The cardiac circadian clock - jetlag the heart hos Biomedicinsk Institut - Københavns Universitet

Molecular clocks are cell autonomous mechanisms, which confer the advantage of anticipation, allowing cells to respond to stimuli in a temporally appropriate manner. Functional circadian clocks have been confirmed in all mammalian cells investigated to date, including cardiomyocytes. Analysis of gene expression in hearts collected from mice suggests that expression of 8-13% of all myocardial genes show 24h regulation in the absence of temporal patterns of environmental stimuli (e.g., light or food). The significance of the circadian clock for optimal cardiovascular health is well established by clinical and experimental studies, exemplified by the observation that sudden cardiac death is most frequent in the early hours of the morning.

In the present project, we will determine if there is an intrinsic, circadian rhythm in the sinus rate of isolated mouse hearts. We will euthanize mice at different time points during the 24h cycle and determine rate in isolated, perfused hearts. In this setup, we can record ECG and several hemodynamic parameters to gauge cardiac function (chronotropy and inotropy), independent of neurohumoral input.

The hypothesis is that the intrinsic sinus rate is faster and ventricular contractility more forceful during the active phase of the animals.

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