Korean Circ J.  2015 May;45(3):184-191. 10.4070/kcj.2015.45.3.184.

Function and Dysfunction of Human Sinoatrial Node

• Joung B
• Chen PS

• KMID: 2389124
• DOI: http://doi.org/10.4070/kcj.2015.45.3.184

Abstract

Sinoatrial node (SAN) automaticity is jointly regulated by a voltage (cyclic activation and deactivation of membrane ion channels) and Ca2+ clocks (rhythmic spontaneous sarcoplasmic reticulum Ca2+ release). Using optical mapping in Langendorff-perfused canine right atrium, we previously demonstrated that the beta-adrenergic stimulation pushes the leading pacemaker to the superior SAN, which has the fastest activation rate and the most robust late diastolic intracellular calcium (Cai) elevation. Dysfunction of the superior SAN is commonly observed in animal models of heart failure and atrial fibrillation (AF), which are known to be associated with abnormal SAN automaticity. Using the 3D electroanatomic mapping techniques, we demonstrated that superior SAN served as the earliest atrial activation site (EAS) during sympathetic stimulation in healthy humans. In contrast, unresponsiveness of superior SAN to sympathetic stimulation was a characteristic finding in patients with AF and SAN dysfunction, and the 3D electroanatomic mapping technique had better diagnostic sensitivity than corrected SAN recovery time testing. However, both tests have significant limitations in detecting patients with symptomatic sick sinus syndrome. Recently, we reported that the location of the EAS can be predicted by the amplitudes of P-wave in the inferior leads. The inferior P-wave amplitudes can also be used to assess the superior SAN responsiveness to sympathetic stimulation. Inverted or isoelectric P-waves at baseline that fail to normalize during isoproterenol infusion suggest SAN dysfunction. P-wave morphology analyses may be helpful in determining the SAN function in patients at risk of symptomatic sick sinus syndrome.

Keyword

Calcium; Sinoatrial node; Adrenergic beta-agonists; Sick sinus syndrome; Biological pacemaker

MeSH Terms

Adrenergic beta-Agonists
Atrial Fibrillation
Biological Clocks
Calcium
Heart Atria
Heart Failure
Humans
Isoproterenol
Membranes
Models, Animal
Sarcoplasmic Reticulum
Sick Sinus Syndrome
Sinoatrial Node*
Adrenergic beta-Agonists
Calcium
Isoproterenol

Figure

• 

  Fig. 1 Effects of isoproterenol infusion on EAS. A: cranial shift of the EAS in a healthy control patient. The EAS at baseline (a) was in the superior one-third of crista terminalis (CT). The EAS during isoproterenol infusion (b) was at the junction between the SVC and the RA. B: impaired cranial shift of the EAS in an AF patient with symptomatic bradycardia. The EAS at baseline (a) was ectopic (at the RA free wall). The EAS during isoproterenol infusion (b) was located at the mid one-third of CT. The superior SAN in this patient was inactive with or without isoproterenol. The dashed line in each panel marks the CT. EAS: earliest atrial activation site, SVC: superior vena cava, RA: right atrial, AF: atrial fibrillation, SAN: sinoatrial node. Modified with permission from Joung et al.26)

• 

  Fig. 2 The different leading pacemaker sites during heart rate acceleration. A 50-year-old women had long-standing persistent AF and SAN dysfunction. A: (a) Junctional rhythm of 40 bpm after termination of AF. (b) Sinus P-wave appeared and sinus rate increased to 110 bpm during isoproterenol infusion of 10 µg/min. B: (a) RA activation map. The superior crista terminalis was recovered as the EAS (arrow) during isoproterenol infusion. (b) RA voltage map. The middle and lower part of RA and crista terminalis is a low voltage area with gray color (<0.5 mV). AF: atrial fibrillation, SAN: sinoatrial node, RA: right atrial, EAS: earliest atrial activation site. Modified with permission from Joung et al.26)

• 

  Fig. 3 Inferior shift of EAS during isoproterenol infusion in a patient taking amiodarone. A: RA activation map at baseline (left panel) and during isoproterenol infusion (right panel). EAS was shifted to the lower part of crista terminalis (arrow) during isoproterenol infusion. B: EKG at baseline (left panel) and during isoproterenol infusion (right panel). Note the decreased amplitude of P-waves in leads II, III, and aVF after inferior shift of EAS during isoproterenol infusion (arrows). EAS: earliest atrial activation site, RA: right atrial. Modified with permission from Mun et al.39)

• 

  Fig. 4 Atrial tachycardia originating from lower crista terminalis. A: RA activation map showing sinus beat (a) and atrial tachycardia (b) from superior and inferior crista terminalis, respectively. B: EKG showing sinus beat (a) and atrial tachycardia (b). Atrial tachycardia originating from lower crista terminalis had decreased amplitude of P-waves in leads II, III, and aVF. RA: right atrium, CT: crista terminalis.

• 

  Fig. 5 The P-wave changes induced by sympathetic stimulation. A: the negative correlation between the distance from the SVC-RA junction to the most cranial EAS and P-wave amplitude in leads II (left panel), III (middle panel), and aVF (right panel). Unfilled and filled circles represent P-wave amplitude at baseline and during isoproterenol infusion, respectively. Black and red circles represent the patients without and with sick sinus syndrome (SSS), respectively. B: the change of P-wave amplitude in leads II (left panel), III (middle panel), and aVF (right panel) during isoproterenol infusion. Note that the patients with SSS tend to have low P-wave amplitude and low EAS location both at baseline and during isoproterenol infusion. SVC-RA: superior vena cavaright atria, EAS: earliest atrial activation site, aVF: , ISO: isoproterenol. Modified with permission from Mun et al.39)

• 

  Fig. 6 Comparative Efficacy of Testing for Symptomatic Bradycardia. A,: the dot plots of the CSNRT from AF patients without (No SSS) and with sinus bradycardia (SSS) at each pacing cycle length (PCL) showing large overlaps between the two groups. The dashed line shows the CSNRT of 550 ms. B: the distance from the SVC-RA junction to the most cranial earliest activation site at baseline and during isoproterenol infusion. CSNRT: corrected sinoatrial node recovery time, AF: atrial fibrillation, SSS: sick sinus syndrome, SVC-RA: superior vena cava-right atrial, ISO: isoproterenol. Modified with permission from Joung et al.26)

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