Effects of acidosis and alkalosis on hypoxic pulmonary vasoconstriction in dogs

1990 ◽  
Vol 258 (2) ◽  
pp. H347-H353 ◽  
Author(s):  
S. Brimioulle ◽  
P. Lejeune ◽  
J. L. Vachiery ◽  
M. Leeman ◽  
C. Melot ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Respiratory Acidosis ◽  
Respiratory Alkalosis ◽  
Oxygen Fraction ◽  
Pulmonary Vasoconstriction ◽  
Linear Relationships ◽  
Pulmonary Capillary ◽  
Anesthetized Dogs ◽  
Pulmonary Arterial

We studied the effects of metabolic and respiratory acidosis (pH 7.20) and alkalosis (pH 7.60) on pulmonary vascular tone in 32 pentobarbital-anesthetized dogs ventilated with hyperoxia (inspired oxygen fraction, FIO2 0.40) and with hypoxia (FIO2 0.10). Ventilation, pulmonary capillary wedge pressure (Ppw), and cardiac output (3 l.min–1.m-2) were maintained constant to prevent passive changes in pulmonary arterial pressure (Ppa). Metabolic acidosis and alkalosis were induced with HCl (2 mmol.kg-1.h-1) and NaHCO3-Na2CO3 (5 mmol.kg-1.h-1) infusions, respectively, and respiratory acidosis and alkalosis by modifying the inspiratory CO2 fraction. The hypoxia-induced rise in Ppa-Ppw gradient increased from 5 to 9 mmHg in metabolic acidosis (P less than 0.001), decreased from 6 to 1 mmHg in metabolic alkalosis (P less than 0.001), remained unchanged in respiratory acidosis, and decreased from 5 to 2 mmHg in respiratory alkalosis (P less than 0.001). Linear relationships were found between pH and Ppa-Ppw gradients. These data indicate that in intact anesthetized dogs, metabolic acidosis and alkalosis, respectively, enhance and reverse hypoxic pulmonary vasoconstriction (HPV). Respiratory acidosis did not affect HPV and respiratory alkalosis blunted HPV, which suggests an pH-independent vasodilating effect of CO2.

PEEP inhibits hypoxic pulmonary vasoconstriction in dogs

1991 ◽  
Vol 70 (4) ◽  
pp. 1867-1873 ◽  
Author(s):  
P. Lejeune ◽  
J. L. Vachiery ◽  
J. M. De Smet ◽  
M. Leeman ◽  
S. Brimioulle ◽  
...  
Keyword(s):  
Inferior Vena ◽  
Intact Animal ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Balloon Catheter ◽  
Vena Cava ◽  
Pulmonary Hemodynamics ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Vasoconstriction ◽  
Anesthetized Dogs ◽  
Pulmonary Arterial

The effects of an increase in alveolar pressure on hypoxic pulmonary vasoconstriction (HPV) have been reported variably. We therefore studied the effects of positive end-expiratory pressure (PEEP) on pulmonary hemodynamics in 13 pentobarbital-anesthetized dogs ventilated alternately in hyperoxia [inspired O2 fraction (FIO2) 0.4] and in hypoxia (FIO2 0.1). In this intact animal model, HPV was defined as the gradient between hypoxic and hyperoxic transmural (tm) mean pulmonary arterial pressure [Ppa(tm)] at any level of cardiac index (Q). Ppa(tm)/Q plots were constructed with mean transmural left atrial pressure [Pla(tm)] kept constant at approximately 6 mmHg (n = 5 dogs), and Ppa(tm)/PEEP plots were constructed with Q kept constant approximately 2.8 l.min-1.m-2 and Pla(tm) kept constant approximately 8 mmHg (n = 8 dogs). Q was manipulated using a femoral arteriovenous bypass and a balloon catheter in the inferior vena cava. Pla(tm) was held constant by a balloon catheter placed by left thoracotomy in the left atrium. Increasing PEEP, from 0 to 12 Torr by 2-Torr increments, at constant Q and Pla(tm), increased Ppa(tm) from 14 +/- 1 (SE) to 19 +/- 1 mmHg in hyperoxia but did not affect Ppa(tm) (from 22 +/- 2 to 23 +/- 1 mmHg) in hypoxia. Both hypoxia and PEEP, at constant Pla(tm), increased Ppa(tm) over the whole range of Q studied, from 1 to 5 l/min, but more at the highest than at the lowest Q and without change in extrapolated pressure intercepts. Adding PEEP to hypoxia did not affect Ppa(tm) at all levels of Q.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of hypoxic pulmonary vasoconstriction by increased left atrial pressure in dogs

