Response of pulmonary circulation of resting, unanesthetized dogs to acute hypoxia

By means of chronically implanted vinyl catheters, pressures in aorta, pulmonary artery (PAP), left atrium (LAP), and intrapleural space (by capsule) were recorded simultaneously and continuously, together with cardiac output (Q) by dye-dilution technic every 2 min, in unanesthetized, unsedated trained dogs for 1 hr during breathing of air and low oxygen mixtures (6–15%) via a chronic tracheostomy. In nearly all of 54 experiments on 5 animals there were striking responses to hypoxia, consisting of a marked rise in PAP (up to 120%), in Q (up to 75%), in pulmonary vascular resistance (PVR) (up to 200%), and of a significant fall in LAP. In some animals these changes were not maintained throughout hypoxia. The PVR usually returned toward normal first, followed by the PAP, while Q remained elevated. The time sequence of these events varied in different animals. Effects of the same magnitude as in hypoxia accompanied restlessness caused by stress, but fluctuated markedly, were of shorter duration, and could largely be climinated by providing quiet surroundings and by avoiding prolonged experiments. It was concluded that active vasoconstriction occurs in the pulmonary vascular bed during acute hypoxia (breathing of 6–15% O2) in the intact, unanesthetized dog. Furthermore, normal values for PAP, Q, and PVR for the resting, waking dog are reported.

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Cardiac responses to hypoxia and reoxygenation in Drosophila

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00164.2015 ◽

2015 ◽

Vol 309 (11) ◽

pp. R1347-R1357 ◽

Cited By ~ 9

Author(s):

Rachel Zarndt ◽

Sarah Piloto ◽

Frank L. Powell ◽

Gabriel G. Haddad ◽

Rolf Bodmer ◽

...

Keyword(s):

Cardiac Output ◽

Genetic Model ◽

Heart Function ◽

Acute Hypoxia ◽

Hypoxia Inducible Factor ◽

High Energy ◽

Hypoxic Exposure ◽

Low Oxygen ◽

Cardiac Responses ◽

Organ Systems

An adequate supply of oxygen is important for the survival of all tissues, but it is especially critical for tissues with high-energy demands, such as the heart. Insufficient tissue oxygenation occurs under a variety of conditions, including high altitude, embryonic and fetal development, inflammation, and thrombotic diseases, often affecting multiple organ systems. Responses and adaptations of the heart to hypoxia are of particular relevance in human cardiovascular and pulmonary diseases, in which the effects of hypoxic exposure can range in severity from transient to long-lasting. This study uses the genetic model system Drosophila to investigate cardiac responses to acute (30 min), sustained (18 h), and chronic (3 wk) hypoxia with reoxygenation. Whereas hearts from wild-type flies recovered quickly after acute hypoxia, exposure to sustained or chronic hypoxia significantly compromised heart function upon reoxygenation. Hearts from flies with mutations in sima, the Drosophila homolog of the hypoxia-inducible factor alpha subunit (HIF-α), exhibited exaggerated reductions in cardiac output in response to hypoxia. Heart function in hypoxia-selected flies, selected over many generations for survival in a low-oxygen environment, revealed reduced cardiac output in terms of decreased heart rate and fractional shortening compared with their normoxia controls. Hypoxia-selected flies also had smaller hearts, myofibrillar disorganization, and increased extracellular collagen deposition, consistent with the observed reductions in contractility. This study indicates that longer-duration hypoxic insults exert deleterious effects on heart function that are mediated, in part, by sima and advances Drosophila models for the genetic analysis of cardiac-specific responses to hypoxia and reoxygenation.

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The active molecular form of plasma adrenomedullin is extracted in the pulmonary circulation in patients with mitral stenosis: possible role of adrenomedullin in pulmonary hypertension

Clinical Science ◽

10.1042/cs1000061 ◽

2000 ◽

Vol 100 (1) ◽

pp. 61-66 ◽

Cited By ~ 4

Author(s):

