Hypoxia and Exercise Increase the Transpulmonary Passage of 99mTc-Labeled Albumin Particles in Humans

Experimental Physiology

Tymko

et al. 2017

What is the central question of this study? The aim was to determine, using the technique of agitated saline contrast echocardiography, whether exercise after 4-7 days at 5050 m would affect blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) compared with exercise at sea level. What is the main finding and its importance? Despite a significant increase in both cardiac output and pulmonary pressure during exercise at high altitude, there is very little Q̇IPAVA at rest or during exercise after 4-7 days of acclimatization. Mathematical modelling suggests that bubble instability at high altitude is an unlikely explanation for the reduced Q̇IPAVA. Blood flow through intrapulmonary arteriovenous anastomoses (Q̇IPAVA) is elevated during exercise at sea level (SL) and at rest in acute normobaric hypoxia. After high altitude (HA) acclimatization, resting Q̇IPAVA is similar to that at SL, but it is unknown whether this is true during exercise at HA. We reasoned that exercise at HA (5050 m) would exacerbate Q̇IPAVA as a result of heightened pulmonary arterial pressure. Using a supine cycle ergometer, seven healthy adults free from intracardiac shunts underwent an incremental exercise test at SL [25, 50 and 75% of SL peak oxygen consumption (V̇O2 peak )] and at HA (25 and 50% of SL V̇O2 peak ). Echocardiography was used to determine cardiac output (Q̇) and pulmonary artery systolic pressure (PASP), and agitated saline contrast was used to determine Q̇IPAVA (bubble score; 0-5). The principal findings were as follows: (i) Q̇ was similar at SL rest (3.9 ± 0.47 l min ) compared with HA rest (4.5 ± 0.49 l min ; P = 0.382), but increased from rest during both SL and HA exercise (P < 0.001); (ii) PASP increased from SL rest (19.2 ± 0.7 mmHg) to HA rest (33.7 ± 2.8 mmHg; P = 0.001) and, compared with SL, PASP was further elevated during HA exercise (P = 0.003); (iii) Q̇IPAVA was increased from SL rest (0) to HA rest (median = 1; P = 0.04) and increased from resting values during SL exercise (P < 0.05), but was unchanged during HA exercise (P = 0.91), despite significant increases in Q̇ and PASP. Theoretical modelling of microbubble dissolution suggests that the lack of Q̇IPAVA in response to exercise at HA is unlikely to be caused by saline contrast instability.

Section: Discussionmentioning

confidence: 98%

Reduced blood flow through intrapulmonary arteriovenous anastomoses during exercise in lowlanders acclimatizing to high altitude

Boulet

Experimental Physiology

Tymko

et al. 2017

“…Mean

\overset{Q}{true}

IPAVA in seven subjects (3 female) has been measured to be 2.5% (±2.6%; range ∼ −0.5 to 7%) with

\overset{Q}{true}

IPAVA increasing in 5/7 subjects during cycle ergometer exercise at 85% of maximal capacity (Bates et al . ). These studies used MAA with a mean diameter of 20–40 μm and ∼90% of MAA between 10 and 90 μm in size.…”

Section: Introductionmentioning

confidence: 97%

“…To date, the majority of work in humans has used TTSCE to detect

\overset{Q}{true}

IPAVA ; however, recent work has demonstrated that

\overset{Q}{true}

IPAVA , measured using 99m Tc‐MAA, is ∼5% of

\overset{Q}{true}

T in healthy humans breathing 10% O 2 (Bates et al . ). Additionally, studies in dogs (Niden & Aviado, ) using microspheres 60–420 μm in diameter, and in rats (Bates et al .…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Intrapulmonary arteriovenous anastomoses in humans – response to exercise and the environment

