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Abstract
The sinoatrial node (SAN) is the primary pacemaker in canine and human hearts. The
SAN in both species has a unique 3-dimensional heterogeneous structure characterized
by small pacemaker myocytes enmeshed within fibrotic strands, which partially insulate
the cells from aberrant atrial activation. The SAN pacemaker tissue expresses a unique
signature of proteins and receptors that mediate SAN automaticity, ion channel currents
and cell-to-cell communication, which are predominantly similar in both species. Recent
intramural optical mapping, integrated with structural and molecular studies, has
revealed the existence of up to five specialized SAN conduction pathways that preferentially
conduct electrical activation to atrial tissues. Intrinsic heart rate, intranodal
leading pacemaker shifts and changes in conduction in response to physiological and
pathophysiological stimuli are similar. Structural and/or functional impairments due
to cardiac diseases including heart failure (HF) cause SAN dysfunctions (SND) in both
species. These dysfunctions are usually manifested as severe bradycardia, tachy-brady
arrhythmias, and conduction abnormalities including exit block and SAN reentry, which
could lead to atrial tachycardia and fibrillation, cardiac arrest and HF. Pharmaceutical
drugs and implantable pacemakers are only partially successful in managing SND, emphasizing
a critical need to develop targeted mechanism-based therapies to treat SND. Since
several structural and functional characteristics are similar between the canine and
human SAN, research in these species maybe mutually beneficial for developing novel
treatment approaches. This review describes structural, functional and molecular similarities
and differences between the canine and human SAN, with special emphasis on arrhythmias
and unique causal mechanisms of SND in diseased hearts.