Patterned cardiovascular responses to sleep and nonrespiratory arousals in a porcine model

Patients with obstructive sleep apnea experiencemarked cardiovascular changes with apnea termination.Based on this observation, we hypothesized that sudden sleep disruptionis accompanied by a specific, patterned hemodynamic response, similarto the cardiovascular defense reaction. To test this hypothesis, werecorded mean arterial blood pressure, heart rate, iliac blood flow andvascular resistance, and renal blood flow and vascular resistance infive pigs instrumented with chronic sleep electrodes. Cardiovascularparameters were recorded during quiet wakefulness, duringnon-rapid-eye-movement and rapid-eye-movement sleep, and duringspontaneous and induced arousals. Iliac vasodilation (iliac vascularresistance decreased by 29.6 ± 4.1% of baseline) associatedwith renal vasoconstriction (renal vascular resistance increased by10.3 ± 4.0%), tachycardia (heart rate increase: +23.8 ± 3.1%), and minimal changes in mean arterial blood pressure were themost common pattern of arousal response, but other hemodynamic patternswere observed. Similar findings were obtained in rapid-eye-movementsleep and for acoustic and tactile arousals. In conclusion, spontaneousand induced arousals from sleep may be associated with simultaneousvisceral vasoconstriction and hindlimb vasodilation, but the responseis variable.

     

Arousal response to upper airway obstruction in young lambs: comparison of nasal and tracheal occlusion

Experiments were done on seven lambs to determine if site of occlusion--nasal versus tracheal--influences the cardiopulmonary and arousal responses from sleep to upper airway obstruction. Each lamb was anesthetized and instrumented for sleep staging and measurements of heart rate and arterial hemoglobin oxygen saturation. A tracheostomy was also done and a fenestrated tracheostomy tube placed in the trachea. Prior to an experiment, A 5F balloon-tipped catheter was inserted through the decannulation cannula into the tracheostomy tube so that tracheal occlusions could be accomplished by inflating the balloon. In addition, a 5F balloon-tipped catheter was inserted into the inlet of a pre-formed silicone mask sealed to the animals snout with silicone rubber foam so that nasal occlusions could be accomplished by inflating the balloon. During an experiment, measurements were made in quiet sleep and in active sleep during control periods of tidal breathing and during experimental periods of nasal or tracheal occlusion. Upper airway obstruction was terminated by deflating the balloon once the animal aroused from sleep. Arousal occurred sooner following nasal occlusion than during tracheal occlusion in quiet sleep; 64 percent of arousals occurred within five seconds of nasal occlusion whereas only 14 percent of arousals occurred within five seconds of tracheal occlusion in quiet sleep. In addition, SaO2 and heart rate decreased more before arousal following tracheal occlusion than following nasal occlusion. However, there was not a significant effect of site of obstruction on time to arousal or the change in SaO2 before arousal in active sleep.(ABSTRACT TRUNCATED AT 250 WORDS)     

Occlusion of the upper airway does not augment the cardiovascular response to arousal from sleep in humans.

The cardiovascular response to an arousal from sleep at the termination of an obstructive apnea is more than double that to a spontaneous arousal. We investigated the hypothesis that stimulation of respiratory mechanoreceptors, by inspiring against an occluded airway during an arousal from sleep, augments the accompanying cardiovascular response. Arousals (>10 s) from stage 2 sleep were induced by a 1-s auditory tone (85 dB) during a concomitant 1-s inspiratory occlusion (O) and without an occlusion [i.e., control arousal (C)] in 15 healthy men (mean +/- SE: age, 25 +/- 1 yr). Arousals were associated with a significant increase in mean arterial blood pressure (MAP) at 4 s (P < 0.001) and a significant decrease in R-R interval at 3 s (P < 0.001). However, the magnitude of the cardiovascular response was not different during C compared with O (MAP: C, 86 +/- 3 to 104 +/- 3 mmHg; O, 86 +/- 3 to 105 +/- 3 mmHg; P = 0.99. R-R interval: C, 1.12 +/- 0.03 to 0.89 +/- 0.04 s; O, 1.11 +/- 0.02 to 0.87 +/- 0.02 s, P = 0.99). Ventilation significantly increased during arousals under both conditions at the second breath (P < 0.001); this increase was not different between the two conditions (C: 4.40 +/- 0.29 to 6.76 +/- 0.61 l/min, O: 4.35 +/- 0.34 to 7.65 +/- 0.73 l/min; P = 0.31). We conclude that stimulation of the respiratory mechanoreceptors by transient upper airway occlusion is unlikely to interact with the arousal-related autonomic outflow to augment the cardiovascular response in healthy young men.     

