Ventilatory response to sustained hypoxia in normal adults

We examined the ventilatory response to moderate (arterial O2 saturation 80%), sustained, isocapnic hypoxia in 20 young adults. During 25 min of hypoxia, inspiratory minute ventilation (VI) showed an initial brisk increase but then declined to a level intermediate between the initial increase and resting room air VI. The intermediate level of VI was a plateau that did not change significantly when hypoxia was extended up to 1 h. The relation between the amount of initial increase and subsequent decrease in ventilation during constant hypoxia was not random; the magnitude of the eventual decline correlated confidently with the degree of initial hyperventilation. Evaluation of breathing pattern revealed that during constant hypoxia there was little alteration in respiratory timing and that the changes in VI were related to significant alterations in tidal volume and mean inspiratory flow (VT/TI). None of the changes was reproduced during a sham control protocol, in which room air was substituted for the period of low fractional concentration of inspired O2. We conclude that ventilatory response to hypoxia in adults is not sustained; it exhibits some biphasic features similar to the neonatal hypoxic response.     

Interaction of hypoxic and hypercapnic stimuli on breathing pattern in the newborn rat

We aimed to investigate whether newborn rats respond to acute hypoxia with a biphasic pattern as other newborn species, the characteristics of their ventilatory response to hypercapnia, and the ventilatory response to combined hypoxic and hypercapnic stimuli. First, we established that newborn unanesthetized rats (2-4 days old) exposed to 10% O2 respond as other species. Their ventilation (VE), measured by flow plethysmography, immediately increased by 30%, then dropped and remained around normoxic values within 5 min. The drop was due to a decrease in tidal volume, while frequency remained elevated. Hence, alveolar ventilation was about 10% below normoxic value. At the same time O2 consumption, measured manometrically, dropped (-23%), possibly indicating a mechanism to protect vital organs. Ten percent CO2 in O2 breathing determined a substantial increase in VE (+47%), indicating that the respiratory pump is capable of a marked sustained hyperventilation. When CO2 was added to the hypoxic mixture, VE increased by about 85%, significantly more than without the concurrent hypoxic stimulus. Thus, even during the drop in VE of the biphasic response to hypoxia, the respiratory control system can respond with excitation to a further increase in chemical drive. Analysis of the breathing patterns suggests that in the newborn rat in hypoxia the inspiratory drive is decreased but the inspiratory on-switch mechanism is stimulated, hypercapnia increases ventilation mainly through an increase in respiratory drive, and moderate asphyxia induces the most powerful ventilatory response by combining the stimulatory action of hypercapnia and hypoxia.     

Recovery of the ventilatory response to hypoxia in normal adults

Recovery of the initial ventilatory response to hypoxia was examined after the ventilatory response had declined during sustained hypoxia. Normal young adults were exposed to two consecutive 25-min periods of sustained isocapnic hypoxia (80% O2 saturation in arterial blood), separated by varying interludes of room air breathing or an increased inspired O2 fraction (FIO2). The decline in the hypoxic ventilatory response during the 1st 25 min of hypoxia was not restored after a 7-min interlude of room air breathing; inspired ventilation (VI) at the end of the first hypoxic period was not different from VI at the beginning and end of the second hypoxic period. After a 15-min interlude of room air breathing, the hypoxic ventilatory response had begun to recover. With a 60-min interlude of room air breathing, recovery was complete; VI during the second hypoxic exposure matched VI during the first hypoxic period. Ventilatory recovery was accelerated by breathing supplemental O2. With a 15-min interlude of 0.3 FIO2 or 7 min of 1.0 FIO2, VI of the first and second hypoxic periods were equivalent. Both the decline and recovery of the hypoxic ventilatory response were related to alterations in tidal volume and mean inspiratory flow (VT/TI), with little alteration in respiratory timing. We conclude that the mechanism of the decline in the ventilatory response with sustained hypoxia may require up to 1 h for complete reversal and that the restoration is O2 sensitive.     