1990 ◽  
Vol 259 (1) ◽  
pp. H93-H100 ◽  
Author(s):  
P. Lejeune ◽  
J. M. De Smet ◽  
P. de Francquen ◽  
M. Leeman ◽  
S. Brimioulle ◽  
...  
Keyword(s):  
Left Atrial ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Atrial Pressure ◽  
Left Atrial Pressure ◽  
Experimental Conditions ◽  
Mean Pulmonary Arterial Pressure ◽  
Pulmonary Vasoconstriction ◽  
Anesthetized Dogs ◽  
Pulmonary Arterial ◽  
The Mean

To further explore the mechanism of hypoxic pulmonary vasoconstriction, we studied the mean pulmonary arterial pressure (Ppa)/left atrial pressure (Pla) relationship at fixed cardiac index (Q) and the Ppa/Q relationship at several levels of fixed Pla in pentobarbital sodium-anesthetized dogs ventilated alternately in hyperoxia [fraction of inspired O2 (FIO2) 0.4 or 1.0] and in hypoxia (FIO2 0.1). In all experimental conditions, Ppa/Q plots were linear with extrapolated pressure intercepts (Pi) not significantly different from Pla. Hypoxia increased the slope of Ppa/Q plots and did not affect Pi. In hyperoxia, increasing Pla (3 to 26 mmHg) induced approximately equal increases in Ppa at fixed Q and shifted Ppa/Q plots toward higher pressures in a parallel manner. In hypoxia, increasing Pla (4 to 25 mmHg) did not affect Ppa at fixed Q until Pla exceeded 16 mmHg and shifted Ppa/Q plots toward higher pressures with a decrease in slope. Consequently, the hypoxia-induced increases in Ppa at constant Q and constant Pla were attenuated at higher Pla. Thus, in anesthetized dogs, hypoxia increases the slope of Ppa/Q plots without affecting Pi at fixed Pla, and an increase in Pla inhibits hypoxic pulmonary vasoconstriction. These results can be explained without invoking a hypoxia-induced Starling resistor mechanism in the pulmonary circulation.

Pulmonary arterial pressure-flow plots in dogs: effects of isoflurane and nitroprusside

1987 ◽  
Vol 63 (3) ◽  
pp. 969-977 ◽  
Author(s):  
R. Naeije ◽  
P. Lejeune ◽  
M. Leeman ◽  
C. Melot ◽  
T. Deloof
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Arachidonic Acid Metabolism ◽  
Minimal Alveolar Concentration ◽  
Vascular Effects ◽  
Pulmonary Vasoconstriction ◽  
Anesthetized Dogs ◽  
Pulmonary Arterial ◽  
End Tidal

