Breathing Lambs Research Articles

Ventilatory and waking responses to laryngeal stimulation in sleeping mature lambs

Ventilatory and waking responses to laryngeal stimulation were studied in six chronically tracheostomized lambs breathing through an endotracheal tube. A balloon catheter inserted in the rostral tracheal segment allowed application of distilled water onto the larynx. Apnea, the main primary ventilatory response, was shorter in wakefulness (7.9 sec) than in quiet (10.7 sec) or active sleep (10.6 sec, residual variance= 3.29), where the response to laryngeal stimulation was poorly reproducible. Arousal delay measured from the neck muscle EMG was longer in active (21.1 sec) than in quiet sleep (5.4 sec, residual variance= 9.05). Arousal preceded apnea termination more often in quiet than in active sleep. When breathing resumed a sigh frequently occurred following prolonged apneas. We conclude that laryngeal stimulation elicits apnea in all states in mature lambs. The termination of apnea is related to waking up in quiet but not in active sleep. where arousal is depressed. A comparison of our results with data from preterm and adult mammals strongly suggests that the ventilatory response to laryngeal stimulation during active sleep is unaffected by maturation.

221 EFFECT OF DECREASING LEVELS OF OXYGEN DELIVERY ON TOTAL BODY OXYGEN CONSUMPTION IN GROWING LAMBS

To determine the effect of decreasing systemic oxygen delivery (SOD) on oxygen consumption (Vo2) in the growing neonatal subject, we conducted 15 studies in 5 three week old lambs. SOD was lowered by progressive pericardial tamponade. SOD was measured as the product of cardiac output (CO) and arterial oxygen content. CO was measured by thermodilution. Pulmonary mixed venous and arterial blood were used to measure Po2, O2 saturation and hgb. Measurements were made every twenty minutes in unanesthetized, spontaneously breathing lambs in which decremental decreases in CO were produced. The change in Vo2 with decreasing SOD was analyzed by grouping data in decreasing ranges of SOD. The chart presents the mean± SD in each range:

Fetal lung liquid absorption and alveolar epithelial solute permeability in surfactant deficient, breathing fetal lambs.

The absorption of liquid volume and radiolabeled tracer solutes from the lungs of premature lambs was investigated during the first hours of ventilation. Exteriorized lambs, 133-141 d gestation, with intact umbilical circulation had [131I]albumin and [125I]cytochrome C added to the fetal lung liquid before breathing, and, additionally, [57Co]cyanocobalamin added to the remaining alveolar liquid after 20, 60, and 120 min of ventilation. Alveolar liquid was rapidly absorbed from the alveolar space, averaging more than 75% absorption in the first hour whether they breathed spontaneously or were ventilated. All animals absorbed proteins and water at the same rate as water during the first 20 min of breathing. Older, spontaneously breathing lambs released more surfactant into the alveolar space (302 +/- 82 microM) than younger ventilated animals (92 +/- 32 microM). After the first 20 min of breathing, older animals no longer absorbed [131I]albumin and [125I]cytochrome C, and at 4 h had near normal lung wet:dry weight ratio, 5.7 +/- 0.2. Younger animals continued to absorb [131I]albumin and [125I]cytochrome C as rapidly or more rapidly than liquid, and after 4 h had retained liquid in the lung wet:dry weight ratio 6.3 +/- 0.2. Alveolar surfactant appears able to alter the solute permeability of ventilated premature lung and the clearance of the fetal liquid from the lungs.

SYSTEMIC AND PULMONARY VASCULAR EFFECTS OF DOBUTAMINE IN NEWBORN LAMBS

Dobutamine is potentially a useful drug for therapy of myocardial dysfunction complicating perinatal asphyxia. To study the effect of the drug on an immature cardiovascular system, we infused dobutamine in stepwise doses from 2.5 to 20mcg/kg/min into 7 newborn lambs chronically instrumented for measurement of systemic and pulmonary artery pressures (SAP, PAP), right and left atrial pressures and pulmonary blood flow (Qp). The infusion was performed first with the lambs breathing room air, and then breathing a 10% O2 mixture. With normoxia, dobutamine produced a significant increase in Qp from 270 ± 69 to 390 ± 92ml/min/kg (mean ± S.D.) (p<0.01). This was due to an increase in heart rate (HR) from 180 ± 28 to 310 ± 26 beats/min (p<0.01). While SAP and PAP did not change, both systemic and pulmonary vascular resistances (SVR, PVR) decreased. During hypoxemia, dobutamine infusion tended to raise Qp and HR, but the changes were not statistically significant. No change was seen in SAP or SVR. PAP rose from 23 ± 2.8 to 29 ± 7.0 mm Hg (p<0.01), but PVR did not change. Thus, dobutamine in normoxic lambs caused an increase in cardiac output with concommitant fall in PVR and SVR. In addition, it had a marked chronotropic effect in these newborn animals. Dobutamine did not alter the pulmonary vascular response to hypoxia. The drug has properties desirable for therapy of newborns with myocardial dysfunction, but if the chronotropic effect is noted in human infants, this may limit dobutamine's utility.

