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Biology subjects

Marrot, M.

Publications and source records attributed to Marrot, M..

2 recordsLinked to original sources

Abnormal autonomic regulation of heart rate underlies age-related and sexdependent cardiac dysfunction in the small primate Microcebus murinus.

Ageing is a major risk factor for cardiovascular disease associated with the decline of maximal heart rate (HR) and HR variability (HRV). Such a decline could reduce cardiac adaptability to physiological needs and increase susceptibility to arrhythmias. The small primate Grey Mouse Lemur (Microcebus murinus), is a valuable model of ageing because it spontaneously develops neurodegenerative diseases. Moreover, in a lifetime it generates about three billion heartbeats as humans. Thus, it could also represent a new effective model to study cardiac ageing. We investigated cardiac responses to handling stress in young (1-5 years) and aged (6-12 years) lemurs of both sexes by using a mini-Holter for electrocardiogram (ECG) recordings. Moreover, we measured urinary catecholamine, the effect of pharmacological blockade of the autonomic modulation and cardiac contractility. Aged lemurs, particularly aged males, displayed slower HR and abnormal HRV under stress, delayed recovery of cardiac rhythm following stress and a dissociation between HR and HRV metrics. They also exhibited reduced adrenaline levels, a blunted response to pharmacological vagal blockade and diastolic dysfunction with preserved ejection fraction. These findings indicate that ageing, especially in male lemurs, impairs cardiac adaptation and recovery from stress through disrupted autonomic balance and sympathetic incompetence.

physiology↗

Characterization of cardiac pacemaker activity in the primate lemur Microcebus murinus.

BackgroundGray mouse lemurs (Microcebus murinus) are the smallest and most ancestral primates known. Their size falls in between that of mice and rats, and their genetic proximity to humans makes them an emerging model to study age-related neurodegeneration. Since mouse lemurs replicate similar senescence processes of humans, they constitute a useful model for studying cardiovascular dysfunctions. However, their cardiac physiology is unknown. Thus, we investigated the cardiac pacemaker activity generated by the sinoatrial node (SAN) of mouse lemurs, presenting the first characterization of heart automaticity in nonhuman primates. Methods and ResultsWe recorded cardiac automaticity in mouse lemurs and in their SAN tissues and pacemaker myocytes. Mouse lemurs have a heart rate (HR) in between those of mice and rats and a similar generation of the SAN electrical impulse. Their SAN myocytes express the main pacemaker currents at densities similar to mice: the hyperpolarization-activated current (If) and the L-type (Ica,L) and T-type (Ica,T) calcium currents. Conversely, their ventricular depolarization resembles that of large mammals and despite the small size of mouse lemurs, the total number of heartbeats in their life corresponds to what can be attained by humans. Using muscle-derived stem cells (MDSCs) from mouse lemurs, we also differentiated pacemaker-like (PML) cells showing spontaneous automaticity and expressing markers of native SAN myocytes (HCN4 and connexin-45). ConclusionsOur characterization of heart automaticity in Microcebus murinus provides new opportunities for comparative cardio-physiology studies in primates and with humans and for testing molecules that could modulate age-related dysfunctions of heart rate.

physiology↗