Effects of amiloride and diethyl pyrocarbonate on CSF HCO-3 and ventilation in hypercapnia

1988 ◽  
Vol 65 (1) ◽  
pp. 242-248 ◽  
Author(s):  
E. E. Nattie ◽  
B. Giddings
Keyword(s):  
Cerebrospinal Fluid ◽  
Direct Effect ◽  
Ventilatory Response ◽  
Blocking Agent ◽  
Ventrolateral Medulla ◽  
Acid Base ◽  
Arterial Pco2 ◽  
Cisterna Magna ◽  
Diethyl Pyrocarbonate

Amiloride (10(-3) M), a Na+-H+ countertransport inhibitor, infused into the cisterna magna (10 microliter/min for 40 min) of ketamine-xylazine-anesthetized rabbits decreased the cerebrospinal fluid (CSF) HCO3- response to 3 h of hypercapnia [arterial PCO2 (PaCO2) = 60 Torr] by 21.6% (mean delta CSF [HCO3-]/delta PaCO2 0.232 vs. 0.296 mmol.l-1.Torr-1, P less than 0.05). Diethyl pyrocarbonate (DEPC, 10(-3) M), a histidine-blocking agent, infused into the cisterna magna decreased the CSF HCO3- response to hypercapnia by 25.3% (mean delta CSF [HCO3-]/delta PaCO2, 0.230 vs. 0.308 mmol.l-1.Torr-1, P less than 0.02). DEPC is known to inhibit the ventilatory response to hypercapnia (E. Nattie. Respir. Physiol. 64: 161-176, 1986) by a direct effect at the ventrolateral medulla (E. Nattie. J. Appl. Physiol. 61: 843-850, 1986). In this study amiloride had no significant effect on the ventilatory response to hypercapnia. The interpretation is that a Na+-H+ countertransport protein, perhaps with a histidine at a key location, is involved in CSF acid-base regulation and that amiloride appears to have no effects on the chemoreception process. DEPC appears to have effects on chemoreception and on CSF acid-base regulation.

Ventilatory response to chronic metabolic acidosis and alkalosis in the dog

1984 ◽  
Vol 56 (6) ◽  
pp. 1640-1646 ◽  
Author(s):  
N. E. Madias ◽  
W. H. Bossert ◽  
H. J. Adrogue
Keyword(s):  
Metabolic Acidosis ◽  
Metabolic Alkalosis ◽  
Ventilatory Response ◽  
Wide Spectrum ◽  
Bicarbonate Concentration ◽  
Acid Base ◽  
Arterial Pco2 ◽  
Plasma Bicarbonate ◽  
Oral Sodium ◽  
Chronic Change

Systematic data are not available with regard to the anticipated appropriate responses of arterial PCO2 to primary alterations in plasma bicarbonate concentration. In the present study, we attempted to rigorously characterize the ventilatory response to chronic metabolic acid-base disturbances of graded severity in the dog. Animals with metabolic acidosis produced by prolonged HCl feeding and metabolic alkalosis of three different modes of generation, i.e., diuretics (ethacrynic acid or chlorothiazide), gastric drainage, and administration of deoxycorticosterone acetate (alone or in conjunction with oral sodium bicarbonate), were examined. The results indicate the existence of a significant and highly predictable ventilatory response to chronic metabolic acid-base disturbances. Moreover, the magnitude of the ventilatory response appears to be uniform throughout a wide spectrum of chronic metabolic acid-base disorders extending from severe metabolic acidosis to severe metabolic alkalosis; on average, arterial PCO2 is expected to change by 0.74 Torr for a 1-meq/l chronic change in plasma bicarbonate concentration of metabolic origin. Furthermore, the data suggest that the ventilatory response to chronic metabolic alkalosis is independent of the particular mode of generation.

