Biomedical Engineering Reference
In-Depth Information
4.1 Functional Inhomogeneity
Figure 7 (taken from [32]) shows the background of functional inhomogeneity and
its consequences for nodal chronotropic effects. Intact rabbit sinus nodes were
sequentially impaled and activation patterns were determined during standard
conditions (no adrenaline, no acetylcholine) and during the presence of either
adrenaline (Adr) or acetylcholine (Ach). This gave rise to three different pacemaker
centres (see also Fig. 5), one located in the superior sinus node (S, neither Adr nor
Ach present), one located in the inferior sinus node (I, in the presence of Adr) and
one located in the transitional zone (Tr), closer to the crista terminalis (CT, in the
presence of Ach). These three centres were separated from each other. This will
deliver three preparations ('S', 'I' and 'Tr') from each individual sinus node. Next
the chronotropic responses to adrenaline and acetylcholine were determined for
each of these centres. The responses of the primary centre (S) were intermediate
both to acetylcholine and to adrenaline. The Adr centre (I) had large responses to
both (neuro)humoural factors. The chronotropic responses to acetylcholine are
depicted by dashed lines at the top of the histogram. There were individual
preparations that turned quiescent in response to acetylcholine. In contrast, the Ach
centre (Tr) hardly changed its cycle length after administration of either substance.
The functional significance of these data is important. It indicates that there is huge
intranodal variability with respect to receptor density and probably also innervation.
Figure 8 (taken from [22]) shows recent data on the effect of vagal stimulation of
the rabbit sinus node on the nodal activation pattern simultaneously assessed by
optical methods. At the top left the field of view is shown with the orifices of the
superior (SVC) and inferior vena cava (IVC) and the crista terminalis (CT) and the
interatrial septum (IAS). The black dotted line indicates a line of block which is
present under normal conditions [5]. EG indicates the site of the atrial electrogram.
The black square indicates the area of optical recordings shown in the bottom
panels a, b and c. Panel A is the last activation just prior to postganglionic vagal
nerve stimulation. This occurs at a frequency which leads to neural firing with no
direct influence on cardiac cells. Panel B is taken just after vagal stimulation and
panel C indicates the fourth activation after stimulation. The normal activation
pattern starts at 'A' in the top left panel and at 'B' after vagal stimulation. The shift
is immediate and leads to a changed activation pattern for four consecutive cycles
(see also the atrial electrogram in the upper right panel). The white zones in panels
B and C show that there are areas that turn electrically quiescent. In addition, the
upper right panel shows a hyperpolarization by 16% in the centre, which is
dominant in the absence of vagal stimulation (trace 1).
This hyperpolarization increases towards the block zone (33%; trace 4). The
importance of this recent study of Fedorov et al. [22] is that it definitely shows that
vagal stimulation can turn areas of the sinus node inexcitable without complete
depression of pacemaker function of the complete sinus node. The lesson to be
learned here is that a biological pacemaker with strong
homogeneous
response to
vagal stimulation or to comparable stimuli may not constitute a sound goal.