Patients with obstructive sleep apnea have an abnormal peripheral vascular response to hypoxia.

Patients with obstructive sleep apnea (OSA) have been reported to have an augmented pressor response to hypoxic rebreathing. To assess the contribution of the peripheral vasculature to this hemodynamic response, we measured heart rate, mean arterial pressure (MAP), and forearm blood flow by venous occlusion plethysmography in 13 patients with OSA and in 6 nonapneic control subjects at arterial oxygen saturations (Sa(O(2))) of 90, 85, and 80% during progressive isocapnic hypoxia. Measurements were also performed during recovery from 5 min of forearm ischemia induced with cuff occlusion. MAP increased similarly in both groups during hypoxia (mean increase at 80% Sa(O(2)): OSA patients, 9 +/- 11 mmHg; controls, 12 +/- 7 mmHg). Forearm vascular resistance, calculated from forearm blood flow and MAP, decreased in controls (mean change -37 +/- 19% at Sa(O(2)) 80%) but not in patients (mean change -4 +/- 16% at 80% Sa(O(2))). Both groups decreased forearm vascular resistance similarly after forearm ischemia (maximum change from baseline -85%). We conclude that OSA patients have an abnormal peripheral vascular response to isocapnic hypoxia.     

Ascending pathways mediating somatoautonomic reflexes in exercising dogs

The ascending spinal pathways mediating somatocardiovascular reflexes during exercise were studied in unanesthetized dogs by placing lesions in the lumbar spinal cord. After training to run on a treadmill with hindlimbs only, 20 dogs were anesthetized and instrumented using sterile surgical techniques. To chronically record heart rate and arterial blood pressure, the aorta was cannulated via the omocervical artery. To test the intactness of descending spinal sympathetic pathways, reflex pressor responses to baroreceptor hypotension were produced by bilateral carotid arterial occlusion using pneumatic vessel occluders placed around the common carotid arteries. To generate transient ischemic exercise (120 s), a pneumatic occluder was placed around the left iliac artery. Eight to 10 days after instrumentation, blood pressure and heart rate were monitored at rest and during hindlimb running with and without simultaneous iliac arterial occlusion. The modest pressor response and tachycardia elicited by hindlimb exercise were markedly augmented by simultaneous hindlimb ischemia (i.e., iliac arterial occlusion). Lesion placement in the dorsolateral sulcus area and the dorsolateral funiculus at L2 significantly reduced the blood pressure and heart rate responses to simultaneous exercise occlusion. The cardiovascular responses to nonischemic exercise and bilateral carotid arterial occlusion were not altered by such spinal sections. It is concluded that in the dog the ascending spinal pathways mediating cardiovascular responses to ischemic exercise are located in the lateral funiculus, including the dorsolateral sulcus area and dorsolateral funiculus.     

