Peripheral Chemoreceptor Denervation Research Articles

Denervation of Peripheral Chemoreceptors Decreases Heart Rate During Bilateral Carotid Occlusion in Unanesthetized Rats

Bilateral carotid occlusion (BCO) has been used as a maneuver to cause global reflex activation of the sympathetic nervous system in both unanesthetized and anesthetized animals. It is known that the cardiovascular effects of BCO involve not only the baroreceptors but also the chemoreceptors. However, to our knowledge, the cardiovascular responses produced during BCO in the absence of the peripheral chemoreceptors has not been studied in unanesthetized rats. Therefore, the present study aimed to examine the responses of arterial pressure and heart rate to BCO in unanesthetized rats with selective denervation of peripheral chemoreceptors. Under ketamine/xylazine anesthesia Wistar Hannover rats were implanted with pneumatic cuffs around the common carotid arteries for BCO. Catheters were also inserted into the femoral artery and vein for blood pressure recording and drug administration (to test the effectiveness of denervation), respectively. Rats were divided into two groups: INTACT (n = 7) and chemoreceptors removed (CHEMO‐X; n = 8). In the next day, BCO was performed for 20s in unanesthetized rats. As compared to baseline condition BCO promoted, in both groups, an increase in systolic (INTACT: 133 ± 5 vs. 211 ± 8 mmHg; CHEMO‐X: 142 ± 3 vs. 210 ± 4 mmHg), diastolic (INTACT: 92 ± 5 vs. 145 ± 7 mmHg; CHEMO‐X: 100 ± 2 vs. 140 ± 3 mmHg) and mean arterial pressure (INTACT: 111 ± 5 vs. 173 ± 7 mmHg; CHEMO‐X: 119 ± 2 vs. 168 ± 3 mmHg). Of note, the increase in arterial pressure was similar in both groups; however, while BCO did not promote a change of the heart rate in the INTACT group (321 ± 9 vs. 318 ± 7 bpm), the rats from the QUIMIO‐X group displayed significant bradycardia (352 ± 7 vs. 315 ± 14 bpm). These findings indicate that the presence of the peripheral chemoreceptors did not affect the hypertensive response elicited by BCO, but their absence determined a reflex bradycardia during this occlusive maneuver. This mechanism deserves further investigation.Support or Funding InformationFAPESP (Proc. 2017/05163‐6 and 2013/20549‐7).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Carotid chemoafferent activity is not necessary for all phrenic long-term facilitation following acute intermittent hypoxia

Phrenic long-term facilitation (pLTF) is a form of respiratory plasticity induced by acute intermittent hypoxia (AIH) or episodic carotid chemoafferent neuron activation. Surprisingly, residual pLTF is expressed in carotid denervated rats. However, since carotid denervation eliminates baroreceptor feedback and causes profound hypotension during hypoxia in anesthetized rats, potential contributions of these uncontrolled factors or residual chemoafferent neuron activity to residual pLTF cannot be ruled out. Since ATP is necessary for hypoxic carotid chemotransduction, we tested the hypothesis that functional peripheral chemoreceptor denervation (with intact baroreceptors) via systemic P2X receptor antagonism blocks hypoxic phrenic responses and AIH-induced pLTF in anesthetized rats. Pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 100 mg/kg i.v.), a non-selective P2X receptor antagonist, was administered to anesthetized, vagotomized, paralyzed and ventilated male Sprague-Dawley rats prior to AIH (3, 5 min episodes of 10% O(2); 5 min intervals). Although PPADS strongly attenuated the short-term hypoxic phrenic response (20 ± 4% vs. 113 ± 15% baseline; P < 0.001), pLTF was reduced but not eliminated 60 min post-AIH (25 ± 4% vs. 51 ± 11% baseline; n = 8 and 7, respectively; P < 0.002). Thus, AIH initiates residual pLTF out of proportion to the diminished hypoxic phrenic response and chemoafferent neuron activation. Although the mechanism of residual pLTF following functional chemo-denervation remains unclear, possible mechanisms involving direct effects of hypoxia on the CNS are discussed.

