Effect of positive end-expiratory pressure on hypoxic pulmonary vasoconstriction in the dog

1990 ◽  
Vol 259 (3) ◽  
pp. H697-H705 ◽  
Author(s):  
K. B. Domino ◽  
M. R. Pinsky
Keyword(s):  
Blood Flow ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Linear Regression Analysis ◽  
Left Lung ◽  
Vena Cava ◽  
Positive End Expiratory Pressure ◽  
Anesthetized Dogs ◽  
Alveolar Hypoxia ◽  
Lung Blood Flow ◽  
The Right

We studied the effects of uni- and bilateral positive end-expiratory pressure (PEEP) on pulmonary artery pressure-flow (Ppa/Q) relationships during unilateral hypoxia in anesthetized dogs. A bronchial divider was inserted, the right lung was ventilated with 100% O2, and the left lung was ventilated with either 100% O2 (hyperoxia) or a hypoxic gas mixture (hypoxia). Left lung blood flow (QL) and aortic flow (QT) were measured by electromagnetic flow probes. Simultaneous Ppa/Q relations for both lungs, with Q on the ordinate, were obtained by altering QT via an arteriovenous fistula and an inferior vena cava occluder. Ppa/Q slopes (delta Q/delta Ppa) and extrapolated zero-flow Ppa intercepts (Pzf) were obtained by linear regression analysis. Bilateral PEEP increased Pzf for both lungs (P less than 0.01) but did not alter delta Q/delta Ppa of either lung. Unilateral PEEP decreased ipsilateral blood flow (P less than 0.001) and increased Pzf for the ipsilateral lung (P less than 0.05). Left lung PEEP did not affect the slope of the left lung Ppa/Q relationship (delta QL/delta Ppa). Hypoxic ventilation of the left lung decreased QL (P less than 0.001), increased Pzf (P less than 0.05), and decreased delta QL/delta Ppa (P less than 0.001). Neither uni- nor bilateral PEEP altered this flow diversion away from the left lung or the reduction in delta QL/delta Ppa with left lung hypoxia. We conclude that PEEP and alveolar hypoxia increase pulmonary vascular resistance at different loci, such that their effects are additive. A net increase in 10 cmH2O of PEEP does not inhibit the pulmonary vascular response to regional alveolar hypoxia.

Effect of a regional increase in alveolar pressure on pulmonary blood flow

1992 ◽  
Vol 73 (4) ◽  
pp. 1291-1296 ◽  
Author(s):  
L. E. Olson ◽  
R. L. Wardle
Keyword(s):  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Left Lung ◽  
Dry Weight ◽  
Test Lung ◽  
Test Segment ◽  
Control Segment ◽  
Lung Segment ◽  
Lung Blood Flow ◽  
The Right

We examined whether wedging a catheter (0.5 cm OD) into a subsegmental airway in dog (n = 6) or pig lungs (n = 5) and increasing pressure in the distal lung segment affected pulmonary blood flow. Dogs and pigs were anesthetized and studied in the prone position. Pulmonary blood flow was measured by injecting radiolabeled microspheres (15 microns diam) into the right atrium when airway pressure (Pao) was 0 cmH2O and pressure in the segment distal to the wedged catheter (Ps) was 0, 5, or 15 cmH2O and when Pao = Ps = 15 cmH2O. The lungs were excised, air-dried, and sectioned. Blood flow per gram dry weight normalized to cardiac output to the right or left lung, as appropriate, was calculated for the test segment, a control segment in the opposite lung corresponding anatomically to the test segment, the remainder of the lung containing the test segment (test lung), and the remainder of the lung containing the control segment (control lung). The presence of the catheter reduced blood flow in the test segment compared with that in the control segment and in the test lung. Blood flow was not affected by increasing pressure in the test segment. We conclude that, in studies designed to measure collateral ventilation in dog lungs, the presence of the wedged catheter is likely to have a greater effect on blood flow than the increase in pressure associated with measuring collateral airway resistance.

