Role of brain lactic acidosis in hypoxic depression of respiration

1988 ◽  
Vol 65 (3) ◽  
pp. 1324-1331 ◽  
Author(s):  
J. A. Neubauer ◽  
A. Simone ◽  
N. H. Edelman
Keyword(s):  
Lactic Acidosis ◽  
Base Line ◽  
Brain Hypoxia ◽  
Arterial Blood ◽  
Lactate Formation ◽  
Low Levels ◽  
End Tidal ◽  
End Tidal Co2 ◽  
Respiratory Depressant

The role of lactic acidosis of progressive brain hypoxia (PBH) as both a central chemoreceptor stimulant and a general respiratory depressant was assessed by preventing lactate formation both locally and globally with dichloroacetate (DCA). Phrenic nerve activity (PN) and ventral medullary pH (Vm pH) responses to PBH (1% CO-40% O2-balance N2) were determined in anesthetized, paralyzed, peripherally chemodenervated, vagotomized cats while fraction of end-tidal CO2 (FETCO2) and mean arterial blood pressure (MABP) were maintained constant. Topical DCA near the central chemoreceptors prevented the progressive Vm acidosis of PBH and was associated with a slightly greater depression of PN for any given level of brain hypoxia [75 +/- 12% base-line mock cerebrospinal fluid compared with 63 +/- 11% base-line topical DCA at O2 content of arterial blood (CaO2) of 7.5 ml O2/dl]. Systemic DCA also prevented the progressive acidosis of PBH and significantly altered the profile of depression with PBH. Before DCA, PBH produced a progressive reduction in PN after reducing CaO2 by 20%. After DCA, PN was not significantly depressed until CaO2 was reduced to very low levels, whereupon there was a sharp decline in PN. Before DCA, reducing CaO2 to 6 ml O2/dl reduced PN by 41 +/- 16%, whereas after DCA there was no significant reduction in PN (4 +/- 5%). We conclude that 1) lactic acidosis near the central chemosensitive regions does produce a small stimulation of respiration during PBH but that 2) the overwhelming response to central lactic acidosis of PBH is respiratory depression.

Role of tracheal and bronchial circulation in respiratory heat exchange

1985 ◽  
Vol 58 (1) ◽  
pp. 217-222 ◽  
Author(s):  
E. M. Baile ◽  
R. W. Dahlby ◽  
B. R. Wiggs ◽  
P. D. Pare
Keyword(s):  
Blood Flow ◽  
Blood Gases ◽  
Lung Parenchyma ◽  
Arterial Blood ◽  
Respiratory Heat Loss ◽  
Reference Flow ◽  
Pulmonary Arterial ◽  
End Tidal ◽  
Humidified Air

Due to their anatomic configuration, the vessels supplying the central airways may be ideally suited for regulation of respiratory heat loss. We have measured blood flow to the trachea, bronchi, and lung parenchyma in 10 anesthetized supine open-chest dogs. They were hyperventilated (frequency, 40; tidal volume 30–35 ml/kg) for 30 min or 1) warm humidified air, 2) cold (-20 degrees C dry air, and 3) warm humidified air. End-tidal CO2 was kept constant by adding CO2 to the inspired ventilator line. Five minutes before the end of each period of hyperventilation, measurements of vascular pressures (pulmonary arterial, left atrial, and systemic), cardiac output (CO), arterial blood gases, and inspired, expired, and tracheal gas temperatures were made. Then, using a modification of the reference flow technique, 113Sn-, 153Gd-, and 103Ru-labeled microspheres were injected into the left atrium to make separate measurements of airway blood flow at each intervention. After the last measurements had been made, the dogs were killed and the lungs, including the trachea, were excised. Blood flow to the trachea, bronchi, and lung parenchyma was calculated. Results showed that there was no change in parenchymal blood flow, but there was an increase in tracheal and bronchial blood flow in all dogs (P less than 0.01) from 4.48 +/- 0.69 ml/min (0.22 +/- 0.01% CO) during warm air hyperventilation to 7.06 +/- 0.97 ml/min (0.37 +/- 0.05% CO) during cold air hyperventilation.

Neurotransmitters and biphasic respiratory response to hypoxia

1984 ◽  
Vol 57 (1) ◽  
pp. 213-222 ◽  
Author(s):  
W. A. Long ◽  
E. E. Lawson
Keyword(s):  
Phrenic Nerve ◽  
Initial Increase ◽  
Base Line ◽  
Respiratory Response ◽  
Biphasic Response ◽  
Controlled System ◽  
Initial Exposure ◽  
End Tidal ◽  
Line Level ◽  
End Tidal Co2