Respiratory Alterations Due to Chronic Long-Term Intermittent Hypobaric Hypoxia in Rabbits: Importance of Peripheral Chemoreceptors

None of the studies carried out so far investigated the effect of denervation of peripheral chemoreceptors on basal ventilation and respiratory responses to acute hypoxia in subjects exposed to chronic long-term intermittent hypobaric hypoxia (CLTIHH). We aimed to research (i) the effect of CLTIHH (430 mmHg, 5 h/day, 5 days/week, 5 weeks) on basal ventilation and respiratory responses to hypoxia and (ii) the effects of CLTIHH on central respiratory mechanisms after peripheral chemodenervation. Sixteen adult albino rabbits were divided into two groups: CLTIHH (n = 8) and control (n = 8). The tidal volume (V(T)) and respiratory frequency (f/min) were initially recorded in both groups and respiratory minute volume (V(E)) was calculated. PaO(2), PaCO(2), and pHa values were determined. The initial values of f/min and V(E) in CLTIHH group were significantly higher than that of control group. After exposure to hypoxic gas mixture (8% O(2)-92% N(2)), the elevations in f/min, V(T), and V(E) in CLTIHH group were significantly higher than those of control group. After denervation of peripheral chemoreceptors, the decrease in V(E) in CLTIHH group was found to be significantly less than that of control group. When the animals in control group were allowed to breathe hypoxic gas mixture, f/min, V(T,) and V(E) decreased significantly and hypoxic depression was obtained. In contrast, hypoxic depression did not occur in the CLTIHH group. Our results suggested that CLTIHH increases the basal ventilation and hypoxic respiratory responses and that enhanced ventilatory responses were due not only to the augmentation of peripheral chemoreceptor activity but also to the augmentation of central respiratory activity.

Peripheral neural modulation of endotoxin-induced hyperventilation.

To delineate the role of the peripheral neural reflexes involved in modulating hyperventilation during endotoxemia. A prospective, randomized, controlled, multigroup study. Research animal laboratory. Adult Sprague-Dawley rats (n=43; 354+/-24 g) of either gender. Eight rats received a sham operation on their vagus, carotid sinus, and aortic nerves before the administration of a saline vehicle to serve as the time control. In the endotoxin group, 11 rats received a sham operation before endotoxin challenge. The remaining 24 rats received bilateral vagotomy (n=8), perivagal capsaicin treatment (n=8), or denervation of peripheral chemoreceptors (n=8) before endotoxin challenge. After the breathing pattern returned to a steady state, endotoxin (L-4130, serotype 0111, B4 lipopolysaccharide; 50 mg/kg) was injected into the vein. The rat's respiration was then monitored continuously for 5 hrs or until the animal died. The respiratory rate and tidal volume did not change over the 5-hr observation period in the time control group. In the endotoxin group, the respiratory rate increased significantly from baseline (135.4%) 2 hrs after endotoxin challenge and increased persistently until the rats died. The tidal volume increased gradually to < or =132.8% of baseline 4 hrs after endotoxin challenge. Bilateral cervical vagotomy and perineural capsaicin treatment of the vagus nerves eliminated the tachypnea response to endotoxin injection. Denervation of the peripheral chemoreceptor accentuated the hyperventilation response to endotoxin, and resulted in the shortest survival time. Both lung vagal C-fiber afferents and peripheral chemoreceptors are involved in modulating the hyperventilation response after endotoxin challenge in rat models. Stimulation of vagal C-fiber afferents increased the respiratory rate. Conversely, the role of peripheral chemoreceptors was to restrain the hyperventilatory response and these receptors may play a protective role during endotoxemia.

Systemic hypoxia facilitates somato-cardiac sympathetic A- and C-reflexes in anesthetized rats

In rats anesthetized with urethane, electrical stimuli applied to tibial nerve afferents produced a somato-sympathetic A-reflex of 41 ± 2 (mean ± SEM) ms latency and C-reflex of 210 ± 13 ms latency recorded in the left inferior cardiac sympathetic nerve. Hypoxia was induced by switching room air to nitrogen/oxygen gas mixture in the inspiratory line reducing end-tidal oxygen from about 18% F ET o 2 to 10% F ET o 2 and 6% F ET o 2 for 60 s, respectively. During 6% F ET o 2 hypoxia, the amplitude of the somato-cardiac sympathetic A-reflex increased significantly to 138 ± 13% of the control, and that of the C-reflex increased to 186 ± 18% of the control. During 10% F ET o 2 hypoxia, the A-reflex increased insignificantly to 117 ± 8%; the amplitude of the C-reflex was augmented significantly to 149 ± 11% of the control. Peripheral carotid chemoreceptor denervation abolished the facilitatory effects of systemic hypoxia. It is concluded that carotid chemoreceptor stimulation enhances the responsiveness of somato-cardiac sympathetic excitatory reflexes originating in the hind limb receptors.