Neonatal intestinal oxygen consumption during arterial hypoxemia.

In 12 chronically catheterized neonatal lambs, we determined intestinal tract blood flow (Qi) and O2 consumption (VO2i) at O2 contents of arterial blood (CaO2) ranging from 15.3 to 3.2 ml O2/dl blood. We measured Qi with the radioactive microsphere technique and computed intestinal O2 delivery (DO2i), VO2i, and O2 extraction (VO2i/DO2i) using the Fick principle. In lambs breathing air, mean Qi = 214 ml X min-1 X 100 g intestine-1, DO2i = 27.0 ml O2 X min-1 X 100 g-1, O2 extraction = 21%, and VO2i = 5.6 ml O2 Xmin-1 X 100 g-1. During reductions in CaO2, Qi and DO2i decreased. Intestinal O2 extraction increased sufficiently, however, so that VO2i was maintained over the range of CaO2 from 15.3 to about 6.5 ml O2/dl blood. VO2i was independent of Qi at Qi greater than 160 ml X min-1 X 100 g-1. When CaO2 was reduced below values of 6.5 ml O2/dl blood, corresponding to Qi less than 160 ml X min-1 X 100 g-1, VO2i fell in association with increases in the H+ concentration difference between mesenteric venous and arterial blood. These data indicate that the intestinal tract of the neonatal lamb can meet its oxygen requirements when O2 supply varies over a wide range. When O2 availability reaches a critically low level, intestinal anaerobic metabolism develops as the O2 supply to the neonatal intestinal tract becomes inadequate for the O2 demand.

Asynchronous respiratory activity of the diaphragm during spontaneous breathing in the lamb.

1. Direct simultaneous recordings from chronically implanted electrodes in different parts of the diaphragm were made in young lambs in which laryngeal adductor (thyroarytenoideus) and intercostal electromyograms, airflow, tracheal pressure and electrocorticogram and electro-oculograms for behavioural state were also recorded.2. An asynchrony of diaphragmatic contraction occurred which was dependent on sleep state. The vertebral portion showed maximal post-inspiratory activity while the lateral paratendinous portion usually terminated abruptly with end-inspiration, reciprocating closely with the onset of expiratory laryngeal adductor activity during quiet sleep. The contraction of the sternal portion was similar to the vertebral portion. In active (rapid eye movement) sleep there was no expiratory laryngeal constriction and post-inspiratory activity occurred in all portions of the diaphragm. During the characteristic bursts of rapid breathing in active sleep all post-inspiratory activity disappeared and the diaphragm contracted synchronously.3. General anaesthesia (Halothane/N(2)O or Nembutal) abolished expiratory laryngeal adductor activity and the discharge pattern became similar in all parts of the diaphragm.4. Intrathoracic vagotomy of Xylocaine blockade below the recurrent laryngeal nerves abolished post-inspiratory activity in all parts of the diaphragm, in contrast to the effect on expiratory laryngeal adductor activity which increased.5. Sustained ;tonic' electromyographic activity was often recorded from the costal and to a lesser extent the paratendinous portion of the diaphragm. This activity related to adjacent intercostal activity:ipsilateral intercostal blockade with local anaesthetic (Xylocaine 1%) abolished both the intercostal and the ;tonic' activity of the costal margins of the diaphragm. Conversely ipsilateral phrenic nerve blockade abolished all but the ;tonic' activity which related to intercostal activity.6. Interpretation of the respiratory activity of the diaphragm could not be made adequately from conventionally placed electrodes (i.e. costal, sternal slip or surface) during spontaneous breathing in unanaesthetized lambs. Simultaneous recordings showed that while expiratory flow and duration were actively controlled by expiratory laryngeal adductor activity and the diaphragm, the latter performed asynchronously. While both laryngeal and diaphragmatic expiratory functions were substantially under vagal control, the former increased and the latter decreased with reduced vagal input.

Heart rate variability, breathing and body movements inhypoxicfetal lambs.

Heart rate variability, breathing and body movements in<u>hypoxic</u>fetal lambs.

Heart rate variability, breathing and body movements innormoxicfetal lambs.

Heart rate variability, breathing and body movements in<u>normoxic</u>fetal lambs.

Respiratory suppression and swallowing from introduction of fluids into the laryngeal region of the lamb.

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.

89 EFFECTS OF ALVEOLAR HYPOXIA AND INTRAVENOUS TOLAZOINE ON PULMONARY HEMODYNAMICS AND LUNG LYMPH FLOW OF AWAKE WEEK-OLD LAMBS

To study the effects of alveolar hypoxia on lung fluid dynamics of newborn lambs, we measured mean pulmonary arterial (Ppa) and left atrial (Pla) pressures, cardiac output (Qb), steady-state lung lymph flow (Ql), and lymph (L) and plasma (P) protein concentrations of 8 awake 1-2 week old lambs breathing air for 2 h, then 10-12% 02 for 2-4 h. The lambs were at least 2 days postoperative during studies. Summary of results (mean):x: per g dry bloodless lung *: significant difference, p<.05 Contrary to results of previous studies of mature sheep (Circ Res 40:269, 1977), Q1 of lambs increased and L:P decreased when pulmonary vascular resistance (PVR) increased 66%, suggesting that alveolar hypoxia increased pulmonary transvascular filtration pressure and resultant fluid exchange,with no change in microvascular permeability to protein. To 6 lambs we infused tolazoline intravenously (2 mg/kg rapidly, then 4 mg/kg.h−1 for 3-4h) during steady-state hypoxia. As PVR diminished 16%, Q1 decreased 23%, showing that tolazoline decreased pulmonary transvascular filtration pressure and net fluid flux into the lung of hypoxic lambs.