Redistribution of pulmonary blood flow during unilateral hypoxia in prone and supine dogs

1998 ◽  
Vol 84 (6) ◽  
pp. 2010-2019 ◽  
Author(s):  
Christopher M. Mann ◽  
Karen B. Domino ◽  
Sten M. Walther ◽  
Robb W. Glenny ◽  
Nayak L. Polissar ◽  
...  
Keyword(s):  
Blood Flow ◽  
Pulmonary Blood Flow ◽  
Regional Distribution ◽  
Left Lung ◽  
Flow Distribution ◽  
Random Order ◽  
Total Flow ◽  
Hypoxic Vasoconstriction ◽  
Anesthetized Dogs ◽  
The Right

We used fluorescent-labeled microspheres in pentobarbital-anesthetized dogs to study the effects of unilateral alveolar hypoxia on the pulmonary blood flow distribution. The left lung was ventilated with inspired O2 fraction of 1.0, 0.09, or 0.03 in random order; the right lung was ventilated with inspired O2 fraction of 1.0. The lungs were removed, cleared of blood, dried at total lung capacity, then cubed to obtain ∼1,500 small pieces of lung (∼1.7 cm3). The coefficient of variation of flow increased ( P < 0.001) in the hypoxic lung but was unchanged in the hyperoxic lung. Most (70–80%) variance in flow in the hyperoxic lung was attributable to structure, in contrast to only 30–40% of the variance in flow in the hypoxic lung ( P < 0.001). When adjusted for the change in total flow to each lung, 90–95% of the variance in the hyperoxic lung was attributable to structure compared with 70–80% in the hypoxic lung ( P < 0.001). The hilar-to-peripheral gradient, adjusted for change in total flow, decreased in the hypoxic lung ( P = 0.005) but did not change in the hyperoxic lung. We conclude that hypoxic vasoconstriction alters the regional distribution of flow in the hypoxic, but not in the hyperoxic, lung.

Prostaglandin I2 supports blood flow to hypoxic alveoli in anesthetized dogs

1984 ◽  
Vol 56 (5) ◽  
pp. 1246-1251 ◽  
Author(s):  
R. S. Sprague ◽  
A. H. Stephenson ◽  
A. J. Lonigro
Keyword(s):  
Blood Flow ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Prostaglandin I2 ◽  
Flow Measurements ◽  
Pulmonary Vasoconstriction ◽  
Cyclooxygenase Activity ◽  
Hypoxic Vasoconstriction ◽  
Anesthetized Dogs ◽  
Alveolar Hypoxia ◽  
Mixed Venous

In an animal model of unilateral alveolar hypoxia, inhibition of cyclooxygenase activity, estimates of immunoreactive 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and administration of prostaglandin I2 (PGI2) were used to evaluate the hypothesis that endogenous PGI2 opposes hypoxic pulmonary vasoconstriction, thereby producing redistribution of blood flow to hypoxic alveoli and reductions in systemic PO2. In anesthetized dogs, one lung was ventilated with 100% N2 and the other with 100% O2. Thermal dilution coupled with electromagnetic flow measurements permitted estimates of blood flow to each lung. Indomethacin or meclofenamate reduced flow to the N2-ventilated lungs (P less than 0.05) and increased systemic PO2 (P less than 0.05). Simultaneously, aortic concentrations of immunoreactive 6-keto-PGF1 alpha decreased 63 +/- 8% (P less than 0.001). Following cyclooxygenase inhibition, incremental doses of PGI2 (0.01, 0.025, and 0.10 micrograms X kg-1 X min-1) increased flow to the N2-ventilated lungs and reduced systemic PO2 (P less than 0.001) without affecting mixed venous PO2. These results suggest that systemic PO2 was reduced because of increased venous admixture. We conclude that PGI2 attenuates hypoxic vasoconstriction which allows flow to be maintained to hypoxic alveoli, resulting in reduced systemic PO2.

