Ventilatory control in peripheral chemoreceptor-denervated ponies during chronic hypoxemia

1976 ◽  
Vol 41 (6) ◽  
pp. 878-885 ◽  
Author(s):  
H. V. Forster ◽  
G. E. Bisgard ◽  
B. Rasmussen ◽  
J. A. Orr ◽  
D. D. Buss ◽  
...  
Keyword(s):  
Sea Level ◽  
Hypobaric Hypoxia ◽  
Acute Hypoxia ◽  
Inhibitory Influence ◽  
Ventilatory Control ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Chronic Hypoxemia ◽  
Insight Into

The present study was designed to provide further insight into the role of the carotid and aortic chemoreceptors in ventilatory (VE) acclimatization during sojourn at altitude. Measurements were made: 1) on 10 ponies near sea level(SL, 740 Torr) under normal conditions, 2) on 6 of these at SL following chemoreceptor denervation (CD), and 3) subsequently on all 10 during 4 days of hypobaric hypoxia (PaO2 = 40–47 Torr). CD resulteo in hypoventilation at SL (deltaPaCO2 = d8 Torr, P less than 0.05), and it prevented hyperventilation normally observed with injection of NaCN and acute exposure to hypoxia (less than 1 h). In contrast, hyperventilation was evidentin normal ponies during acute hypoxia (deltaPaCO2 = -6.7 Torr). Ventilationincreased in both groups between the 2nd and 8th h of hypoxia (deltaPaCO2 from 1 h = -4 Torr, P less than 0.05). This change, a common characteristic of acclimatization, persisted throughout 4 days of hypoxia in the normal ponies. However, in the CD ponies this change was evident consistently only through the 12th h and after the 44 h hyperventilation was no longer evident.We conclude that the peripheral chemoreceptors are essential in ponies for normal VE acclimatization to this degree of hypoxemia. Two additional findingsin CD ponies suggest the presence of a CNS inhibitory influence on theVEcontrol center during chronic hypoxemia. First, acute hyperoxygenation on the 4th day of hypoxemia induced hyperventilation (deltaPaCO2 = -5 Torr, P less than 0.05). Second, again on the 4th day and during hyperoxygenation, VE responsiveness to CO2 and doxapram HCl was greater than at sea level.

Ventilatory interaction between hypoxia and [H+] at chemoreceptors of man

1975 ◽  
Vol 39 (2) ◽  
pp. 292-296 ◽  
Author(s):  
R. A. Gabel ◽  
R. B. Weiskopf
Keyword(s):  
Experimental Design ◽  
High Altitude ◽  
Sea Level ◽  
Acute Hypoxia ◽  
Simulated Altitude ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Central Chemoreceptors ◽  
Progressive Hypoxia ◽  
The Mean

By measuring ventilation during isocapnic progressive hypoxia, peripheral chemoreceptor sensitivity to acute hypoxia (deltaV40) was measured in five normal young men under four sets of conditions: 1) at sea level at the subject's resting PCO2, 2) at sea level with PCO2 5 Torr above resting PCO2, 3) after 24 h at a simulated altitude of 4,267 m (PB = 447 Torr) at the subject's resting PCO2 measured during acute hyperoxia, and 4) after 24 h at high altitude, with PCO2 elevated to the subject's sea-level resting PCO2. With this experimental design, we were able to systematically vary the PCO2 and [H+] at the peripheral and central chemoreceptors of man. When mean pHa was decreased from 7.424 to 7.377 without significant change in PACO2, the mean deltaV40 increased from 18.0 to 55.9 1/min. Conversely, when mean PACO2 was altered between 33.8 and 41.6 Torr with pHa held relatively constant, the mean deltaV40 did not change. This suggests that it is the H+ and not CO2 which interacts with hypoxia in stimulating the ventilation of man. An additional finding was that the intrinsic sensitivity of the peripheral chemoreceptors to acute hypoxia did not change during 24 h of acclimatization to high altitude.

