Alterations in Intracellular Calcium Handling Associated With the Inverse Force-Frequency Relation in Human Dilated Cardiomyopathy

Abstract

These data indicate that the altered force-frequency relation of the failing human myocardium results from disturbed excitation-contraction coupling with decreased calcium cycling at higher rates of stimulation.

Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic‐Banded Mini‐Swine

“…Representative shortening and calcium transients from the CON group illustrating our experimental paradigm are presented in Figure 4A. A negative shortening‐frequency relationship, a cellular characteristic of HF,28 was observed in the HF group compared to CON animals at absolute lengths (Figure 4B; group×pacing interaction) and relative to 0.25 Hz (Figure 4C; group×pacing interaction). Both saxagliptin and tadalafil prevented the aortic banding–induced negative shortening‐frequency relationship.…”

Determinants of frequency-dependent contraction and relaxation of mammalian myocardium

“…This important regulatory mechanism was first described in the year 1871; Henry Bowditch noted that the contractile force of the frog heart increased when it was paced at increasing frequency [1]. Since the first description of this force frequency relationship (FFR), the underlying mechanism has been a target for experimental investigation [2][3][4][5][6][7]. Although several contributing factors and modifiers of the FFR have been identified, our current understanding of frequency dependent activation is far from complete.…”

Reduced Myocardial Sarcoplasmic Reticulum Ca 2+ -ATPase mRNA Expression and Biphasic Force-Frequency Relations in Patients With Hypertrophic Cardiomyopathy

“…4 -9 Conversely, in the failing human heart, a flat or even negative forcefrequency relation (FFR) has been observed and is considered to represent limited functional reserve of the heart. 10,11 It is not clear, however, whether FFR is preserved in HCM patients whose resting systolic LV function is still preserved.…”

“…11 The negative FFR in human heart failure has been suggested to reflect disturbances of Ca 2ϩ handling in terminally failing human myocardium. 11,12 Unlike studies on altered Ca 2ϩ handling in end-stage failing myocardium, however, which can be performed on explanted hearts obtained after cardiac transplantation, studies that address the subcellular mechanisms of altered myocardial properties in human HCM are rare, probably because of the limited access to adequate human tissue.…”