Spatial distribution of pulmonary blood flow in the dog with PEEP ventilation

1979 ◽  
Vol 47 (5) ◽  
pp. 938-946 ◽  
Author(s):  
G. Hedenstierna ◽  
F. C. White ◽  
P. D. Wagner
Keyword(s):  
Mechanical Ventilation ◽  
Blood Flow ◽  
Spatial Distribution ◽  
Left Lung ◽  
Flow Distribution ◽  
Vertical Gradient ◽  
Lung Blood Flow ◽  
Peep Ventilation ◽  
The Right ◽  
Spontaneously Breathing

The effects of mechanical ventilation without and with a positive end-expiratory pressure (PEEP) of 20 cmH2O and, after hemorrhage, on the spatial distribution of lobar lung blood flow were studied by means of iv injections of radioactive microspheres in supine dogs. The lungs were excised and dried at an inflation pressure of 30 cmH2O. Each lobe was cut into slices. In five slices from each lobe, 30--60 samples were punched out. The activity was measured in a gamma counter. By this means distribution of lobar blood flow could be described three-dimensionally. In dogs awake and spontaneously breathing or anesthetized and mechanically ventilated, blood flow distribution was rather even, except for a vertical gradient. PEEP caused a) a two- to threefold reduction in total lung blood flow, b) a redistribution from the right to the left lung, and c) a redistribution from the core to the periphery of the lung. This pattern of redistribution could not be reproduced by reducing cardiac output by hemorrhage during mechanical ventilation without PEEP.

Chemoreflex blunting of hypoxic pulmonary vasoconstriction is vagally mediated

1989 ◽  
Vol 66 (2) ◽  
pp. 782-791 ◽  
Author(s):  
L. B. Wilson ◽  
M. G. Levitzky
Keyword(s):  
Blood Flow ◽  
Nervous System ◽  
Pulmonary Blood Flow ◽  
Parasympathetic Nervous System ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Left Lung ◽  
Pulmonary Vasoconstriction ◽  
Anesthetized Dogs ◽  
Bilateral Vagotomy ◽  
Carotid Body Chemoreceptors

We investigated the role of the autonomic nervous system in the arterial chemoreceptor attenuation of hypoxic pulmonary vasoconstriction (HPV) using anesthetized dogs. Total pulmonary blood flow (Qt) and left pulmonary blood flow (Ql) were determined using electromagnetic flow probes. Carotid body chemoreceptors were perfused using blood pumped from an extracorporeal circuit containing an oxygenator. Four groups were used: 1) prevagotomy (control), 2) bilateral vagotomy, 3) post-atropine, and 4) post-propranolol. Left lung hypoxia decreased Ql/Qt from 42.9 +/- 2.9 to 28.1 +/- 3.0%, from 41.1 +/- 5.3 to 26.7 +/- 4.2%, from 38.6 +/- 1.3 to 22.2 +/- 2.4%, and from 48.2 +/- 4.2 to 28.5 +/- 3.7% in the four groups, respectively. Chemoreceptor stimulation during unilateral hypoxia increased Ql/Qt from 28.1 +/- 3.0 to 39.1 +/- 4.9% and from 28.5 +/- 3.7 to 40.6 +/- 3.7% in the control and propranolol groups. However, chemoreceptor stimulation had no effect on Ql/Qt during left lung hypoxia after vagotomy or atropine, as Ql/Qt went from 26.7 +/- 4.2 to 29.3 +/- 5.2% and from 22.2 +/- 2.4 to 24.1 +/- 1.5% in groups 2 and 3, respectively. Because chemoreceptor stimulation did not affect HPV in groups 2 and 3, we conclude that the chemoreceptor attenuation of HPV is mediated by the parasympathetic nervous system.

Effect of regional alveolar hypoxia on gas exchange in dogs

1989 ◽  
Vol 67 (2) ◽  
pp. 730-735 ◽  
Author(s):  
K. B. Domino ◽  
M. P. Hlastala ◽  
B. L. Eisenstein ◽  
F. W. Cheney
Keyword(s):  
Blood Flow ◽  
Gas Exchange ◽  
Lower Lobe ◽  
Dispersion Index ◽  
Anesthetized Dogs ◽  
Alveolar Hypoxia ◽  
The Right ◽  
Increased Blood Flow ◽  
Hypoxic Gas Mixture ◽  
Hypoxic Region

