Changes in Heart Rate Volatility In A Murine Model Of SepsisChanges in Heart Rate Volatility In A Murine Model Of Sepsis

Goel N, Skaf J, Guglielmi M, Foley B, Zanotti S, Parrillo JE, Hollenberg SM Cardiology and Critical Care, Cooper University Hospital, Camden, NJ

Background

• Nonlinear analysis of hemodynamic parameters such as Heart Rate Variability (HRV) may provide insights not available from standard linear measures

• Power spectral analysis of HRV is commonly used. However, challenges arise from artifacts and dense data capture.

Hypothesis

• Sepsis will be associated with perturbations in Heart Rate Volatility (standard deviation variability), a means of assessing HRV that minimizes artifact-induced error.

Methods

• C57/Bl6 mice (8-12 weeks, 20 g., n=24)• Radiotelemeters for hemodynamic measurements in

awake animals were implanted in the ascending aorta via the carotid artery.

• Animals were allowed to recover for 5 to 7 days.• Baseline data was obtained for 24 hours.• Sepsis was induced by cecal ligation and puncture

(CLP, n=20).• Controls received sham-operation (SO, n = 4).• Animals were resuscitated with fluids and antibiotics

every 6 hours.• Heart Rate (HR) was calculated from blood pressure

waveforms obtained from radiotelemeters.• HR standard deviations (SD) were calculated on each

5 minute interval.

Methods

• For each animal, SD histograms were constructed and the cutoff that represented the lowest 5% was calculated for the baseline period.

• The percentage of low SD’s (representing low HRV) in the entire experimental period was defined by this cutoff.

• A time course was generated by calculating the percentage of low HRV over 4 hour intervals.

Results

• Animals in the control group had low HRV detected in 1.5% of all intervals (p =NS versus baseline)

• Animals in the septic group had low HRV in 38.72% of intervals post-CLP (p<0.01 versus baseline and versus controls)

• Mortality in the septic group was 60%.• Survivors and nonsurvivors had a similar decrease in

HR volatility early, with partial recovery, but then HRV responses diverged, with normalization in survivors, and further perturbation in non-survivors.

Conclusions

• Analysis of Heart Rate Volatility is less demanding, more intuitive and less susceptible to artifact as a means of measuring HRV than spectral analysis.

• We have shown dramatic differences between septic and control animals in a clinically relevant murine model of sepsis using these techniques.

• Extrapolation of this methodology to critically ill patients has the potential to provide novel markers of hemodynamic decompensation.

Control Group - Baseline HR Histogram

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Control Group - Post-SO HR Histogram

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Septic Group - Baseline HR Histogram

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Septic Group - Post-CLP HR Histogram

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Heart Rate - Septic Animal

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Heart Rate - Control Animal

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HR vs. HR volatility in Septics and Controls

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HR vs. HR volatility in Septics and Controls

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