Evaluation of muscle metaboreflex function through graded reduction in forearm blood flow during rhythmic handgrip exercise in humans

Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Our aim was to determine the muscle metaboreflex threshold and gain in humans by creating an open-loop relationship between active muscle blood flow and hemodynamic responses during a rhythmic handgrip exercise. Eleven healthy subjects performed the exercise at 5 or 15% of maximal voluntary contraction (MVC) in random order. During the exercise, forearm blood flow (FBF), which was continuously measured using Doppler ultrasound, was reduced in five steps by manipulating the inner pressure of an occlusion cuff on the upper arm. The FBF at each level was maintained for 3 min. The initial reductions in FBF elicited no hemodynamic changes, but once FBF fell below a threshold, mean arterial blood pressure (MAP) and heart rate (HR) increased and total vascular conductance (TVC) decreased in a linear manner. The threshold FBF during the 15% MVC trial was significantly higher than during the 5% MVC trial. The gain was then estimated as the slope of the relationship between the hemodynamic responses and FBFs below the threshold. The gains for the MAP and TVC responses did not differ between workloads, but the gain for the HR response was greater in the 15% MVC trial. Our findings thus indicate that increasing the workload shifts the threshold for the muscle metaboreflex to higher blood flows without changing the gain of the reflex for the MAP and TVC responses, whereas it enhances the gain for the HR response.     

Comparison of arousal responses to tracheal and face mask occlusions in sleeping newborn piglets.

The arousal responses after occlusion of the airway at the mid-trachea were compared with the responses after occlusion of the airway in a face mask in chronically instrumented 3- to 5-day-old piglets. For each site of occlusion arousal latency was significantly longer from active sleep than from quiet sleep. There was a significant increase in the frequency of early arousals after face mask occlusions compared with tracheal occlusions in both sleep states. During quiet sleep the frequency of arousal by 1 s after occlusion was 0.55 with face mask occlusions compared with 0.28 with tracheal occlusion (P less than 0.01). During active sleep the frequency of arousal by 3 s after a face mask occlusion was 0.32 compared with 0.08 after tracheal occlusion (P less than 0.05). Arousal from quiet sleep occurred before changes in arterial oxygen saturation. During active sleep mean saturation at arousal was not different between face mask and tracheal occlusions. Exposure of the upper airway to the pressures generated during airway occlusions results in earlier arousal in both quiet and active sleep, indicating a potential role for upper airway mechanoreceptors in initiating arousal in the newborn piglet.     

Cardiovascular responses to exercise in the rat: role of corticotropin-releasing factor

The effects of intracerebroventricular (icv) administration of a corticotropin-releasing factor (CRF) receptor antagonist, alpha-helical CRF, on systemic and regional hemodynamic adjustments to exercise were studied in conscious rats. On consecutive days, rats received saline icv, alpha-helical CRF icv, and no treatment 30 min before treadmill exercise (TMX). Increases in heart rate (HR) and mean arterial pressure (MAP) in response to TMX (16.1-28.6 m/min) were similar after icv administration of saline or no treatment. In rats receiving saline icv or no treatment, estimated vascular resistance increased in the mesenteric and renal regions and declined in the iliac (hindlimb) region. After icv administration of alpha-helical CRF9-41, HR and MAP responses during TMX were significantly attenuated. In addition, TMX-induced elevations of estimated mesenteric vascular resistance and iliac blood flow velocity were blunted after CRF receptor blockade. These altered cardiovascular and hemodynamic responses were ultimately reflected in the animals' compromised ability to run. The results suggest that the central nervous system actions of endogenous CRF are necessary for the full expression of the cardiovascular adjustments to TMX in the conscious rat.     

Differential arterial blood flow response of splanchnic and renal organs during low-intensity cycling exercise in women

