Two temporal components within the human pulmonary vascular response to ∼2 h of isocapnic hypoxia

2005 ◽  
Vol 98 (3) ◽  
pp. 1125-1139 ◽  
Author(s):  
Nick P. Talbot ◽  
George M. Balanos ◽  
Keith L. Dorrington ◽  
Peter A. Robbins
Keyword(s):  
Cardiac Output ◽  
Time Course ◽  
Vascular Tone ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Initial Response ◽  
Plateau Phase ◽  
Vascular Response ◽  
Pulmonary Vasoconstriction ◽  
End Tidal ◽  
Underlying Processes

The time course of the pulmonary vascular response to hypoxia in humans has not been fully defined. In this investigation, study A was designed to assess the form of the increase in pulmonary vascular tone at the onset of hypoxia and to determine whether a steady plateau ensues over the following ∼20 min. Twelve volunteers were exposed twice to 5 min of isocapnic euoxia (end-tidal Po2 = 100 Torr), 25 min of isocapnic hypoxia (end-tidal Po2 = 50 Torr), and finally 5 min of isocapnic euoxia. Study B was designed to look for the onset of a slower pulmonary vascular response, and, if possible, to determine a latency for this process. Seven volunteers were exposed to 5 min of isocapnic euoxia, 105 min of isocapnic hypoxia, and finally 10 min of isocapnic euoxia. For both studies, control protocols consisting of isocapnic euoxia were undertaken. Doppler echocardiography was used to measure cardiac output and the maximum tricuspid pressure gradient during systole, and estimates of pulmonary vascular resistance were calculated. For study A, the initial response was well described by a monoexponential process with a time constant of 2.4 ± 0.7 min (mean ± SE). After this, there was a plateau phase lasting at least 20 min. In study B, a second slower phase was identified, with vascular tone beginning to rise again after a latency of 43 ± 5 min. These findings demonstrate the presence of two distinct phases of hypoxic pulmonary vasoconstriction, which may result from two distinct underlying processes.

Time course of hypoxic pulmonary vasoconstriction after endotoxin infusion in unanesthetized sheep

1991 ◽  
Vol 70 (5) ◽  
pp. 2120-2125 ◽  
Author(s):  
J. L. Theissen ◽  
H. M. Loick ◽  
B. B. Curry ◽  
L. D. Traber ◽  
D. N. Herndon ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Time Course ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Left Lung ◽  
Arterial Blood Flow ◽  
Endotoxin Infusion ◽  
Pulmonary Vasoconstriction ◽  
Arterial Blood ◽  
Time Period

Endotoxin [lipopolysaccharide (LPS)] has been reported to reduce hypoxic pulmonary vasoconstriction and thus increases venous admixture. The time course of this failure of pulmonary blood flow regulation was investigated in six chronically instrumented unanesthetized sheep after infusion of Escherichia coli LPS (1 microgram/kg). The change in left pulmonary arterial blood flow (LPBF, ultrasonic transit time) in response to unilateral lung hypoxia (10 min of N2 alternately to the left and right lungs) was compared before and at various time intervals after the administration of LPS. During baseline conditions, LPBF was 33% of total cardiac output and decreased to 15% when the left lung was ventilated with a hypoxic gas mixture. One hour after endotoxin infusion, LPBF remained at 33% of total cardiac output yet only decreased to 28% during the hypoxic challenge. The response to one-lung hypoxia was still significantly depressed 10 h post-LPS administration. It is concluded that hypoxic pulmonary vasoconstriction is almost completely abolished for a prolonged time period after a small dose of LPS.