Reflex changes in breathing pattern evoked by inhalation of wood smoke in rats

The acute ventilatory response to inhalation of wood smoke was studied in 58 anesthetized Sprague-Dawley rats. Wood smoke (approximately 6 ml) was inhaled spontaneously via a tracheal cannula. Within the first two breaths of smoke inhalation, either a slowing of respiration (SR) (n = 39) or an augmented inspiration (AI) (n = 19) was elicited consistently in each rat. The SR was primarily due to a prolongation of expiratory duration, whereas the AI was characterized by a two-step inspiratory flow leading to an exceedingly large tidal volume. Both initial responses, usually accompanied by bradycardia and hypotension, were reduced by inhaling smoke at a decreased concentration. After these initial responses, a delayed tachypnea developed and reached its peak 6-10 breaths after inhalation of smoke. Both the SR and AI were completely abolished by bilateral cervical vagotomy. In contrast, the delayed tachypneic response was not prevented by vagotomy but was significantly attenuated by denervation of peripheral chemoreceptors. We conclude that the initial responses to inhalation of several tidal breaths of wood smoke are mediated through vagal bronchopulmonary afferents, whereas the delayed tachypnea may involve nonvagal mechanisms that include a stimulation of peripheral chemoreceptors.

Effect of medullary lesions, vagotomy and carotid sinus denervation on fetal breathing

Chronically prepared fetal sheep were subjected to bilateral surface lesions of the Area “S” on the ventrolateral medulla and/or to peripheral chemoreceptor denervation by section of the vagus, sinus or both nerves. Sino-aortic denervation or Area “S” lesions reduced the incidence of fetal breathing (FB) for several days. Area “S” lesions also disrupted the pattern of GB; diaphragmatic EMG activity initially was mostly tonic and then of very high frequency, up to 7 Hz. Incidence and pattern of FB generally recovered by 7 days, but mean Ti was reduced in Area “S” lesioned fetuses (0.14 ± 0.01 sec) compared to nonlesioned fetuses (0.19 ± 0.01 sec ( P < 0.0001). Respiratory sensitivity to CO 2 was variable but not different between control, denervated, and Area “S” lesioned groups. Eight of eight fetuses with Area “S” lesions were unable to initiate breathing at birth, but three sham operated fetuses were born normally. These data suggest that the classical peripheral and central chemoreceptors have a negligible influence on the control of FB, and that breathing activity in the fetus is mediated by a different mechanism than during postnatal life.

Effect of chemoreceptor stimulation on the periodicity of renal sympathetic nerve activity in anesthetized cats

The effect of chemoreceptor stimulation, with asphyxia (1 min), hypoxia (2 min) or hypercapnia (2 min), on the periodicity of synchronized renal sympathetic nerve activity (RNA) was examined in anesthetized cats before and after peripheral chemoreceptor and baroreceptor denervation. RNA was filtered between 50–3000 Hz, rectified and integrated. Time intervals, less than 500 ms, between synchronized interburst intervals were measured and used to produce periodicity histograms. Under control normoxia two major periodicities were evident, a Tc rhythm between 6 and 17 c/s comprising 34 ± 5% (± SE) of measured intervals and a Tb rhythm between 2 and 6 c/s with a 66% probability. The mean periods of Tc and Tb were 110 + 6 ms and 299 ± 7 ms respectively. The periodicity distribution and mean Tc and Tb rhythms for RNA discharge under various chemoreceptor stimulations were not significantly changed despite significant increases in arterial blood pressure in all cases. The amplitude and overall number of synchronized RNA peaks were however increased with chemoreceptor stimulation. When asphyxia was applied under a constant arterial pressure the periodicity of synchronized RNA still was not significantly altered. Baroreceptor and peripheral chemoreceptor denervation led to an increase in the probability of the Tc mode and reduction in the Tb mode, once again the application of chemoreceptor stimulation did not significantly alter the frequency distribution of synchronized RNA. The results indicate that chemoreceptor stimulation does not affect the 10 c/s fundamental rhythm and the stability of gate operators altering Tc/Tb proportions, although it can alter the number of active fibres and interacts with the baroreflexes to maintain RNA at elevated blood pressures. The results support our model that the Tc mode reflects a fundamental periodicity of central origin and the Tb mode a periodicity of cardiac related RNA, which is produced by the opening and closing of gate operators to the fundamental rhythm.