Toshio NISHIKIMI ◽

Seiki NAGATA ◽

Tatsuya SASAKI ◽

Fumiki YOSHIHARA ◽

Noritoshi NAGAYA ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Artery ◽

Left Atrium ◽

Pulmonary Circulation ◽

Mitral Stenosis ◽

Molecular Form ◽

Femoral Vein ◽

Active Form ◽

Molecular Forms ◽

Main Site

Adrenomedullin (AM), a novel hypotensive peptide, preferentially dilates pulmonary vessels rather than systemic vessels. This suggests the possibility that AM is a circulating hormone which participates in regulation of the pulmonary circulation. A recent study revealed that two molecular forms of AM, i.e. a mature, active form of AM (AM-m) and an intermediate, inactive, glycine-extended form of AM (AM-Gly), circulate in human plasma. In the present study we investigated the production and clearance sites and pathophysiological significance of the two molecular forms of AM in the pulmonary circulation in patients with mitral stenosis. We measured the plasma levels of AM-m and total AM (AM-T; AM-m+AM-Gly) using a recently developed specific immunoradiometric assay, and thus calculated plasma AM-Gly levels, in blood samples obtained from the femoral vein, pulmonary artery, left atrium and aorta of 28 consecutive patients with mitral stenosis (20 females and eight males; age 53±10 years). Patients with mitral stenosis had significantly higher venous concentrations of AM-T, AM-Gly and AM-m than age-matched normal controls (AM-T, 15.9±2.5 and 10.6±2.1 pmol/l respectively; AM-Gly, 14.0±2.1 and 9.8±1.9 pmol/l respectively; AM-m, 1.9±0.6 and 1.1±0.3 pmol/l respectively; each P < 0.001). There was a significant decrease in the concentrations of AM-m and AM-T between the pulmonary artery and the left atrium (AM-T, 16.1±2.7 and 14.0±2.4 pmol/l respectively; AM-m, 2.0±0.6 and 0.7±0.2 pmol/l respectively; each P < 0.001); however, there were no differences in plasma AM-Gly levels between the pulmonary artery and the left atrium (14.1±2.3 and 13.5±2.3 pmol/l respectively). The venous concentrations of AM-m, AM-Gly and AM-T showed similar correlations with mean pulmonary artery pressure (AM-T, r = 0.67; AM-Gly, r = 0.63; AM-m, r = 0.59; each P < 0.001) and total pulmonary vascular resistance (AM-T, r = 0.77; AM-Gly, r = 0.70; AM-m, r = 0.75; each P < 0.001). These results suggest that the plasma concentration of AM-m is increased in parallel with those of AM-Gly and AM-T, and that the main site for clearance of AM-m from the plasma is the lung; the extracted AM-m in the lungs may help to attenuate the increased pulmonary arterial resistance in secondary pulmonary hypertension due to mitral stenosis.

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Influence of Age on Pulmonary Haemodynamics at Rest and during Supine Exercise

Clinical Science ◽

10.1042/cs0650653 ◽

1983 ◽

Vol 65 (6) ◽

pp. 653-660 ◽

Cited By ~ 54

Author(s):

Rolf E. Ehrsam ◽

André Perruchoud ◽

Martin Oberholzer ◽

Felix Burkart ◽

Heinrich Herzog

Keyword(s):

Cardiac Output ◽

Pulmonary Artery ◽

Pressure Gradient ◽

Pulmonary Circulation ◽

Flow Resistance ◽

Right Heart Catheterization ◽

Right Atrial ◽

Heart Catheterization ◽

Asymptomatic Subjects ◽

Wedge Pressure

1. To determine the effects of age on the pulmonary circulation at rest and on exercise we analysed the results of right heart catheterization studies performed in 125 asymptomatic subjects aged 14-68 years, who were healthy or had indispositions which did not impair cardiac or pulmonary function. 2. Age accounted for less than 10% of total variation in resting values of right atrial, pulmonary artery and wedge pressures, and of cardiac output. 3. The pulmonary artery-wedge pressure gradient and flow resistance at rest significantly increased with age. 4. On exercise there were significant increases with age in right atrial, pulmonary artery and wedge pressures, pulmonary to wedge pressure gradient and flow resistance, but cardiac output was not influenced by age. 5. Pulmonary circulation variables at rest are mainly influenced by sex and size, but during exercise significant effects of age are apparent.

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Dexamethasone mimics aspects of physiological acclimatization to 8 hours of hypoxia but suppresses plasma erythropoietin

Journal of Applied Physiology ◽

10.1152/japplphysiol.01414.2012 ◽

2013 ◽

Vol 114 (7) ◽

pp. 948-956 ◽

Cited By ~ 13

Author(s):

Chun Liu ◽

Quentin P. P. Croft ◽

Swati Kalidhar ◽

Jerome T. Brooks ◽

Mari Herigstad ◽

...

Keyword(s):