To investigate the regional hemodynamic responses of abdominal arteries at the onset of exercise and to focus on their transient responses, eight female subjects (21-30 yr) performed ergometer cycling exercise at 40 W for 4 min in a semi-supine position. Mean blood velocities (MBVs) in the right renal (RA), superior mesenteric (SMA), and splenic (SA) arteries were measured by pulsed echo-Doppler ultrasonography, with beat-by-beat measurements of heart rate (HR) and mean arterial pressure (MAP). The vascular resistance index (RI) of each artery was calculated from MBV/MAP. MAP (76 +/- 9 to 83 +/- 8 mmHg at 4 min) and HR (60 +/- 7 to 101 +/- 9 beats/min at 4 min) increased during exercise (P < 0.05). The MBV of RA and SA rapidly decreased after the onset of exercise (30 s; -19 +/- 5% and -19 +/- 12%, respectively), reaching -27 +/- 7% and -27 +/- 15% at the end of exercise (P < 0.05). RI did not change during the initial 30 s of exercise, reflecting a reduction in MAP, and increased toward the end of the exercise (+55 +/- 21% and +59 +/- 39%, respectively). In contrast, both the MBV and RI in the SMA remained constant throughout the exercise. The results indicate that, whereas the responses of renal and splenic vessels changed similarly throughout the protocol, the vascular response of SMA that mainly supplies blood to the intestinal tract was unchanged during exercise. We, therefore, conclude that low-intensity cycling exercise resulted in differential blood flow responses in arteries supplying the abdominal organs.     

Induction of upper airway occlusion in sleeping individuals with subatmospheric nasal pressure

In collapsible biologic conduits, occlusion and cessation of flow occur when upstream pressure falls below a critical pressure (Pcrit). To examine the relationship between Pcrit and the development of upper airway occlusion, we examined the relationship between maximal inspiratory airflow and nasal pressure in seven normal subjects during sleep. At varying levels of subatmospheric pressure applied to a nasal mask during non-rapid-eye-movement (NREM) sleep, maximal inspiratory airflow decreased in proportion to the level of nasal pressure. When nasal pressure fell below a Pcrit, subjects demonstrated upper airway occlusions terminated by arousals. In these normal subjects, the upper airway Pcrit was found to be -13.3 +/- 3.2 (SD) cmH2O. In four subjects who sustained sleep while nasal pressure remained below the Pcrit, recurrent occlusive apneas were demonstrated. The relationship between maximal inspiratory airflow and nasal pressure in each subject was fit by linear regression and demonstrated upper airway Pcrit at the zero-flow intercept that were not significantly different from those observed experimentally. These data demonstrate that the normal human upper airway during sleep is characterized by a negative Pcrit and that occlusion may be induced when nasal pressure is decreased below this Pcrit.     

Intrarenal infusion of bradykinin elicits a pressor response in conscious rats via a B2-receptor mechanism.

Bradykinin (BK) is a peptide known to activate afferent nerve fibers from the kidney and elicit reflex changes in the cardiovascular system. The present study was specifically designed to test the hypothesis that bradykinin B2 receptors mediated the pressor responses elicited during intrarenal bradykinin administration. Pulsed Doppler flow probes were positioned around the left renal artery to measure renal blood flow (RBF). A catheter, to permit selective intrarenal administration of BK, was advanced into the proximal left renal artery. The femoral artery was cannulated to measure mean arterial pressure (MAP). MAP, heart rate (HR), and RBF were recorded from conscious unrestrained rats while five-point cumulative dose-response curves during an intrarenal infusion of BK (5-80 microg x kg(-1) x min(-1)) were constructed. Intrarenal infusion of BK elicited dose-dependent increases in MAP (maximum pressor response, 26+/-3 mmHg), accompanied by a significant tachycardia (130+/-18 beats/min) and a 28% increase in RBF. Ganglionic blockade abolished the BK-induced increases in MAP (maximum response, -6+/-5 mmHg), HR (maximum response 31+/-14 beats/min), and RBF (maximum response, 7+/-2%). Selective intrarenal B2-receptor blockade with HOE-140 (50 microg/kg intrarenal bolus) abolished the increases in MAP and HR observed during intrarenal infusion of BK (maximum MAP response, -2+/-3 mmHg; maximum HR response, 15+/-11 beats/min). Similarly, the increases in RBF were prevented after HOE-140 treatment. In fact, after HOE-140, intrarenal BK produced a significant decrease in RBF (22%) at the highest dose of BK. Results from this study show that the cardiovascular responses elicited by intrarenal BK are mediated predominantly via a B2-receptor mechanism.     

