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Left Ventricular Dynamics and Pulsatile Hemodynamics During Resuscitation of the Fibrillating Heart Using Direct Mechanical Ventricular Actuation

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Left Ventricular Dynamics and Pulsatile Hemodynamics During Resuscitation of the Fibrillating Heart Using Direct Mechanical Ventricular Actuation Left Ventricular Dynamics and Pulsatile Hemodynamics during Resuscitation of the Fibrillating Heart Using Direct Mechanical Ventricular Actuation A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy By YIRONG ZHOU M.S., Wuhan University, 2011 B. Med., Wuhan University, 2009 _____________________________ 2018 Wright State University COPYRIGHT BY YIRONG ZHOU 2018 WRIGHT STATE UNIVERSITY GRADUATE SCHOOL December 10, 2018 I HEREBY RECOMMEND THAT THE DISSERTATION PREPARED UNDER MY SUPERVISION BY Yirong Zhou ENTITLED Left Ventricular Dynamics and Pulsatile Hemodynamics during Resuscitation of the Fibrillating Heart Using Direct Mechanical Ventricular Actuation BE ACCEPTED IN PARTIAL FULFUILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF Doctor of Philosophy. _____________________________ Mark P. Anstadt, M.D. Dissertation Director _____________________________ Mill W. Miller, Ph.D. Director, Biomedical Sciences Ph.D. Program _____________________________ Barry Milligan, Ph.D. Interim Dean of the Graduate School Committee on Final Examination _____________________________ Mark P. Anstadt, M.D. _____________________________ J. Ashot Kozak, Ph.D. _____________________________ David Cool, Ph.D. _____________________________ Lucile E. Wrenshall, M.D. Ph.D. _____________________________ Lynn K. Hartzler, Ph.D. ABSTRACT Zhou, Yirong. Ph.D., Biomedical Sciences Ph.D. Program, Wright State University, 2018. Left Ventricular Dynamics and Pulsatile Hemodynamics during Resuscitation of the Fibrillating Heart Using Direct Mechanical Ventricular Actuation. The application of mechanical forces during resuscitation of the arrested heart can be used to restore life-sustaining circulation. Open-chest manual massage represents the earliest application of this concept (first described by professor Moritz Schiff in 1874). Many cardiac compression devices have been developed for cardiac support since that time. Direct mechanical ventricular actuation (DMVA) is a non-blood-contacting device that has demonstrated efficacy of providing both systolic and diastolic support. The device encompasses the heart and can provide total circulatory support during ventricular fibrillation (VF) or cardiac arrest. DMVA resuscitative support during VF has been shown to be nontraumatic to the myocardium. Notably, resuscitative support using DMVA has the advantage of generating pulsatile flow without blood contact which benefits vital organ perfusion and post-resuscitation neurologic outcome. However, ventricular and blood flow dynamics during DMVA support have not been well characterized. Specifically, it remains unclear if DMVA support during VF generates ventricular pump function mimicking the native beating heart, or pulsatile flow characteristics similar to the physiological state. The purpose of this dissertation iv was to better characterize these fundamental aspects of DMVA support during VF. Experimental data herein demonstrate that DMVA support during VF arrest can result in LV pump function similar to the native beating heart and near-physiological pulsatile flow dynamics. The physiological pulsatile flow generated by DMVA may explain DMVA’s capability for improving resuscitation results. A biventricular mock circulatory system (BMCS) incorporating an anatomical mock ventricle provided supportive in vitro data to further confirm these findings. v TABLE OF CONTENTS CHAPTER I: Hypothesis and Specific Aims………………..………………………...1 CHAPTER II: Introduction………………………………………………………...11 Ventricular Fibrillation and Cardiac Arrest………..………………………….11 Resuscitative Mechanical Circulatory Support Devices……………….14 Direct Mechanical Ventricular Actuation………..…………………………..22 Biventricular Mock Circulatory System……..………………….…………….26 CHAPTER III: Materials and Methods...…………………………………………….33 CHAPTER IV: Direct Mechanical Ventricular Actuation during Ventricular Fibrillation Results in Near-Physiological Left Ventricular Myocardial Mechanics……………………………………………………………......…..55 CHAPTER V: Left Ventricular Diastolic Function Is Returned during Direct Mechanical Ventricular Actuation of the Arrested Heart…………….……....84 CHAPTER VI: Direct Mechanical Ventricular Actuation during Cardiac Arrest Generates Pulsatile Hemodynamics Similar to the Native Beating Heart…...111 CHAPTER VII: Echocardiographic Characteristics of a Mock Ventricle are Similar to the Fibrillating in vivo Ventricle during Direct Mechanical Ventricular Actuation...….……………………………………………….…..138 CHAPTER VIII: Conclusions and Future Directions………………….................171 CHAPTER IX: References……….