Effect of acute hypoxia on respiration and brain stem blood flow in the piglet

Changes in local brain stem perfusion that alter extracellular fluid Pco2 and/or [H+] near central chemoreceptors may contribute to the decrease in respiration observed during hypoxia after peripheral chemoreceptor denervation and to the delayed decrease observed during hypoxia in the newborn. In this study, we measured the changes in respiration and brain stem blood flow (BBF) during 2-4 min of hypoxic hypoxia in both intact and denervated piglets and calculated the changes in brain stem Pco2 and [H+] that would be expected to occur as a result of the changes in BBF. All animals were anesthetized, spontaneously breathing, and between 2 and 7 days of age. Respiratory and other variables were measured before and during hypoxia in all animals, and BBF (microspheres) was measured in a subgroup of intact and denervated animals at 0, 30, and 260 s and at 0 and 80 s, respectively. During hypoxia, minute ventilation increased and then decreased (biphasic response) in the intact animals but decreased only in the denervated animals. BBF increased in a near linear fashion, and calculated brain stem extracellular fluid Pco2 and [H+] decreased over the first 80 s both before and after denervation. We speculate that a rapid increase in BBF during acute hypoxia decreases brain stem extracellular fluid Pco2 and [H+], which, in turn, negatively modulate the increase in respiratory drive produced by peripheral chemoreceptor input to the central respiratory generator.

Pulmonary vascular responses to surgical chemodenervation and chemical sympathectomy in dogs.

We investigated the effects of surgical peripheral chemoreceptor denervation, chemical sympathectomy with 6-hydroxydopamine (6-OHDA), and the peripheral chemoreceptor stimulant almitrine on multipoint pulmonary arterial pressure-cardiac index (PAP/Q) plots in 30 pentobarbital sodium-anesthetized dogs ventilated alternatively in hyperoxia [fraction of inspired O2, (FIO2) = 0.4] and hypoxia (FIO2 = 0.1). A hypoxic pulmonary vasoconstriction (HPV), i.e., a hypoxia-induced increase in PAP over the entire range of Q studied, from 2 to 5 l.min-1.m-2, was elicited in all the animals. Surgical denervation of the carotid and aortic chemoreceptors in a first group of nine dogs increased PAP at the lowest Q of 2 and 3 l.min-1.min-2 in hyperoxia and increased PAP at all levels of Q in hypoxia, so that HPV was enhanced. Chemical sympathectomy in a second group of eight dogs increased PAP at all levels of Q to a comparable extent in hyperoxia and hypoxia so that HPV remained unchanged. Almitrine (8 micrograms.kg-1.min-1 iv) in a third group of eight dogs increased PAP at all levels of Q in hyperoxia but had no effect on PAP/Q plots in hypoxia, so that HPV was inhibited. Almitrine had these same pulmonary vascular effects when administered to the chemodenervated and the sympathectomized dogs. Sham operation and a 2-h delay in a final group of five dogs had no effect on hyperoxic or hypoxic PAP/Q plots. We conclude that in intact dogs 1) the sympathetic nervous system reduces both hyperoxic and hypoxic pulmonary vascular tone, 2) stimulation of the peripheral chemoreceptors inhibits HPV, and 3) almitrine has direct pulmonary vasoconstricting effects in hyperoxia but not hypoxia.