We investigated the effects of nitroprusside and isoflurane on multipoint pulmonary arterial pressure (PAP)/cardiac index (Q) plots in pentobarbital sodium-anesthetized dogs ventilated alternatively in hyperoxia (fraction of inspired O2, FIO2, 0.4) and hypoxia (FIO2 0.1). Over the entire range of Q studied, 2–5 l.min-1.m-2, hypoxia increased PAP in 16 dogs (“responders”) and did not affect PAP in 16 other dogs (“nonresponders”). A hypoxic pulmonary vasoconstriction (HPV) was restored in the nonresponders by intravenous administration of 1 g of acetylsalicylic acid (ASA). Nitroprusside (5 micrograms.kg-1.min-1) inhibited HPV in responders (n = 8) and nonresponders treated with ASA (n = 8). End-tidal 1.41% isoflurane (a minimal alveolar concentration equal to one for dogs) did not affect HPV in responders (n = 8) and nonresponders treated with ASA (n = 8). In the latter group isoflurane increased PAP at the highest Q studied (3–5 l.min-1.m-2) in hyperoxia and hypoxia. In a final group of eight dogs with Q kept constant, PAP remained unchanged during two consecutive sequences of alternated 30-min periods (maximum time to generate a PAP/Q plot) successively at FIO2 0.4 and 0.1, and the hypoxia-induced increase in PAP was reproducible. Thus the present experimental model appeared suitable for the study of the effects of hypoxia and drugs on pulmonary vascular tone of intact dogs. At the given doses HPV was inhibited by nitroprusside and not affected by isoflurane. Products of arachidonic acid metabolism possibly could be implicated in the pulmonary vascular effects of isoflurane.

Pulmonary vascular responses to surgical chemodenervation and chemical sympathectomy in dogs

1989 ◽  
Vol 66 (1) ◽  
pp. 42-50 ◽  
Author(s):  
R. Naeije ◽  
P. Lejeune ◽  
M. Leeman ◽  
C. Melot ◽  
J. Closset
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Sham Operation ◽  
Chemical Sympathectomy ◽  
Vascular Effects ◽  
Peripheral Chemoreceptor ◽  
Pulmonary Vasoconstriction ◽  
Anesthetized Dogs ◽  
Pulmonary Arterial ◽  
6 Hydroxydopamine ◽  
Final Group

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.

Relative influence of respiratory and metabolic acid-base changes on renal acid excretion

1960 ◽  
Vol 198 (2) ◽  
pp. 237-243 ◽  
Author(s):  
Daniel H. Simmons ◽  
Nicholas A. Assali ◽  
Melvin Avedon
Keyword(s):  
Metabolic Acidosis ◽  
Metabolic Alkalosis ◽  
Time Lag ◽  
Respiratory Acidosis ◽  
Respiratory Alkalosis ◽  
Acid Excretion ◽  
Acid Base ◽  
Urine Ph ◽  
Renal Handling ◽  
Anesthetized Dogs

Arterial pH of anesthetized dogs was maintained constant for 90 minutes during continuous infusion of 0.15 m HCl or NaHCO3 (0.3 cc/kg/min.) by adjusting alveolar ventilation with a respiration pump. This resulted in simultaneous metabolic acidosis and respiratory alkalosis (acid infusion) or metabolic alkalosis and respiratory acidosis (base infusion) equal in degree with respect to their effect on blood pH. Since urine pH dropped and renal acid excretion increased during metabolic acidosis and respiratory alkalosis, while pH rose and acid excretion decreased during metabolic alkalosis and respiratory acidosis, metabolic acid-base disturbances appear to exert more influence on renal acid excretion than do respiratory disturbances comparable in terms of their effect on pH. This difference in response was shown not to be due to a time lag in renal response to respiratory disturbances, nor could it be explained by effects on urine flow, renal hemodynamics or renal handling of sodium.

Inhibition of hypoxic pulmonary vasoconstriction by antagonists of store-operated Ca2+ and nonselective cation channels

2005 ◽  
Vol 289 (1) ◽  
pp. L5-L13 ◽  
Author(s):  
Letitia Weigand ◽  
Joshua Foxson ◽  
Jian Wang ◽  
Larissa A. Shimoda ◽  
J. T. Sylvester
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Acute Hypoxia ◽  
Pulmonary Arteries ◽  
Cation Channels ◽  
Pulmonary Vasoconstriction ◽  
Nonselective Cation Channels ◽  
Pressor Responses ◽  
Intracellular Ca ◽  
Pulmonary Arterial

