Abstract 3607: Early AV-Nodal Remodeling in Pigs with Persistent Atrial Fibrillation and Heart Failure
Background: Heart failure (HF) is a common cause for the worldwide morbidity and mortality. In up to 30 % of HF-patients conduction disturbances are present. Both bundle branch- as well as AV-block may occur which often worsen the prognosis. The aim of the present study was to investigate early processes of AV-nodal remodeling in pigs with persistent atrial fibrillation (AF) and HF.
Methods: In 5 domestic pigs a pacemaker (PM) capable of 42 Hz bursting was implanted into the right atrium. Before implantation of PMs and 20 days thereafter Wenckebach-cycle-length (WCL), PQ- and QRS-duration were determined during sinus rhythm. To evaluate changes on a protein level western blot analysis were performed on extracted AV-nodes. Five sham-operated pigs served as control-group.
Results: After 5±1 days all pigs were in persistent AF. Twenty days after PM-implantation left ventricular ejection fraction decreased from 69±3 to 33±3 % (p,0.05). Comparing heart rates recorded during early stages of persistent AF and on day 20 after PM-implantation a moderate decrease could be observed (293±19 bpm vs. 271±16 bpm, p<0.05). During the same period PQ- (102 ± 22 ms vs. 164±26 ms,p<0.05), QRS-duration (50±7 ms vs. 76±20 ms, p<0.05) and WCL (208±5 ms vs. 278±9 ms, p<0.05) significantly increased. These findings were accompanied by a 56 % increase in Gi alpha expression (p<0.05), a counterpart of the Gs protein and L-type Calcium channel (LCa), decreasing AV-node conduction. In addition expression of β1-integrins, an activator of LCa, decreased significantly (−44 %, p<0.05). Surprisingly, these changes were counteracted by an upregulation of the Gs protein (+100 %, p<0.05) and the repolarising-currents Herg (+75 %, p<0.05) as well as KCNQ1 (+119 %, p<0.05).
Conclusions: During early stages of HF AV-nodal remodeling is already evident. Changes of protein expression, which affects the L-type Calcium channel, a regulator of conduction propagation in AV-nodes, were partly compensated by an upregulation of the Gs protein and the delayed rectifier potassium channels. This study demonstrates early compensatory mechanisms to prevent worsening of AV-nodal impulse propagation in HF.