Fetalden yenidoğan dolaşımına geçişte kan akış dinamikleri: klinikteki prenatal ve perinatal müdahelelerin modellenmesi

Lumped parameter models (LPM) are used extensively for the investigation of the global adult and fetal circulatory blood flow physiology. A LPM is developed for the healthy fetal circulation at term. Two applications of the fetal LPM are the investigation of 1) the effect of umbilical cord clamping on the hemodynamics and gas exchange of the transition from fetal to neonatal circulation, 2) the impact of maternal hyperoxygenation on the arterial flow dynamics for the promotion of vascular growth in the hypoplastic left heart syndrome (HLHS) fetus. Hemodynamics of fetal to neonatal transition is orchestrated through complex physiological changes and results in cardiovascular adaptation to adult biventricular circulation. Clinical practice during this critical period can influence vital organ physiology both for normal newborns and for patients with congenital heart defects. Particularly, the cord clamping procedure, immediate (ICC) vs. delayed cord clamping (DCC) is observed to be an important factor for the transitory fetal hemodynamics. The clinical need for a quantitative understanding of this physiology motivated the development of a LPM of the fetal cardio-respiratory system covering late-gestation to neonatal period. In the first application, ICC and DCC procedures are investigated to elucidate their relative influence on the ventricular and respiratory performances during the transition to extrauterine circulation. LPM is validated and employed to predict the effects of cord clamping procedures on the hemodynamics and vital gases. We introduced clinical time-dependent resistance functions to simulate the vascular changes. For DCC, placental transfusion (53 ml) increased neonatal blood volume by 19.3%. This increased blood volume is reflected in an increase in preload pressures by 32% in left and by 73% in right ventricles compared to ICC , which in turn increased the cardiac output (CO) by 20% (COICC= 1148 ml/min; CODCC=1379 ml/min). Our model accurately predicted dynamic flow patterns in vivo. DCC was shown to maintain oxygenation if the onset of pulmonary respiration is delayed or impaired. On the other hand, significant decrease by 20-25% in oxygen saturations was observed in the ICC under the same physiological conditions. We conclude that DCC has a significant impact on newborn hemodynamics, mainly because of the improved blood volume, and the sustained placental respiration. The second application is devoted to the parametric investigation of the impact of pulmonary and ductus arteriosus (DA) vasomodeling under increased fetal oxygen tension on the steady and pulsatile flow dynamics in the aortic region of HLHS. LPM parameters are altered to model fetal HLHS circulation by decreasing the size of left ventricle and aortic vasculature. Vasoconstriction of the DA and vasodilatation in the pulmonary bed were modeled as an increase in the DA resistance (maximal increase by sixteen folds) and a decrease in the pulmonary vascular resistance (PVR) (maximal decrease by 75%). Vasoconstriction of ductus arteriosus and vasodilatation of pulmonary vasculature effectively improved the pulmonary venous return and the left ventricular output compared to baseline conditions. Pulsatile and mean flow rates in the ascending aorta and in the aortic arch increased by two folds under maximal hyperoxygenation conditions. Pulsatility index (PI) in the ascending aorta is consistent in all cases indicating that flow pulsatility changes proportionally with the mean aortic flow. PI in the DA decreases with increased DA resistance, and increased with decreased PVR. Chapter 1 is devoted to the introduction to the cardiovascular physiology and LPM. Chapter 2, Chapter 3, and Chapter 4 provides necessary background for the theroretical and numerical aspects of the governing equations employed in the hemodynamic and respiratory LPM. In Chapter 5, LPM of the fetal circulation is constructed and validated with clinical data. In Chapter 6 and Chapter 7, applications of umbilical cord clamping and maternal hyperoxygenation therapy are presented.