Denervation of peripheral chemoreceptors decreases breathing movements in fetal sheep

The role of the peripheral chemoreceptors in the control of fetal breathing movements has not been fully defined. To determine whether denervation of the peripheral chemoreceptors affects fetal breathing movements, we studied 14 chronically catheterized fetal sheep from 120 to 138 days of gestation. In seven fetuses the chemoreceptors were denervated by bilateral section of the vagus and carotid sinus nerves; in seven others, sham operations were performed. We compared several variables during two study periods: 0-5 and 6-13 days after operation. In the denervated fetuses there were significant decreases in the incidence and amplitude of fetal breathing movements during both study periods. There were no differences between the two groups in incidence of low-voltage electrocortical activity, arterial pH and blood gas tensions, fetal heart rate, mean arterial blood pressure, or duration of survival after operation or birth weight. We conclude that denervation of the peripheral chemoreceptors decreases fetal breathing movements. These results indicate that the peripheral chemoreceptors are active during fetal life and participate in the control of fetal breathing movements.

290 DENERVATION OF PERIPHERAL OSMORECEPTORS AND LUNG RECEPTORS DOES NOT AFFECT PRODUCTION OF TRACHEAL FLUID IN FETAL SHEEP

The factors that affect production of fetal tracheal fluid have not been completely elucidated. We studied 14 chronically catheterized fetal sheep (120-130 days) to determine if bilateral sections of the carotid sinus and vagus nerves affect production of tracheal fluid. Each fetus had ligation of the trachea and cannulation with a catheter (100 cm long, 1.5 mm I.D.) that diverted all tracheal fluid into a soft intrauterine bag. A loop of catheter was exteriorized to permit collection of fluid from the lungs and bag. Fluid was collected once daily for 6 days after surgery. Seven fetuses had bilateral sections of the carotid sinus and vagus nerves; 7 had sham operations, all fetuses had similar arterial blood gas tensions, pH and mean blood pressures and low voltage electrocortical activity. The incidence of fetal breathing movements was lower in the denervated fetuses; however the production of tracheal fluid was not significantly different except for POD# 1 (table). (Values are mean±;SD; POD=post operative day; p<0.05) We conclude that denervation of peripheral chemoreceptors and lung receptors with afferent nerves in the vagus nerve does not affect production of tracheal fluid in fetal sheep.(USPHSHL27356)

Regional hemodynamic effects of changes in PaCO 2 in the vagotomized, sino-aortic de-afferented rat

Rats were anesthetized with urethane (1.5 g/kg i.p.) paralyzed with gallamine (3 mg/kg, i.v.), artificially ventilated and the vagi, carotid sinus and aortic nerves were cut. PaCO 2 levels of 16.4 ± 0.8, 23.3 ± 1.6, 32.3 ± 1.8 and 51.9 ± 2.2 mm Hg were obtained by hyperventilation in 0%, 3%, 5% and 8% CO 2 in O 2, respectively. Radioactive microspheres labelled with 57Co or 113Sn were injected into the left ventricle and cardiac output and regional blood flows were determined by the ‘arterial reference sample’ method. Increasing PaCO 2 induced an increase in systemic arterial pressure which was predominantly due to a significant increase in total peripheral resistance, while the increase in cardiac output was much less pronounced and no changes in heart rate were observed. The effect of increasing PaCO 2 on regional vascular resistance (VR) was not uniformly distributed. CO 2 induced a dilatation in the cerebral, bronchial and hepatic artery vascular beds. Coronary VR was not affected while vasoconstriction was induced by CO 2 in the other vascular territories. This vascoconstriction was most significant in skeletal muscle, skin, pancreas, large intestine and kidneys. In most of these territories the vasoconstrictor effect of CO 2 was observed at PaCO 2 levels above 23.3 mm Hg, while between 16.4 and 23.3 mm Hg there was either no change or a decrease in VR. Propranolol and phentolamine (1 mg/kg and 10 mg/kg, i.v., respectively), which caused a 78% ± 2% adrenergic blockade, significantly reduced the CO 2 pressor and vasoconstrictor effects. Our experiments show that, after peripheral chemoreceptor denervation in the rat: (a) there is a direct relationship between PaCO 2 and VR mediated by the sympathetic nervous system over the whole range of PaCO 2 values from hypocapnia to hypercapnia, and (b) the various vascular territories contribute to a different extent to the CO 2-induced changes in total peripheral resistance.

