Auckland Bioengineering Institute, The University of Auckland, Auckland, New Zealand.
Department of Physiology, The University of Auckland, Auckland, New Zealand.
Am J Physiol Heart Circ Physiol. 2022 Sep 1;323(3):H461-H474. doi: 10.1152/ajpheart.00074.2022. Epub 2022 Jul 29.
Conventional experimental methods for studying cardiac muscle in vitro often do not expose the tissue preparations to a mechanical impedance that resembles the in vivo hemodynamic impedance dictated by the arterial system. That is, the afterload in work-loop contraction is conventionally simplified to be constant throughout muscle shortening, and at a magnitude arbitrarily defined. This conventional afterload does not capture the time-varying interaction between the left ventricle and the arterial system. We have developed a contraction protocol for isolated tissue experiments that allows the afterload to be described within a Windkessel framework that captures the mechanics of the large arteries. We aim to compare the energy expenditure of cardiac muscle undergoing the two contraction protocols: conventional versus Windkessel loading. Isolated rat left-ventricular trabeculae were subjected to the two force-length work-loop contractions. Mechanical work and heat liberation were assessed, and mechanical efficiency quantified, over wide ranges of afterloads or peripheral resistances. Both extent of shortening and heat output were unchanged between protocols, but peak shortening velocity was 39.0% lower and peak work output was 21.8% greater when muscles contracted against the Windkessel afterload than against the conventional isotonic afterload. The greater work led to a 25.2% greater mechanical efficiency. Our findings demonstrate that the mechanoenergetic performance of cardiac muscles in vitro may have been previously constrained by the conventional, arbitrary, loading method. A Windkessel loading protocol, by contrast, unleashes more cardiac muscle mechanoenergetic potential, where the slower shortening increases efficiency in performing mechanical work. Cardiac muscle samples were allowed to describe their natural shortening dynamics while performing force-length work and liberating heat. The muscle shortened more slowly and produced greater force and work output against a time-varying "Windkessel" load than during conventional constant-force shortening, thereby yielding greater mechanical efficiency. A key finding is that the slower shortening kinetics developed in the face of a time-varying load enhances the mechanical efficiency of cardiac muscle during work-loop contractions.
传统的心肌体外实验方法通常不会使组织标本承受类似于动脉系统所决定的体内血液动力学阻抗的机械阻抗。也就是说,在工作环收缩过程中的后负荷通常简化为在整个肌肉缩短过程中保持恒定,并任意定义其大小。这种传统的后负荷并不能捕捉到左心室与动脉系统之间的时变相互作用。我们已经开发出一种用于离体组织实验的收缩方案,该方案允许在后负荷框架内描述,该框架可捕获大动脉的力学特性。我们旨在比较两种收缩方案(常规与 Windkessel 加载)下心肌的能量消耗。对离体大鼠左心室小梁进行了两种力-长度工作环收缩。在广泛的后负荷或外周阻力范围内评估了机械功和热释放,并量化了机械效率。两种方案下的缩短程度和热量输出均无差异,但与常规等张后负荷相比,肌肉抵抗 Windkessel 后负荷时的峰值缩短速度降低了 39.0%,峰值功输出增加了 21.8%。更大的功导致机械效率提高了 25.2%。我们的发现表明,以前体外心肌的机械能量性能可能受到传统的任意加载方法的限制。相比之下,Windkessel 加载方案释放了更多的心肌机械能量潜力,其中较慢的缩短可提高执行机械功的效率。在进行力-长度功和释放热量时,允许心肌样本描述其自然缩短动力学。与常规的恒定力缩短相比,肌肉在面对时变“Windkessel”负载时缩短更慢,产生更大的力和功输出,从而产生更高的机械效率。一个关键发现是,在面对时变负荷时,较慢的缩短动力学可提高工作环收缩过程中心肌的机械效率。