Effect of peripheral chemoreceptor denervation on acclimatization of goats during hypoxia

1981 ◽  
Vol 50 (2) ◽  
pp. 392-398 ◽  
Author(s):  
H. V. Forster ◽  
G. E. Bisgard ◽  
J. P. Klein
Keyword(s):  
Sea Level ◽  
Chronic Hypoxia ◽  
Alveolar Ventilation ◽  
Simulated Altitude ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Carotid Chemoreceptors ◽  
Co2 Output

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.

Cerebrospinal fluid in man native to high altitude

1964 ◽  
Vol 19 (2) ◽  
pp. 319-321 ◽  
Author(s):  
J. W. Severinghaus ◽  
A. Carceleń B.
Keyword(s):  
Cerebrospinal Fluid ◽  
High Altitude ◽  
Sea Level ◽  
Regulation Of Respiration ◽  
Acid Base ◽  
Peripheral Chemoreceptor ◽  
Arterial Blood ◽  
Blood Ph ◽  
The Difference

CSF pH was shown in a prior report to remain essentially constant during 8 days of acclimatization to 3,800 m. In order to further evaluate the possible role of CSF acid-base equilibria in the regulation of respiration, 20 Peruvian Andean natives were studied at altitudes of 3,720–4,820 m. In ten subjects at 3,720 m, means were: CSF pH 7.327, Pco2 43, HCO3- 21.5, Na+ 136, K+ 2.6, Cl- 124, lactate 30 mg/100 ml. Arterial blood: pH 7.43, Pco2 32.5, HCO3- 21.3, Na+ 136, K+ 4.2, Cl- 107, hematocrit 49, SaOO2 89.6. In six subjects at 4,545 m and four at 4,820 m CSF values were not significantly different; mean arterial Pco2 was 32.6 and 32.3, respectively. The only significant variations with altitude were the expected lowering of PaOO2 to 47 and 43.5 mm Hg, and of SaOO2 to 84.2 and 80.7, and increase of hematocrit to 67% and 75%, respectively. The natives differed from recently acclimatized sea-level residents in showing less ventilation (higher Pco2) in response to the existing hypoxia, and less alkaline arterial blood. The difference appears to relate to peripheral chemoreceptor response to hypoxia rather than central medullary chemoreceptor. respiratory regulation at high altitude; chronic acclimatization to altitude; peripheral chemoreceptor response to hypoxia; CSF and medullary respiratory chemoreceptors Submitted on June 12, 1963

Peripheral chemoreceptors respond to hypoxia in pontine-lesioned fetal lambs in utero

1993 ◽  
Vol 75 (3) ◽  
pp. 1027-1034 ◽  
Author(s):  
B. M. Johnston ◽  
P. D. Gluckman
Keyword(s):  
Acute Hypoxia ◽  
In Utero ◽  
Fetal Life ◽  
Peripheral Chemoreceptors ◽  
Fetal Breathing Movements ◽  
Pontine Lesion ◽  
Regulation Of Breathing ◽  
Peripheral Arterial ◽  
Stimulation Of

Acute hypoxia inhibits, rather than stimulates, fetal breathing movements (FBM), but there has been controversy as to the activity and role of the peripheral arterial chemoreceptors in the regulation of breathing movements in the unanesthetized fetus in utero. However, after midcollicular brain stem transection or lateral pontine lesion, hypoxia causes FBM to become continuous and stimulated in rate and depth. To determine whether this stimulatory response involves peripheral chemoreceptors, we used a two-stage approach to examine the response to hypoxia after peripheral chemodenervation in lateral pontine-lesioned fetal lambs. The lateral pons was lesioned at 119–121 days, and the response to hypoxia was tested in the unanesthetized fetus 4 days afterward. Fourteen fetuses in which hypoxia stimulated FBM underwent either peripheral chemodenervation or sham denervation in a second operation. Hypoxia had no effect when the fetus was tested 4–5 days after peripheral chemodenervation, and the basal incidence of FBM was significantly lower. The stimulatory response was unchanged by sham denervation. We conclude that the peripheral chemoreceptors are active in fetal life and that they mediate the stimulation of FBM seen in response to hypoxia after removal of the lateral pontine inhibition. In addition, after pontine lesion there is evidence of tonic chemoreceptor-mediated influences on FBM, which are normally overriden in the intact fetus.

