1. Opening and effects of intrapulmonary arteriovenous anastomoses and patent foramen ovale on arterial oxygenation and systemic microembolisation
- Author
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Lozo, Mislav, Dujić, Željko, Valić, Zoran, Fabijanić, Damir, and Samaržija, Miroslav
- Subjects
Heart Failure ,Arteriovenska anastomoza ,Pluća ,Pulmonary Hypertension ,Physiology ,Arteriovenous Anastomosis ,Transkranijalni Doppler ultrazvuk ,Patent Foramen Ovale ,Ehokardiografija ,Zatajenje srca ,Transcranial Doppler Ultrasonography ,udc:612(043.3) ,Plućna hipertenzija ,BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences. Human Physiology ,Fiziologija ,Echocardiography ,Otvoreni foramen ovale ,BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti. Fiziologija čovjeka ,Lung - Abstract
IPAVA su krvne žile velikog promjera 15-500 μm (čak i do 1000 μm), prisutne u >95% zdravih osoba, dok je PFO prisutan u ~ 1/3 opće populacije i oboje predstavljaju mogući izvor desno-lijevog šanta. U Studiji I smo istražili učinak nitroglicerina, noradrenalina i aminofilina na otvaranje i novačenje intrapulmonalnih arteriovenskih anastomoza u zdravih ispitanika u mirovanju. Ovi lijekovi primijenjeni u ranije navednim dozama nisu imali učinka na filtrirajuću sposobnost pluća u zdravih ljudi u mirovanju. Čini se da ovi lijekovi nemaju utjecaja na otvaranje i novačenje IPAVA, krvnih žila velikog promjera, kako direktnim (putem receptora) tako niti indirektnim (putem povećanja tlaka ili protoka) učinkom. Unatoč njihovim različitim vazoaktivnim i hemodinamskim učincima, nijedan od lijekova nije uzrokovao značajan porast srčanog minutnog volumena i/ili sistoličkog tlaka u plućnoj arteriji stimulusa ranije dokazanih da pasivno otvaraju i novače IPAVA. Naposljetku valja naglasiti da primjena ovih lijekova, u navedenim dozama, ne otvara mogući put za sistemsku embolizaciju vitalnih organa. U Studiji II smo istražili mogući doprinos protoka krvi kroz IPAVA-e i PFO na arterijsku hipoksemiju u CHF bolesnika sa i bez plućne hipertenzije. Otkrili smo da je arterijska hipoksemija u mirovanju bila prisutna samo kod CHF PH+ bolesnika s PFO-om. S obzirom da protok krvi kroz IPAVA-e nije bio prisutan ili je bio beznačajan, čak i kod onih s plućnom hipertenzijom, zaključujemo da protok krvi kroz IPAVA-e nije pod utjecajem povećanog tlaka u plućnoj arteriji te da isti ne pridonosi arterijskoj hipoksemiji kod ovih bolesnika. Pridonosi li PFO vježbanjem induciranoj arterijskoj hipoksemiji u CHF bolesnika ostaje nepoznato. Podatci dobiveni u ovoj studiji, kao i prethodno publicirani, dokazuju da starenje negativno utječe na IPAVA-e, što podrazumijeva da se sa povećanjem životne dobi protok krvi kroz IPAVA-e značajno smanjuje. Potrebno je istražiti kakve su posljedice, ako ih ima, povezane s tim smanjenjem. Također, u ovoj studiji smo dokazali izvrsnu podudarnost detekcije i kvantificiranja desno-lijevog šanta (protok krvi kroz IPAVA-e i/ili PFO) transtorakalnom kontrastnom ehokardiografijom i transkranijskim doplerom. Dakle, obje metode mogu poslužiti za istu svrhu, što je osobito značajno kada izvođenje jedne od njih nije podobno ili nije moguće. Kirurško/intervencijsko zatvaranje PFO-a može se uraditi zbog različitih indikacija, kao što su, npr. preboljeni ishemijski moždani udar ili tranzitorna ishemijska ataka. Međutim, s obzirom da PFO pridonosi arterijskoj hipoksemiji u CHF bolesnika s plućnom hipertenzijom, ova grupa bolesnika mogla bi profitirati od zatvaranja PFO-a s ciljem da se poboljša i oksigenacija, osobito u onih s težim stupnjem hipoksemije. Postojanje IPAVA je poznato najmanje posljednjih 50 godina, međutim, njihova fiziološka i klinička značajnost nije do kraja istražena. Iako, trenutno predložene uloge uključuju mogućnost alternativnog puta embolima iz venskog sustava da dosegnu sistemsku cirkulaciju, zatim da služe kao paralelna vaskularna mreža, koja se u određenim uvjetima otvara za preusmjeravanje potencijalno štetne hidrodinamske energije od krhkih plućnih kapilara čime čine desno-lijevi šant, zbog čega mogu negativno