Molekularni mehanizmi vazoplegije

master's thesis

• Title (english): Molecular mechanisms of vasoplegic syndrome
• Author: Deni Rkman
• Mentor: Frane Paić (mentor)
• Committee member: Igor Rudež (predsjednik povjerenstva)
• Committee member: Ljiljana Šerman (član povjerenstva)
• Committee member: Frane Paić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Biology); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Vazoplegija predstavlja gubitak tonusa krvnih žila koji nastankom vazodilatacije i
hipotenzije dovodi do distributivnog oblika šoka. Vazoplegični sindrom (VS) karakterizira
hipotenzija uz smanjenu sistemsku vaskularnu rezistenciju (SVR) što može dovesti do
hipoperfuzije organa unatoč normalnom ili povećanom srčanom volumenu. Javlja se u
9% do 44% bolesnika nakon postavljanja kardiopulmonalne premosnice. Transplantacija
srca, opekline i sepsa neki su od čimbenika rizika koji mogu dovesti do vazoplegije.
Molekularni mehanizmi koji dovode do vazoplegije su složeni, brojni i ne do kraja
razjašnjeni. Inducibilna dušik oksid sintetaza (iNOS) čija je ekspresija u ovom stanju
povećana, kao odgovor na čimbenike upale proizvodi povećanu koncentraciju dušičnog
oksida (NO). Putem povećanja intracelularne koncentracije cikličkog gvanozinmonofosfata
(cGMP) onemogućuje vazokonstrikciju koja dovodi do hipotenzije.
Povećana koncentracija NO i smanjena koncentracija vazopresina aktivacijom KATP
kanala dovode do hiperpolarizacije stanične membrane koja sprječava ulazak kalcija
putem kalcijskih naponskih kanala. Prostaciklini, endotelin-1, sumporovodik,
komponentne komplementa, slobodni radikali, kortikosteroidi i rezistencija na
kateholamine također imaju ulogu u nastanku vazoplegije. U nemogućnosti terapije
noradrenalinom i vazopresinom, potencijalne putevi liječenja predstavljaju metilensko
modrilo, hidroksikobalamin, hidrokortizon, vitamin C, angiotenzin II, agonisti α1 i blokatori
β2 receptora. Daljnja istraživanja su potrebna da se pronađe adekvatan režim liječenja.

Abstract (english)

Vasoplegia is a loss of vascular muscle tone which leads to distributive shock by the
vasodilation and hypotension. Vasoplegic syndrome (VS) is characterized by
hypotension with reduced systemic vascular resistance (SVR) which can lead to
hypoperfusion of the organs despite normal or increased cardiac output. It occurs in 9%
to 44% of patients after cardiopulmonary bypass surgery. Heart transplantation, burns
and sepsis represent some of the clinical factors that can cause vasoplegia. Molecular
mechanisms leading to vasoplegia are complex, numerous and not entirely clarified.
Inducible nitric oxide synthase (iNOS) which expression in this condition is increased,
produces an increased concentration of nitric oxide (NO) in response to inflammatory
factors. By increasing the intracellular concentration of cyclic guanosine monophosphate
(cGMP), it prevents vasoconstriction which leads to hypotension. Increased NO
concentration and decreased vasopressin concentrations by activation of KATP channels
result with hyperpolarization of cell membrane that prevents calcium influx through
voltage-gated calcium channels. Prostacylins, endothelin-1, hydrogen sulphide,
complement components, free radicals, corticosteroids and catecholamine resistance
also have the role in aetiology of vasoplegic syndrome. When patients become refractory
to noradrenaline and vasopressin, the potential treatment modalities include methylene
blue, hydroxycobalamin, hydrocortisone, vitamin C, angiotensin II, α1 agonists and β2
receptor blockers. Further research is needed to find the adequate treatment regimen.

• Keywords: vazoplegija; vazoplegični sindrom (VS); dušikov oksid (NO); KATP kanali
• Keywords (english): vasoplegia; vasoplegic syndrome (VS); nitrogen oxide (NO); KATP channel
• Language: croatian
• URN:NBN: urn:nbn:hr:105:396049
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2020-02-17 15:35:22