Heart Rate ◽

Cardiac Output ◽

Pulmonary Artery ◽

Pulmonary Artery Pressure ◽

Acute Hypoxia ◽

Acute Mountain Sickness ◽

Control Period ◽

Plasma Concentrations ◽

Air Breathing ◽

Artery Pressure

Dexamethasone ameliorates the severity of acute mountain sickness (AMS) but it is unknown whether it obtunds normal physiological responses to hypoxia. We studied whether dexamethasone enhanced or inhibited the ventilatory, cardiovascular, and pulmonary vascular responses to sustained (8 h) hypoxia. Eight healthy volunteers were studied, each on four separate occasions, permitting four different protocols. These were: dexamethasone (20 mg orally) beginning 2 h before a control period of 8 h of air breathing; dexamethasone with 8 h of isocapnic hypoxia (end-tidal Po2 = 50 Torr); placebo with 8 h of air breathing; and placebo with 8 h of isocapnic hypoxia. Before and after each protocol, the following were determined under both euoxic and hypoxic conditions: ventilation; pulmonary artery pressure (estimated using echocardiography to assess maximum tricuspid pressure difference); heart rate; and cardiac output. Plasma concentrations of erythropoietin (EPO) were also determined. Dexamethasone had no early (2-h) effect on any variable. Both dexamethasone and 8 h of hypoxia increased euoxic values of ventilation, pulmonary artery pressure, and heart rate, together with the ventilatory sensitivity to acute hypoxia. These effects were independent and additive. Eight hours of hypoxia, but not dexamethasone, increased the sensitivity of pulmonary artery pressure to acute hypoxia. Dexamethasone, but not 8 h of hypoxia, increased both cardiac output and systemic arterial pressure. Dexamethasone abolished the rise in EPO induced by 8 h of hypoxia. In summary, dexamethasone enhances ventilatory acclimatization to hypoxia. Thus, dexamethasone in AMS may improve oxygenation and thereby indirectly lower pulmonary artery pressure.

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Measurement of regional bronchial arterial blood flow and bronchovascular resistance in dogs

Journal of Applied Physiology ◽

10.1152/jappl.1982.53.4.1044 ◽

1982 ◽

Vol 53 (4) ◽

pp. 1044-1049 ◽

Cited By ~ 39

Author(s):

E. M. Baile ◽

J. M. Nelems ◽

M. Schulzer ◽

P. D. Pare

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Pulmonary Artery ◽

Left Atrium ◽

Left Atrial ◽

Main Pulmonary Artery ◽

Left Lung ◽

Arterial Blood Flow ◽

Left Main ◽

Reference Flow

Little is known about normal variations and control of bronchial blood flow and bronchovascular resistance. We have used the reference-flow technique and 15-microns-diameter microspheres to measure bronchial blood flow under physiological conditions. Dogs (n = 13) were anesthetized and ventilated, and their chests were opened. A ligature was placed loosely around the left main pulmonary artery, and the left atrium was cannulated. In six dogs three sets of microspheres were injected simultaneously into the left atrium, and in another seven dogs the three sets of microspheres were injected sequentially at 0.5-h intervals. Prior to each injection measurements of pulmonary arterial, left atrial, and aortic pressures, cardiac output, and blood gases were made. Five seconds after injection the left main pulmonary artery was transiently occluded to prevent recirculation. After the final injection, dogs were killed, the lungs were removed, and the parenchyma was stripped off the large and small airways of the left lung. Knowing the radioactivity in the trachea, bronchi, parenchyma, and in the reference flow blood and also the aortic and left atrial pressures, we calculated bronchial blood flow (ml X min-1 X g dry lung-1) and bronchovascular resistance (cmH2O X ml-1 X min X 100 g dry lung). Results showed that there were no significant differences between the three measurements of bronchial blood flow when microspheres were injected simultaneously or sequentially. Bronchial blood flow to the left lung was 0.4% of cardiac output; 55% of the total flow went to lung parenchyma and 45% to trachea and bronchi. Expressed as flow/g dry lung the greatest flow was to the airways.

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Ventilatory effects of high and pulsatile blood flow in the pulmonary circulation

Journal of Applied Physiology ◽

10.1152/jappl.1990.68.1.181 ◽

1990 ◽

Vol 68 (1) ◽

pp. 181-186

Author(s):

G. G. Giesbrecht ◽

M. Younes

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Pulmonary Artery ◽

Pulse Pressure ◽

Pulmonary Circulation ◽

Dynamic Component ◽

Mean Pulmonary Arterial Pressure ◽

Right Pulmonary Artery ◽

Ventilatory Effects ◽

The Right

The mechanism of ventilatory stimulation that accompanies increases in cardiac output is unknown. Previous studies addressing this issue have been inconclusive. However, only steady pulmonary blood flow was used. The effect of flow pulsatility merits consideration, because increasing cardiac output raises not only mean pulmonary arterial pressure but also pulse pressure; mechanoreceptors with an important dynamic component to their responses may cause a response to pulsatile, but not steady, flow. Studies were done on anesthetized cats (n = 4) and dogs (n = 4). The right pulmonary artery was cannulated within the pericardium, and systemic blood was pumped from the left atrium to the right pulmonary artery. The right pulmonary circulation was perfused at different levels of flow, which was either steady or pulsatile. Steady-state flow of up to 150 ml.kg-1.min-1 (270 ml.kg-1.min-1 when corrected for the proportion of lung tissue perfused) did not affect breathing pattern. When high pulmonary flow was made pulsatile (pulse pressure approximately 23 mmHg), breath duration decreased from 3.7 +/- 0.72 to 3.4 +/- 0.81 (SD) s (P less than 0.01), representing a change in frequency of only 9%. There was no change in peak inspiratory activity. It was concluded that pulmonary vascular mechanoreceptors are not likely to contribute significantly to the increase in ventilation in association with increases in cardiac output.

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