utjecati na plućnu izmjenu plinova. Proučavanje protoka krvi kroz IPAVA-e i PFO predstavlja značajno istraživačko područje s ciljem da se predložene uloge bolje odrede, zbog čega detektiranje i kvantificiranje protoka kroz IPAVA-e i PFO može postati mnogo važnije i u kliničkoj praksi., IPAVA are large diameter 15-500 μm (up to 1000 μm) vascular conduits, present in >95% of healthy humans, while PFO is present in ~ 1/3 of general population and both represent possible source of right to left shunt. In Study I we investigated the effects of nitroglicerine, norepinephrine and aminophylline on opening and recruitment of intrapulmonary arteriovenous anastomoses in healty humans at rest. We found that these drugs applied in above named doses did not seem to modify the filtering capability of the lung in healthy humans at rest which speakes in fovour that drugs are not affecting the large-diameter inducible intrapulmonary arteriovenous anastomoses by direct effect on opening and recruitment of the IPAVA (via receptors) nor indirect (via increase in pressure and flow). Despite their various vasoactive and hemodynamic effects, none of the drugs caused a substantial increase in QT and/or PASP, stimuli previously shown to passively open IPAVA. Finally, application of these drugs, in named doses, does not open the pathway for systemic micro/embolization of vital organs. However, further research is needed to examine their effect on IPAVA during physical activity intensities required for ordinary daily activities or in moderate and strenuous exercise as well as in others than healthy subjects. In Study II we examined the potential contributions of blood flow through IPAVA and PFO to arterial hypoxaemia in subjects with CHF with and without pulmonary hypertension. We found that arterial hypoxaemia at rest was present in CHF PH+ subjects with PFO. Given that blood flow through IPAVA was absent or insignificant, even in those subjects with pulmonary hypertension, we conclude that blood flow through IPAVA is not influenced by increased pulmonary pressures and does not contribute to arterial hypoxaemia in these subjects. Whether or not PFO contributes to exercise-induced arterial hypoxaemia in subjects with CHF remains unknown. Data from our study and previous data indicate that aging process may negatively affect IPAVA, assuming that blood flow through IPAVA is reduced with increasing age. We still need to investigate what consequences, if any, are associated with this decline. Also, in this study we have shown excellent correlation between detection and quantification of right to left shunt (blood flow through IPAVA and /or PFO) using transthoracic contrast echocardiography and transcranial Doppler. Thus, both methods can be used for the same purpose which is especially important when performing one of them is not suitable or possible. Surgical closure of the PFO may be undertaken for various reasons, such as history of stroke or transient ischaemic attack, yet PFO closure for this purpose remains controversial. However, because PFO contributes to arterial hypoxaemia in subjects with CHF and pulmonary hypertension, these specific subjects may also benefit from PFO closure as an intervention to improve oxygenation, particularly in those subjects with more severe levels of hypoxaemia. IPAVA have been known to exist for over 50 years, but their physiological and clinical significance are still being established; although, currently suggested roles for IPAVA include allowing emboli to reach the systemic circulation, also serve as a parallel vascular network that under certain conditions open to divert potentially damaging hydrodynamic energy from fragile pulmonary capillaries thus creating the right to left shunt which could adversely affect the pulmonary gas exchange. Studying blood flow through IPAVA, as well as through PFO, is an important area of research and as the suggested roles become better established, detecting and quantifying flow throug IPAVA and PFO may become significantly more important in the clinic.
- Published
- 2023