本研究目標為探討反脈動(Counterpulsation)主動脈側血泵(Para-aortic Blood Pump;簡稱PABP)輔助對腦循環之影響。藉由本研究群發展出的傾斜式循環測試平台(Tilting-base Mock Circulation Loop)做實驗探討，以模擬重力(Gravity)對人體血液循環由臥姿至站姿的影響。本測試台依據混合循環模式(Hybrid Circulation Model)原理而設計，一維血管系統包含主要的左右心、主動脈、腦循環中樞的威利氏環(Circle of Willis)、頸動脈與上肢臂動脈，並與藉由區塊參數法所架構的體循環系統與肺循環系統接合。實驗中將血液循環分成健康狀態、心衰竭狀態以及反脈動輔助之情況作血動力特徵之模擬，依照反脈動輔助之性能指標參數及波強度分析法(Wave Intensity Analysis)進行探討分析。實驗時將血泵充氣時間點設置在最佳的主動脈瓣關閥時間點，並探討PABP洩氣時間對心臟卸載及腦部灌流之影響。結果發現在主動脈瓣開閥後 毫秒(msec)到 毫秒(msec)為PABP最佳卸載時間區域，其性能指標參數：心肌耗氧指標(Tension Time Index)減少4%，心肌養分供需比例(Endocardial Viability Ratio)增益49%，心輸出量(Cardiac Output)增益9.7%，冠狀動脈灌流(CoPerf)增益28%，內頸動脈灌流(ICAPerf)增益15.8%，前腦動脈灌流(ACAPerf)增益16.7%，中腦動脈灌流(MCAPerf)增益18.2%，後腦動脈灌流(PCAPerf)增益17.9%，脊椎動脈灌流(VAPerf) 增益19.3%。本研究發現隨著PABP卸載時間提前，導致PABP在收縮卸載時使腦循環產生較大的初始逆流，但不致造成腦部總灌流量的減少。由波強度分析可知，於反脈動輔助之下，PABP 卸載時間越早於主動脈瓣開閥點會協助左心室射血，減低左心室耗功量，產生高強度的正向膨脹波，使腦動脈壓力與流量降低，導致逆流偷血現象(Blood Steal)；反之，在主動脈瓣開閥點之後作動PABP 卸載，腦動脈壓力及正向膨脹波不會大幅下降，可減少卸載對腦灌流的逆流現象。在PABP 舒張強化時，皆能誘導出正向壓縮波，促使腦動脈流量與壓力升高，並產生高於未輔助時的波強度與灌流增益。在PABP不同輔助頻率(1:1, 1:2, 1:3)的情況下，其輔助頻率1:1對腦動脈的灌流增益最多，且隨著心博量減少，PABP的輔助效益越明顯。本研究發現在人體站姿的狀態下，PABP過早卸載會減少腦部的灌流，形成缺血現象。然而若選擇主動脈瓣開閥後卸載，無論重力效應為何，其反脈動輔助皆能有效的提供較佳的左心室卸載及腦部增益。

In order to study the influences on cerebral circulation when supported by a counter-pulsatile para-aortic blood pump (PABP), an experimental investigation using a specially designed tilting-base mock circulation loop was performed. This mock loop was constructed basing on a hybrid one-dimensional flow and lumped parameter circulation model. The base of the mock loop can tilt to simulate the gravity effect on human circulation from supine to vertical-up posture angles (0<ψ<90 deg). This mock loop consists of major cardiovascular components including left and right hearts, aorta, Circle of Willis, carotid arteries, brachial arteries while connected with the rest systemic and pulmonary segments represented by lumped resistors and compliance chambers. Hemodynamics characterized by healthy and heart failure conditions were generated, and the support efficacy of PABP counterpulsation was evaluated. Both traditional counterpulsation indices and wave intensity analysis (WIA) were employed in the assessment. Optimal PABP inflation was timed at aortic valve closure, and deflation timing around heart ejection was thoroughly studied to investigate the effect of PABP unloading on brain perfusion. Results show that the best PABP deflation timing locates around 25 to 50 millisecond after the aortic valve opening. When supported with such optimal inflation/deflation timing, it was shown that substantial gains in counterpulsatile effectiveness were achieved (tension time index 4%, endocardial viability ratio 49%, cardiac output 9.7%, and coronary perfusion 28%). The perfusion increases in internal carotid, anterior and middle cerebral arteries are ICAPerf 15.8%, ACAPerf 16.7%, MCAPerf 18.2%, PCAPerf 17.9% and VAPerf 19.3%, respectively. However, if unloading is operated using traditional deflation timing ahead of ejection, regurgitation