We studied the effects of left lower lobe (LLL) alveolar hypoxia on pulmonary gas exchange in anesthetized dogs using the multiple inert gas elimination technique (MIGET). The left upper lobe was removed, and a bronchial divider was placed. The right lung (RL) was continuously ventilated with 100% O2, and the LLL was ventilated with either 100% O2 (hyperoxia) or a hypoxic gas mixture (hypoxia). Whole lung and individual LLL and RL ventilation-perfusion (VA/Q) distributions were determined. LLL hypoxia reduced LLL blood flow and increased the perfusion-related indexes of VA/Q heterogeneity, such as the log standard deviation of the perfusion distribution (log SDQ), the retention component of the arterial-alveolar difference area [R(a-A)D], and the retention dispersion index (DISPR*) of the LLL. LLL hypoxia increased blood flow to the RL and reduced the VA/Q heterogeneity of the RL, indicated by significant reductions in log SDQ, R(a-A)D, and DISPR*. In contrast, LLL hypoxia had little effect on gas exchange of the lung when evaluated as a whole. We conclude that flow diversion induced by regional alveolar hypoxia preserves matching of ventilation to perfusion in the whole lung by increasing gas exchange heterogeneity of the hypoxic region and reducing heterogeneity in the normoxic lung.

scholarly journals SUN-932 Successful Response of Temozolomide (TMZ) in two Patients with Metastatic Pheochromocytoma/Paragangliomas (PPGLs)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Tobias Skrebsky de Almeida ◽  
Roberta P Borges ◽  
Janeczko Laís ◽  
Giovana Caroline Marx Becker ◽  
Ticiana Costa Rodrigues ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Left Lung ◽  
Vena Cava ◽  
Lung Lesion ◽  
Chest Ct ◽  
Complete Regression ◽  
Lung Lesions ◽  
The Right ◽  
Urinary Metanephrines

Abstract Introduction: PPGLs are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla or their neural crest progenitors, being able to secrete catecholamines. Its treatment is primarily surgical; however, for metastatic/inoperable tumors, effective treatments are lacking. The use of TMZ, an oral alkylating agent, has been scarcely reported with variable response rates. We report 2 patients with reasonable clinical, biochemical and structural responses. Case Reports: Case 1) A 14-year old girl presented with neck pain, sweating, hypertension and tachycardia. Urinary hormonal profile revealed metanephrines 80 (up to 320 ug/24h) and normetanephrines 2983 (up to 390 ug/24h). Abdominal MRI showed a 10x6x5 cm retroperitoneal lesion in close contact with celiac trunk, superior mesenteric artery, renal arteries, aorta, left renal vein and vertebral bodies of T10, T11 and T12. A chest CT revealed multiple lung metastases. After 11 months, both the primary abdominal lesion and lung metastases increased in size.. Due to disease severity, after excluding surgical possibilities and confirming diagnosis by lesion biopsy, rescue treatment with TMZ was started for 5 days on a 28-day cycle. After 11 cycles, lung and abdominal lesions decreased more than 30% in size, and urinary metanephrines decreased 53.4%. After 21 cycles, there is no evidence of disease progression. Case 2) A 44-year old female was first diagnosed at the age of 31 with a right adrenal mass invading the kidney and the inferior vena cava associated with hypertension, sweating, headaches and palpitations. She underwent right adrenalectomy and nephrectomy. Immunohistochemistry confirmed the diagnosis of pheochromocytoma. Seven years later, follow-up CT`s showed a 3 x 2 cm liver metastasis, which was resected, and two lung lesions, one located at the right inferior lobe (1.6 cm) and the other at the left superior lobe (0.9 cm), which initially were just followed-up. At this time, a 7-month sorafenib trial was performed but the drug was stopped due to intolerable side effects. After 3 years of follow-up, the lung lesions increased in size and the right lesion was resected, but the patient refused surgery for the remainder left lung lesion. After 1 year, left lung lesion increased to 2.4 cm and mediastinal and paratracheal lymphadenomegaly developed. TMZ in the same aforementioned schedule was prescribed and after 7 cycles a new chest CT revealed complete regression of the lung and lymph node metastases.. Urinary metanephrines were 2.1 times the upper limit of normal before TMZ and decreased to normal range. Conclusion: These cases highlight the promising role of a well-tolerated single drug chemotherapy regimen in severe cases of metastatic and inoperable PPGLs. TMZ could be considered an alternative strategy for the treatment of these cases and, if possible, should be tested in adequate clinical trials.

