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Updated: Dec 26, 2025
Myocardial Infarction and Functional Outcome Assessment in Pigs
Published on: April 25, 2014
Accumulation of Pericardial Fat Is Associated With Alterations in Heart Rate Variability Patterns in
Domingo E Uceda1, Xiang-Yang Zhu1, John R Woollard1
1Division of Nephrology and Hypertension (D.E.U., X.-Y.Z., J.R.W., C.M.F., I.P., L.O.L.), Mayo Clinic, Rochester, MN.
Insights
Progressive pericardial fat accumulation and inflammation in pigs led to reduced heart rate variability (HRV), indicating autonomic nervous system imbalance. This suggests increased pericardial fat negatively impacts cardiovascular health.
Area of Science:
- Cardiovascular Physiology
- Autonomic Nervous System Function
- Metabolic Disease Research
Background:
- Heart rate variability (HRV) reflects autonomic cardiac modulation.
- Increased pericardial fat is linked to adverse cardiovascular outcomes.
- Pericardial fat accumulation may negatively impact HRV.
Purpose of the Study:
- To investigate the relationship between increasing pericardial fat volume, inflammation, and HRV in hypercholesterolemic pigs.
- To determine if pericardial fat accumulation prospectively dampens HRV.
Main Methods:
- Hypercholesterolemic Ossabaw mini-pigs (WT and PCSK9 gain-of-function) were fed normal or high-fat diets (HFD) for 6 months.
- Heart rate variability (HRV) indices were analyzed from arterial pulse waveforms.
- Pericardial fat volume, inflammation (TNF-α), lipid profiles, and norepinephrine levels were measured.
Main Results:
- Hypercholesterolemic pigs on HFD showed significantly depressed HRV and increased sympathovagal balance.
- Pericardial fat volume and LDL cholesterol correlated inversely with HRV and directly with sympathovagal balance.
- Pericardial fat TNF-α expression was upregulated, correlating with reduced HRV indices.
Conclusions:
- Progressive pericardial fat expansion and inflammation are associated with decreased HRV in pigs.
- These findings imply aggravated autonomic imbalance due to pericardial fat.
- Pericardial fat accumulation is linked to alterations in HRV and autonomic nervous system function.
Background:
Heart rate variability (HRV) and pulse rate variability are indices of autonomic cardiac modulation. Increased pericardial fat is associated with worse cardiovascular outcomes. We hypothesized that progressive increases in pericardial fat volume and inflammation prospectively dampen HRV in hypercholesterolemic pigs.
Methods:
WT (wild type) or PCSK9 (proprotein convertase subtilisin-like/kexin type-9) gain-of-function Ossabaw mini-pigs were studied in vivo before and after 3 and 6 months of a normal diet (WT-normal diet, n=4; PCSK9-normal diet, n=6) or high-fat diet (HFD; WT-HFD, n=3; PCSK9-HFD, n=6). The arterial pulse waveform was obtained from an arterial telemetry transmitter to analyze HRV indices, including SD (SD of all pulse-to-pulse intervals over a single 5-minute period), root mean square of successive differences, proportion >50 ms of normal-to-normal R-R intervals, and the calculated ratio of low-to-high frequency distributions (low-frequency power/high-frequency power). Pericardial fat volumes were evaluated using multidetector computed tomography and its inflammation by gene expression of TNF (tumor necrosis factor)-α. Plasma lipid panel and norepinephrine level were also measured.
Results:
At diet completion, hypercholesterolemic PCSK9-HFD had significantly (P<0.05 versus baseline) depressed HRV (SD of all pulse-to-pulse intervals over a single 5-minute period, root mean square of successive differences, proportion >50 ms, high-frequency power, low-frequency power), and both HFD groups had higher sympathovagal balance (SD of all pulse-to-pulse intervals over a single 5-minute period/root mean square of successive differences, low-frequency power/high-frequency power) compared with normal diet. Pericardial fat volumes and LDL (low-density lipoprotein) cholesterol concentrations correlated inversely with HRV and directly with sympathovagal balance, while sympathovagal balance correlated directly with plasma norepinephrine. Pericardial fat TNF-α expression was upregulated in PCSK9-HFD, colocalized with nerve fibers, and correlated inversely with root mean square of successive differences and proportion >50 ms.
Conclusions:
Progressive pericardial fat expansion and inflammation are associated with a fall in HRV in Ossabaw mini-pigs, implying aggravated autonomic imbalance. Hence, pericardial fat accumulation is associated with alterations in HRV and the autonomic nervous system. Visual Overview: A visual overview is available for this article.