Previous studies indicated that acute hypoxia increased intracellular Ca2+ concentration ([Ca2+]i), Ca2+ influx, and capacitative Ca2+ entry (CCE) through store-operated Ca2+ channels (SOCC) in smooth muscle cells from distal pulmonary arteries (PASMC), which are thought to be a major locus of hypoxic pulmonary vasoconstriction (HPV). Moreover, these effects were blocked by Ca2+-free conditions and antagonists of SOCC and nonselective cation channels (NSCC). To test the hypothesis that in vivo HPV requires CCE, we measured the effects of SOCC/NSCC antagonists (SKF-96365, NiCl2, and LaCl3) on pulmonary arterial pressor responses to 2% O2 and high-KCl concentrations in isolated rat lungs. At concentrations that blocked CCE and [Ca2+]i responses to hypoxia in PASMC, SKF-96365 and NiCl2 prevented and reversed HPV but did not alter pressor responses to KCl. At 10 μM, LaCl3 had similar effects, but higher concentrations (30 and 100 μM) caused vasoconstriction during normoxia and potentiated HPV, indicating actions other than SOCC blockade. Ca2+-free perfusate and the voltage-operated Ca2+ channel (VOCC) antagonist nifedipine were potent inhibitors of pressor responses to both hypoxia and KCl. We conclude that HPV required influx of Ca2+ through both SOCC and VOCC. This dual requirement and virtual abolition of HPV by either SOCC or VOCC antagonists suggests that neither channel provided enough Ca2+ on its own to trigger PASMC contraction and/or that during hypoxia, SOCC-dependent depolarization caused secondary activation of VOCC.

Endothelium-derived relaxing factor activity in rat lung during hypoxic pulmonary vascular remodeling

1993 ◽  
Vol 74 (3) ◽  
pp. 1061-1065 ◽  
Author(s):  
L. Zhao ◽  
D. E. Crawley ◽  
J. M. Hughes ◽  
T. W. Evans ◽  
R. J. Winter
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Hypoxic Exposure ◽  
Control Group ◽  
Pulmonary Vascular Remodeling ◽  
Relaxing Factor ◽  
Pulmonary Vasoconstriction ◽  
O2 Concentration ◽  
Pulmonary Arterial ◽  
Endothelium Derived Relaxing Factor

We have investigated the role of endothelium-derived relaxing factor in modulating hypoxic pulmonary vasoconstriction by inhibiting its synthesis with the false substrate NG-monomethyl-L-arginine (L-NMMA) in the isolated blood-perfused lungs of Wistar rats after chronic hypoxia (CH, fractional inspiratory O2 concentration 10%) for 15 h, 2 days, and 7 days. Lungs were perfused with blood of normal hematocrit at constant flow (18 ml/min) ventilated with 1) 95% air-5% CO2 (normoxia) and 2) 2% O2–5% CO2-93% N2 (hypoxia) and were studied in the absence and presence of L-NMMA (30 and 300 microM) or L-arginine (L-Arg, 1 and 6 mM) in separate groups. Pulmonary arterial pressure (Ppa) rose incrementally with hypoxic exposure (all P < 0.05 vs. normoxic control group). Hypoxic pulmonary vasoconstriction (HPV) was markedly reduced after 15 h and 2 days of CH: the mean increases in Ppa (delta Ppa) in hypoxia were 15.3, 3.5, 3.8, and 13.6 mmHg in control rats and rats exposed to 15 h (P < 0.05 vs. control and 7 days of CH), 2 days (P < 0.001 vs. control and 7 days of CH), and 7 days of CH, respectively. Ppa in control rats and rats exposed to 15 h, 2 days, and 7 days of CH were 137, 179, 184, and 166% of control, respectively, after 30 microM L-NMMA (all P < 0.05 when expressed as percent change vs. no L-NMMA). Similar augmentation in HPV was seen after 30 microM L-NMMA, with all hypoxic groups having a greater response than control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Stability of cerebrospinal fluid pH in chronic acid-base disturbances in blood

