Impact of heart rate on cross-bridge cycling kinetics in failing and non-failing human myocardium.

Impact of heart rate on cross-bridge cycling kinetics in failing and non-failing human myocardium. Am J Physiol Heart Circ Physiol. 2019 Jul 26;: Authors: Chung JH, Milani-Nejad N, Davis JP, Weisleder N, Whitson BA, Mohler PJ, Janssen PML Abstract The force-frequency relationship (FFR) is an important regulatory mechanism that increases the force-generating capacity as well as the contraction and relaxation kinetics in human cardiac muscle as the heart rate increases. In human heart failure, the normally positive FFR often becomes flat, or even negative. The rate of cross-bridge cycling, which has been reported to affect cardiac output, could be potentially dysregulated and contribute to blunted or negative FFR in heart failure. We recently developed and here use a novel method for measuring the rate of tension redevelopment (ktr). This method allows us to obtain an index of the rate of cross-bridge cycling in intact contracting cardiac trabeculae at physiological temperature and assess physiological properties of cardiac muscles while preserving post-translational modifications representative of those that occur in vivo. We observed that trabeculae from failing human hearts indeed exhibit an impaired FFR, and reduced speed of relaxation kinetics. However, stimulation frequencies in the lower spectrum did not majorly affect cross-bridge cycling kinetics in non-failing and failing trabeculae when assessed at maximal activation. Trabec...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research