Biomedical Engineering Reference
In-Depth Information
pacemaker ion channels. Indeed, addition of 100 ȝM ZD7288 significantly reduced
the beating rate of the co-culture by fivefold (Fig. 3b; P < 0.05). Addition of neither
isoproterenol nor ZD7288 affected quiescent NRVMs without engrafted hEBs. The
synchronous beating could be terminated by crushing or surgically excising the
transplanted human cells (n = 17; analogous to ablation), further proving that hEB
pacemakers were indeed the origin of pacing.
Fig. 3. a
Gap-junction un-coupler heptanol reversibly eliminated action potential propagation to
neighboring NRVM sites but did not affect APs in pacing origin of hEB at heptanol
concentration of 0.4 mM.
b
ȕ
-Adrenergic stimulation with 1
ȝ
M isoproterenol (Iso)
significantly accelerated spontaneous beating rate of hEB (P = 0.01), whereas ZD7288
significantly attenuated the beating activity (n = 9 for each group).
c
Optical mapping of guinea
pig left ventricle pre-injected with hEBs (
bottom
) or saline (
top
) after atrioventricular nodal
cryoablation without external pacing.
We then went on to examine the biological pace-maker activity in a whole heart by
injecting spontaneously beating hEBs into the left ventricular anterior wall of a guinea
pig in vivo. In order to distinguish ectopic ventricular beats originated from the site of
injection from the animal's own sinus rhythm, the animal's endogenous SA nodal
pacemaker activity was terminated by cryoablation of the atrioventricular node. Upon
the ablation, ex vivo optical mapping of control (un-injected or saline-injected) guinea
pig hearts exhibited complete electrical silence throughout the entire left ventricle
(
n
= 6). However, spontaneous action potentials could be readily recorded from the
epicardial surface of left ventricle of animals that had been transplanted with
spontaneously beating hEBs in vivo (
n
= 4, Fig. 3c). Furthermore, the spontaneous
action potentials were initiated from the injection site; the origin of the spread of
