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.

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.

Alkaline shift in lumbar and intracranial CSF in man after 5 days at high altitude

1976 ◽  
Vol 41 (1) ◽  
pp. 93-97 ◽  
Author(s):  
R. B. Weiskopf ◽  
R. A. Gabel ◽  
V. Fencl
Keyword(s):  
Blood Flow ◽  
Cerebrospinal Fluid ◽  
High Altitude ◽  
Sea Level ◽  
Jugular Bulb ◽  
Alveolar Ventilation ◽  
Simulated Altitude ◽  
Healthy Male ◽  
Alkaline Shift ◽  
Breathing Room

In six healthy male volunteers at sea level (PB 747–759 Torr), we measured pH and PCO2 in cerebrospinal fluid (CSF), and in arterial and jugular bulb blood; from these data we estimated PCO2 (12) and pH for the intracranial portion of CSF. The measurements were repeated after 5 days in a hypobaric chamber (PB 447 Torr). Both lumbar and intracranial CSF were significantly more alkaline at simulated altitude than at sea level. Decrease in[HCO3-] IN lumbar CSF at altitude was similar to that in blood plasma. Bothat sea level and at high altitude, PCO2 measured in the lumbar CSF was higher than that estimated for the intracranial CSF. At altitude, hyperoxia, incomparison with breathing room air, resulted in an increase in intracranialPCO2, and a decrease in the estimated pH in intracranial CSF. With hyperoxia at altitude, alveolar ventilation was significantly higher than during sea-level hyperoxia or normoxia, confirming that a degree of acclimatization hadoccurred. Changes in cerebral arteriovenous differences in CO2, measuredinthree subjects, suggest that cerebral blood flow may have been elevated after 5 days at altitude.

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.

Peripheral chemoreceptors in health and disease

2004 ◽  
Vol 96 (1) ◽  
pp. 359-366 ◽  
Author(s):  
Nanduri R. Prabhakar ◽  
Ying-Jie Peng
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Defense Mechanism ◽  
Experimental Models ◽  
Cellular Mechanisms ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Oxygen Homeostasis ◽  
Arterial Blood ◽  
Carotid Bodies

Peripheral chemoreceptors (carotid and aortic bodies) detect changes in arterial blood oxygen and initiate reflexes that are important for maintaining homeostasis during hypoxemia. This mini-review summarizes the importance of peripheral chemoreceptor reflexes in various physiological and pathophysiological conditions. Carotid bodies are important for eliciting hypoxic ventilatory stimulation in humans and in experimental animals. In the absence of carotid bodies, compensatory upregulation of aortic bodies as well as other chemoreceptors contributes to the hypoxic ventilatory response. Peripheral chemoreceptors are critical for ventilatory acclimatization at high altitude. They also contribute in part to the exercise-induced hyperventilation, especially with submaximal and heavy exercise. During pregnancy, hypoxic ventilatory sensitivity increases, perhaps due to the actions of estrogen and progesterone on chemoreceptors. Augmented peripheral chemoreceptors have been implicated in early stages of recurrent apneas, congestive heart failure, and certain forms of hypertension. It is likely that chemoreceptors tend to maintain oxygen homeostasis and act as a defense mechanism to prevent the progression of the morbidity associated with these diseases. Experimental models of recurrent apneas, congestive heart failure, and hypertension offer excellent opportunities to unravel the cellular mechanisms associated with altered chemoreceptor function.

Pulmonary gas exchange in humans exercising at sea level and simulated altitude

1986 ◽  
Vol 61 (1) ◽  
pp. 260-270 ◽  
Author(s):  
P. D. Wagner ◽  
G. E. Gale ◽  
R. E. Moon ◽  
J. R. Torre-Bueno ◽  
B. W. Stolp ◽  
...  
Keyword(s):  
Gas Exchange ◽  
Arterial Pressure ◽  
Sea Level ◽  
Pulmonary Arterial Pressure ◽  
Minute Ventilation ◽  
Statistical Significance ◽  
Random Order ◽  
Normal Subjects ◽  
Simulated Altitude ◽  
Pulmonary Arterial