scholarly journals The regulation role of carotid body peripheral chemoreceptors in physiological and pathophysiological conditions

2016 ◽  
Vol 69 (11-12) ◽  
pp. 385-390 ◽  
Author(s):  
Biljana Lazovic ◽  
Mirjana Zlatkovic-Svenda ◽  
Tijana Durmic ◽  
Zoran Stajic ◽  
Vesna Djuric ◽  
...  
Keyword(s):  
The Body ◽  
Internal Organs ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Oxygen Homeostasis ◽  
Pathological Conditions ◽  
Obstructive Sleep ◽  
Functional Sympatholysis ◽  
The Common

Introduction. The major oxygen sensors in the human body are peripheral chemoreceptors, also known as interoreceptors-as connected with internal organs, located in the aortic arch and in the body of the common carotid artery. Chemoreceptor function under physiological conditions. Stimulation of peripheral chemoreceptors during enviromental hypoxia causes a reflex-mediated increased ventilation, followed by the increase of the muscle sympatic activity, aiming to maintain tissue oxygen homeostatis, as well as glucosae homeostatis. Besides that, peripheral chemoreceptors interact with central chemoreceptors, responsible for carbon dioxide changes, and they are able to modulate each other. Chemoreceptor function in pathophysiological conditions. Investigations of respiratory function in many pathological processes, such as hypertension, obstructive sleep apnea, congestive heart failure and many other diseases that are presented with enhanced peripheral chemosensitivity and impaired functional sympatholysis ultimately determine the peripheral chemoreceptor role and significance of peripheral chemoreceptors in the process of those pathological conditions development. Considering this, the presumed influence of peripheral chemoreceptors is important in patients having the above mentioned pathology. Conclusion. The importance and the role of peripheral chemoreceptors in the course of the breathing control is still controversial, despite many scientific attempts to solve this problem. The main objective of this review is to give the latest data on the peripheral chemoreceptor role and to highlight the importance of peripheral chemoreceptors for maintaining of oxygen homeostasis in pateints with hypoxia caused by either physiological or pathological conditions.

scholarly journals Hypobaric Hypoxia Induces Hypercoagulability Due to an Increase in Microparticles

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3549-3549
Author(s):  
Cécile H. Kicken ◽  
Marisa Ninivaggi ◽  
Joke Konings ◽  
Martijn Moorlag ◽  
Leslie In het Panhuis ◽  
...  
Keyword(s):  
Heart Rate ◽  
Sea Level ◽  
Platelet Activation ◽  
Whole Blood ◽  
Hypobaric Hypoxia ◽  
Statistical Significance ◽  
Acute Mountain Sickness ◽  
Peak Height ◽  
Mountain Sickness