Carbon dioxide effects on the ventilatory response to sustained hypoxia

We examined the interrelation between CO2 and the ventilatory response to moderate (80% arterial saturation) sustained hypoxia in normal young adults. On a background of continuous CO2-stimulated hyperventilation, hypoxia was introduced and sustained for 25 min. Initially, with the introduction of hypoxia onto hypercapnia, there was a brisk additional increase in inspiratory minute ventilation (VI) to 284% of resting VI, but the response was not sustained and hypoxic VI declined by 36% to a level intermediate between the initial increase and the preexisting hypercapnic hyperventilation. Through the continuous hypercapnia, the changes in hypoxic ventilation resulted from significant alterations in tidal volume (VT) and mean inspiratory flow (VT/TI) without changes in respiratory timing. In another experiment, sustained hypoxia was introduced on the usual background of room air, either with isocapnia or without maintenance of end-tidal CO2 (ETCO2) (poikilocapnic hypoxia). Regardless of the degree of maintenance of ETCO2, during 25 min of sustained hypoxia, VI showed an initial brisk increase and then declined by 35-40% of resting VI to a level intermediate between the initial response and resting room air VI. For both isocapnia and poikilocapnic conditions, the attenuation of VI was an expression of a diminished VT. Thus the decline in ventilation with sustained hypoxia occurred regardless of the background ETCO2, suggesting that the mechanism underlying the hypoxic decline is independent of CO2.     

Diaphragmatic and ventilatory responses to alveolar hypoxia and hypercapnia in conscious kittens.

Ventilation and electromyographic (EMG) activity of the diaphragm were recorded in unanesthetized kittens 2 and 10 wk of age during normoxia, hypercapnia (2 and 4% CO2), and hypoxia (12 and 10% O2). We measured integrated diaphragmatic EMG activity at end inspiration (DIAI) and end expiration (DIAE); the difference (DIAI-E), which represents the phasic change of the diaphragmatic activity, was considered responsible for a given tidal volume (VT). During hypercapnia, the 2-wk-old kittens increased minute ventilation (V) by increases in both VT and respiratory frequency (f), whereas the 10-wk-old kittens increased V primarily by an increase in VT. At both ages, DIAI and DIAI-E increased during hypercapnia, whereas DIAE did not change significantly. During hypoxia, in the young kittens, V and VT decreased while f increased markedly; in the older kittens, V, VT, and f did not change significantly. In kittens of both ages, DIAI increased during hypoxia; because diaphragmatic activity persisted into expiration, DIAE also increased. DIAI-E, as well as VT, was decreased in the young kittens, whereas in the older ones DIAI-E was slightly increased despite an unchanged VT. Finally, the ventilatory and diaphragmatic response to hypoxia changes with maturation in contrast to the response to hypercapnia. It is concluded that 1) the hypoxia-induced reduction of VT may result from prolongation of diaphragmatic activity into expiration, inasmuch as it induces a reduction of the phasic change of the diaphragmatic activity, and 2) because DIAI-E indirectly reflects central inspiratory output, a central mechanism should be involved in the reduced VT and V in response to hypoxia in newborns.     

Elevated diaphragm electromyogram during neonatal hypoxic ventilatory depression

Diaphragmatic electromyogram (EMG) was obtained in eight 48-h-old unanesthetized monkeys while breathing air and then either of two different hypoxic gas mixtures (12 or 8% O2 in N2) for 5 min. Minute ventilation (VI) rose significantly above control levels by 1 min of hypoxemia while animals were breathing either of the hypoxic gas mixtures as tidal volume (VT) and slope and rate moving average EMG increased. The relative gains in VI were associated with comparable increases in diaphragmatic neural activity per minute (EMG/min = peak EMG X frequency) during this early phase of hypoxemia. VI subsequently fell to control levels (inspired O2 fraction = 12%, arterial PO2 = 23 +/- 3 Torr) or significantly below (inspired O2 fraction = 8%, arterial PO2 = 18 +/- 0.4 Torr) by 5 min of hypoxemia, secondary to changes in VT. Despite the decline in VI, slope and rate moving average EMG, and EMG/min remained statistically above control values by 5 min of hypoxemia, although there was a trend for EMG/min to decrease slightly from the 1-min peak response. These findings demonstrate that hypoxic-induced depression of neural input to the diaphragm is not independently responsible for the biphasic nature of the newborn ventilatory response, although it cannot be ruled out as a contributor. The fall in inspiratory volumes despite constant elevated EMG activity suggests the presence of a change in respiratory mechanics and/or an impairment in diaphragmatic contractile function without offsetting neural compensatory activity.     