In a previous study of normal subjects exercising at sea level and simulated altitude, ventilation-perfusion (VA/Q) inequality and alveolar-end-capillary O2 diffusion limitation (DIFF) were found to increase on exercise at altitude, but at sea level the changes did not reach statistical significance. This paper reports additional measurements of VA/Q inequality and DIFF (at sea level and altitude) and also of pulmonary arterial pressure. This was to examine the hypothesis that VA/Q inequality is related to increased pulmonary arterial pressure. In a hypobaric chamber, eight normal subjects were exposed to barometric pressures of 752, 523, and 429 Torr (sea level, 10,000 ft, and 15,000 ft) in random order. At each altitude, inert and respiratory gas exchange and hemodynamic variables were studied at rest and during several levels of steady-state bicycle exercise. Multiple inert gas data from the previous and current studies were combined (after demonstrating no statistical difference between them) and showed increasing VA/Q inequality with sea level exercise (P = 0.02). Breathing 100% O2 did not reverse this increase. When O2 consumption exceeded about 2.7 1/min, evidence for DIFF at sea level was present (P = 0.01). VA/Q inequality and DIFF increased with exercise at altitude as found previously and was reversed by 100% O2 breathing. Indexes of VA/Q dispersion correlated well with mean pulmonary arterial pressure and also with minute ventilation. This study confirms the development of both VA/Q mismatch and DIFF in normal subjects during heavy exercise at sea level. However, the mechanism of increased VA/Q mismatch on exercise remains unclear due to the correlation with both ventilatory and circulatory variables and will require further study.

Oxygen transport to exercising leg in chronic hypoxia

1988 ◽  
Vol 65 (6) ◽  
pp. 2592-2597 ◽  
Author(s):  
P. R. Bender ◽  
B. M. Groves ◽  
R. E. McCullough ◽  
R. G. McCullough ◽  
S. Y. Huang ◽  
...  
Keyword(s):  
Blood Flow ◽  
Sea Level ◽  
Chronic Hypoxia ◽  
Peripheral Resistance ◽  
Hemoglobin Concentration ◽  
Barometric Pressure ◽  
Ambient Air ◽  
Leg Blood Flow ◽  
State Cycle ◽  
O2 Delivery

Residence at high altitude could be accompanied by adaptations that alter the mechanisms of O2 delivery to exercising muscle. Seven sea level resident males, aged 22 +/- 1 yr, performed moderate to near-maximal steady-state cycle exercise at sea level in normoxia [inspired PO2 (PIO2) 150 Torr] and acute hypobaric hypoxia (barometric pressure, 445 Torr; PIO2, 83 Torr), and after 18 days' residence on Pikes Peak (4,300 m) while breathing ambient air (PIO2, 86 Torr) and air similar to that at sea level (35% O2, PIO2, 144 Torr). In both hypoxia and normoxia, after acclimatization the femoral arterial-iliac venous O2 content difference, hemoglobin concentration, and arterial O2 content, were higher than before acclimatization, but the venous PO2 (PVO2) was unchanged. Thermodilution leg blood flow was lower but calculated arterial O2 delivery and leg VO2 similar in hypoxia after vs. before acclimatization. Mean arterial pressure (MAP) and total peripheral resistance in hypoxia were greater after, than before, acclimatization. We concluded that acclimatization did not increase O2 delivery but rather maintained delivery via increased arterial oxygenation and decreased leg blood flow. The maintenance of PVO2 and the higher MAP after acclimatization suggested matching of O2 delivery to tissue O2 demands, with vasoconstriction possibly contributing to the decreased flow.

Effect of temperature on central chemical control of ventilation in the alligator Alligator mississippiensis

1993 ◽  
Vol 179 (1) ◽  
pp. 261-272
Author(s):  
L. G. Branco ◽  
S. C. Wood
Keyword(s):  
Fourth Ventricle ◽  
Ventilatory Response ◽  
Pulmonary Ventilation ◽  
Gas Mixtures ◽  
Alligator Mississippiensis ◽  
Effect Of Temperature ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Ph Values ◽  
Arterial Ph

Central chemoreceptor function was assessed in unanesthetized alligators, Alligator mississippiensis, at body temperatures of 15, 25 and 35 degrees C. Two experiments were performed. In the first experiment, the fourth ventricle was perfused with mock cerebrospinal fluid (CSF) solutions of different pH values (7.1-7.9). Changes in pulmonary ventilation were evaluated with a pneumotachograph and arterial pH (pHa) was measured. Perfusion with low-pH solutions increased ventilation and arterial pH. Perfusion with high-pH solutions decreased ventilation and arterial pH. Mock CSF pH had a greater effect at higher temperatures. In the second experiment, the relative contributions of central and peripheral chemoreceptor drive to breathing were evaluated using hypercapnic gas mixtures to stimulate both central and peripheral chemoreceptors. Hypercapnia caused an increase in ventilation which was larger at higher temperatures. To stimulate only the peripheral chemoreceptors, the same hypercapnic gas mixtures were applied while the CSF pH of the fourth ventricle was kept constant by perfusion with a mock CSF solution. This reduced significantly the ventilatory response induced by hypercapnia. These data indicate that, regardless of the temperature, central chemoreceptors play a major role in the ventilatory regulation of the alligator. The change in pHa with temperature is compatible with the alphastat hypothesis.