Abstract Studies investigating the role of hypoxia on coagulation, either by going to high altitude or after a long-haul flight, reveal contrasting results. Previous work from our group suggests that the cellular part of the blood is involved in causing a prothrombotic phenotype. Therefore this study investigated the effect of hypobaric hypoxia on blood coagulation, focusing on the role of cellular components. After approval from the local medical ethics committee, 16 healthy participants (aged 20 to 50 years old) were included in this study. Exclusion criteria were a history of cardiovascular disease or pulmonary disease, impaired mobility, and medication known to interfere with coagulation. Participants ascended by cable car to 3,883 meters above sea level, after acclimatizing to altitude for 6 days. At 50 meters and 3,883 meters above sea level, blood was drawn and vital signs (SpO2, heart rate) and the Lake Louise acute mountain sickness questionnaire (LLQ) were recorded. The following tests were performed on whole blood: hemoglobin (Hb), hematocrit (Ht), leucocyte count (L), platelet count (PC) and mean platelet volume (MPV); thrombin generation (TG) in whole blood (WB-TG) with 0.5 pM tissue factor (TF); platelet activation test (PAc-T) triggered by adenosine diphosphate (ADP), thrombin receptor activating peptide (TRAP) and collagen related peptide (CRP) in end concentrations of respectively 10 µM, 30 µM and 1 µg ml-1. The remainder of the blood was centrifuged to obtain platelet rich plasma (PRP) (once for 15 minutes at 230 g) and platelet poor plasma (PPP) (twice for 10 minutes at 2,821 g). PRP was used to test PRP-TG (1 pM TF) and plasma was used for PPP-TG (1 pM TF) and microparticles (MP)-TG (0 pM TF). The paired t-test with p <0.05 was used to determine statistical significance within participants. At 3,883 meters above sea level, oxygen saturation decreased and heart rate increased significantly. LLQ scores revealed mild acute mountain sickness (AMS) symptoms. One participant was withdrawn from the study at 3,030 meters due to moderate AMS. After applying TG in PPP, PRP and whole blood, we found that peak height and endogenous thrombin potential (ETP) were increased. Interestingly, we found a decrease in platelet activation and a decreased MPV. To find an explanation for the increased TG in the different media, we performed a TG assay specially designed to detect microparticles. As with the PPP-TG, PRP-TG and WB-TG, we found an increase in ETP and peak height, proving increased content of MPs. In conclusion, we found that exposure to hypobaric hypoxia increased TG in PPP, PRP and in whole blood. In contrast we found that platelet activation was decreased, indicating that platelets do not play a role in hypoxia-induced hypercoagulability. The increase in peak and ETP in the MP-sensitive TG assay indicates that MPs play a major role in hypoxia-induced hypercoagulability. Disclosures De Laat: Synapse bv: Employment.

Effect of dichloroacetate on PaCO2 responses to hypoxia in awake goats

1996 ◽  
Vol 80 (1) ◽  
pp. 176-181 ◽  
Author(s):  
E. A. Aaron ◽  
H. V. Forster ◽  
T. F. Lowry ◽  
M. J. Korducki ◽  
P. J. Ohtake
Keyword(s):  
Lactic Acidosis ◽  
Ventilatory Response ◽  
Acute Hypoxia ◽  
Lactic Acid Production ◽  
Saline Infusion ◽  
Hypoxic Ventilatory Response ◽  
Arterial Pco2 ◽  
Arterial Po2 ◽  
Insight Into

To gain insight into the role of cerebral lactic acidosis in the hypoxic ventilatory response, we administered dichloroacetate (DCA) intravenously to inhibit lactic acid production in 7 awake goats (40-70 kg) during 0.5 h of normoxia (inspired O2 fraction = 0.209) and 5 h of poikilocapnic hypoxia (inspired O2 fraction = 0.125). On separate days, these goats were also studied with a continuous saline infusion (18 ml/h iv) during 5 h of normoxia and hypoxia. Arterial PCO2 (PaCO2) did not change during the 5-h normoxic period. During hypoxia, arterial PO2 fell significantly (P < 0.05) with both saline (from 111.3 to 39.0 Torr) and DCA (from 111.8 to 42.0 Torr) infusions. PaCO2 decreased (P < 0.05) during the first 0.5 h of both the saline and DCA hypoxia protocols. The decrease was greater (P < 0.05) during DCA (from 36.5 to 33.5 Torr) than during saline infusion (from 37.7 to 36.3 Torr). With saline infusion, PaCO2 decreased (P < 0.05) by 4.9 Torr between 0.5 and 5.0 h of hypoxia. However, over this period of DCA hypoxia, PaCO2 did not significantly decrease (P = 0.05). We conclude that the enhanced hyperventilation with DCA during acute hypoxia is consistent with brain lactic acidosis depressing breathing. Absence of additional significant hyperventilation after 0.5 h of DCA hypoxia suggests that a time-dependent alleviation of brain lactic acidosis might normally contribute to ventilatory acclimatization to hypoxia.