Kinetics of cardiorespiratory response to dynamic and rhythmic-static exercise in men

Kinetics of cardiorespiratory response to dynamic (DE) and then to rhythmic-static exercise (RSE) was compared in nine male subjects exercising in an upright position on a cycle ergometer at an intensity of about 50% VO2max and a mean pedalling frequency of 60 rpm over 5 min. Respiratory frequency (fR), tidal volume (VT), minute ventilation (VE), heart rate (fc), stroke volume (SV), and cardiac output (Qt) were measured continuously. The RSE caused a greater increase in fR than DE, whereas VT increased more during DE. The effect of reciprocal changes in fR and VT was that VE and its kinetics, expressed as a time constant (tau), did not differ between experimental situations. The ventilatory equivalent for O2 (VE: VO2) was greater for RSE (31.3) than for DE (23.0, P less than 0.01). Elevation of fc was similar for both types of exercise. The SV increased suddenly at the beginning of DE from 54 ml to 74 ml and then decreased to the end of exercise. At the onset of RSE only a moderate increase in SV was observed, from 56 ml to 62 ml, and then SV remained stable. The DE caused a greater and faster increase in Qt (4.20 l.min-1, for tau equal to 16.1 s) than RSE (3.25 l.min-1, for tau equal to 57.0 s, P less than 0.05 and P less than 0.002, respectively). Total peripheral resistance was almost 40% greater for RSE than for DE. No relationship was found between Qt and VE at the first 15 s of both types of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

MK-801 alters diaphragmatic activities in unanesthetized rats differently between normoxia and hypoxia

This study was designed to examine how systemic administration of an N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, altered respiratory timing in unanesthetized rats under normoxia and hypoxia. To detect fine changes in inspiratory time (TI) and expiratory time (TE), and cycle duration (TTOT), we prepared a diaphragmatic electromyogram (EMGdia). Diaphragm electrodes and arterial and venous catheters were inserted into Wistar rats (n = 8) under pentobarbital anesthesia. The next day, EMGdia was recorded before and after intravenous administration of MK-801 (3 mg/kg) under normoxia and hypoxia (12% O2) without anesthesia, and the respiratory timing (TI, TE, TTOT), respiratory frequency (fR), and amplitude of the integrated EMGdia were measured. Arterial blood gases (ABGs), mean arterial pressure (MAP), and heart rate (fH) were also measured with the EMGdia. Under normoxia, MK-801 increased fR owing to a significant decrease in TE, and elevated both MAP and fH. Under hypoxia, MK-801 suppressed an increase in fR owing to a significant increase in TI, and did not accelerate fH. In both gaseous conditions, on ABGs, MK-801 did not alter partial pressure of O2 (PaO2) or CO2 (PaCO2), and slightly decreased pH (but not less than 7.4). MK-801 significantly decreased hypoxic response (%change from normoxia) in fR, and increased that in EMGdia amplitude, and did not alter a total ventilatory index (fRxEMGdia amplitude). The results suggest that an NMDA receptor-mediated mechanism partially determines fR through significant alterations in respiratory timing, particularly in which the hypoxic ventilatory response was obtained in unanesthetized rats.     

Lung mechanics and end-expiratory lung volume during hypoxia in rats.

We investigated whether an hypoxia-induced increase in airway resistance mediated by vagal efferents participates in the increase in end-expiratory lung volume (EELV) observed in hypoxia. We also assessed the contribution of the end-expiratory activity of the diaphragm (DE) to this phenomenon. Therefore, we measured EELV, total lung resistance (RL), dynamic lung compliance (Cdyn), DE, and minute ventilation (VE) in anesthetized rats during normoxia and hypoxia (10% O(2)) before (control) and after administration of atropine or saline. In the control group, hypoxia increased EELV, Cdyn, DE, and VE but slightly decreased RL. These changes were unaffected by saline or atropine, except that, in the atropine-treated rats, hypoxia did not change RL. These results suggest that 1) the increase in EELV observed in hypoxia cannot result from an increase in airway resistance; 2) the increased and persistent activity of inspiratory muscles during expiration is the most likely cause of the increase in EELV during hypoxia; and 3) the decrease in RL induced by hypoxia could result from the increase in lung volume including EELV.     

Effects of CO2 breathing on ventilatory response to sustained hypoxia in normal adults

