Analiza sistemica a procesului de reglare cardiovascular. - Rezumat

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1 Analiza sistemica a procesului de reglare cardiovascular - Rezumat Doctorand: ing. Alexandru Codrean Conducător științific: prof. univ. dr. ing. Toma-Leonida Dragomir 1. Introducere Analiza sistemica a sistemelor biomedicale reprezinta o provocare actuala a comunitatii stiintifice. Din punct de vedere practic, complexitatea diverselor afectiuni patologice descoperite, precum si a metodelor de tratament (de la medicamente la echipamente) adoptate impun o solutie sistemica, care sa creasca eficienta dar si sa conduca la solutii noi (non-intuitive). In acest context, analiza sistemului cardiovascular impreuna cu mecanismele de reglare specifice prezinta o prioritate, datorita ratei mari a mortalitatii in urma afectiunilor cardiovasculare din lumea intreaga. Studiul de fata is propune sa faca o serie de primi pasi in aceasta drectie, analizand sistemic reglarea cardiovasculara intreprinsa de catre sistemul nervos mai exact mecanismul baroreflex. Desi exista multe modele in literatura care surprind reglarea cardiovasculara (la nivelul mecanismului baroreflex), marea parte a studiilor de analiza sunt intreprinse la nivel de simulari pe scenarii particulare. Datorita complexitatii modelelor multiple neliniaritati, sisteme de mari dimensiuni o analiza sistemica (e.g. studiu de stabilitate, robustete) nu este fezabila. Din aceste motive, in studiul de fata s-a urmarit analiza stabilitatii reglarii cardivasculare pe un model calitativ cat mai simplu, dar care sa suprinda totusi dinamica de baza a sistemului vizat. Rezultatele obtinute arata ca astfel de analize pot conduce la o mai buna intelegere din punct de vedere functional al posibilelor patologii la nivelul reglarii cardiovasculare, ceea ce ar putea conduce in viitor la imbunatatiri a metodelor de diagnoza si tratament.

2 2. Conținutul tezei Teza incepe cu o scurta introducere (Capitolul 1) care include motivatia asupra intregului studiu, notiuni preliminare despre sistemele biomedicale in general si despre reglarea cardiovasculara in particular, precum si notiuni preliminare despre sisteme neliniare, clase de sisteme neliniare, si metode de analiza. Capitolul 2 contine tot ce se refera la partea de modelare matematica, simplificarea modelelor, mediere, iar in final validarea modelelor prin simulari. Dupa o scurta motivatie asupra nevoii de a lucra cu modele atat de simple pe cat este posibil, modelul sistemului cardiovascular adoptatat din literatura este prezentat si explicat. Apoi modelul este adus la forma unui sistem liniar cu comutatii. Intr-un al doilea pas, in faza de modelare, un model pentru mecanismul baroreflex este adoptat din literatura si adus la o forma simplificata. Modelul in bucla inchisa (pulsatil) al reglarii cardiovasculare este mai departe obtinut prin cuplarea modelelor sistemului cardiovascular si mecanismului baroreflex, si prin luarea in considerare a interactiunulor care apar atat pe calea directa cat si pe calea de reactie. In final, dupa adaptarea metodei conventionale de mediere astfel incat sa suporte si sisteme cu impulsuri modulate in frecventa asa cum este in cazul reglarii cardiovasculare un model in bucla inchisa mediat al reglarii cardiovasculare este obtinut. Rezultatele de simulare, atat in bucla deschisa cat si in bucla inchisa, arata ca modelul mediat surpinde dinamica de baza a sistemului original (pulsatil). Validarea modelelor este realizata de asemenea prin simulari, comparand rezultatele obtinute pentru un scenariu pathologic hemoragie cu data experimentale din literatura. Capitolul 3 furnizeaza un cadru teorertic pentru metoda de mediere dezvoltata in capitolul anterior. Capitolul incepe cu o scurta sinteza in legatura cu metodele de mediere dezvoltate in literatura de-a lungul anilor. Mai departe, formularea problemei defineste clasa de sisteme luata in considerare sisteme cu impulsuri modulate in frecventa cu factor de umplere constant si defineste obiectivul studiului: sa conduca la obtinerea unei metode de mediere care aproximeaza sistemul original intr-o anumita margine de eroare, iar sistemul mediat rezultat sa fie dependent de perioada de modulatie. Cadrul teoretic prezentat mai departe este compus din trei teoreme adaptate din literatura (care apeleaza la teoria perturbatiei) la aceasta clasa noua de sisteme. In ultima parte a studiului o descriere pas cu pas este furnizata, asupra modalitatii in care metoda de mediere propusa poate fi folosita intr-un studiu de caz referitor la sistemul cardiovascular, indicand maniera in care se pot adresa diversele probleme de natura practica care apar pe parcurs. Rezultatele numerice de la final, obtinute prin simulari, ilustreaza eficienta metodei de mediere propusa. Cea mai elaborata parte a tezei este data de Capitolul 4, care se refera la analiza sistemica a reglarii cardiovasculare obiectivul principal al tezei, atat la nivel local cat si la nivel global. Analiza locala a stabilitatii utilizeaza un model