Cyclic hypoxic pulmonary vasoconstriction induced by concomitant carbon dioxide changes

1976 ◽  
Vol 41 (4) ◽  
pp. 466-469 ◽  
Author(s):  
J. L. Benumof ◽  
J. M. Mathers ◽  
E. A. Wahrenbrock
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Regional Blood Flow ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Lower Lobe ◽  
Co2 Concentration ◽  
Hypoxic Area ◽  
Pulmonary Vasoconstriction ◽  
End Tidal ◽  
End Tidal Co2

We examined the stability of acute lobar hypoxic pulmonary vasoconstriction. In 12 mongrel dogs the left lower lobe (LLL) was selectively ventilated with a constant minute molume with nitrogen and the electromagnetically measured fraction of the cardiac output perfusing the LLL and the LLL end-tidal CO2 concentration were observed for 1 h. We found that both the fraction of the cardiac output perfusing the LLL and the LLL end-tidal CO2 concentration initially decreased during LLL hypoxia and then oxcillated in a progressively damped fashion. When LLL end-tidal CO2 was kept constant by CO2 infusion during LLL hypoxia or when LLL hypoxia was induced by LLL atelectasis, no oscillations were observed. We conclude that if minute ventilation of a hypoxic area of lung is kept constant, then decreased regional blood flow decreases regional alveolar PCO2. As a consequence of these two opposinginfluences, blood flow to an acutely hypoxic area will be oscillatory.

scholarly journals The influence of hemoconcentration on hypoxic pulmonary vasoconstriction in acute, prolonged, and lifelong hypoxemia

2021 ◽  
Vol 321 (4) ◽  
pp. H738-H747
Author(s):  
Mike Stembridge ◽  
Ryan L. Hoiland ◽  
Alexandra M. Williams ◽  
Connor A. Howe ◽  
Joseph Donnelly ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Blood Cell ◽  
Hypobaric Hypoxia ◽  
Cell Concentration ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Pulmonary Vasculature ◽  
Red Cell ◽  
Vascular Response ◽  
Pulmonary Vasoconstriction ◽  
High Altitude Natives

Red blood cell concentration influences the pulmonary vasculature via direct frictional force and vasoactive signaling, but whether the magnitude of the response is modified with duration of exposure is not known. By assessing the pulmonary vascular response to hemodilution in acute normobaric and prolonged hypobaric hypoxia in lowlanders and lifelong hypobaric hypoxemia in Andean natives, we demonstrated that a reduction in red cell concentration augments the vasoconstrictive effects of hypoxia in lowlanders. In high-altitude natives, hemodilution lowered pulmonary vascular resistance, but a compensatory increase in cardiac output following hemodilution rendered PASP unchanged.

Contribution of endothelin to pulmonary vascular tone under normoxic and hypoxic conditions

2002 ◽  
Vol 283 (2) ◽  
pp. H568-H575 ◽  
Author(s):  
Wendy Johnson ◽  
Anju Nohria ◽  
Leslie Garrett ◽  
James C. Fang ◽  
James Igo ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Vascular Resistance ◽  
Vascular Tone ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Acute Hypoxia ◽  
Hemodynamic Effects ◽  
Hypoxic Conditions ◽  
Pulmonary Vasoconstriction ◽  
Endothelin Type A Receptor ◽  
Vehicle Treated Control

The contribution of endothelin to resting pulmonary vascular tone and hypoxic pulmonary vasoconstriction in humans is unknown. We studied the hemodynamic effects of BQ-123, an endothelin type A receptor antagonist, on healthy volunteers exposed to normoxia and hypoxia. Hemodynamics were measured at room air and after 15 min of exposure to hypoxia (arterial Po 2 99.8 ± 1.8 and 49.4 ± 0.4 mmHg, respectively). Measurements were then repeated in the presence of BQ-123. BQ-123 decreased pulmonary vascular resistance (PVR) 26% and systemic vascular resistance (SVR) 21%, whereas it increased cardiac output (CO) 22% (all P < 0.05). Hypoxia raised CO 28% and PVR 95%, whereas it reduced SVR 23% (all P< 0.01). During BQ-123 infusion, hypoxia increased CO 29% and PVR 97% and decreased SVR 22% (all P < 0.01). The pulmonary vasoconstrictive response to hypoxia was similar in the absence and presence of BQ-123 [ P = not significant (NS)]. In vehicle-treated control subjects, hypoxic pulmonary vasoconstriction did not change with repeated exposure to hypoxia ( P = NS). Endothelin contributes to basal pulmonary and systemic vascular tone during normoxia, but does not mediate the additional pulmonary vasoconstriction induced by acute hypoxia.

Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography

2003 ◽  
Vol 94 (4) ◽  
pp. 1543-1551 ◽  
Author(s):  
George M. Balanos ◽  
Nicholas P. Talbot ◽  
Keith L. Dorrington ◽  
Peter A. Robbins
Keyword(s):  
Pulmonary Hypertension ◽  
Pressure Gradient ◽  
Doppler Echocardiography ◽  
Time Course ◽  
Vascular Tone ◽  
Animal Experiments ◽  
Vascular Response ◽  
Circulatory Response ◽  
Breathing Control ◽  
End Tidal

Hypercapnia has been shown in animal experiments to induce pulmonary hypertension. This study measured the sensitivity and time course of the human pulmonary vascular response to sustained (4 h) hypercapnia and hypocapnia. Twelve volunteers undertook three protocols: 1) 4-h euoxic (end-tidal Po 2 = 100 Torr) hypercapnia (end-tidal Pco 2 was 10 Torr above normal), followed by 2 h of recovery with euoxic eucapnia; 2) 4-h euoxic hypocapnia (end-tidal Pco 2 was 10 Torr below normal) followed by 2 h of recovery; and 3) 6-h air breathing (control). Pulmonary vascular resistance was assessed at 0.5- to 1-h intervals by using Doppler echocardiography via the maximum tricuspid pressure gradient during systole. Results show progressive changes in pressure gradient over 1–2 h after the onset or offset of the stimuli, and sensitivities of 0.6 to 1 Torr change in pressure gradient per Torr change in end-tidal Pco 2. The human pulmonary circulatory response to changes in Pco 2 has a slower time course and greater sensitivity than is commonly assumed. Vascular tone in the normal pulmonary circulation is substantial.

Vascular adaptations to hypoxia: molecular and cellular mechanisms regulating vascular tone

2007 ◽  
Vol 43 ◽  
pp. 105-120 ◽  
Author(s):  
Michael L. Paffett ◽  
Benjimen R. Walker
Keyword(s):  
Vascular Tone ◽  
Cellular Proliferation ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Hypoxia Inducible Factor ◽  
Systemic Circulation ◽  
Cellular Mechanisms ◽  
Hypoxia Inducible Factor 1 ◽  
Pulmonary Vasoconstriction ◽  
Adaptive Mechanisms ◽  
Adaptive Processes

Several molecular and cellular adaptive mechanisms to hypoxia exist within the vasculature. Many of these processes involve oxygen sensing which is transduced into mediators of vasoconstriction in the pulmonary circulation and vasodilation in the systemic circulation. A variety of oxygen-responsive pathways, such as HIF (hypoxia-inducible factor)-1 and HOs (haem oxygenases), contribute to the overall adaptive process during hypoxia and are currently an area of intense research. Generation of ROS (reactive oxygen species) may also differentially regulate vascular tone in these circulations. Potential candidates underlying the divergent responses between the systemic and pulmonary circulations may include Nox (NADPH oxidase)-derived ROS and mitochondrial-derived ROS. In addition to alterations in ROS production governing vascular tone in the hypoxic setting, other vascular adaptations are likely to be involved. HPV (hypoxic pulmonary vasoconstriction) and CH (chronic hypoxia)-induced alterations in cellular proliferation, ionic conductances and changes in the contractile apparatus sensitivity to calcium, all occur as adaptive processes within the vasculature.

Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1

2002 ◽  
Vol 92 (6) ◽  
pp. 2501-2507 ◽  
Author(s):  
George M. Balanos ◽  
Keith L. Dorrington ◽  
Peter A. Robbins
Keyword(s):  
Pressure Gradient ◽  
Continuous Infusion ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Gene Activation ◽  
Maximum Pressure ◽  
Vascular Response ◽  
Vascular Regulation ◽  
End Tidal

Hypoxia-inducible factor (HIF)-1 is stabilized by hypoxia and iron chelation. We hypothesized that HIF-1 might be involved in pulmonary vascular regulation and that infusion of desferrioxamine over 8 h would consequently mimic hypoxia and elevate pulmonary vascular resistance. In study A, we characterized the pulmonary vascular response to 4 h of isocapnic hypoxia; in study B, we measured the pulmonary vascular response to 8 h of desferrioxamine infusion. For study A, 11 volunteers undertook two protocols: 1) 4 h of isocapnic hypoxia (end-tidal Po2= 50 Torr), followed by 2 h of recovery with isocapnic euoxia (end-tidal Po2= 100 Torr), and 2) 6 h of air breathing (control). For study B, nine volunteers undertook two protocols while breathing air: 1) continuous infusion of desferrioxamine (4 g/70 kg) over 8 h and 2) continuous infusion of saline over 8 h (control). In both studies, pulmonary vascular resistance was assessed at 0.5- to 1-h intervals by Doppler echocardiography via the maximum pressure gradient during systole across the tricuspid valve. Results show a progressive rise in pressure gradient over the first 3–4 h with both isocapnic hypoxia ( P < 0.001) and desferrioxamine infusion ( P < 0.005) to increases of ∼16 and 4 Torr, respectively. These results support a role for HIF-regulated gene activation in human hypoxic pulmonary vasoconstriction.

Preservation of Hypoxic Pulmonary Vasoconstriction during Sevoflurane and Desflurane Anesthesia Compared to the Conscious State in Chronically Instrumented Dogs 

1998 ◽  
Vol 89 (6) ◽  
pp. 1501-1508 ◽  
Author(s):  
Marc A. Lesitsky ◽  
Steve Davis ◽  
Paul A. Murray
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Main Pulmonary Artery ◽  
General Characteristic ◽  
Face Mask ◽  
Conscious State ◽  
Pressure Flow ◽  
Pulmonary Vasoconstriction ◽  
End Tidal ◽  
The Right ◽  
Chronically Instrumented Dogs

Background The authors' objective was to assess the extent to which sevoflurane and desflurane anesthesia alter the magnitude of hypoxic pulmonary vasoconstriction compared with the response measured in the same animal in the conscious state. Methods Left pulmonary vascular pressure-flow plots were generated in seven chronically instrumented dogs by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure-left atrial pressure) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. Pressure-flow plots were generated during normoxia and hypoxia on separate days in the conscious state, during sevoflurane (approximately 3.5% end-tidal), and during desflurane (approximately 10.5% end-tidal) anesthesia. Values are mean+/-SEM. Results In the conscious state, administration of the hypoxic gas mixture by conical face mask decreased (P &lt; 0.01) systemic arterial PO2 from 94+/-2 mmHg to 50+/-1 mmHg and caused a leftward shift (P &lt; 0.01) in the pressure-flow relationship, indicating pulmonary vasoconstriction. The magnitude of hypoxic pulmonary vasoconstriction in the conscious state was flow-dependent (P &lt; 0.01). Neither anesthetic had an effect on the baseline pressure-flow relationship during normoxia. The magnitude of hypoxic pulmonary vasoconstriction during sevoflurane and desflurane was also flow-dependent (P &lt; 0.01). Moreover, at any given value of flow the magnitude of hypoxic pulmonary vasoconstriction was similar during sevoflurane and desflurane compared with the conscious state. Conclusion These results indicate that hypoxic pulmonary vasoconstriction is preserved during sevoflurane and desflurane anesthesia compared with the conscious state. Thus, inhibition of hypoxic pulmonary vasoconstriction is not a general characteristic of inhalational anesthetics. The flow-dependent nature of the response should be considered when assessing the effects of physiologic or pharmacologic interventions on the magnitude of hypoxic pulmonary vasoconstriction.

Sign in / Sign up

Export Citation Format

Share Document