Pirenzepine prevents diethyl pyrocarbonate inhibition of central CO2 sensitivity

1988 ◽  
Vol 65 (5) ◽  
pp. 1962-1966 ◽  
Author(s):  
E. E. Nattie ◽  
J. W. Mills ◽  
L. C. Ou
Keyword(s):  
Ventral Surface ◽  
Blocking Agent ◽  
Inhibitory Effect ◽  
Ventrolateral Medulla ◽  
Inhibitory Effects ◽  
Co2 Sensitivity ◽  
Diethyl Pyrocarbonate ◽  
Maximum Value ◽  
Chemosensitive Areas ◽  
Co2 Chemosensitivity

Application by pledget of the M1-antimuscarinic receptor agent pirenzepine (40 mM) to the rostral chemosensitive areas of the ventrolateral medulla in anesthetized, paralyzed, vagotomized, glomectomized, and servoventilated cats inhibited the slope of the integrated phrenic response to CO2 by 32.5% (P less than 0.03) and the maximum value by 21.1% (P less than 0.01). Similar application of the imidazole-histidine blocking agent diethyl pyrocarbonate (DEPC) decreased the slope by 40.3% (P less than 0.01) and the maximum value by 29.3% (P less than 0.05). Both responses confirm previous results. DEPC treatment decreased the effectiveness of subsequent pirenzepine application such that although slope and maximum were further decreased, the values were not significantly different from those after DEPC. Pirenzepine treatment prevented any subsequent DEPC inhibitory effect. The results raise the possibility that the inhibitory effects of DEPC on CO2 chemosensitivity are via muscarinic receptors and that muscarinic receptor involvement in CO2 chemosensitivity requires the presence of imidazole-histidine. Analysis by scintillation counting of successive 100-micron sections of medulla after rostral area application of [3H]pirenzepine indicated that the pirenzepine and DEPC effects are most probably within 2.0 mm of the ventral surface as measured from the midline, well away from the dorsal and ventral respiratory group neurons.

Central chemical control of ventilation and response of turtles to inspired CO2

1985 ◽  
Vol 249 (3) ◽  
pp. R323-R328 ◽  
Author(s):  
B. M. Hitzig ◽  
J. C. Allen ◽  
D. C. Jackson
Keyword(s):  
Cerebrospinal Fluid ◽  
Tidal Volume ◽  
Chemical Control ◽  
Ventilatory Response ◽  
Freshwater Turtles ◽  
Acid Base ◽  
Ventilatory Responses ◽  
Acid Base Status ◽  
Homeostatic Mechanisms

The role of central chemosensors in the overall ventilatory response of freshwater turtles (Chrysemys scripta elegans) to the addition of CO2 in inspired gas was measured. Centrally mediated ventilatory responses were isolated in the unanesthetized animal by combining CO2 breathing and brain ventricular perfusion with mock cerebrospinal fluid (CSF) of varying acid-base status. Breathing 4.5% CO2 resulted in increases in both ventilatory frequency (f) and tidal volume (VT), with increases in VT providing most of the overall ventilatory change. Alterations in the acid-base status of the perfusate produced highly significant changes in f. VT changes were divorced from the acid-base status of the mock CSF perfusate. We therefore conclude that ventilatory changes in turtles, mediated by central chemosensors, are primarily affected by alterations in f. VT changes, associated with acid-base homeostatic mechanisms, are mediated by receptors outside the blood-brain barrier in these animals. On the basis of these data, we hypothesize that the increase in f observed when turtles breathe 4.5% CO2 is primarily mediated by the central chemosensors.

Cerebral interstitial fluid acid-base status follows arterial acid-base perturbations

1982 ◽  
Vol 53 (6) ◽  
pp. 1551-1555 ◽  
Author(s):  
D. G. Davies ◽  
W. F. Nolan
Keyword(s):  
Cerebrospinal Fluid ◽  
New Zealand ◽  
Interstitial Fluid ◽  
Acid Base ◽  
Arterial Pco2 ◽  
Ph Probe ◽  
Arterial Blood ◽  
Blood Ph ◽  
New Zealand White Rabbits ◽  
Acid Base Status

Cerebral interstitial fluid (ISF) pH of ventral medulla or thalamus, cisternal cerebrospinal fluid (CSF) pH, and arterial blood pH, PCO2, and [HCO-3] were measured in chloralose-urethan-anesthetized, gallamine-paralyzed New Zealand White rabbits during 30-min episodes of either HCl or NaHCO3 intravenous infusions. ISF pH was measured continuously with glass microelectrodes (1- to 2-microns tip diameter). Cisternal CSF pH was measured continuously with an indwelling pH probe (1-mm tip diameter). Both ventral medullary and thalamic ISF [H+] changed significantly, whereas arterial PCO2 remained constant. CSF [H+] did not change. We conclude from these data that 1) changes in blood acid-base conditions are rapidly reflected in cerebral ISF and 2) transient differences in [H+] and [HCO-3] can exist between cerebral ISF and CSF.