EFFECT OF CPAP VIA ENDOTRACHEAL TUBE ON ORGAN BLOOD FLOWS IN NEWBORN LAMBS

Although CPAP is widely used in newborns, little is known of its effects on organ blood flows. We have shown head-box CPAP with a loose neck collar adversely affects cardiac output (C.O.) and retinal and renal blood flows in newborn lambs. The purpose of this study was to evaluate changes in C.O. and organ flows during endotracheal CPAP. Organ blood flows were measured with labeled 25 μ microapheres at CPAP pressures of 0, 6, 11, and 0 mnHg in 8 spontaneously breathing lambs, 3 to 8 days old. Twenty-three to 44% of the airway pressure was transmitted to the esophagus. Heart rate, left ventricular pressure and arterial blood gaaes were unchanged. Cardiac output (ml/min·kg) fell from a control of 248 ± 22 (mean ± SE) to 206 ± 11* and 202 ± 15† at 6 and 11 mmHg, respectively. Central venous pressure (CVP, mmHg) rose from 7.0 ± 1.4 to 10.9 ± 3.1% and 12.0 ± 2.7*, and jugular venous pressure (JVP) from 11.5 ± 1.8 to 13.9 ± 2.1† and 15.3 ± 2.2* at 6 and 11 mnHg, respectively. Blood flow to spleen, heart, brain, and choroid-retina did not change. Renal and gastrointestinal blood flows were unchanged at 6 mmHg, but fell 16.6 ± 5.1%* and 23.9 t 6.4%* at 11 mmHg. These data show that endotracheal CPAP caused moderate falls in C.O. and renal and gastrointestinal flows. However, endotracheal CPAP did not result in the fall in ocular blood flow or the extreme rise in CVP and JVP observed with head-box CPAP.* p < 0.05, † 0.10 > p > 0.05.

Control of breathing using an extracorporeal membrane lung.

Various amounts of carbon dioxide were removed through an extracorporeal membrane lung in spontaneously breathing lambs. The decrease in alveolar ventilation was proportional to the fraction of total carbon dioxide removed by the membrane lung. When extracorporeal CO2 removal approximated CO2 production (VCO2), alveolar ventilation almost ceased. Pulmonary ventilation can be controlled by extracorporeal carbon dioxide removal.

POSITIVE AIRWAY PRESSURE IN LAMBS SPONTANEOUSLY BREATHING AIR AND OXYGEN

Abstract The effects of 10 cm H2O positive endexpiratory pressure (PEEP) were studied in 26 unrestrained Hampshire and Corriedale lambs, breathing spontaneously air or pure oxygen. No changes in lung morphology, pulmonary mechanics or arterial blood gas tensions were detected after air breathing with 10 cm H2O PEEP for one week. No changes were found in mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance or cardiac output in oxygen breathing lambs until minutes before death. Addition of PEEP to oxygen breathing accelerated the development of respiratory acidemia and death (PEEP group mean lifespan 54 3 4 hr, without PEEP mean lifespan 71 3 4 hr). Morphologic changes of acute oxygen toxicity were present in oxygen breathing lambs and lung water was increased. Oxygen breathing lambs died from apnea with hypercarbia and a markedly increased (A-a) DO2. An increase in pulmonary vascular resistance or right ventricular failure do not appear to be major factors in the syndrome of fulminant acute respiratory insufficiency due to oxygen toxicity in lambs.

Positive airway pressure in lambs spontaneously breathing air and oxygen

The effects of 10 cm H 2O positive endexpiratory pressure (PEEP) were studied in 26 unrestrained Hampshire and Corriedale lambs, breathing spontaneously air or pure oxygen. No changes in lung morphology, pulmonary mechanics or arterial blood gas tensions were detected after air breathing with 10 cm H 2O PEEP for one week. No changes were found in mean pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance or cardiac output in oxygen breathing lambs until minutes before death. Addition of PEEP to oxygen breathing accelerated the development of respiratory acidemia and death (PEEP group mean lifespan 54 3 4 hr, without PEEP mean lifespan 71 3 4 hr). Morphologic changes of acute oxygen toxicity were present in oxygen breathing lambs and lung water was increased. Oxygen breathing lambs died from apnea with hypercarbia and a markedly increased ( A-a) DO 2. An increase in pulmonary vascular resistance or right ventricular failure do not appear to be major factors in the syndrome of fulminant acute respiratory insufficiency due to oxygen toxicity in lambs.