Heart of the matter: assessing human cardiomyopathies with Spontaneous Oscillatory Contractions (SPOC)

Amy Li, James E. Wolfe, Eleanor Kable, Filip Braet, Dane A. King, Tatsuya Kagemoto, Peter S. Macdonald, Shinichi Ishiwata, Cristobal G. dos Remedios

Research output: Contribution to journalMeeting abstractpeer-review

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 Ca2þ 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.
Original languageEnglish
Article number1793-Pos
Pages (from-to)353A-353A
Number of pages1
JournalBiophysical Journal
Volume102
Issue number3
DOIs
Publication statusPublished - 31 Jan 2012
Externally publishedYes
Event56th Annual Meeting of the Biophysical Society - San Diego, United States
Duration: 25 Feb 201229 Feb 2012

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