Cerebrospinal fluid ions in metabolic acidosis in dogs: effects of acetazolamide

1986 ◽  
Vol 61 (2) ◽  
pp. 633-639 ◽  
Author(s):  
S. Javaheri ◽  
J. Kennealy ◽  
C. D. Runck ◽  
R. G. Loudon ◽  
M. B. Pine ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Mechanical Ventilation ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Metabolic Acidosis ◽  
Control Group ◽  
Acid Base ◽  
Arterial Pco2 ◽  
Group I ◽  
The Central Nervous System

We hypothesized that, during isosmotic isonatremic HCl acidosis with maintained isocapnia in cisternal cerebrospinal fluid (CSF), acetazolamide, by inhibiting carbonic anhydrase (CA) in the central nervous system (CNS), should produce an isonatric hyperchloric metabolic acidosis in CSF. Blood and CSF ions and acid-base variables were measured in two groups of anesthetized and paralyzed dogs with bilateral ligation of renal pedicles during 5 h of HCl acidosis (plasma [HCO3-] = 11 meq/l). Mechanical ventilation was regulated such that arterial PCO2 dropped and CSF Pco2 remained relatively constant. In group I (control group, n = 6), CSF [Na+] remained unchanged, [HCO3-] and strong ions difference (SID) fell, respectively, 6.1 and 5 meq/l, and [Cl-] rose 3.5 meq/l after 5 h of acidosis. In acetazolamide-treated animals, (group II, n = 7), CSF [Na+] remained unchanged, [HCO3-], and SID fell 11 and 7.1 meq/l, respectively, and [Cl-] rose 7.1 meq/l. We conclude that during HCl acidosis inhibition of CNS CA by acetazolamide induces an isonatric hyperchloric metabolic acidosis in CSF, which is more severe than that observed in controls.

Acid-Base Balance in Cerebrospinal Fluid

1965 ◽  
Vol 12 (5) ◽  
pp. 479-496 ◽  
Author(s):  
J. B. POSNER ◽  
A. G. SWANSON ◽  
F. PLUM
Keyword(s):  
Cerebrospinal Fluid ◽  
Acid Base Balance ◽  
Acid Base ◽  
Base Balance

Increases in coronary vein CO2 during cardiac resuscitation

1990 ◽  
Vol 68 (4) ◽  
pp. 1405-1408 ◽  
Author(s):  
C. V. Gudipati ◽  
M. H. Weil ◽  
R. J. Gazmuri ◽  
H. G. Deshmukh ◽  
J. Bisera ◽  
...  
Keyword(s):  
Spontaneous Circulation ◽  
Co2 Production ◽  
Acid Base ◽  
Coronary Vein ◽  
Arterial Pco2 ◽  
Control Value ◽  
Great Cardiac Vein ◽  
Aortic Blood ◽  
Highly Correlated ◽  
Mixed Venous

We investigated the aortic, mixed venous, and great cardiac vein acid-base changes in eight domestic pigs during cardiac arrest produced by ventricular fibrillation and during cardiopulmonary resuscitation (CPR). The great cardiac vein PCO2 increased from a control value of 52 +/- 2 to 132 +/- 28 (SD) Torr during CPR, whereas the arterial PCO2 was unchanged (39 +/- 4 vs. 38 +/- 4). The coronary venoarterial PCO2 gradient, therefore, increased remarkably from 13 +/- 2 to 94 +/- 29 Torr. The simultaneously measured great cardiac vein lactate concentrations increased from 0.24 +/- 0.06 to 7.3 +/- 2.34 mmol/l. Much more moderate increases in the lactate content of aortic blood from 0.64 +/- 0.25 to 2.56 +/- 0.27 mmol/l were observed. Increases in great cardiac vein PCO2 and lactate were highly correlated during CPR (r = 0.91). After successful CPR, the coronary venoarterial PCO2 gradient returned to normal levels within 2 min after restoration of spontaneous circulation. Lactate content was rapidly reduced and lactate extraction was reestablished within 30 min after CPR. These studies demonstrate marked but reversible acidosis predominantly as the result of myocardial CO2 production during CPR.