3 liniarizat in jurul punctului de echilibru. Accentul cade mai departe pe rolul timpilor morti multipli in generarea unui comportament stabil sau instabil. Dupa evidentierea faptului ca problema timpilor morti multipli este una recenta, cu putine metode raportate in literatura de specialitate, cea mai potrivita metoda de stabilitate gasita in literatura este prezentata metoda care furnizeaza conditii necesar si suficiente de stabilitate. Rezultatele numerice consista in harti de stabilitate pentru anumite coordonate ale timpilor morti impuse a priori in raport cu anumite scenarii patologice. Urmeaza o discutie asupra interpretarii rezultatelor, concluzionand ca de multe ori se dovedeste a fi mai importanta interactiunea dintre timpii morti multipli, decat valorile absolute ale timpilor morti luati independenti. Asta inseamna ca o scadere a valorii specifice unui anumit timp mort nu conduce neaparat la o imbunatare a stabilitatii, ci din contra, poate conduce chiar la deteriorarea stabilitatii. Analiza globala utilieaza teoria contractiei cu referire la sistemele convergente in care dinamica sistemelor este descrisa in termeni de traiectorii (solutii) nominale catre care toate celelalte traiectorii (solutii) converg. Conditiile pentru care un sistem este convergent sunt prezentate mai departe, impreuna cu un studiu de caz referitor la reglarea cardiovasculara. Scenariile din simulari confirma aspectele referitoare la proprietatea de convergenta (contractie) a sistemului in cauza. Ca si o extensie a studiului, problema robustetii este abordata, aratand ca sistemul este robust in raport cu incertitudini parametrice sau cu un anumit tip de perturbatii (rezultatele numerice permit delimitarea unei zone de incertitudine in care sistemului isi mentine proprietatea de convergenta). Urmeaza o scurta discutie asupra principalelor aspecte caracteristice prin care reglarea cardiovasculara se asemenea cu un sistem automat. Concluzia de final mentioneaza ca reglarea cardiovasculara, ca si sistem, nu este stabila independenta de timpii morti, dar este convergenta independent de timpii morti. Capitolul 5 prezinta concluziile finale ale intregului studiu, subliniaza principalele contributii stiintifice originale, alaturi de un scurt rezumat al tezei, iar in final indica posibilele directii de cercetari ulterioare.

4 3. Contribuții Principalele contribuții ale tezei sunt: Dezvoltarea unui model mediat simplificat al reglarii cardiovasculare pornind de la un model pentru sistemul cardiovascular si un model pentru sistemul baroreflex din literatura. Dezvoltarea unei noi metode de mediere impreuna cu cadrul sau teoretic,. care poate fi aplicata nu numai pentru sistemul cardiovascular, ci si pentru o clasa intreaga de sisteme neliniare. O analiza a stabilitatii locale a reglarii cardiovasculare care evidentiaza rolul timpilor morti multipli in generarea stabilitatii sau instabilitatii, impreuna cu posibilele implicatii fiziologice. O analiza globala a stabilitatii reglarii cardiovasculare care evidentiaza proprietati precum convergenta traiectoriilor si marginire, impreuna cu un studiu de robustete in raport cu incertitudini parametrice.

5 4. Lucrări publicate Teza de doctorat este susținută de următoarele publicații: Stefan O., Codrean A., Dragomir T.-L., A Network Control Structure with a Switched PD Delay Compensator and a Nonlinear Network Model, American Control Conference (ACC), Washington, USA, 2013, pp (IEEE Xplore, ISI). Codrean A., Dragomir T.-L., Averaged modeling of the cardiovascular system, IEEE 52nd Annual Conference on Decision and Control (CDC), Florence, Italy, 2013, pp (IEEE Xplore, ISI) Codrean A., Dragomir T.-L., Period dependent averaging of a class of pulse modulated systems. Application to the cardiovascular system, Journal of Control Engineering an Applied Informatics (CEAI), vol. 17, no. 1, 2015, pp (ISI, Scopus) Codrean A., Dragomir T.-L., Delay effect on cardiovascular regulation - a systems analysis approach, European Control Conference (ECC), Linz, Austria, 2015, in press. (IEEE Xplore, ISI) Codrean A., Dragomir T.-L., Stability analysis of cardiovascular regulation, 23rd Mediterranean Conference on Control and Automation (MED), Torremolinos, Spain, 2015, accepted. (IEEE Xplore, Scopus)

6 5. Bibliografie selectivă [1] M. Ursino, Interaction between carotid baroregulation and the pulsating heart: a mathematical model, Am. J. Physiol. Heart Circ. Physiol., vol. 275, 1998, pp [2] R Sipahi, II Delice, Advanced clustering with frequency sweeping methodology for the stability analysis of multiple time-delay systems, IEEE Transactions on Automatic Control, vol. 56, no. 2, pp , [3] T. Heldt, J.L. Chang, J.J.S. Chen, G.C. Verghese, and R.G. Mark, Cycleaveraged dynamics of a periodically driven, closed-loop circulation model, Control Engineering Practice, Vol. 13, pp , 2005 [4] W. Lohmiller and J.J. Slotine, On contraction analysis for non-linear systems, Automatica, vol. 34, no. 6, 1998, pp [5] H.K. Khalil, Nonlinear Systems, 3rd Edition, Prentice-Hall, [6] Guyton A. C., Hall J. E., Textbook of Medical Physiology, 11th Edition, Elsevier Saunders, [7] C. Pedicini, F. Vasca, L. Iannelli, and U. Jonsson, An Overview on Averaging for Pulse-modulated Switched Systems, in Proc. of 50th IEEE Conference on Decision and Control and European Control Conference, Orlando, 2011, pp [8] S.I. Niculescu, Delay Effects on Stability, Springer-Verlag, [9] R. Freeman, Autonomic peripheral neuropathy, The Lancet, vol. 365, no. 9466, pp , 2005.

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