Sinus venosus incorporation: contentious issues and operational criteria for developmental and evolutionary studies

Abstract

The sinus venosus is a cardiac chamber upstream of the right atrium that harbours the dominant cardiac pacemaker. During human heart development, the sinus venosus becomes incorporated into the right atrium. However, from the literature it is not possible to deduce the characteristics and importance of this process of incorporation, due to inconsistent terminology and definitions in the description of multiple lines of evidence. We reviewed the literature regarding the incorporation of the sinus venosus and included novel electrophysiological data. Most mammals that have an incorporated sinus venosus show a loss of a functional valve guard of the superior caval vein together with a loss of the electrical sinuatrial delay between the sinus venosus and the right atrium. However, these processes are not necessarily intertwined and in a few species only the sinuatrial delay may be lost. Sinus venosus incorporation can be characterised as the loss of the sinuatrial delay of which the anatomical and molecular underpinnings are not yet understood.

Keywords: development; evolution; heart; sinuatrial valve.

Figure 1

Gradations of sinus venosus incorporation into the right atrium. The region of the dominant pacemaker is schematised in red. (A) In the embryological and reptilian settings, there is no anatomical and no electrical incorporation. This is reflected in the early deflection of the sinus venosus (SV) on the electrocardiogram as compared to the atrial deflection (P) and in the differences in blood pressure in the sinus venosus (dark grey) and the right atrium (light grey). The onset of the sinus systole and atrial systole are marked with arrows in the blood pressure trace and coincides with the SV and P deflections, respectively, on the electrocardiogram. (B) In the mouse at neonatal day 1 there is no anatomical but only an electrical incorporation. The SV‐wave in the electrocardiogram is lost, and the systole of the sinus venosus and the right atrium coincide. Nonetheless, higher blood pressures in the right atrium can be envisioned to have a limited impact on the blood pressures in the sinus venarum due to the presence of a competent sinuatrial valve. (C) In the fully incorporated sinus venosus, in addition to the electrical incorporation, the competence of the sinuatrial valve is lost, resulting in a similar blood pressure during systole in the sinus venosus and the right atrium.

Figure 2

Comparative anatomy of sinus venosus incorporation. When comparing the configuration of the sinus horns, or systemic veins, of reptiles, as exemplified here by the Gila monster (Heloderma suspectum) (A), the setting is similar to that of human hearts with a persistent left superior caval vein (PLSCV) (B). The dorsal view of the normal adult human heart (C). Note that the orientation of the hearts corresponds to the orientation they have in the thoracic cavity. ICV, inferior caval vein; LA, left atrium; LSH, left sinus horn; PSH, posterior sinus horn; pv, pulmonary vein; RSH, right sinus horn; SCV, superior caval vein; ss, sinus septum; Ven, ventricle; X, sinuatrial junction.

Figure 3

Anatomy and physiology of the embryonic mouse heart. (A) A transverse section of the sinuatrial valve of a mouse of embryonic day 14.5 stained with in situ hybridisation for a mix of myocardial RNA probes as described in Soufan et al. (2003). The valve is large enough to potentially guard the entire sinus venosus from the right atrium. Asterisks indicate the sinuatrial valve leaflets. (B) Optically recorded action potentials from the dorsal side of another mouse heart of embryonic day 14.5. The early activation of the sinus venosus (SV), precedes the early atrial activation by 31 ms. (C) Reconstructed activation patterns showing the start of activation in the region of the sinus venosus and activation of the atria after a substantial delay. The delay between sinus venosus and atrial activation is 31 ms on a cardiac cycle of 488 ms. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; SV, sinus venosus.

Figure 4

Anatomy and physiology of the neonatal mouse sinuatrial junction. (A) Transverse section of the sinuatrial valve of a 1‐day‐old mouse stained with in situ hybridisation for a cTnI RNA probe as described in Aanhaanen et al. (2011). Asterisks indicate the sinuatrial valve leaflets. (B) Electrocardiogram of a mouse of neonatal day 1. Only a P‐wave can be seen before the QRS complex. P, atrial activation wave; QRS, ventricular activation wave; SV, sinus venosus.

Figure 5

Anatomy and physiology of the adult mouse heart. (A) A transverse section of the sinuatrial valve of an adult mouse stained with in situ hybridisation for an Nppa RNA probe as described in Hoogaars et al. (2007). There is no evidence of leaflets of the sinuatrial valve that can cover the cavity now known as the sinus venarum (SV). Blood in the cavities has been masked with white. (B) Optical mapping of the epicardial side of the right atrium and intercaval area in the adult mouse. (C) Reconstructed activation patterns show a delay between sinus node activation and working myocardium activation but the caval veins and right atrium activate simultaneously. Colours in the trace also correspond to the colours used in (B). (D) In this case, Under isoproterenol stimulation, only one in two of the sinus node activations (arrows) is propagated to the surrounding working myocardium, suggesting the presence of junctional tissue. ICV, inferior caval vein; RA, right atrium; SAN, sinuatrial node; SCV, superior caval vein; SV, sinus venarum.

Figure 6

Anatomy and inferred physiology of the platypus heart. (A) Cross‐section of the Platypus (Ornithorhynchus anatinus) sinus nodal region, where the sinus node, according to Davies (1931), could be recognised as a region of pale‐stained myocardium (encircled by a red line) receiving a large coronary artery (Cor). The myocardium from the superior caval vein (SCV) to the right atrial wall (RA‐wall) is continuous. Modified from Davies (1931). Compared with the electrical activity of the reptile heart (B), modified from Jensen et al. (2017), the monotreme heart is likely without a sinuatrial delay (C), as the pacemaker myocardium does not form a complete junction between the myocardium of the SCV and right atrium (the electrophysiology of the monotreme is inferred by us, the traces are not based on actual recordings). Cor, coronary artery of the sinus node; P, atrial activation wave; QRS, ventricular activation wave; RA, right atrium; SCV, superior caval vein; SV, sinus venosus activation wave. For methods see previously published literature (Aanhaanen et al. 2011).