PERIPHERAL CHEMORECEPTOR DEN ERVATICN AFFECTS FETAL BREATHING MOVEMENTS (FBM) IN SHEEP

FBM in chronic ovine fetal preparations are not affected by vagus or carotid sinus nerve sections. However, the aortic bodies may acquire respiratory chemoreceptivity after carotid body denervation. To better define the role of these chemoreceptors on the control of FBM, we chronically studied 14 fetuses; 7 had bilateral section of carotid sinus and vagus nerves and 7 had sham operations. FBM (by tracheal catheter) and electrocortical activity (ECoA) were recorded continuously after surgery. The incidence of FBM and amplitudes of tracheal pressure during 2 periods, 1-5 and 6-13 postoperative (PO) days were: [Values=X(SD); all comparisons of denerv to sham, p<0.05 except day 5.] ECoA, arterial pH, PO2, PCO2 and blood pressures were similar in both groups. Throughout this study, the daily mean incidence of FBM and tracheal pressures during FBM in the denervated group were lower than in the sham group. We conclude that total peripheral chemoreceptor denervation significantly affects the incidence and amplitudes of FBM in sheep. (USPHS HL-27356).

THE EFFECTS OF PROSTAGLAN DIN E2 (PGE2) AND MECLOFENAMATE (M) IN BREATHING MOVEMENTS IN FETAL SHEEP ARE NOT MEDIATED THROUGH PERIPHERAL CHEMORECEPTORS

PGE2 inhibits fetal breathing movements (FBM); the prostaglandin synthetase inhibitor, M, stimulates FBM. To determine if these effects are mediated through the peripheral chemoreceptors, we studied 13 chronically catheterized fetuses; 7 had bilateral sections of carotid sinus and vagus nerves; 6 had sham operations. FBM (by tracheal catheter) and electrocortical activity (ECoA) were recorded continuously. After a control (C) period (19.9±4.5h; mean±SD) we infused PGE2 (0.6±0.2 μg/kg/min) or M (0.4±0.2 mg/kg/h) for 20.0±2.1 h per infusion. Infusions were separated ≥ 48 h. The incidences and amplitudes of FBM were lower in the denervated group (Table).(values=mean±SD; °P<0.05 compared to C; ¶P<0.05 compared to Sham). However, the % change from C during infusions was similar in both groups as were the ECoA, arterial pH, PO2, PCO2 and pressures. We conclude that peripheral chemoreceptor denervation significantly affects FBM; however the effects of PGE2 and M on FBM are not mediated through the peripheral chemoreceptors. (USPHS HL-27356).

Effect of peripheral chemoreceptor denervation on acclimatization of goats during hypoxia

The purpose of this study was to determine the effect of peripheral chemoreceptor denervation on ventilatory acclimatization of goats during chronic hypoxia. After 1 h of stimulated altitude (PB 450 Torr), arterial O2 tension (PaO2) in seven normal goats averaged 42 Torr, and arterial CO2 tension (PaCO2) was 1.3 Torr below control (P less than 0.001). In these goats nearly 66% of the increase in alveolar ventilation (VA) associated with acclimatization occurred between 1.5 and 4 h of hypoxia. Acclimatization was complete by the 3rd day of hypoxia, and it caused 1) a 23% increase in VA/CO2 output (P less than 0.001); 2) a 5-Torr increase in PaO2 (P less than 0.001); and 3) a 6.5-Torr decrease in PaCO2 (P less than 0.001). Denervation of the carotid chemoreceptors in seven goats caused hypoventilation during eupnea at sea level (PaCO2 change from control +7 Torr, P less than 0.001). Denervation also attenuated but did not eliminate peripheral chemoreceptor responsiveness. No additional changes were observed following attempted denervation of the aortic chemoreceptors. After 1 h of simulated altitude (PB 530 Torr), PaO2 in the denervated goats averaged 46 Torr, and PaCO2 was increased 1.1 Torr above control (P less than 0.001). In these goats VA did not change significantly during the subsequent 3 days of hypoxia. Accordingly, we conclude that the peripheral chemoreceptors are essential for ventilatory acclimatization of goats during chronic hypoxia.

