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Global Cardiology Congress 2019
Journal of Cardiovascular Medicine and Therapeutics | Volume 3
June 19-20, 2019 | Dublin, Ireland
OF EXCELLENCE
IN INTERNATIONAL
MEETINGS
alliedacademies.comYEARS
CARDIOLOGY AND
CARDIOVASCULAR MEDICINE
6
th
International Conference on
AN INCREASE IN CO
2
LEVELS BY UPREGULATING LATE SODIUM CURRENT IS PROAR-
RHYTHMIC IN THE HEART
LinWu
Peking University First Hospital, China
I
ncreased CO
2
levels in general circulation and/or in the myocardium are common under pathological condi-
tions. To test the hypothesis that an increase in CO
2
levels, but not just the subsequent extra- or intra-cellular
acidosis, would augment late sodiumcurrent (INa,L) and contribute to arrhythmogenesis in hearts with reduced
repolarization reserve. Monophasic action potential durations at 90% completion of repolarization (MAPD90)
from isolated rabbit hearts, INa,L and extra- (pHo) and intra-cellular pH (pHi) values from cardiomyocytes using
the whole-cell patch-clamp techniques and BCECF-AM respectively, were measured. Increasing CO
2
level from
5% to 10% and 20% and administration of 1 nM sea anemone toxin (ATX)-II increased INaL and prolonged both
epi- and endo-MAPD90 (n=7 and 10) without causing arrhythmic activities. Compared to 5% CO
2
, 10% and
20% CO
2
decreased pHo and pHi, in hearts treated with 1 nM ATX-II caused a greater prolongation of MAPD90
and elicited ventricular tachycardias. Increasing CO
2
levels from 5% to 10% and 20% with pHo remained at 7.4
produced smaller changes in pHi (P <0.05) but similar increase in INa,L prolongation in MAPD90 and incidence
of ventricular tachycardias (n=8). Inhibition of INa,L reversed the increase in INa,L suppressed MAPD90 prolon-
gations and ventricular tachycardias induced by 20% CO
2
. Increased phospho-CaMKIIδ and phospho-NaV1.5
protein levels in hearts treated with 20% CO
2
was attenuated by eleclazine. In conclusion, increased CO
2
levels
enhance INa,L and are proarrhythmic factors in the heart with reduced repolarization reserve, possibly through
mechanisms related to the phosphorylations of CaMKIIδ and NaV1.5.
Lin Wu, J Cardiovasc Med Ther 2019, Volume 3
LinWu received his MD Degree from Beijing Medical University, completed his Postdoctoral training at the University of Florida and
worked as a Senior Research Scientist at CV Therapeutics and Gilead Sciences in California, USA. Now he is a full-time Professor and
Chief Physician at Department of Cardiology, Peking University First Hospital, China. He has made important contributions to our
understanding of the role of endogenous and enhanced late sodium current in ventricular and atrial arrhythmias. He has in-depth
experience in cardiac electrophsiology, especially in late sodium current-associated cardiac arrhythmias and myocardial ischemia,
evidenced by 36 world-circulated reputed journals and over 34 presentations at international scientific conferences.
lin_wu@163.comBIOGRAPHY