Title Akutno izazvan poremećaj protoka krvi pogoršava endotelnu disfunkciju u umjerenoj do vrlo teškoj kroničnoj opstrukcijskoj plućnoj bolesti Title (english) Disturbed blood flow worsens endothelial dysfunction in moderate-very severe chronic obstructive pulmonary disease Author Suzana Mladinov Mentor Željko Dujić (mentor)Committee member Marko Ljubković (predsjednik povjerenstva)Committee member Darko Duplančić (član povjerenstva)Committee member Miroslav Samaržija (član povjerenstva)Granter University of Split Defense date and country 2019, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Universal decimal classificationUDC ) 612 - Physiology Abstract Endotelna disfunkcija se smatra jednom od patofizioloških poveznica KOPB-a i kardiovaskularnih bolesti, koje su među najčešćim komorbiditetima i uzrocima smrti oboljelih od KOPB-a. Mehanizmi koji su odgovorni za poremećaj funkcije endotela s pro-aterogenim fenotipom endotelnih stanica u bolesnika s KOPB-om su u značajnoj mjeri još neistraženi. Cilj ovog istraživanja bio je ispitati u bolesnika sa stabilnim, napredovalim KOPB-om i kroničnom respiracijskom insuficijencijom hemodinamiku brahijalne arterije i pokazatelje endotelne funkcije: dilataciju brahijalne arterije posredovanu protokom (FMD) i plazmatsku koncentraciju endotelnih mikročestica (EMP). Također planirano je utvrditi pogoršava li akutni poremećaj protoka krvi, u obliku oscilirajućeg smičnog opterećenja, endotelnu funkciju te kakva je uloga kronične hipoksemije i njezine korekcije na hemodinamiku brahijalne arterije, poboljšava li korekcija hipoksemije akutnim udisanjem kisika endotelnu funkciju, odnosno štiti li je od eventualnog dodatnog pogoršanja induciranog oscilirajućim smičnim opterećenjem.
U 17 hipoksemičnih bolesnika s KOPB-om i 10 kontrolnih zdravih ispitanika odgovarajuće dobi ispitani su pri udisanju sobnog zraka: obrazac smicanja (antegradna stopa smicanja (aSR), retrogradna stopa smicanja (rSR) i oscilirajući smični indeks (OSI)), FMD brahijalne arterije te razina cirkulirajućih EMP-ova prije i nakon 20 minuta eksperimentalno induciranog oscilirajućeg smičnog opterećenja inflacijom podlaktične manžete na 75 mm Hg. Bolesnici s KOPB-om su ponovno podvrgnuti testiranju nakon korekcije hipoksemije 20-minutnim udisanjem kisika preko nosnih vila. U bolesnika s KOPB-om je, u odnosu na zdrave ispitanike, utvrđen oko šest puta veći bazalni rSR (p<0.05) te manji bazalni FMD (p<0.05). Intervencija oscilirajućim smicanjem je uzrokovala značajno smanjenje FMD-a u svim skupinama (p<0.01), dok je značajni porast plazmatske koncentracije biljega apoptoze, odnosno CD31+/CD41- EMP-ova, zabilježen samo u bolesnika s KOPB-om pri udisanju sobnog zraka. Normalizacijom oksigenacije je u bolesnika s KOPB-om poništeno povećanje CD31+/CD41- EMP-ova izazvano oscilirajućim smicanjem, a istovremeno je došlo do značajnog povećanja FMD-a uz korekciju za intenzitet podražaja smičnim opterećenjem i početni promjer brahijalne arterije. Pokazano je da akutni poremećaj protoka krvi s povećanim retrogradnim smicanjem u bolesnika sa stabilnim KOPB-om i kroničnom respiracijskom insuficijencijom dodatno pogoršava već oštećenu endotelnu funkciju, što je praćeno porastom cirkulirajućih biljega endotelne apoptoze. Rezultati ovog temeljnog istraživanja pridonose boljem razumijevanju kompleksnih mehanizama koji su odgovorni za fiziologiju endotela u zdravih ljudi, odnosno za pro-aterogeni fenotip endotelnih stanica u bolesnika s napredovalim KOPB-om i kroničnom respiracijskom insuficijencijom. Ovim je istraživanjem, također, potvrđena uloga kronične hipoksemije u ekspresiji vulnerabilnog endotelnog fenotipa te pokazan dodatni protektivni učinak terapije kisikom. S obzirom na povezanost endotelne disfunkcije i povećanog rizika od kardiovaskularnih bolesti u KOPB-u, očekuje se da bolje razumijevanje funkcije endotela pridonese boljoj fenotipizaciji bolesnika s KOPB-om i preciznijoj procjeni kardiovaskularnog rizika.