…………………………………………………174 APPENDIX: Commonly Used Abbreviations .................................................... 197 vi LIST OF FIGURES Figure 1. Contemporary resuscitative ventricular mechanical support devices……15 Figure 2. Illustrations of various VA ECMO cannulations……………….……...….. 18 Figure 3. Classification of mechanical circulatory support devices…….….………...20 Figure 4. Schematic of DMVA depicting diastolic expansion (left) and systolic compression (right)…………………………………………….. 23 Figure 5. Decision tree for DMVA support post SCA…………………..……..……27 Figure 6. The biventricular mock circulatory system (BMCS)…..……………….….29 Figure 7. Sample mock circulation waveforms…………………….……..………….32 Figure 8. Schematic of experimental instrumentation……………….…………..…..35 Figure 9. Four chamber echocardiogram views of three experimental stats..........…..36 Figure 10. Experimental timeline designed to produce VF arrest..……………...…..38 Figure 11. Mathematical relationship among different deformation parameters.....…40 Figure 12. Schematic of circumferential, radial, and longitudinal strain…..……....42 Figure 13. Example volume output from VVI software……………………….….....45 Figure 14. Example strain rate output from VVI software…………………………..46 Figure 15. Image of 3-D printed mold design and the silicone mock ventricle…...…54 Figure 16. Schematic of the DMVA support system (canine study)…………………72 Figure 17. Experimental design. ………………………………………………….…73 Figure 18. Experimental instrumentation…..………………………………..……….74 vii Figure 19. Four chamber echocardiogram views of (A) native beating heart, (B) arrested unsupported fibrillating heart, and (C) DMVA supported VF arrest heart……………………………………………...…………….. 75 Figure 20. LV geometry profiles of native beating heart and DMVA support during VF arrest. ……………………………………………………...….. 77 Figure 21. LV strain heat maps: (A) regional end-systolic longitudinal strain (sRLS, %); (B) regional end-diastolic longitudinal strain (dRLS, %); (C) color scale. ……………………………………….. 80 Figure 22. LV strain rate heat maps: (A) regional peak longitudinal systolic strain rate (sRLSR, 1/s); (B) regional peak longitudinal diastolic strain rate (dRLSR, 1/s); (C) color scale.………………………..81 Figure 23. Schematic of the DMVA support system (swine study)………...…….101 Figure 24. Experimental instrumentation………...……...…………………..……102 Figure 25. Four chamber view Echocardiogram Images of (A) native beating heart (end-diastole), (B) unsupported VF arrested heart, and (C) DMVA supported VF arrested heart (end-diastole) in swine…….…103 Figure 26. LV geometry of native beating heart and DMVA support during VF arrest………………………………...……………….105 Figure 27. LV heat maps: (A) regional end-diastolic longitudinal strain (dRLS, %); (B) regional peak longitudinal diastolic strain rate (dRLSR, 1/s)………………………….…………………...….108 Figure 28. Regional diastolic strain intra-group comparisons.……………….…109 viii Figure 29. Regional peak strain rate intra-group comparisons……………………110 Figure 30. Experimental design (pulsatility study)…………………….…………127 Figure 31. Comparisons of all the normalized hemodynamics and pulsatility measures included in this study…………………………. 131 Figure 32. Aortic power waveforms for three experimental states at different flow levels. …………………………………….…………… 133 Figure 33. Animal experimental design (mock study)……………………………156 Figure 34. Schematic of the complete mock circulatory system with biventricular mock heart attached………………………………………..157 Figure 35. Comparable swine and mock ventricles………….……………………160 Figure 36. Mechanical diastolic actuation on the (A) fibrillating swine heart and (B) mock bi-ventricle. ………………………………………………156 Figure 37. Summary heat map of peak regional longitudinal strains (RLS, %) at both (A) end-systole and (B) end-diastole between swine and mock model….……………………………...……… 162 Figure 38. LV GLS and RLS comparison between animal and mock model……164 Figure 39. LV mechanical inotropy and lusitropy reflected by peak strain rate….166 ix APPENDIX Figure S1. Regional wall strain intra-group comparisons (canine study)……….....82 Figure S2. Regional strain rate intra-group comparisons……..……...…………….83 Figure S3. Aortic power waveforms of canine and swine………………..……….136 Figure S4. Regional wall strain intra-group comparisons (mock study)…..…..…169 Figure S5. Regional strain rate intra-group comparisons…………………………170 x LIST OF TABLES Table 1. Characteristics of resuscitative MCS devices…………………..……….…. 16 Table 2. Summary of parameters to quantify vascular pulsatility…………...………49 Table 3. Basic pressure characteristics of native beating heart and DMVA support during VF…………………………………………..… 76 Table 4. Left ventricular pump function and myocardial mechanics………….…..…78 Table 5. Hemodynamic characteristics of native beating and DMVA supported arrested hearts……………………………………….… 104 Table 6. LV diastolic function of native beating and DMVA supported arrested hearts…………………………………………….…..……………106 Table 7. Estimates of pulsatility
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