Shockwave for the abrogation of heart failure in myocardial ischaemia-reperfusion injury
File(s)
Author(s)
Narodden, Salomon
Type
Thesis
Abstract
BACKGROUND: Although reperfusion of STEMI has markedly improved acute patients’ survival, more patients are living with heart failure. Theoretically, more myocardial tissue is salvageable if reperfusion injury could be alleviated, limiting the risk of developing heart failure.
AIM: To assess the combination shockwave treatment with DPP4-inhibitor as a treatment adjunct for cardiac IR injury.
HYPOTHESIS: Shockwave provides cardioprotection from IR injury, improves cardiac function and cell-homing, and when shockwave used in conjunction with DPP4-inhibitor, the effects are augmented.
METHOD:
In-vivo: Surgical IR-rat models imaged using Bruker-BioSpec-9.4T. Multi-sequence CMR similar to clinical multi-planar acquisition using: (a) FLASH-CINE, (b) INTRAGATE-CINE, (c) MESE-T2-map, (d) T2-star, and (e) IR-LGE; in experimental groups: (1) Healthy versus IR-MI [a,b,c,e]; (2) Healthy versus Healthy-SW [a,b] ; (3) Healthy-SW versus Healthy-SW-inhibitor [a]; (4) IR-MI versus IR-MI-SW versus IR-MI-SW-inhibitor [a,b,c,e]; (5) iron pretreament then shockwave [c]; and (6) shockwave BOLD [d]. Segment(Medviso) post-processing to derive EDV, ESV, SV, CO, EF, T2-maps and T2star-maps; and Image-Arena(Tomtec) to derive GLS, GCS, GRS and segmental-strains; (6)multi-colour-flow-cytometry CD45-CD90+ and CD45+CD34+ on PBMC after shockwave.
In-vitro: (7) Shockwave-treated HCF, HVT, HUVEC, and cardiomyocytes qPCR-assessed for SDF1. (8) Shockwave or SDF1-spiking treatment on oxygen-deprived cardiomyocytes and assessed for viability.
RESULTS: (1) Segmental-strains distinguished phenotypes of Healthy, AAR and Infarction; global-strains detected IR-MI better than EF. (2) Shockwave induced inotropy. (3) DPP4-inhibitor prolonged shockwave-inotropic effect. (4) Smaller infarction in shockwave group; reduced transmurality with DPP4-inhibitor; stronger GLS, GCS, GRS in IR-MI-SW than IR-MI; stronger GLS and GRS in IR-MI-SW-inhibitor had than IR-MI-SW while GCS was unchanged. (5) Shockwave reduced T2, signifying cell-homing. (6) Shockwave increased BOLD signifying angiogenesis. (7) SDF1 expression increased in HCF, HVT, HUVEC but not in cardiomyocytes. (8) Shockwave and SDF1-spiking improved cardiomyocytes viability.
CLINICAL CONTEXT: Shockwave with DPP4-inhibitor treatment in reperfused-STEMI could limit infarct size and improve cardiac function.
AIM: To assess the combination shockwave treatment with DPP4-inhibitor as a treatment adjunct for cardiac IR injury.
HYPOTHESIS: Shockwave provides cardioprotection from IR injury, improves cardiac function and cell-homing, and when shockwave used in conjunction with DPP4-inhibitor, the effects are augmented.
METHOD:
In-vivo: Surgical IR-rat models imaged using Bruker-BioSpec-9.4T. Multi-sequence CMR similar to clinical multi-planar acquisition using: (a) FLASH-CINE, (b) INTRAGATE-CINE, (c) MESE-T2-map, (d) T2-star, and (e) IR-LGE; in experimental groups: (1) Healthy versus IR-MI [a,b,c,e]; (2) Healthy versus Healthy-SW [a,b] ; (3) Healthy-SW versus Healthy-SW-inhibitor [a]; (4) IR-MI versus IR-MI-SW versus IR-MI-SW-inhibitor [a,b,c,e]; (5) iron pretreament then shockwave [c]; and (6) shockwave BOLD [d]. Segment(Medviso) post-processing to derive EDV, ESV, SV, CO, EF, T2-maps and T2star-maps; and Image-Arena(Tomtec) to derive GLS, GCS, GRS and segmental-strains; (6)multi-colour-flow-cytometry CD45-CD90+ and CD45+CD34+ on PBMC after shockwave.
In-vitro: (7) Shockwave-treated HCF, HVT, HUVEC, and cardiomyocytes qPCR-assessed for SDF1. (8) Shockwave or SDF1-spiking treatment on oxygen-deprived cardiomyocytes and assessed for viability.
RESULTS: (1) Segmental-strains distinguished phenotypes of Healthy, AAR and Infarction; global-strains detected IR-MI better than EF. (2) Shockwave induced inotropy. (3) DPP4-inhibitor prolonged shockwave-inotropic effect. (4) Smaller infarction in shockwave group; reduced transmurality with DPP4-inhibitor; stronger GLS, GCS, GRS in IR-MI-SW than IR-MI; stronger GLS and GRS in IR-MI-SW-inhibitor had than IR-MI-SW while GCS was unchanged. (5) Shockwave reduced T2, signifying cell-homing. (6) Shockwave increased BOLD signifying angiogenesis. (7) SDF1 expression increased in HCF, HVT, HUVEC but not in cardiomyocytes. (8) Shockwave and SDF1-spiking improved cardiomyocytes viability.
CLINICAL CONTEXT: Shockwave with DPP4-inhibitor treatment in reperfused-STEMI could limit infarct size and improve cardiac function.
Version
Open Access
Editor(s)
Harding, Sian
Nihoyannopoulos, Petros
Punjabi, Prakash
Date Issued
2021-05-11
Date Awarded
2021-06
Citation
2021
Advisor
Harding, Sian
Nihoyannopoulos, Petros
Publisher Department
National Heart & Lung Institute
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)