The relationship between CO2 and ventilatory response to sustained hypoxia was examined in nine normal young adults. At three different levels of end-tidal partial pressure of CO2 (PETCO2, approximately 35, 41.8, and 44.3 Torr), isocapnic hypoxia was induced for 25 min and after 7 min of breathing 21% O2, isocapnic hypoxia was reinduced for 5 min. Regardless of PETCO2 levels, the ventilatory response to sustained hypoxia was biphasic, characterized by an initial increase (acute hypoxic response, AHR), followed by a decline (hypoxic depression). The biphasic response pattern was due to alteration in tidal volume, which at all CO2 levels decreased significantly (P less than 0.05), without a significant change in breathing frequency. The magnitude of the hypoxic depression, independent of CO2, correlated significantly (r = 0.78, P less than 0.001) with the AHR, but not with the ventilatory response to CO2. The decline of minute ventilation was not significantly affected by PETCO2 [averaged 2.3 +/- 0.6, 3.8 +/- 1.3, and 4.5 +/- 2.2 (SE) 1/min for PETCO2 35, 41.8, and 44.3 Torr, respectively]. This decay was significant for PETCO2 35 and 41.8 Torr but not for 44.3 Torr. The second exposure to hypoxia failed to elicit the same AHR as the first exposure; at all CO2 levels the AHR was significantly greater (P less than 0.05) during the first hypoxic exposure than during the second. We conclude that hypoxia exhibits a long-lasting inhibitory effect on ventilation that is independent of CO2, at least in the range of PETCO2 studied, but is related to hypoxic ventilatory sensitivity.     

Ventilatory response to sustained hypoxia in carotid body denervated rats

Hypoxia stimulates ventilation, but when it is sustained, a decline in the ventilatory response is seen. The mechanism responsible for this decline lies within the CNS, but still remains unknown. In this study, we attempted to elucidate the possible role of hypoxia-induced depression of respiratory neurons by comparing the ventilatory response to hypoxia in intact rats and those with denervated carotid bodies. A whole-body plethysmograph was used to measure tidal volume, frequency of breathing and minute ventilation (VE) in awake and anesthetized intact rats and rats after carotid body denervation during exposure to hypoxia (FIO2 0.1). Fifteen-minute hypoxia induced an initial increase of VE in intact rats (to 248% of control ventilation in awake and to 227% in anesthetized rats) followed by a consistent decline (to 207% and 196% of control VE, respectively). Rats with denervated carotid bodies responded with a smaller increase in VE (to 134% in awake and 114% in anesthetized animals), but without a secondary decline (145% and 129% of control VE in the 15th min of hypoxia). These results suggest that afferentation from the carotid bodies and/or the substantial increase in ventilation are crucial for the biphasicity of the ventilatory response to sustained hypoxia and that a central hypoxic depression cannot fully explain the secondary decline in VE.     

Importance of vagal afferents in determining ventilation in newborn rats

We studied the effect of acute bilateral vagotomy on ventilation and ventilatory pattern in rats. In 1- to 6-day-old unanesthetized rats, vagotomy resulted in a substantial decrease (38%) in ventilation during air breathing. After vagotomy there was a threefold increase in tidal volume (VT), inspiratory time (TI) doubled, and expiratory time (TE) was six times longer. When studied under isoflurane anesthesia, newborn rats showed decreases in ventilation similar to that observed without anesthesia, whereas anesthetized adult rats had no consistent changes in ventilation. Adult and newborn rats had nearly identical proportionate increases in VT and TI after vagotomy, but TE lengthened to a greater extent in the newborns. Additionally, we demonstrated a significant decrease in ventilation when 100% O2 rather than air was supplied to nonvagotomized unanesthetized newborn rats. Ventilation decreased by 19% after vagotomy under hyperoxic conditions. We conclude that vagal afferent input, probably of pulmonary mechanoreceptor origin, provides positive feedback to respiration in newborn rats and that newborn rats greater than 24 h old also have a degree of peripheral chemoreceptor drive during air breathing.     

Increased chemoreceptor output and ventilatory response to sustained hypoxia

In adult humans the ventilatory response to sustained hypoxia (VRSH) is biphasic, characterized by an initial brisk increase, due to peripheral chemoreceptor (PC) stimulation, followed by a decline attributed to central depressant action of hypoxia. To study the effects of selective stimulation of PC on the ventilatory response pattern to hypoxia, the VRSH was evaluated after pretreatment with almitrine (A), a PC stimulant. Eight subjects were pretreated with A (75 mg po) or placebo (P) on 2 days in a single-blind manner. Two hours after drug administration, they breathed, in succession, room air (10 min), O2 (5 min), room air (5 min), hypoxia [25 min, arterial O2 saturation (SaO2) = 80%], O2 (5 min), and room air (5 min). End-tidal CO2 was kept constant at the normoxic base-line values. Inspiratory minute ventilation (VI) and breathing patterns were measured over the last 2 min of each period and during minutes 3-5 of hypoxia, and nadirs in VI were assessed just before and after O2 exposure. Independent of the day, the VRSH was biphasic. With P and A pretreatment, early hypoxia increased VI 4.6 +/- 1 and 14.2 +/- 1 (SE) l/min, respectively, from values obtained during the preceding room-air period. On A day the hypoxic ventilatory decline was significantly larger than that on P day, and on both days the decline was a constant fraction of the acute hypoxic response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of haloperidol and domperidone on ventilatory roll off during sustained hypoxia in cats.

