE EXCITATORY RESPONSE TO CAROTID SINUS NERVE STIMULATION

The biphasic respiratory response (hyperpnea followed by hypoventilation) of the newborn human has been attributed to central hypoxic depression of the respiratory centers. Recently, we have shown that, in the absence of hypoxia, the excitatory effect of continued carotid sinus nerve (CSN) stimulation fatigues in piglets 4-14 days of age (The Physiologist 23:140, 1980). To study maturation of the excitatory effects of the CSN without confounding blood gas changes, we compared changes in respiratory output (RO=f × neural tidal volume) during electrical CSN stimulation in young and older piglets (7 piglets 4-14 days; 7 piglets 20-34 days). The piglets were anesthetized, vagotomized, paralyzed and ventilated (FIO2=1.0). End-tidal CO2 was kept constant with a servo-controller (mean end-tidal CO2=30.2mmHg). RO was quantified by moving average of the rectified phrenic neurogram. The RO of all piglets increased (p<.01) at the onset of CSN stimulation due to change in both frequency and neural tidal volume. However, by 50-60s, the average RO had decreased to 54±7% (±SEM) of peak RO in young piglets whereas in the 7 older piglets respiratory output was 78±5% of peak. This difference was significant (p<.025). Again, change in both frequency and neural tidal volume accounted for the changes in RO. These findings demonstrate that central neural mechanisms control the biphasic respiratory response to hypoxia. We conclude that neural maturation during the first 4 weeks of life permits the more sustained response seen in the older animals.

1688 NALOXONE ENHANCES RESPIRATORY OUTPUT IN PIGLETS XHROUGH FOUR WEEKS OF AGE

Endorphins, endogenous neurotransmitters with opiate-like properties, are suspected to modify respiratory drive. Naloxone, a specific opiate antagonist, has been shown to enhance respiratory output (RO) in adult cats (Lawson, JAP 47:1105, 1979) and spontaneously breathing rabbits ≤4 days but not in rabbits ≥5 days (Hazinsky, Ped Res 14:643, 1980). To further investigate the central response to naloxone in young animals without confounding blood gas changes, 5 young piglets (<7 days) and 5 older piglets (≥21 days) were anesthetized, vagotomized, paralyzed and ventilated (FIO2=1.0). End tidal CO2 was kept. constant by a servo-controller (mean end tidal CO2=31.5mmHg). RO was quantified by moving average of the phrenic neurogram. Breath-by-breath frequency, neural tidal volume, inspiratory rate of rise, TI and TE were calculated by an on-line computer. A baseline period of RO was recorded following which naloxone (.4 mg/kg) was given intravenously. RO 5 minutes after naloxone was compared to baseline. In young piglets RO increased to 192±27% (±SEM) of baseline. RO of older piglets increased to 141±7% of the baseline value. In both young and older piglets the increase in RO was due to increased neural tidal volume (185±21% and 137±5% respectively) which resulted from enhanced inspiratory rate of rise (218±31% and 147±16% respectively). TI was slightly shortened in 8/10 animals. TE remained effectively unchanged. We conclude that 1) naloxone enhances the RO in both younger and older piglets; and 2) the increase in RO is due to increased central respiratory drive.

Circulatory effects related to alterations of the ambient environment of the term fetal lamb

The environmental temperature of term fetal lambs was altered by changing the temperature of water immersing the animals (Group I) or by release from warm water into room air (Group II). Circulatory changes suggesting sympathetic activation were observed with cooling by these methods (i.e., decreased peripheral blood flow, preservation of flow through the internal maxillary artery, tachycardia), accompanied by slight increase in adrenal secretion of epinephrine and norepinephrine. Since these effects were similar in both groups and only Group I lambs breathed vigorously with cooling, no circulatory factor was identified as vital in initiation of respiration in this manner.

Effects of hypoxia and acidity on the initiation of respiration

The effects of hypoxia and acidity on the initiation of respiration of term lambs were studied by two methods that discern chemoreceptor activation. (1) Perfusion of the right common carotid artery with blood with lower pO2, but similar pGO2 and pH to that in the fetal carotid artery invoked slow and erratic respirations after 15 sec. in 2 of 4 lambs and none in 2 other lambs. In contrast, perfusion of blood with lowered pH as well as low pO2 invoked more rapid and persistent respirations in all 5 additional lambs studied. (2) In another group of experiments, fetal carotid sinus nerve potentials were amplified for simultaneous oscillographic visualization, for broadcast by loud speaker, and for FM tape recording. The magnitude of chemoreceptor activity was determined, during ventrlcular diastole to preclude baroreceptor activity, by integrating and summating the recorded wave forms. The degree of chemoreceptor activity, as determined during basal fetal conditions, during administration of hypoxic and hypoxic-hypercarblc gas mixtures to the ewes, and after clamping of the umbilical cord was found to be proportional to the magnitude of the stimulus, such that after cord occlusion a marked increase in chemoreceptor activity was noted. The experiments show that increased H + ion concentration in carotid arterial blood potentiates the hypoxic stimulation of chemoreceptors and that a marked chemoreceptor discharge follows clamping of the umbilical cord. The results are compatible with a hypothesis that respirations are initiated in the newborn by a summation of neural stimuli, including an important traffic of chemoreceptor impulses, to the medullary respiratory centers.