Adaptation of cardiac myosin and creatine kinase to chronic hypoxia: role of anorexia and hypertension

1997 ◽  
Vol 272 (4) ◽  
pp. H1690-H1695 ◽  
Author(s):  
M. Pissarek ◽  
X. Bigard ◽  
P. Mateo ◽  
C. Y. Guezennec ◽  
J. A. Hoerter
Keyword(s):  
Pulmonary Hypertension ◽  
Creatine Kinase ◽  
Hypobaric Hypoxia ◽  
Chronic Hypoxia ◽  
Specific Activity ◽  
Cardiac Myosin ◽  
Simulated Altitude ◽  
Biochemical Basis ◽  
Threefold Increase

The effects of chronic hypobaric hypoxia (CHH, 28 days, simulated altitude 5,500 m) on the cardiac expression of myosin heavy chain (MHC) and creatine kinase (CK) was studied in rat left (LV) and right (RV) ventricle. To separate the effects of hypoxia from its associated perturbations, anorexia and pulmonary hypertension (resulting in RV hypertrophy), CHH animals were compared with normoxic controls (C) and with rats restricted in food supply (pair fed, PF). In RV, the increased proportion of beta-MHC in CHH (20 +/- 3%) vs. C (7 +/- 2%, P < 0.01) and vs. PF (12 +/- 2%, P < 0.05) rats was mainly attributed to hypertension. In contrast, the higher beta-MHC of CHH (23 +/- 2%) vs. C (13 +/- 2%, P < 0.05) in LV was mainly ascribed to anorexia (PF = 21 +/- 3%, not significant). A major contribution of anorexia was also evidenced in the isozymic profile of CK; anorexia accounted for a 25% decrease in mito-CK specific activity in LV, whereas hypertension partly accounted for the threefold increase in BB-CK in RV. CHH specifically induced a twofold rise in LV BB-CK. This suggests that both the expression of slow myosin, improving the economy of contraction, and the changes in CK isozymic profile could provide a biochemical basis for the CHH resistance to ischemia.

Ventilatory effects of acetazolamide in cats during hypoxemia

1992 ◽  
Vol 72 (5) ◽  
pp. 1717-1723 ◽  
Author(s):  
L. J. Teppema ◽  
F. Rochette ◽  
M. Demedts
Keyword(s):  
Steady State ◽  
Ventilatory Response ◽  
Significant Rise ◽  
Hypoxic Ventilatory Response ◽  
Peripheral Chemoreceptor ◽  
Peripheral Chemoreceptors ◽  
Relative Contribution ◽  
Ventilatory Effects ◽  
Arterial Po2 ◽  
Mean Alveolar Pco2

In normoxemic cats, acetazolamide (ACTZ) has been shown to cause a large rise in ventilation (VE) but a decrease in peripheral chemoreceptor activity. The relative contribution of the peripheral chemoreceptors to ventilation is higher during hypoxemia than during normoxemia. Therefore, what are the effects of ACTZ during steady-state hypoxemia? The aims of this study in anesthetized cats were 1) to study the effect of ACTZ (50 mg/kg iv) on mean hypoxemic [arterial PO2 (PaO2) approximately 6 kPa] ventilation and 2) to study the effect of ACTZ on the isocapnic hypoxic ventilatory response. In the first study, in six cats with an inspiratory CO2 fraction of 0, ACTZ led to an insignificant rise in mean VE of 119 ml.min-1.kg-1 after 1 h. In five other cats maintained at an inspiratory CO2 fraction of 0.015, ACTZ resulted in a significantly larger response in VE (268 and 373 ml.min-1.kg-1 after 1 and 2 h, respectively). In the second study, before infusion in five cats, an isocapnic fall in mean PaO2 from 13 to 4.7 kPa led to a significant rise in mean VE of 385 ml.min-1.kg-1; 1 h later, the response (at the same mean alveolar PCO2) was reduced to an insignificant rise of 38 ml.min-1.kg-1. Before infusion four other cats showed a significant rise in mean VE of 390 ml.min-1.kg-1 when mean PaO2 was lowered isocapnically from 12.4 to 6.8 kPa; 2 h after infusion, an isocapnic fall in mean PaO2 from 13.9 to 7.2 kPa led to an insignificant rise of 112 ml.min-1.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

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