Recent work from this laboratory (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 55:483–488, 1983) has shown that the biphasic respiratory response to hypoxia in piglets is due to changing central neural respiratory output. To test the hypothesis that either adenosine or opiatelike neurotransmitters mediate the failure to sustain hyperpnea in response to hypoxia, 12 piglets were studied ata mean age of 2.9 +/- 0.4 days (range 2–6 days). Animals were anesthetized, paralyzed, and ventilatedusing a servo-controlled system that maintained end-tidal CO2 constant. Electrical activity of the phrenic nerve was recorded as the index of breathing. An initial experimental trial of 6 min ventilation with 15% O2 was performed in all 12 piglets. Thereafter all 12 piglets were treated with aminophylline (n = 6), naloxone (n = 3), or naltrexone (n = 3) and again subjected to 15% O2. During initial exposure to hypoxia there was an initial increase in phrenic activity that was not sustained. During recovery ventilation with 100% O2, phrenic activity transiently declined below the base-line level and then gradually returned. Subsequent intravenous administration of aminophylline, naloxone, or naltrexone caused base-line phrenic activity to increase. Thereafter repeat exposures to 15% O2 were carried out. During these posttreatment trials of hypoxia, phrenic activity further increased, but the hyperventilation was again not sustained. These findings suggest it is unlikely that either adenosine or mu-endorphin neurotransmitters are the primary mediators of the biphasic response to hypoxia in newborns.

End-tidal CO2 response to low levels of inspired CO2 in awake beagle dogs

1980 ◽  
Vol 48 (6) ◽  
pp. 1077-1082 ◽  
Author(s):  
P. Reischl ◽  
D. M. Stavert ◽  
S. M. Lewis ◽  
L. C. Murdock ◽  
B. J. O'Loughlin
Keyword(s):  
Steady State ◽  
Dead Space ◽  
Resolving Power ◽  
Beagle Dogs ◽  
Co2 Response ◽  
Arterial Pco2 ◽  
Control Of Ventilation ◽  
Low Levels ◽  
End Tidal ◽  
End Tidal Co2

The steady-state end-tidal CO2 tension (PCO2) was examined during control and 1% CO2 inhalation periods in awake beagle dogs with an intact airway breathing through a low dead-space respiratory mask. A total of eight experiments were performed in four dogs, comprising 31 control observations and 23 CO2 inhalation observations. The 1% inhaled CO2 produced a significant increase in the steady-state end-tidal PCO2 comparable to the expected 1 Torr predicted from conventional CO2 control of ventilation. We conclude that 1% inhaled CO2 results in a hypercapnia. Any protocol that is to resolve the question of whether mechanisms are acting during low levels of inhaled CO2 such that ventilation increases without any change in arterial PCO2 must have sufficient resolving power to discriminate changes in gas tension in magnitude predicted from conventional (i.e., arterial PCO2) control of ventilation.

Relation between work output of respiratory muscles and end-tidal CO2 tension

1963 ◽  
Vol 18 (3) ◽  
pp. 497-504 ◽  
Author(s):  
J. Milic-Emili ◽  
J. M. Tyler
Keyword(s):  
Carbon Dioxide ◽  
Pulmonary Ventilation ◽  
Respiratory Muscles ◽  
Normal Subjects ◽  
Work Output ◽  
Inspiratory Muscles ◽  
Expiratory Muscles ◽  
End Tidal ◽  
End Tidal Co2

End-tidal CO2 tension, pulmonary ventilation, and work output of respiratory muscles were determined in six normal subjects breathing various mixtures of carbon dioxide in air, with three graded resistances added to both inspiration and expiration. In two individuals, the resistances were also added separately to inspiration or expiration. A linear relationship was found between work output of inspiratory muscles and end-tidal CO2 tension; this relationship was uninfluenced by added resistance. No consistent relationship was observed between either ventilation or work output of expiratory muscles and end-tidal CO2 tension. These results suggest that carbon dioxide controls directly the activity of inspiratory muscles alone and that the activity of expiratory muscles is only coincidentally involved. The possible role of intrinsic properties of respiratory muscles and of nervous mediation in the control of breathing is discussed. Submitted on October 22, 1962

CO2 sensitivity of cat phrenic neurogram during hypoxic respiratory depression

1988 ◽  
Vol 65 (2) ◽  
pp. 736-743 ◽  
Author(s):  
J. E. Melton ◽  
J. A. Neubauer ◽  
N. H. Edelman
Keyword(s):  
Blood Pressure ◽  
Metabolic Acidosis ◽  
Lactic Acidosis ◽  
Respiratory Depression ◽  
Separate Group ◽  
Respiratory Neurons ◽  
Co2 Response ◽  
Co2 Sensitivity ◽  
Lactate Formation ◽  
End Tidal