Abstract (english) Endothelial dysfunction is considered to be one of the pathophysiological links of COPD and cardiovascular diseases, which are among the most common comorbidities and causes of death in COPD. Mechanisms that are responsible for the endothelial dysfunction with pro-atherogenic phenotype of endothelial cells in COPD patients are significantly unexplored.
The aim of this study was to examine brachial artery hemodynamics and endothelial function indicators in patients with stable, advanced COPD and chronic respiratory insufficiency: flow-mediated dilation (FMD) of brachial artery and plasma concentration of endothelial microparticles (EMP). It was also planned to test whether acutely induced oscillatory shear stress worsens endothelial function in hypoxemic, stable COPD patients, how chronic hypoxemia and its correction influence brachial artery hemodynamics, whether acute low-flow oxygen administration improves endothelial function and if it is protective against potential oscillatory shear stress-induced endothelial dysfunction.
In 17 hypoxemic, stable COPD patients and 10 age-matched, non-smoking, healthy control subjects shear pattern (antegrade and retrograde shear rate (aSR and rSR), oscillatory shear index (OSI)), brachial artery FMD and circulating EMPs were examined during room air breathing before and after 20 minutes of experimentally-induced oscillatory shear stress (forearm cuff inflated to 75 mm Hg). COPD patients underwent the same protocol a second time following a 20-minute wash-in period of low-flow supplemental oxygen to normalize arterial oxygen saturation.
Compared to healthy controls, COPD patients had around six-fold greater baseline rSR (p<0.05) and lower baseline FMD (p<0.05). The oscillatory shear stress intervention induced significant decreases in brachial artery FMD of all groups (p<0.05) and significantly increased circulating markers of endothelial cell apoptosis (CD31+/CD41- EMPs) in COPD patients during room air breathing, but not age-matched controls. Supplemental oxygen administration abrogated the oscillatory shear stress-induced increase in CD31+/CD41- EMPs and improved FMD after accounting for the shear stress stimulus and brachial artery diameter.
It has been demonstrated that acutely disturbed blood flow, with increased retrograde shear stress, further deteriorates the already impaired endothelial function with attendant increase in circulating markers of endothelial apoptosis in patients with stable COPD and chronic respiratory insufficiency. The results of this fundamental research contribute to a better understanding of the complex mechanisms responsible for endothelial physiology in healthy people and for pro-atherogenic endothelial cell phenotype in patients with advanced COPD and chronic respiratory insufficiency. This research also confirmes the role of chronic hypoxemia in expressing a vulnerable endothelial phenotype and showes additional protective effect of oxygen therapy. Given the association between endothelial dysfunction and increased risk of cardiovascular disease in COPD, a better understanding of endothelial function is expected to contribute to better phenotyping of patients with COPD and a more accurate assessment of cardiovascular risk.
Keywords
kronična opstruktivna plućna bolest
endotel
krvotok
Keywords (english)
Chronic Obstructive Pulmonary Disease
Endothelium
Blood Circulation
Language croatian URN:NBN urn:nbn:hr:171:490642 Study programme Title: Evidence-Based Clinical Medicine Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2023-05-10 08:14:27