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)

Effect of cold and warm dry air hyperventilation on canine airway blood flow

1987 ◽  
Vol 62 (2) ◽  
pp. 526-532 ◽  
Author(s):  
E. M. Baile ◽  
R. W. Dahlby ◽  
B. R. Wiggs ◽  
G. H. Parsons ◽  
P. D. Pare
Keyword(s):  
Blood Flow ◽  
Left Lung ◽  
Tissue Temperature ◽  
Humid Air ◽  
Dry Air ◽  
Airway Mucosa ◽  
Anesthetized Dogs ◽  
Tracheal Tissue ◽  
Group 2 ◽  
Central Airway

Tracheobronchial blood flow increases with cold air hyperventilation in the dog. The present study was designed to determine whether the cooling or the drying of the airway mucosa was the principal stimulus for this response. Six anesthetized dogs (group 1) were subjected to four periods of eucapnic hyperventilation for 30 min with warm humid air [100% relative humidity (rh)], cold dry air (-12 degrees C, 0% rh), warm humid air, and warm dry air (43 degrees C, 0% rh). Five minutes before the end of each period of hyperventilation, tracheal and central airway blood flow was determined using four differently labeled 15-micron diam radioactive microspheres. We studied another three dogs (group 2) in which 15- and 50-micron microspheres were injected simultaneously to determine whether there were any arteriovenous communications in the bronchovasculature greater than 15 micron diam. After the last measurements had been made, all dogs were killed, and the lungs, including the trachea, were excised and blood flow to the trachea, left lung bronchi, and parenchyma was calculated. Warm dry air hyperventilation produced a consistently greater increase in tracheobronchial blood flow (P less than 0.01) than cold dry air hyperventilation, despite the fact that there was a smaller fall (6 degrees C) in tracheal tissue temperature during warm dry air hyperventilation than during cold dry air hyperventilation (11 degrees C), suggesting that drying may be a more important stimulus than cold for increasing airway blood flow. In group 2, the 15-micron microspheres accurately reflected the distribution of airway blood flow but did not always give reliable measurements of parenchymal blood flow.

Effect of PEEP on discharge of pulmonary C-fibers in dogs

1985 ◽  
Vol 59 (4) ◽  
pp. 1085-1089 ◽  
Author(s):  
M. P. Kaufman ◽  
G. A. Ordway ◽  
T. G. Waldrop
Keyword(s):  
Cardiac Output ◽  
Arterial Pressure ◽  
Impulse Activity ◽  
Vena Cava ◽  
Laboratory Animals ◽  
Positive End Expiratory Pressure ◽  
Firing Rates ◽  
C Fibers ◽  
Anesthetized Dogs ◽  
Stimulation Of

Although positive end-expiratory pressure (PEEP) is believed to depress cardiac output and arterial pressure by compressing the vena cava and the heart, it is unclear whether PEEP also depresses these variables by a reflex arising from an inflation-induced stimulation of pulmonary C-fibers. We therefore recorded the impulse activity of 17 pulmonary C-fibers in barbiturate-anesthetized dogs with closed chests, while we placed the expiratory outlet of a ventilator under 5–30 cmH2O. Increasing PEEP in a ramp-like manner stimulated 12 of the 17 pulmonary C-fibers, with activity increasing from 0.0 +/- 0.1 to 0.9 +/- 0.2 imp/s when end-expiratory pressure equaled 15 cmH2O. When PEEP was increased in a stepwise manner to 15–20 cmH2O and maintained at this pressure for 15 min, pulmonary C-fibers increased their firing rates, but the effect was small averaging 0.2–0.3 imp/s after the 1st min of this maneuver. We conclude that pulmonary C-fibers are unlikely to be responsible for causing much of the decreases in cardiac output and arterial pressure evoked by sustained periods of PEEP in both patients and laboratory animals. These C-fibers, however, are likely to be responsible for causing the reflex decreases in these variables evoked by sudden application of PEEP.

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