Effect of chemorceptor denervation on the pulmonary vascular response to atelectasis

Six dogs anesthetized with 30 mg/kg pentobarbital were ventilated after differential cannulation of the main stem bronchi. Following sternotomy, blood flow was monitored byelectromagnetic flow probes on the left pulmonary artery (Q l) and on the pulmonary truck or aorta (Q t). Following 10 min of bilateral 100% O 2, Q l was 37.4 ± 5.8% of Q t. When left lung actelectasis was induced whiel the right lung remained on 100% O 2, Pa O 2 remained above 75 mm Hg and Q l fell to 26.1 ± 5.0% of Q t. However, when the right lung was ventilated with room air while the left lung remained atelectatic, Pa O 2 fell to 50.0 ± 2.6 mm Hg and Q l rose to 36.7 ± 6.2% of Q t. Six dogs which had undergone peripheral chemoreceptor denervation prior to these experiments showed a similar decrease in perfusion of the atelectatic left lung when the right lung was ventilated with 100% O 2, but did not increase blood flow to the atelectatic lung during systemic hypoxemia. Thus, the increased blood flow to the atelectatic lung which occurs during systemic hypoxemia appears to be mediated by the arterial chemoreceptors.

CO2-dependent component of the neurogenic vascular tone in the cat.

Complete vascular isolation of the hindlimbs was performed in vagotomized cats under Sodium Pentobarbital anesthesia. The hindlimbs were perfused at constant flow with blood kept at a constant and physiological PO2, PCO2, and pH values by means of a specially designed pump-oxygenator system. The animals were hyperventilated with different CO2 mixtures (0%, 5%, 7% and 10% in O2) thereby changing blood gases and pH levels in the upper body but not in the hindlimb vascular bed. At body PaCO2 (mm Hg) of 13.7 +/- 1.0 (means +/- SE), 30.6 +/- 1.05, 40,4 +/- 0,9 and 58.4 +/- 2.9 the hindlimb perfusion pressure (mm Hg) was, respectively 124 +/- 7.6, 138 +/- 7.4, 156 +/- 11.9 and 187 +/- 15.1. These changes in perfusion pressure were still present after complete peripheral chemoreceptor denervation but were abolished after section of the spinal cord at the T5 level. Since hindlimb perfusion pressure fell when body PaCO2 was lowered below physiological levels it is concluded that part of the neurogenic vascular tone of the hindlimbs is maintained by a CO2 mediated stimulation of supraspinal structures.

Chemoreceptor influence on pulmonary blood flow during unilateral hypox1a in dogs

Dogs anesthetized with 30 mg/kg pentobarbital were artificially respired after differential cannulation of the main stem bronchi. Following median sternotomy. blood flow was monitored by electromagnetic flow probes on Ihe left pulmonary artery (Q L) and on the pulmonary trunk or aorta, Q-p Following 10 min of bilateral 100% O 2, Q L was 42.5 ± 7% of Qr. When 6 % O 2 was substituted as the gas mixture inspired by the left lung while the right lung remained on 100% O 2, Pa o, was above 70 mm Hg and Q, tell to 24.5+5% of Qr. Room air was then used to ventilate the right lung while the left lung remained on 6% O 2. This caused Pa O2 to fall to 42.3 ± 3 mm Hg and Q L to rise to 38.3+6% Qr. This increase in blood flow to the unilaterally hypoxic lung during systemic hypoxemia did not occur in dogs after peripheral chemoreceptor denervation. Therefore, interference with the local response to alveolar hypoxia during systemic hypoxemia appears to be mediated by the arterial chemoreceptors.

Ventilatory response in the fetal lamb following peripheral chemodenervation.

Carotid infusions of sodium cyanide solution and perfusions of hypoxemic or hypercapnic fetal blood were done before and after peripheral chemoreceptor denervation. Step changes in PaO2 ranged from -11 to -22 Torr; step changes in PaCO2 ranged from +17 to +42 Torr. The cyanide dose was 0.2 mg/kg per loop system. Control perfusions consisted of 25 ml of fetal blood without changes in pH and blood gases. A ventilatory response occurred in the majority of all experimental perfusions regardless of innervation status of the peripheral chemoreceptors. No response occurred with control perfusions. There was a marked variability in the time of onset of ventilatory activity with a delay of greater than 10 s occurring following most perfusions. These studies demonstrate that the fetus has an attenuated ventilatory response to chemical stimuli and that hypoxia stimulates ventilation in the absence of peripheral chemoreceptors.