Abstract
SPontaneous Oscillatory Contraction (SPOC) is a physiological state induced in striated muscle fibres under conditions of partial activation. SPOC is characterised by repetitive auto-oscillations between cycles of rapid lengthening and slow shortening that correlate with diastole and systole respectively. We activate cardiomyocytes using ADP-induced SPOC and Ca2+ induced SPOC. Ca-SPOC correlates well with heart rate observed in a number of animal models.The current study quantifies contractile performance of cardiomyocytes isolated from human dilated and hypertrophic cardiomyopathies (some with known mutations) and compares them with age-matched non-failing donors. Measured parameters of contractile performance include the velocity, period and amplitude of contraction, relaxation and SPOC-wave. We compare changes in contractile performance between (1) failing and non-failing hearts, (2) hearts from a wide range of donor ages, and (3) differences between ADP- and Ca-SPOC. These observations are then related to patient clinical data (e.g. ejection fraction).Interestingly, human heart samples flash frozen (−200°C) within minutes of the loss of coronary blood flow can be re-activated even after up to 20 years of storage. Cardiac muscle fibres from the left atria and left ventricles, interventricular septa and papillary muscles were specially defrosted prior to microdissection. Length changes were measured using a Leica SP5 multi-photon microscope and then averaged at high spatial and temporal resolution.Preliminary data identify measureable changes in contractile performance between non-failing and failing hearts. Samples of hypertrophic cardiomyopathy exhibit decreased rates of relaxation consistent with their clinical diagnosis. These observations reveal SPOC to yield a range of functional parameters that can be used to evaluate the functional state of human heart muscle fibres. Thus, SPOC may prove to be a valuable measurement that can objectively assess the state of human heart failure.
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