in cerebral flow may occur at high posture angle close to vertical-up. Wave energy transported due to counterpulsation was examined using WIA. Strong suction wave was found with pre-systole unloading, which accompanied cerebral blood steal. For post-systole deflation timings, the native heart systolic compression wave merged with PABP-induced decompression wave, resulting in wave cancellation signified by smaller unloading wave strengths and reduced or completely annihilated cerebral blood steal. Study of support frequency shows that 1:1 mode achieved the highest efficacy compared to the other slower modes (1:2 and 1:3). Also, PABP counterpulsation performed better in decompressed heart, implying PABP is uniformly applicable to a wide range of moderate-to-severe heart failure patient cohort.

[1] Alastruey, J., Parker, K. H., Peiró, J., Byrd, S. M., Sherwin, S. J., “Modelling the circle of Willis to assess the effects of anatomical variations
and occlusions on cerebral flows,” Journal of Biomechanics, Vol. 40, 2007, pp. 1794-1805.
[2] Moore, S., David, T., Chase, J. G., Arnold, J., Fink, J., “3D models of blood flow in the cerebral vasculature,” Journal of Biomechanics, Vol. 39, 2006, pp. 1454-1463.
[3] Frank, O., “Die groundform des arteriellen pulse,” ErsteAbhandlung.
Mathematische Analyse. Z. Biol 37, 1899, pp. 483-526.
[4] Milnor, W. R., Hemodynamics, Williams & Wilkins, 1989.
[5] Stergiopulos, N., Westerhof, B. E., and Westerhof, N., “Total arterial
inertance as the fourth element of the windkessel model,” American Journal of Physiology, Vol. 276, 1999, pp. H81-H88.
[6] Sharp, M. K., and Dharmalingam, R. K., “Development of a hydraulic
model of the human systemic circulation,” ASAIO Journal, Vol. 45,
1999, pp. 535-540.
[7] Stamatelopoulos, S. F., Nanas, J. N., Saridakis, N. S., et al., “Treating
severe cardiogenic shock by large counter-pulsation volumes,” The Annals of Thoracic Surgery,Vol. 62, 1996, pp. 1110-7.
[8] Bolooki, H., “Clinical application of the intra-aortic balloon pump,”
3rd Ed., 1998, Futura Pulishing Company, Inc. Armonk, New York.
[9] Papaioannou, T. G., and Stefanadis, C., “Basic principles of the
intraaortic balloon and mechanisms affecting its performance,”ASAIO
Journal, Vol. 51, 2005, pp. 296-330.
[10] Saavedra, W. F., Tunin, R. S., Paolocci, N., et al., “Reverse
remodeling and enhanced adrenergic reserve from passive external
support in experimental dilated heart failure,” Journal of the
American College of Cardiology, Vol. 39, No.12, 2002, pp. 2096-76.
[11] Mancini, D., and Burkhoff, D., “Mechanical device-based methods of
managing and treating heart failure,” Circulation, Vol. 112, 2005, pp.
483-448.
[12] Pieske, B., “Reverse remodeling in heart failure-fact or fiction? ,”
European Heart Journal, Vol. 6, Supplement D, 2004, pp. D66-D78.
[13] Simon, M. A., Kormos, R. L., Murali, S., et al., “Myocardial recovery
using ventricular assist device: prevalence, clinical characteristics,
and outcomes,” Circulation, Vol. 112, 2005, pp. 32-36.
