Experimental studies of the dissolution of gas bubbles in whole blood and plasma—II. Moving bubbles or liquids

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: 89%

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

Boulet

Experimental Physiology

Tymko

et al. 2017

“…A comprehensive review of the bubble physics literature is beyond the scope of this review, and as such we refer the reader to prior work in this area (Yang, ; Yang et al . ,b; Butler & Hills, ; Meltzer et al . , ; Roelandt, ; Meerbaum et al .…”

Section: Introductionmentioning

confidence: 99%

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...

“…Thus, when breathing 100% O 2 , the nitrogen within intravenously injected bubbles created from room air should very quickly diffuse out of the bubbles and cause them to dissolve down to ~20% of their original size. 16,17,74,89–91 Subsequently, other influences (e.g. surface tension, pressure, and flow), should further promote their rapid dissolution before the bubbles ever reach the left heart, regardless of the patency of intrapulmonary arteriovenous anastomoses.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary pathways and mechanisms regulating transpulmonary shunting into the general circulation: An update

Elliott

Beasley

et al. 2010

Injury

Embolic insults account for a significant number of neurologic sequelae following many routine surgical procedures. Clearly, these post-intervention embolic events are a serious public health issue as they are potentially life altering. However, the pathway these emboli utilize to bypass the pulmonary microcirculatory sieve in patients without an intracardiac shunt such as an atrial septal defect or patent foramen ovale, remains unclear. In the absence of intracardiac routes and large diameter pulmonary arteriovenous malformations, inducible large diameter intrapulmonary arteriovenous anastomoses in otherwise healthy adult humans may prove to be the best explanation. Our group and others have demonstrated that inducible large diameter intrapulmonary arteriovenous anastomoses are closed at rest but can open during hyperdynamic conditions such as exercise in more than 90% of healthy humans. Furthermore, the patency of these intrapulmonary anastomoses can be modulated through the fraction of inspired oxygen and by body positioning. Of particular clinical interest, there appears to be a strong association between arterial hypoxemia and neurologic insults, suggesting a breach in the filtering ability of the pulmonary microvasculature under these conditions. In this review, we present evidence demonstrating the existence of inducible intrapulmonary arteriovenous anastomoses in healthy humans that are modulated by exercise, oxygen tension and body positioning. Additionally, we identify several clinical conditions associated with both arterial hypoxemia and an increased risk for embolic insults. Finally, we suggest some precautionary measures that should be taken during interventions to keep intrapulmonary arteriovenous anastomoses closed in order to prevent or reduce the incidence of paradoxical embolism.