In a previous work, we showed that the adult cat demonstrates a ventilatory decline during sustained hypoxia (the "roll off" phenomenon) and that the mechanism responsible for this secondary decrease in ventilation lies within the central nervous system (J. Appl. Physiol. 63: 1658-1664, 1987). In this study, we sought to determine whether central dopaminergic mechanisms could have a role in the roll off. We studied the effects of haloperidol, a peripheral and centrally acting dopamine receptor antagonist, on the ventilatory response to sustained isocapnic hypoxia (end-tidal PO2 40-50 Torr, 20-25 min) in awake cats. In vehicle control cats (n = 5), sustained hypoxia elicited a biphasic respiratory response, during which an initial ventilatory stimulation is followed by a 24 +/- 6% (P less than 0.01) reduction. In contrast, in haloperidol- (0.1 mg/kg) treated cats (n = 5) the ventilatory roll off was virtually abolished (-1 +/- 1%; P = NS). We also measured ventilatory, carotid sinus nerve (CSN) and phrenic nerve (PhN) responses to sustained isocapnic hypoxia in anesthetized animals (n = 6) to explore the influence of haloperidol on peripheral and central response during the roll off. Control responses to hypoxia showed an initial increase in ventilation, PhN, and CSN activity, followed by a subsequent decline in ventilation and PhN activity of 17 +/- 3 and 17 +/- 5%, respectively (P less than 0.05). In contrast, CSN activity remained unchanged during the roll off. Administration of haloperidol (1 mg/kg) reduced the initial increment in ventilation, while the initial increase in CSN activity was augmented.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilatory response to hypoxia in unanesthetized newborn kittens

We studied the ventilatory response to hypoxia in 11 unanesthetized newborn kittens (n = 54) between 2 and 36 days of age by use of a flow-through system. During quiet sleep, with a decrease in inspired O2 fraction from 21 to 10%, minute ventilation increased from 0.828 +/- 0.029 to 1.166 +/- 0.047 l.min-1.kg-1 (P less than 0.001) and then decreased to 0.929 +/- 0.043 by 10 min of hypoxia. The late decrease in ventilation during hypoxia was related to a decrease in tidal volume (P less than 0.001). Respiratory frequency increased from 47 +/- 1 to 56 +/- 2 breaths/min, and integrated diaphragmatic activity increased from 14.9 +/- 0.9 to 20.2 +/- 1.4 arbitrary units; both remained elevated during hypoxia (P less than 0.001). Younger kittens (less than 10 days) had a greater decrease in ventilation than older kittens. These results suggest that the late decrease in ventilation during hypoxia in the newborn kitten is not central but is due to a peripheral mechanism located in the lungs or respiratory pump and affecting tidal volume primarily. We speculate that either pulmonary bronchoconstriction or mechanical uncoupling of diaphragm and chest wall may be involved.     

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.     

Ventilatory response to sustained hypoxia after pretreatment with aminophylline

During sustained hypoxia the decline in ventilation that occurs in normal adult humans may be related to central accumulation of a neurochemical with net inhibitory effect. Recent investigations have shown that the putative neurotransmitter adenosine can effect a prolonged respiratory inhibition. Therefore we evaluated the possible role of adenosine in the hypoxia ventilatory decline by employing aminophylline as an adenosine blocker. We evaluated the ventilatory response to 25 min of sustained hypoxia (80% arterial O2 saturation), in eight young adults after pretreatment with either intravenous saline or aminophylline. With a mean serum aminophylline level of 15.7 mg/l, over 25 min of sustained hypoxia, peak hypoxic ventilation decreased by only 12.8% compared with 24.8% with saline, a significant difference. However, the ventilatory decline during sustained hypoxia was not abolished by the aminophylline pretreatment. Unlike the usual tidal volume-dependent attenuation of hypoxic ventilation exhibited after saline, after aminophylline the ventilatory decline was achieved predominantly through alterations in respiratory timing. Thus aminophylline pretreatment did alleviate the hypoxic ventilatory decline, although the associated alterations in breathing pattern were uncharacteristic. We conclude that adenosine may play a contributing role in the hypoxic ventilatory decline.     