Wave intensity in the ascending aorta: effects of arterial occlusion

We examine the effects of arterial occlusion on the pressure, velocity and the reflected waves in the ascending aorta using wave intensity analysis. In 11 anaesthetised, open-chested dogs, snares were used to produce total arterial occlusion at 4 sites: the upper descending aorta at the level of the aortic valve (thoracic); the lower thoracic aorta at the level of the diaphragm (diaphragm); the abdominal aorta between the renal arteries (abdominal) and the left iliac artery, 2 cm downstream from the aorta iliac bifurcation (iliac). Pressure and flow in the ascending aorta were measured, and data were collected before and during the occlusion. During thoracic and diaphragm occlusions a significant increase in mean aortic pressure (46% and 23%) and in wave speed (25% and 10%) was observed, while mean flow rate decreased significantly (23% and 17%). Also, the reflected compression wave arrived significantly earlier (45% and 15%) and its peak intensity was significantly greater (257% and 125%), all compared with control. Aortic occlusion distal to the renal arteries, however, caused an indiscernible change in the pressure and velocity waveforms, and in the intensities and timing of the waves in the forward and backward directions. The measured pressure and velocity waveforms are the result of the interaction between the heart and the arterial system. The separated pressure, velocity and wave intensity are required to provide information about arterial hemodynamic such as the timing and magnitude of the forward and backward waves. The net wave intensity is simpler to calculate but provides information only about the predominant direction of the waves and can be misleading when forward and backward waves of comparable magnitudes are present simultaneously.     

The effect of short-term sleep fragmentation produced by intense auditory stimuli on the arousal response to upper airway obstruction in lambs

Upper airway obstruction is recognized to cause apnoea in newborns as well as in adults. However, very little is known about factors that influence the arousal response from sleep during upper airway obstruction in newborns. Experiments were therefore done to investigate the effect of short-term sleep fragmentation on the arousal response to upper airway obstruction in six lambs aged 8 to 14 days. Each lamb was anaesthetized and instrumented for recordings of electrocorticogram, electro-oculogram, nuchal and diaphragm electromyograms and measurements of systemic arterial blood pressure and oxygen saturation (fiberoptic catheter oximeter). A tracheostomy was done and a fenestrated tracheostomy tube placed in the trachea. Experiments were not done before the third postoperative day. During a study, a 5F balloon tipped catheter was inserted into the tube so that airflow could be obstructed by inflating the balloon. Measurements were made during 30 s control periods and during experimental periods of upper airway obstruction in at least three epochs of quiet sleep and active sleep in each animal. These measurements were made following a period of uninterrupted sleep and repeated following a 36-42 h period of sleep fragmentation. Sleep fragmentation was produced by 30 s of noise separated by 2 min of quiet. Sleep fragmentation produced small but statistically significant increases in the time to arousal and decreases in the haemoglobin oxygen saturation at arousal during upper airway obstruction in quiet sleep but not active sleep. However, these changes, although consistent, were small and are of questionable biological significance. Therefore, I believe it is unlikely that short-term sleep fragmentation per se significantly impairs the arousal response to respiratory stimuli in newborns.     

Response of genioglossus muscle activity to nasal airway occlusion in normal sleeping adults

To determine the combined effect of increased subatmospheric upper airway pressure and withdrawal of phasic volume feedback from the lung on genioglossus muscle activity, the response of this muscle to intermittent nasal airway occlusion was studied in 12 normal adult males during sleep. Nasal occlusion at end expiration was achieved by inflating balloon-tipped catheters located within the portals of a nose mask. No seal was placed over the mouth. During nose breathing in non-rapid-eye-movement (NREM) sleep, nasal airway occlusion resulted in multiple respiratory efforts before arousal. Mouth breathing was not initiated until arousal. Phasic inspiratory genioglossus activity was present in eight subjects during NREM sleep. In these subjects, comparison of peak genioglossus inspiratory activity on the first three occluded efforts to the value just before occlusion showed an increase of 4.7, 16.1, and 28.0%, respectively. The relative increases in peak genioglossus activity were very similar to respective increases in peak diaphragm activity. Arousal was associated with a large burst in genioglossus activity. During airway occlusion in rapid-eye-movement (REM) sleep, mouth breathing could occur without a change in sleep state. In general, genioglossus responses to airway occlusion in REM sleep were similar in pattern to those in NREM sleep. A relatively small reflex activation of upper airway muscles associated with a sudden increase in subatmospheric pressure in the potentially collapsible segment of the upper airway may help compromise upper airway patency during sleep.     