The Journal of Physiology

Duke

Elliott

2015

Intrapulmonary arteriovenous anastomoses (IPAVA) have been known to exist in human lungs for over 60 years. The majority of the work in this area has largely focused on characterizing the conditions in which IPAVA blood flow (Q IPAVA ) is either increased, e.g. during exercise, acute normobaric hypoxia, and the intravenous infusion of catecholamines, or absent/decreased, e.g. at rest and in all conditions with alveolar hyperoxia (F IO 2 = 1.0). Additionally,Q IPAVA is present in utero and shortly after birth, but is reduced in older (>50 years) adults during exercise and with alveolar hypoxia, suggesting potential developmental origins and an effect of age. The physiological and pathophysiological roles ofQ IPAVA are only beginning to be understood and therefore these data remain controversial. Although evidence is accumulating in support of important roles in both health and disease, including associations with pulmonary arterial pressure, and adverse neurological sequelae, there is much work that remains to be done to fully understand the physiological and pathophysiological roles of IPAVA. The development of novel approaches to studying these pathways that can overcome the limitations of the currently employed techniques will greatly help to better quantifyQ IPAVA and identify the consequences ofQ IPAVA on physiological and pathophysiological processes. Nevertheless, based on currently published data, our proposed working model is thatQ IPAVA occurs due to passive recruitment under conditions of exercise and supine body posture, but can be further modified by active redistribution of pulmonary blood flow under hypoxic and hyperoxic conditions. AbbreviationsA − aD O2 , alveolar-to-arterial partial pressure of O 2 difference; C aO2 , arterial O 2 content; F IO2 , fraction of inspired oxygen; HHT, hereditary haemorrhagic telangiectasia; HPV, hypoxic pulmonary vasoconstriction; IPAVA, intrapulmonary arteriovenous anastomoses; MAA, macroaggregates of albumin; MIGET, multiple inert gas elimination technique; Pv O2 , mixed venous partial pressure of O 2 ; P aO2 , arterial partial pressure of O 2 ; PASP, pulmonary artery systolic pressure; PAVM, pulmonary arteriovenous malformation; PFO, patent foramen ovale; S aO2 , arterial O 2 saturation; S pO2 , peripheral estimate of arterial O 2 saturation; 99m Tc-MAA, technetium-99m-labelled MAA; TIA, transient ischaemic attack; TTSCE, transthoracic saline contrast echocardiography;Q T , cardiac output;Q IPAVA , blood flow through IPAVA;Q S /Q T , shunt fraction;V O2 , O 2 consumption, ventilation to perfusion ratio (V/Q ).Andrew Lovering, PhD, is an integrative physiologist who has investigated a wide range of respiratory system questions from understanding how medullary respiratory neurons reconfigure their activity during hypoxia-induced periodic breathing in sleeping cats to understanding the roles of intracardiac and intrapulmonary shunt on the regulation of pulmonary gas exchange efficiency in humans exercising above 5000 m; he thinks that the patent foramen ov...

“… b ; Bates et al . ). Despite the anatomical and biophysical evidence, the functional significance of IPAVA (if any) is unclear.…”

Section: Introductionmentioning

confidence: 97%

Hypoxia, not pulmonary vascular pressure, induces blood flow through intrapulmonary arteriovenous anastomoses

Tremblay

The Journal of Physiology

Ainslie

et al. 2014

Key pointsr Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased by acute hypoxia during rest by unknown mechanisms.r Oral administration of acetazolamide blunts the pulmonary vascular pressure response to acute hypoxia, thus permitting the observation of IPAVA blood flow with minimal pulmonary pressure change.r Hypoxic pulmonary vasoconstriction was attenuated in humans following acetazolamide administration and partially restored with bicarbonate infusion, indicating that the effects of acetazolamide on hypoxic pulmonary vasoconstriction may involve an interaction between arterial pH and P CO 2 .r We observed that IPAVA blood flow during hypoxia was similar before and after acetazolamide administration, even after acid-base status correction, indicating that pulmonary pressure, pH and P CO 2 are unlikely regulators of IPAVA blood flow.Abstract Blood flow through intrapulmonary arteriovenous anastomoses (IPAVA) is increased with exposure to acute hypoxia and has been associated with pulmonary artery systolic pressure (PASP). We aimed to determine the direct relationship between blood flow through IPAVA and PASP in 10 participants with no detectable intracardiac shunt by comparing: (1) isocapnic hypoxia (control); (2) isocapnic hypoxia with oral administration of acetazolamide (AZ; 250 mg, three times a day for 48 h) to prevent increases in PASP; and (3) isocapnic hypoxia with AZ and 8.4% NaHCO 3 infusion (AZ + HCO 3 -) to control for AZ-induced acidosis. Isocapnic hypoxia (20 min) was maintained by end-tidal forcing, blood flow through IPAVA was determined by agitated saline contrast echocardiography and PASP was estimated by Doppler ultrasound. Arterial blood samples were collected at rest before each isocapnic-hypoxia condition to determine pH, and P a,CO 2 . AZ decreased pH (-0.08 ± 0.01), (−7.1 ± 0.7 mmol l −1 ) and P a,CO 2 (−4.5 ± 1.4 mmHg; P < 0.01), while intravenous NaHCO 3 restored arterial blood gas parameters to control levels. Although PASP increased from baseline in all three hypoxic conditions (P < 0.05), a main effect of condition expressed an 11 ± 2% reduction in PASP from control (P < 0.001) following AZ administration while intravenous NaHCO 3 partially restored the PASP response to isocapnic hypoxia. Blood flow through IPAVA increased during exposure to isocapnic hypoxia (P < 0.01) and was unrelated to PASP, cardiac output and pulmonary vascular resistance for all conditions. In conclusion, isocapnic hypoxia induces blood flow through IPAVA independent of changes in PASP and the influence of AZ on the PASP response to isocapnic hypoxia is dependent upon the H + concentration or P a,CO 2 .