Ventilatory responses to cooling the ventrolateral medullary surface of awake and anesthetized goats

1995 ◽  
Vol 78 (1) ◽  
pp. 247-257 ◽  
Author(s):  
P. J. Ohtake ◽  
H. V. Forster ◽  
L. G. Pan ◽  
T. F. Lowry ◽  
M. J. Korducki ◽  
...  
Keyword(s):  
Pulmonary Ventilation ◽  
Respiratory Rhythm ◽  
Respiratory Neurons ◽  
Ventrolateral Medulla ◽  
Arterial Pco2 ◽  
Respiratory Rhythmogenesis ◽  
Ventilatory Responses ◽  
Anesthesia Breathing ◽  
A Site ◽  
Caudal Area

The ventrolateral medulla (VLM) has been reported to be important as a source of tonic facilitation of dorsal respiratory neurons and as a site critical for respiratory rhythmogenesis. We investigated these theories in awake and anesthetized goats (n = 13) by using chronically implanted thermodes to create reversible neuronal dysfunction at superficial VLM sites between the first hypoglossal rootlet and the pontomedullary junction (area M (rostral) and area S). During halothane anesthesia (arterial PCO2 = 57.4 +/- 4.5 Torr), bilateral cooling (thermode temperature = 20 degrees C) of 60–100% of areas M and S for 30 s produced a sustained apnea (46 +/- 4 s) that lasted beyond the period of cooling. While the animals were awake (arterial PCO2 = 36.0 +/- 1.9 Torr), cooling the identical region in the same goats resulted in a decrease (approximately 50%) in pulmonary ventilation, with a brief apnea seen only in one goat. Reductions in both tidal volume and frequency were observed. Qualitatively similar responses were obtained when cooling caudal area M-rostral area S and rostral area M, but the responses were less pronounced. Minimal effects were seen in response to cooling caudal area S. During anesthesia, breathing is critically dependent on superficial VLM neurons, whereas in the awake state these neurons are not essential for the maintenance of respiratory rhythm. Our data are consistent with these superficial VLM neuronal regions providing tonic facilitation to more dorsal respiratory neurons in both the anesthetized and awake states.

Effect of systemic acid-base disorders on ileal intracellular pH and ion transport

1986 ◽  
Vol 250 (5) ◽  
pp. G588-G593 ◽  
Author(s):  
J. D. Wagner ◽  
P. Kurtin ◽  
A. N. Charney
Keyword(s):  
Intracellular Ph ◽  
Respiratory Acidosis ◽  
Strong Correlations ◽  
Sprague Dawley ◽  
Acid Base ◽  
Ileal Mucosa ◽  
Arterial Pco2 ◽  
Co2 Partial Pressure ◽  
Arterial Ph ◽  
Acute Metabolic Acidosis

We previously reported that changes in ileal net Na absorption correlated with arterial pH, changes in net HCO3 secretion correlated with the plasma HCO3 concentration, and changes in net Cl absorption correlated with arterial CO2 partial pressure (PCO2) during the systemic acid-base disorders. To determine whether changes in intracellular pH (pHi) and HCO3 concentration [( HCO3]i) mediated these effects, we measured pHi and calculated [HCO3]i in the distal ileal mucosa of anesthetized, mechanically ventilated Sprague-Dawley rats using 5,5-[14C]dimethyloxazolidine-2,4,-dione and [3H]inulin. Rats were studied during normocapnia, acute respiratory acidosis, and alkalosis, and uncompensated and pH-compensated acute metabolic acidosis and alkalosis. When animals in all groups were considered, mucosal pHi was not altered, but there were strong correlations between mucosal [HCO3]i and both arterial PCO2 (r = 0.97) and [HCO3] (r = 0.61). When we considered the rates of ileal electrolyte transport that characterized these acid-base disorders [A. N. Charney and L.P. Haskell, Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G230-G235, 1983], we found strong correlations between mucosal [HCO3]i and both net Cl absorption (r = 0.88) and net HCO3 secretion (r = 0.82). These findings suggest that the systemic acid-base disorders do not affect ileal mucosal pHi but do alter mucosal [HCO3]i as a consequence of altered arterial PCO2 and [HCO3]. The effects of these disorders on ileal net Cl absorption and HCO3 secretion may be mediated by changes in [HCO3]i. Arterial pH does not appear to alter ileal Na absorption through changes in the mucosal acid-base milieu.

Sign in / Sign up

Export Citation Format

Share Document