The CO2 response of the phrenic neurogram before and during CO-induced isocapnic brain hypoxia was studied in peripherally chemodenervated, vagotomized, paralyzed, ventilated cats with blood pressure held constant. During inhalation of 0.5% CO in 40% O2, arterial O2 content (CaO2) was reduced to 40% and minute phrenic activity to 38.4 +/- 9.4% (SE; n = 9) of prehypoxic levels, primarily due to depression of peak phrenic amplitude (PP). CO2 response, defined as the slope of the plot of PP vs. end-tidal PCO2 during CO2 rebreathing, was unaffected by phrenic depression even to the point of total suppression of phrenic activity in two cats. The effect of the tissue metabolic acidosis associated with hypoxia on phrenic CO2 sensitivity was assessed in a separate group of cats by blocking lactate formation during hypoxia with dichloroacetate (DCA). Preventing lactic acidosis during hypoxia did not affect the CO2 response of the phrenic activity during hypoxia. We conclude that 1) hypoxic depression does not limit the ability of central respiratory neurons to respond to CO2, and 2) the failure of DCA to affect the CO2 response of the phrenic neurogram suggests that brain intracellular lactic acidosis does not modify the phrenic response to hypercapnia.

Naloxone enhances respiratory output in cats

1979 ◽  
Vol 47 (5) ◽  
pp. 1105-1111 ◽  
Author(s):  
E. E. Lawson ◽  
T. G. Waldrop ◽  
F. L. Eldridge
Keyword(s):  
Phrenic Nerve ◽  
Opiate Receptors ◽  
Physiological Role ◽  
Opiate Antagonist ◽  
Nerve Activity ◽  
Phrenic Nerve Activity ◽  
End Tidal ◽  
Decerebrate Cats ◽  
End Tidal Co2

To investigate the physiological role of opiate receptors and opiatelike neurotransmitters, which are present in brain-stem respiratory centers, we administered naloxone to 10 cats by intravenous injection. These animals were vagotomized, paralyzed, and servo-ventilated to maintain constant end-tidal CO2; in addition, their carotid sinus nerves were sectioned bilaterally. Respiratory output was assessed by integration of phrenic nerve activity. Control saline infusions had no effect on respiratory output. However, administration of naloxone (0.4 mg/kg) caused phrenic minute output to increase significantly in each of five anesthetized cerebrate cats (control 7,272 +/- 1,615 U/min; 30 min postnaloxone 12,920 +/- 3,857 U/min; P less than 0.05) and five unanesthetized decerebrate cats (control 10,368 +/- 1,222 U/min; naloxone 14,648 +/- 3,225 U/min; P less than 0.05). In addition to the effect on phrenic minute output, naloxone infusion resulted in an increase of the inspiratory rate of rise of phrenic nerve activity in each cat. There was no change in the ratio of inspiratory duration to total respiratory period (TI/Ttot). Because naloxone is a specific opiate antagonist, we suggest that endogenous opiatelike neurotransmitters (endorphins) may modulate central inspiratory drive.

Influence of pregnancy on ventilatory and carotid body neural output responsiveness to hypoxia in cats

1989 ◽  
Vol 67 (2) ◽  
pp. 797-803 ◽  
Author(s):  
B. Hannhart ◽  
C. K. Pickett ◽  
J. V. Weil ◽  
L. G. Moore
Keyword(s):  
Carotid Body ◽  
Ventilatory Response ◽  
Hypoxic Ventilatory Response ◽  
Air Ventilation ◽  
Near Term ◽  
End Tidal ◽  
Neural Influences ◽  
End Tidal Co2 ◽  
Ventilatory Response To Hypoxia

Pregnancy increases ventilation and ventilatory sensitivity to hypoxia and hypercapnia. To determine the role of the carotid body in the increased hypoxic ventilatory response, we measured ventilation and carotid body neural output (CBNO) during progressive isocapnic hypoxia in 15 anesthetized near-term pregnant cats and 15 nonpregnant females. The pregnant compared with nonpregnant cats had greater room-air ventilation [1.48 +/- 0.24 vs. 0.45 +/- 0.05 (SE) l/min BTPS, P less than 0.01], O2 consumption (29 +/- 2 vs. 19 +/- 1 ml/min STPD, P less than 0.01), and lower end-tidal PCO2 (30 +/- 1 vs. 35 +/- 1 Torr, P less than 0.01). Lower end-tidal CO2 tensions were also observed in seven awake pregnant compared with seven awake nonpregnant cats (28 +/- 1 vs. 31 +/- 1 Torr, P less than 0.05). The ventilatory response to hypoxia as measured by the shape of parameter A was twofold greater (38 +/- 5 vs. 17 +/- 3, P less than 0.01) in the anesthetized pregnant compared with nonpregnant cats, and the CBNO response to hypoxia was also increased twofold (58 +/- 11 vs. 29 +/- 5, P less than 0.05). The increased CBNO response to hypoxia in the pregnant compared with the nonpregnant cats persisted after cutting the carotid sinus nerve while recording from the distal end, indicating that the increased hypoxic sensitivity was not due to descending central neural influences. We concluded that greater carotid body sensitivity to hypoxia contributed to the increased hypoxic ventilatory responsiveness observed in pregnant cats.

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