Cardiovascular and Autonomic Dysfunction in Murine Ligature-Induced Periodontitis

Abstract

The present study examined the hemodynamics [arterial pressure (AP), AP variability (APV), heart rate (HR), and heart rate variability (HRV)], cardiac function (echocardiographycally), and myocardial inflammation in Balb/c mice submitted to Periodontitis, through the ligation of the left first molar, or Sham surgical procedure. The first protocol indicated that the AP was similar (136 ± 2 vs. 132 ± 3 mmHg in Sham), while the HR was higher in mice with Periodontitis (475 ± 20 vs. 412 ± 18 bpm in Sham), compared to their Sham counterparts. The APV was higher in mice with Periodontitis when evaluated in the time domain (4.5 ± 0.3 vs. 3.4 ± 0.2 mmHg in Sham), frequency domain (power of the LF band of systolic AP), or through symbolic analysis (patterns 0V + 1V), indicating a sympathetic overactivity. The HRV was similar in the mice with Periodontitis, as compared to their Sham counterparts. In the second protocol, the mice with Periodontitis showed decreased cardiac output (10 ± 0.8 vs. 15 ± 1.4 mL/min in Sham) and ejection fraction (37 ± 3 vs. 47 ± 2% in Sham) associated with increased myocardial cytokines (Interleukin-17, Interleukin-6, and Interleukin-4). This study shows that experimental Periodontitis caused cardiac dysfunction, increased heart cytokines, and sympathetic overactivity, in line with epidemiological studies indicating an increased risk of cardiovascular events in clinical Periodontitis.

Figure 1

Effect of periodontitis in alveolar bone loss. (A) Protocol of experiments of mice ligature periodontitis model. Linear and area of the alveolar bone loss was measured macroscopically in the lingual (Panels B,C) and buccal (Panels D,E) surfaces in mice with Sham (Panels B,D) or dental ligation (Panels C,E). Bar graphs show the linear alveolar bone loss and alveolar bone loss area from the lingual (Panel F,H, respectively) and buccal (Panel G,I, respectively) surfaces. The white dashed lines indicate the three distances measured in the teeth and yellow solid lines indicate alveolar bone loss area. Data are mean ± SEM *P < 0.05. Ligature: Periodontitis elicited by the ligation of the mandibular left first molar. Sham: Sham ligation.

Figure 2

Systolic Arterial Pressure Variability in Time and Frequency Domain, and Symbolic Dynamics Analysis. Bar graphs show in the Upper Panels the systolic arterial pressure (SAP; Panel A) and the standard deviation of SAP (SD; Panel B); and, in the Lower Panels the power of the low-frequency component of heart rate variability (LF; Panel C), and Families from the Symbolic Dynamics Analysis (0V + 1V Families; Panel D). Data are mean ± SEM. *P < 0.05. Ligature: Periodontitis elicited by the ligation of the mandibular left first molar. Sham: Sham ligation.

Figure 3

Heart Rate Variability in Time and Frequency Domain, and Symbolic Dynamics Analysis. Bar graphs show: Panel A, Mean Pulse Interval; Panel B, Standard Deviation of the NN interval (SDNN) and The Square Root of the Mean Squared Differences of Successive NN Intervals (RMSSD) from the Pulse Interval; Panel C, The ratio between the powers of Low Frequency (LF) and High Frequency (HF) components of Heart Rate Variability; Panel D, Families (0V and 2UV) from Symbolic Dynamics Analysis of Pulse Interval. Data are mean ± SEM. *P < 0.05. Ligature: Periodontitis elicited by ligation of the mandibular left first molar. Sham: Sham ligation.

Figure 4

Cardiac Function in Periodontitis Elicited by Ligation of Mandibular Left First Molar. Bar Graphs show: Panel A, Cardiac Output; Panel B, Ejection Fraction; Panel C, Fractional Shortening. Data are mean ± SEM. *P < 0.05. Ligature: Periodontitis elicited by ligation of the mandibular left first molar. Sham: Sham ligation.

Figure 5

Inflammatory Cytokine Concentration in the Cardiac Tissue, in Periodontitis Elicited by Ligation of Mandibular Left First Molar. Bar Graphs show: Panel A, interleukin-6 (IL-6); Panel B, interleukin-4 (IL-4); Panel C, IL-17. Data are mean ± SEM. *P < 0.05. Ligature: Periodontitis elicited by ligation of the mandibular left first molar. Sham: Sham ligation.