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Published on: May 28, 2019
Reconstituted high-density lipoprotein shortens cardiac repolarization
Hester M Den Ruijter1, Remco Franssen, Arie O Verkerk
1Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands.
Insights
Increasing high-density lipoprotein cholesterol (HDL-C) shortens cardiac repolarization. This finding suggests a new mechanism by which HDL infusion may reduce sudden cardiac death risk.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Electrophysiology
Background:
- High-density lipoprotein cholesterol (HDL-C) is inversely associated with sudden cardiac death.
- The direct relationship between HDL-C levels and cardiac repolarization remains largely unexplored.
Purpose of the Study:
- To investigate the hypothesis that elevated HDL-C shortens cardiac repolarization.
- To explore a potential novel mechanism linking HDL to cardiac electrical stability.
Main Methods:
- Cardiac repolarization was assessed using the patch clamp technique on isolated rabbit cardiomyocytes exposed to reconstituted HDL (rHDL).
- Surface electrocardiograms (ECG) were recorded in dyslipidemic patients and healthy volunteers before and after rHDL infusion (40 mg/kg).
Main Results:
- rHDL and purified apolipoprotein AI significantly shortened repolarization in isolated cardiomyocytes by approximately 25%.
- rHDL infusion led to a significant shortening of the heart rate-corrected QT interval in all human participants.
Conclusions:
- Reconstituted HDL effectively shortens cardiac repolarization.
- These findings provide evidence for a novel mechanism through which HDL infusion may reduce the risk of sudden cardiac death.
Objectives:
We hypothesize that increasing high-density lipoprotein cholesterol (HDL-C) shortens cardiac repolarization.
Background:
HDL-C is inversely associated with sudden death. The relation between HDL-C and repolarization of the heart is unexplored.
Methods:
HDL-C was elevated with reconstituted high-density lipoprotein (rHDL). Cardiac repolarization was studied by recording cardiac transmembrane potentials with the patch clamp technique from isolated rabbit cardiomyocytes that were superfused with rHDL. Infusions with rHDL (40 mg/kg body weight) were performed in dyslipidemic patients and healthy volunteers. Electrocardiograms were recorded to assess cardiac repolarization before and 24 h after infusion with rHDL.
Results:
rHDL as well as purified human apolipoprotein AI shortened repolarization of isolated rabbit cardiomyocytes by ∼25% (p < 0.05). rHDL infusion shortened the heart rate-corrected QT interval on surface electrocardiograms in all participants (p < 0.001).
Conclusions:
rHDL shortens cardiac repolarization. These data provide evidence for a novel mechanism of HDL infusion that may contribute to reduction of sudden cardiac death.
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