[14] Stamatelopoulos, S. F., Nanas, J. N., Saridakis, N. S., et al.,“Treating
severe cardiogenic shock by large counterpulsation volumes,” The
Annals of Thoracic Surgery, Vol. 62, 1996, pp. 1110-7.
[15] Terrovitis, J. V., Charitos, C. E., Tsolakis, E. J., et al., “Superior
performance of a paraaortic counterpulsation device compared to the
intraaortic balloon pump,” World Journal of Surgery, Vol. 27, No. 12,
2003, pp. 1311-1316.
[16] Stergiopulos, N., Young, D. F., and Rogge, T. R., “Computer
simulation of arterial flow with applications to arterial and aortic
stenoses,” Journal of Biomechanics, Vol. 25, 1992, pp. 1477-1488.
[17] Westerhof, N., Bosman, F., DeVries, C. J., and Noordergraaf, A.,
“Analog studies of the human systemic arterial tree,” Journal
of Biomechanics, Vol. 2, 1969, pp. 121-143.
[18] Pantalos, G. M., Koenig, S. C., Gillars, K. J., Guruprasad, A. G., and
Ewert, D. L., “Characterization of an adult mock circulation for
testing cardiac support devices,” ASAIO Journal, Vol. 50, 2004, pp.
37-46.
[19] Rosenberg, G., Phillips, W. M., Landis, D. L., and Pierce, W. S.,
“Design and evaluation of the pennsylvania state university mock
circulatory system,” ASAIO Journal, Vol. 4, 1981, pp. 41-49.
[20] Werner, J., Böhringer, D., and Hexamer, M. “Simulation and
prediction of cardiotherapeutical phenomena from a pulsatile model coupled to the guyton circulatory model,” IEEE Transaction on Biomedical Engineering, Vol. 49, No. 5, 2002, pp. 430-439.
[21] Timms, D., Hayne, M., McNeil, K., and Galbraith, A., “A complete
mock circulation loop for the evaluation of left, right, and
biventricular assist devices,” The International Journal of Artificial
Organs, Vol. 29, 2005, pp. 564-572.
[22] Ferrari, G., De Lazzari, C., and Kozarski, M., “A hybrid mock
circulatory system: testing a prototype under physiologic and
pathological conditions,” ASAIO Journal, Vol. 48, 2002, pp.487-494.
[23] De Lazzari, C., Darowski, M., Ferrari, G., Clemente F., and Guaragno,
M., “Computer simulation of hemodynamic parameters changes with
left ventricle assist device and mechanical ventilation,” Computers
in Biology and Medicine, Vol. 30, 2000, pp.55-69.
[24] Sharp, M. K., and Dharmalingam, R. K., “Development of a hydraulic
model of the human systemic circulation,” ASAIO Journal, Vol. 45,
1999, pp. 535-540.
[25] Stergiopulos, N., Meister, J. J., and Westerhof, N., “Evaluation of
method for estimation of total arterial compliance,” American
Journal of Physiology, Vol. 268, 1995, pp. H1540-H1548.
[26] Liu, Z., Brin, K. P., and Yin, F. C., “Estimatiom of total arterial
compliance: improved method and evaluation of current methods,”
American Journal of Physiology, Vol. 251, 1986, pp. H588-H600.
[27] Woodruff, S. Sharp, M. K., and Pantalos, G. M., “Compact
compliance chamber design for the study of cardiac performance
in microgravity,” ASAIO Journal, Vol. 43, 1997, pp. 316-320.
[28] Sharp, M. K., and Dharmalingam, R. K., “Development of a hydraulic
model of the human systemic circulation,” ASAIO Journal, Vol. 45,
1999, pp. 535-540.
[29] De Lazzari, C., Darowski, M., Ferrari, G., Clemente F., and Guaragno,
M., “Computer simulation of hemodynamic parameters changes with
left ventricle assist device and mechanical ventilation,” Computers in
Biology and Medicine, Vol. 30, 2000, pp. 55-69.