Pulmonary vascular resistance after cessation of positive end-expiratory pressure

This report describes the pulmonary vascular response of infant lamb lung to abrupt cessation of positive end-expiratory pressure (PEEP) during volume-regulated continuous positive-pressure breathing (CPPB). In an intact, endobronchially ventilated preparation, the increase in left lung blood flow (QL) after abrupt cessation of 11 Torr left lung PEEP was found to be gradual, although peak airway pressure (Pmax) fell promptly from 36 to 14 Torr; 49% of the increase in QL occurred greater than 10 s after cessation of PEEP. Recruitment of zone I vasculature that had been created by balloon occlusion of the left pulmonary artery was found to occur promptly after balloon deflation. Isolated neonatal lamb lungs, perfused at constant flow rate, showed similar persistent elevation of pulmonary vascular resistance after cessation of 15 Torr PEEP, although Pmax fell abruptly from 39 to 12 Torr. This hysteresis was eliminated by calcium channel blockade with verapamil, and the magnitude of the change in pulmonary arterial pressure after either application or cessation of PEEP was reduced (25 and 26%, respectively). These observations suggest that, during CPPB, lung stretch alters neonatal pulmonary vascular tone or, by causing calcium channel-dependent lung volume hysteresis, modulates pulmonary vascular resistance. This interaction exaggerates the effect of airway pressure changes on pulmonary vascular resistance during mechanical ventilation.     

Sleep states alter ventral medullary surface responses to blood pressure challenges

Ventral medullary surface (VMS) activity declines during rapid eye movement (REM) sleep, suggesting a potential for reduced VMS responsiveness to blood pressure challenges during that state. We measured VMS neural activity, assessed as changes in reflected 660-nm wavelength light, during pressor and depressor challenges within sleep/waking states in five adult, unrestrained, unanesthetized cats and in two control cats. Phenylephrine elevated blood pressure and elicited an initial VMS activity decline and a subsequent rise in VMS activity in all states, although the initial decline during quiet sleep occurred only in rostral placements. Phasic REM periods elicited a momentary recovery from the evoked activity rise, and arousals diminished the overall elevation in activity. A sodium nitroprusside depressor challenge increased VMS activity more in REM sleep than in quiet sleep, with the increase being even less in waking. Enhanced responses to depressor challenges during REM sleep suggest a loss of dampening of evoked activity during that state; state-related differential baroreflex sensitivity may result from sleep-waking changes in VMS responses to blood pressure challenges.     

Cardiac changes during arousals from non-REM sleep in healthy volunteers

Our aim was to evaluate cardiac changes evoked by spontaneous and sound-induced arousals from sleep. Cardiac responses to spontaneous and auditory-induced arousals were recorded during overnight sleep studies in 28 young healthy subjects (14 males, 14 females) during non-rapid eye movement sleep. Computerized analysis was applied to assess beat-to-beat changes in heart rate, atrio-ventricular conductance, and ventricular repolarization from 30 s before to 60 s after the auditory tone. During both types of arousals, the most consistent change was the increase in the heart rate (in 62% of spontaneous and in 89% of sound-induced arousals). This was accompanied by an increase or no change in PR interval and by a decrease or no change in QT interval. The magnitude of all cardiac changes was significantly higher for tone-induced vs. spontaneous arousals (mean +/- SD for heart rate: +9 +/- 8 vs. +13 +/- 9 beats per min; for PR prolongation: 14 +/- 16 vs. 24 +/- 22 ms; for QT shortening: -12 +/- 6 vs. -20 +/- 9 ms). The prevalence of transient tachycardia and PR prolongation was also significantly higher for tone-induced vs. spontaneous arousals (tachycardia: 85% vs. 57% of arousals, P < 0.001; PR prolongation: 51% vs. 25% of arousals, P < 0.001). All cardiac responses were short-lasting (10-15 s). We conclude that cardiac pacemaker region, conducting system, and ventricular myocardium may be under independent neural control. Prolongation of atrio-ventricular delay may serve to increase ventricular filling during arousal from sleep. Whether prolonged atrio-ventricular conductance associated with increased sympathetic outflow to the ventricular myocardium contributes to arrhythmogenesis during sudden arousal from sleep remains to be evaluated.     