Endogenous opioid effects on abdominal muscle activity during inspiratory loading

In a previous study in unanesthetized goats, we demonstrated that continuous naloxone (NLX) administration during inspiratory flow-resistive loading (IRL) significantly increased tidal volume (VT) but not diaphragm electromyogram (EMGdi). End-expiratory gastric pressure did increase with NLX, implying that increased abdominal muscle activity may have accounted for the NLX effect. In the current study we directly tested the hypothesis that endogenous opioid elaboration depresses the abdominal muscle response to a continuous inspiratory flow-resistive load. In seven unanesthetized goats, VT, arterial blood gases, EMGdi, and EMG activity of external oblique (EMGeo), transversus abdominis (EMGta), and external intercostal (EMGei) muscles were monitored. IRL (50 cmH2O.l-1.s) was continued for 3 h, after which NLX (0.1 mg/kg) or saline was given. Our results showed that VT decreased from 323 +/- 32 (SE) ml at baseline to 260 +/- 16 ml 5 min after the load was imposed (P less than 0.05) and further decreased to 229 +/- 18 and 217 +/- 15 ml by 120 and 180 min, respectively (180 vs. 5 min, P less than 0.05). EMGdi increased from 62 +/- 5 to 83 +/- 4% max at 5 min (P less than 0.05) but was unchanged thereafter. In contrast, for this same time period EMGeo increased from 35 +/- 5 to 58 +/- 11% max but decreased from 67 +/- 11% max at 120 min to 37 +/- 5% max at 180 min (P less than 0.05). NLX administration resulted in significant increases in EMGeo (91% above 180-min value). In contrast, EMGdi increased minimally after NLX (15% above 180-min value).(ABSTRACT TRUNCATED AT 250 WORDS)     

Enkephalin-induced changes in ventilation and ventilatory pattern in adult dogs

We studied the changes in ventilation induced by intracisternal administration of enkephalins in four unanesthetized adult dogs. Instantaneous minute ventilation (VT/TT) decreased markedly after D-Ala-Met-enkephalinamide (DAME). Mean VT/TT decreased maximally by 20-50 min after DAME and lasted an additional 15-60 min; by 2 h, VT/TT had returned to base line. Four doses (5, 25, 60, and 125 micrograms/kg) of DAME were used, and the ventilatory response depended on the dose. Mean inspiratory time decreased but mean expiratory time and mean TT showed a marked prolongation. Periodic breathing (2-3 breaths separated by long apneic pauses) occurred in every study and the frequency of sighs increased considerably. All these ventilatory changes were reversed by low doses of naloxone or naltrexone; in addition, VT/TT increased well above base line after the administration of these antagonists. However, naloxone did not increase VT/TT when injected without prior administration of DAME. We conclude that 1) the decrease in VT/TT is due to a decrease in respiratory duty cycle; 2) periodic breathing and increased frequency of sighs constitute part of the changes in the ventilatory pattern induced by DAME; 3) a ventilatory withdrawal reaction may occur after a receptor-agonist interaction of short duration; and 4) although enkephalins can modulate ventilation and the breathing pattern in a major way, these data provide no evidence suggesting that this modulation is tonic.     

Effects of acute hyperbaric oxygenation on respiratory control in cats

We studied ventilatory responsiveness to hypoxia and hypercapnia in anesthetized cats before and after exposure to 5 atmospheres absolute O2 for 90-135 min. The acute hyperbaric oxygenation (HBO) was terminated at the onset of slow labored breathing. Tracheal airflow, inspiratory (TI) and expiratory (TE) times, inspiratory tidal volume (VT), end-tidal PO2 and PCO2, and arterial blood pressure were recorded simultaneously before and after HBO. Steady-state ventilation (VI at three arterial PO2 (PaO2) levels of approximately 99, 67, and 47 Torr at a maintained arterial PCO2 (PaCO2, 28 Torr) was measured for the hypoxic response. Ventilation at three steady-state PaCO2 levels of approximately 27, 36, and 46 Torr during hyperoxia (PaO2 450 Torr) gave a hypercapnic response. Both chemical stimuli significantly stimulated VT, breathing frequency, and VI before and after HBO. VT, TI, and TE at a given stimulus were significantly greater after HBO without a significant change in VT/TI. The breathing pattern, however, was abnormal after HBO, often showing inspiratory apneusis. Bilateral vagotomy diminished apneusis and further prolonged TI and TE and increased VT. Thus a part of the respiratory effects of HBO is due to pulmonary mechanoreflex changes.