[30] Olufsen, M., “Modeling the arterial system with reference to an
anesthesia simulator,” Ph.D. thesis, Roskilde: IMFUFA, Roskilde
University, Denmark, Text No. 345, 1998.
[31] Ferrari, G., Nicoletti, A., and De Lazzari, C., “A physical model of the
human systemic arterial tree,” The International of Journal Artificial
Organs Vol. 23, 2000, pp. 647-657.
[32] Segers, P., Dubois, F., Wachter, D. De, and Verdonck, P., “Role and
relevancy of a cardiovascular simulator,” Journal of Cardiovascular
Engineering Vol. 3, 1998, pp. 48-56.
[33] Parker, K. H., and Jones, C. J. H., “Forward and backward running
waves in the arteries: analysis using the method of characteristics,”
Journal of Biomechanical Engineering, Vol. 112, 1990, pp. 322-326.
[34] Khir, A. W., and Parker, K. H., “Wave intensity in the ascending
aorta: effects of arterial occlusion,” Journal of Biomechanics, Vol.38,
2005, pp. 647-655
[35] Sun, Y. H., Anderson, T. J., Parker, K. H., and Tyberg, J. V.,
“Wave-intensity: a new approach to coronary hemodynamics,”
Journal of Applied Physiology, Vol. 89, 2000, pp. 1636-1644.
[36] Wedterhof, N., Sipkema, P., Van Den Bos, G. C., and Elzinga, G.,
“Forward and backward waves in the arterial system,”Cardiovascular
Research, Vol. 6, 1972, pp. 648-656.
[37] Barnea, O., Moore, T. W., Dubin, S. E., and Jaron, D., “Cardiac energy
considerations during intra-aortic balloon pumping,” IEEE
Transactions on Biomedical Engineering, Vol. 37, No. 2, 1990,
pp.170-181.
[38] Zelano, J. A., Li, J. K.-J., and Welkowitz, W., “A closed-loop control
scheme for intra-aortic balloon pumping,” IEEE Transactions on
Biomedical Engineering, Vol. 37, No. 2, 1990, pp. 182-192.
[39] Devault, K., Gremaud, P., Novak, V., Zhao, P., “Blood flow in the
circle of willis: modeling and calibration,”Multiscale Model Simul ,Vol.
23, 2008, pp. 2-30.
[40] Sylvia Kamath., “Observations on the length and diameter of vessels
forming the circle of Willis,” Journal of Biomechanics, Vol. 3. pp.
419-423.
[41] Reymond, P., Merenda, F., Perren, F., Rufenacht, D., Stergiopulos. N.,
“Validation of a one-dimensional model of the systemic arterial tree,”
American Journal of Physiology, Vol. 297, 2009, pp. H208-H222.
[42] Kolyva, C., Biglino, G., Pepper R. J., Khir W. A., “A mock circulatory
system with physiological distribution of terminal resistance and
compliance: application for testing the intra-aortic balloon pump.”
Artificial Organs, 2010, pp. 1-9.
[43] Viedma, A., Jiménez-Ortiz, C., Marco, V., “Extended willis circle
model to explain clinical observations in periorbital arterial flow,”
Journal of Biomechanics, Vol. 30. No. 3. 1997, pp. 265-272.
[44] 陳瑞龍, “聚氨酯人工心瓣之製作與性能評估,”成功大學航空太空
工程研究所論文, 2003.
[45] 林純玄, “反脈動左心室輔助器之離體測試,”成功大學航空太空工
程研究所論文, 2006.
[46] 林博文, “反脈動式循環輔助之波動強度分析,”成功大學航空太空
工程研究所論文, 2007.
[47] 李炳宏 , “反脈動主動脈側血泵輔助下之波傳現象實驗探討,”成功
大學航空太空工程研究所論文, 2009.
[48] 李應續, “椎動脈的解剖學研究及其臨床意義,“ 咸寧醫學院學報第
16卷, 第03期, 2002.