Carotid baroreflex pressor responses at rest and during exercise: cardiac output vs. regional vasoconstriction

The arterial baroreflex mediates changes in arterial pressure via reflex changes in cardiac output (CO) and regional vascular conductance, and the relative roles may change between rest and exercise and across workloads. Therefore, we quantified the contribution of CO and regional vascular conductances to carotid baroreflex-mediated increases in mean arterial pressure (MAP) at rest and during mild to heavy treadmill exercise (3.2 kph; 6.4 kph, 10% grade; and 8 kph, 15% grade). Dogs (n = 8) were chronically instrumented to measure changes in MAP, CO, hindlimb vascular conductance, and renal vascular conductance in response to bilateral carotid occlusion (BCO). At rest and at each workload, BCO caused similar increases in MAP (average 35 +/- 2 mmHg). In response to BCO, neither at rest nor at any workload were there significant increases in CO; therefore, the pressor response occurred via peripheral vasoconstriction. At rest, 10.7 +/- 1.4% of the rise in MAP was due to vasoconstriction in the hindlimb, whereas 4.0 +/- 0.7% was due to renal vasoconstriction. Linear regression analysis revealed that, with increasing workloads, relative contributions of the hindlimb increased and those of the kidney decreased. At the highest workload, the decrease in hindlimb vascular conductance contributed 24.3 +/- 3.4% to the pressor response, whereas the renal contribution decreased to only 1.6 +/- 0.3%. We conclude that the pressor response during BCO was mediated solely by peripheral vasoconstriction. As workload increases, a progressively larger fraction of the pressor response is mediated via vasoconstriction in active skeletal muscle and the contribution of vasoconstriction in inactive beds (e.g., renal) becomes progressively smaller.     

Arousal responses to airway occlusion in sleeping dogs: comparison of nasal and tracheal occlusions

Previous studies have shown that the arousal threshold to hypoxia, hypercapnia, and tracheal occlusions is greatly depressed in rapid-eye-movement (REM) sleep compared with slow-wave sleep (SWS). The aim of this study was to compare the arousal thresholds in SWS and REM sleep in response to an upper airway pressure stimulus. We compared the waking responses to tracheal (T) vs. nasal (N) occlusion in four unanesthetized, naturally sleeping dogs. The dogs either breathed through a tracheal fistula or through the snout using a fiberglass mask. A total of 295 T and 160 N occlusion tests were performed in SWS and REM sleep. The mean time to arousal during N and T tests was variable in the same dog and among the dogs. The mean time to arousal in SWS-tracheal occlusion was longer than that in N tests in only two of the four dogs. The total number of tests inducing arousal within the first 15 s of SWS-nasal occlusion tests was significantly more than that of T tests (N: 47%; T: 27%). There was a marked depression of arousal within the initial 15 s of REM sleep in T tests compared with N tests (N: 21%; T: 0%). The frequency of early arousals in REM tests was less than that of SWS for both N and T tests. The early arousal in N occlusion is in sharp contrast to the well-described depressed arousal responses to hypoxia, hypercapnia, and asphyxia. This pattern of arousal suggests that the upper airway mechanoreceptors may play an important role in the induction of an early arousal from nasal occlusion.