1965 ◽  
Vol 20 (3) ◽  
pp. 443-452 ◽  
Author(s):  
R. A. Mitchell ◽  
C. T. Carman ◽  
J. W. Severinghaus ◽  
B. W. Richardson ◽  
M. M. Singer ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Active Transport ◽  
Respiratory Acidosis ◽  
Normal Subjects ◽  
Respiratory Alkalosis ◽  
Regulation Of Respiration ◽  
Respiratory Drive ◽  
Acid Base ◽  
Peripheral Chemoreceptors ◽  
Mean Values

In chronic acid-base disturbances, CSF pH was generally within the normal limits (7.30–7.36 units, being the range including two standard deviations of 12 normal subjects). The mean values of CSF and arterial pHH, respectively, were: 1) metabolic alkalosis, 7.337 and 7.523; 2) metabolic acidosis, 7.315 and 7.350; 3) respiratory alkalosis, 7.336 and 7.485; and 4) respiratory acidosis (untreated), 7.314 and 7.382. Other investigators report similar values. The constancy of CSF pH cannot be explained by a poorly permeable blood-CSF barrier in chronic metabolic acidosis and alkalosis, nor can it be explained by respiratory compensation. It cannot be explained by renal compensation in respiratory alkalosis (high altitude for 8 days), although it may be explained by renal compensation in respiratory acidosis. The former three states suggest that active transport regulation of CSF pH is a function of the blood-CSF barrier. Since CSF pH is constant, so also must that portion of the respiratory drive originating in the superficial medullary respiratory chemoreceptors be constant. Ventilation changes in chronic acid-base disturbances thus may result from changes in the activity of peripheral chemoreceptors, in response to changes in arterial pH, arterial PO2, and possibly in neuromuscular receptors. regulation of respiration; medullary respiratory; chemoreceptors; peripheral chemoreceptors; metabolic acidosis and alkalosis; respiratory acidosis and alkalosis; active transport; blood-brain barrier; pregnancy Submitted on July 27, 1964

Does leukotriene C4 mediate hypoxic vasoconstriction in isolated ferret lungs?

1990 ◽  
Vol 68 (1) ◽  
pp. 253-259 ◽  
Author(s):  
C. M. Tseng ◽  
M. McGeady ◽  
T. Privett ◽  
A. Dunn ◽  
J. T. Sylvester
Keyword(s):  
Pulmonary Arterial Pressure ◽  
Pressor Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Physiological Salt Solution ◽  
Leukotriene C4 ◽  
Prostaglandin F2 Alpha ◽  
Pulmonary Vasoconstriction ◽  
Vasoconstrictor Response ◽  
Hypoxic Vasoconstriction ◽  
Pulmonary Arterial

To evaluate leukotriene (LT) C4 as a mediator of hypoxic pulmonary vasoconstriction, we examined the effects of FPL55712, a putative LT antagonist, and indomethacin, a cyclooxygenase inhibitor, on vasopressor responses to LTC4 and hypoxia (inspired O2 tension = 25 Torr) in isolated ferret lungs perfused with a constant flow (50 ml.kg-1.min-1). Pulmonary arterial injections of LTC4 caused dose-related increases in pulmonary arterial pressure during perfusion with physiological salt solution containing Ficoll (4 g/dl). FPL55712 caused concentration-related inhibition of the pressor response to LTC4 (0.6 micrograms). Although 10 micrograms/ml FPL55712 inhibited the LTC4 pressor response by 61%, it did not alter the response to hypoxia. At 100 microgram/ml, FPL55712 inhibited the responses to LTC4 and hypoxia by 73 and 71%, respectively, but also attenuated the vasoconstrictor responses to prostaglandin F2 alpha (78% at 8 micrograms), phenylephrine (68% at 100 micrograms), and KCl (51% at 40 mM). At 0.5 microgram/ml, indomethacin significantly attenuated the pressor response to arachidonic acid but did not alter responses to LTC4 or hypoxia. These results suggest that in isolated ferret lungs 1) the vasoconstrictor response to LTC4 did not depend on release of cyclooxygenase products and 2) LTC4 did not mediate hypoxic vasoconstriction.

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