Differential role of the paraventricular nucleus of the hypothalamus in modulating the sympathoexcitatory component of peripheral and central chemoreflexes

2005 ◽  
Vol 289 (3) ◽  
pp. R789-R797 ◽  
Author(s):  
Maram K. Reddy ◽  
Kaushik P. Patel ◽  
Harold D. Schultz
Keyword(s):  
Paraventricular Nucleus ◽  
Potassium Cyanide ◽  
Reflex Response ◽  
Nerve Activity ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Arterial Blood ◽  
Central Chemoreceptors ◽  
Stimulation Of

In the present study we investigated the involvement of the hypothalamic paraventricular nucleus (PVN) in the modulation of sympathoexcitatory reflex activated by peripheral and central chemoreceptors. We measured mean arterial blood pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and phrenic nerve activity (PNA) before and after blocking neurotransmission within the PVN by bilateral microinjection of 2% lidocaine (100 nl) during specific stimulation of peripheral chemoreceptors by potassium cyanide (KCN, 75 μg/kg iv, bolus dose) or stimulation of central chemoreceptors with hypercapnia (10% CO2). Typically stimulation of peripheral chemoreceptors evoked a reflex response characterized by an increase in MAP, RSNA, and PNA and a decrease in HR. Bilateral microinjection of 2% lidocaine into the PVN had no effect on basal sympathetic and cardiorespiratory variables; however, the RSNA and PNA responses evoked by peripheral chemoreceptor stimulation were attenuated ( P < 0.05). Bilateral microinjection of bicuculline (50 pmol/50 nl, n = 5) into the PVN augmented the RSNA and PNA response to peripheral chemoreceptor stimulation ( P < 0.05). Conversely, the GABA agonist muscimol (0.2 nmol/50 nl, n = 5) injected into the PVN attenuated these reflex responses ( P < 0.05). Blocking neurotransmission within the PVN had no effect on the hypercapnia-induced central chemoreflex responses in carotid body denervated animals. These results suggest a selective role of the PVN in processing the sympathoexcitatory and ventilatory component of the peripheral, but not central, chemoreflex.

Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP

1992 ◽  
Vol 67 (01) ◽  
pp. 111-116 ◽  
Author(s):  
Marcel Levi ◽  
Jan Paul de Boer ◽  
Dorina Roem ◽  
Jan Wouter ten Cate ◽  
C Erik Hack
Keyword(s):  
Monoclonal Antibodies ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Fold Increase ◽  
Fibrinolytic System ◽  
Plasminogen Activation ◽  
Plasminogen Activator Activity ◽  
Insight Into

SummaryInfusion of desamino-d-arginine vasopressin (DDAVP) results in an increase in plasma plasminogen activator activity. Whether this increase results in the generation of plasmin in vivo has never been established.A novel sensitive radioimmunoassay (RIA) for the measurement of the complex between plasmin and its main inhibitor α2 antiplasmin (PAP complex) was developed using monoclonal antibodies preferentially reacting with complexed and inactivated α2-antiplasmin and monoclonal antibodies against plasmin. The assay was validated in healthy volunteers and in patients with an activated fibrinolytic system.Infusion of DDAVP in a randomized placebo controlled crossover study resulted in all volunteers in a 6.6-fold increase in PAP complex, which was maximal between 15 and 30 min after the start of the infusion. Hereafter, plasma levels of PAP complex decreased with an apparent half-life of disappearance of about 120 min. Infusion of DDAVP did not induce generation of thrombin, as measured by plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III (TAT) complex.We conclude that the increase in plasminogen activator activity upon the infusion of DDAVP results in the in vivo generation of plasmin, in the absence of coagulation activation. Studying the DDAVP induced increase in PAP complex of patients with thromboembolic disease and a defective plasminogen activator response upon DDAVP may provide more insight into the role of the fibrinolytic system in the pathogenesis of thrombosis.

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