Jenny S Choy, Lei Fan, Yousif Awakeem, Chenghan Cai, Farshad Raissi, Lik Chuan Lee, Ghassan S Kassab
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引用次数: 0
Abstract
Background: Patients with heart failure frequently develop mechanical dyssynchrony, which impairs ventricular function, coronary perfusion and their interactions. The underlying mechanisms, however, remain poorly understood due to numerous confounding factors. The objective of this study was to determine the acute effects of mechanical dyssynchrony on global and regional left ventricular (LV) function, coronary perfusion and their interactions based on experimental and computational approaches.
Methods: Mechanical dyssynchrony was created with right ventricular apical pacing in Yorkshire domestic swine (n = 9). The heart was paced at 100 and 140 bpm and the results were compared to right atrial pacing. An inverse finite element computational framework based on an animal-specific geometry of the LV and measurements was developed to investigate the effects of mechanical dyssynchrony on LV function and its correlation with regional coronary perfusion.
Results: Cardiac dyssynchrony induced significant decrease in LV pressure, volume, dP/dt(min), stroke volume, ejection fraction, and regional longitudinal and circumferential strain. With mechanical dyssynchrony, passive flow decreased by 70% in the left anterior descending artery (LAD) and 67% in the left circumflex (LCX). An animal-specific inverse finite element computational model predicted that in mechanical dyssynchrony, global and regional LV contractility in the septum and LV free wall (LVFW), and myocardial work done in the septum and LVFW decreased.
Conclusion: The computational model predicted reduction in global and regional contractility, and regional myocardial work done in the septum and LVFW with mechanical dyssynchrony are positively correlated with the corresponding decrease in experimentally measured regulated coronary flow in the LAD and LCX. These findings demonstrate that this interrelated mechanism between LV function and coronary flow in mechanical dyssynchrony may affect cardiac resynchronization therapy responder rate.
期刊介绍：
The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs.
In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.
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