Læknablaðið - 15.02.2003, Síða 32

FRÆÐIGREINAR / NÝR DOKTOR í LÆKNISFRÆÐI
Purkinje kerfi hjartans og sleglatakttruflanir
við blóðþurrð og endurflæði
Davíð O. Arnar.
Davíð O. Arnar varði ritgerð sína við læknadeild
Háskóla Islands þann 7. desember 2002. Andmæl-
endur voru prófessor Michiel J. Janse frá Amster-
damháskóla og prófessor Þórður Harðarson frá Há-
skóla Islands. Heiti ritgerðarinnar er The Cardiac
Purkinje System and the Ventricular Tachyarrhyth-
mias of Ischemia and Reperfusion og byggist hún á
rannsóknum sem Davíð vann undir handleiðslu James
B. Martins prófessors við University of Iowa Hospi-
tals and Clinics þegar Davíð stundaði sérfræðinám
þar í hjartalækningum og hjartaraflífeðlisfræði. Hér á
eftir fer enskt ágrip ritgerðarinnar.
Ventricular tachycardia (VT) and ventricular fibrilla-
tion (VF) are commonly associated with both acute
myocardial ischemia and reperfusion. These arrhyth-
mias may be due to reentry or have a focal origin
where the underlying mechanism might be automati-
city or triggered activity. The cardiac Purkinje sys-
tem has been suspected of playing a role in the deve-
Iopment of ischemic VT, while the subendocardium
has been shown to be an important source of focal
VTs during reperfusion.
Until recently the heart was thought to be devoid
of postjunctional a-2 adrenoceptors. However, con-
vincing evidence now exists that these may be pre-
sent in Purkinje tissue but not myocardium in the
canine species. Stimulation of these receptors pro-
longs the action potential duration in vitro and the
Purkinje relative refractory period in vivo and thus
may have a potential physiologic role.
The main goals of this investigation were twofold:
1) To examine the role of the Purkinje system in the
genesis of ventricular arrhythmias of ischemia and
reperfusion. 2) To further study the mechanism of
Purkinje action potential prolongation seen during a-
2 adrenergic stimulation and examine a potential
physiologic role for these postjunctional a-2 adreno-
ceptors on Purkinje cells.
This investigation was undertaken using a intact,
open chest, canine model where the left anterior des-
cending coronary artery was occluded after instru-
mentation of the ischemic risk zone with 21 multi-
polar plunge needles each recording 6 bipolar elec-
trograms. The electrograms were sampled at 3.2
kHZ and filtered from 3-1300 Hz. Three dimensional
activation mapping characterized the mechanism
and site of origin of VT. VT of Purkinje origin was
defined as focal endocardial VT with a Purkinje
potential preceding the earliest muscle activity for a
given complex. Additionally, standard microelec-
trode studies were performed to assess the mecha-
nism of action potential prolongation by a-2 adre-
nergic stimulation.
The main results suggest that the Purkinje system
may be importantly involved in the initiation of both
early spontaneous ischemic VT and reperfusion VT.
These arrhythmias commonly have a focal origin and
may be due to triggered activity from delayed after-
depolarizations, although other arrhythmia mecha-
nisms may also play a role. The Purkinje system was
also associated with the development of VT indu-
cible with programmed extrastimulus technique in
the first three hours after coronary artery occlusion.
A mechanism of the a-2 adrenergic prolongation of
the Purkinje action potential duration might be via
inhibition of the transient outward current, Ito. In
addition, these data suggest that administration of
the a-2 adrenergic agonists clonidine and UK14,304
may selectively inhibit induction of ischemic VT of
Purkinje origin only while not affecting inducibility
of VT from the myocardium.
Thus, at the same time that the Purkinje system is
identified to play a important role in arrhythmo-
genesis during acute ischemia and reperfusion the
presence of a-2 adrenoceptors on Purkinje tissue
might present a unique pharmacological target.
Stimulation of these receptors may result in inhibi-
tion of Vt of Purkinje origin. These findings in a
canine model are novel and potentially important,
although further studies are needed to determine
whether these results can be extrapolated to humans.
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