{
  "abstract": "Introduction Sudden cardiac death (SCD) is a leading cause of mortality worldwide, most commonly caused by ventricular fibrillation (VF). Studies using male animal models have identified abnormal autonomic nerve activity as a predictor of ventricular arrythmias. However, emerging evidence suggests that sex differences in the autonomic nervous system (ANS) may regulate cardiac electrophysiology differently in males and females. For example, males exhibit a sympathetic-dominant ANS, whereas women exhibit a parasympathetic-dominant ANS. Despite this research, how these differences affect underlying electrophysiological characteristics, which may influence susceptibility to VF and SCD, remains unclear. Thus, this study aimed to investigate sex differences in the effects of autonomic nerve stimulation on ventricular electrophysiology and arrhythmia susceptibility.Methods Using the isolated innervated rabbit heart preparation, a series of pacing protocols were performed on male (n = 6) and female (n = 4) New Zealand White rabbits (2-2.5 kg) under control conditions, sympathetic nerve stimulation, and vagal nerve stimulation. These protocols were used to assess electrophysiological parameters associated with arrhythmia susceptibility and SCD, including heart rate (HR), action potential duration (APD), electrical restitution, effective refractory period (ERP), and VF threshold (VFT).Results Under sympathetic stimulation, male rabbits exhibited a significantly greater increase in HR than females when stimulated at the same voltages and frequencies ( figure 1A and 1B). At 5hz, the largest difference in the change of HR between sexes occurred at 5V (126 ± 7.57 bpm males, 56 ± 15.08 bpm females, p = 0.0003), and significant differences were also observed at 2V, 7V, and 10V. The frequency response curves showed significant differences between sexes at 7Hz and 10Hz (p = 0.0327 and 0.0455, respectively). This result was also reflected in the protocols, as males showed a trend towards larger decreases in ERP (-9 ± 1.87 ms males, -7.5 ± 3.23 ms Females) and VFT (-1.20 ± 0.20 mA males, -0.7 ± 0.28 mA females) during sympathetic stimulation than females, although these differences were not significant. No significant differences were observed in the vagus nerve responses (p > 0.05) (figures 1C and 1D).Conclusion These findings suggest that sex-specific differences in autonomic regulation contribute to differential susceptibility to ventricular arrhythmia, with male rabbits exhibiting heightened sensitivity to sympathetic stimulation. Consistent with previous studies, males demonstrated a greater sympathetic influence on ventricular electrophysiology, a mechanism closely linked to pro-arrhythmic risk. These results highlight the importance of considering biological sex when assessing autonomic contributions to arrhythmia risk and suggest that sex-specific strategies for risk stratification and clinical therapeutics may be required.Abstract 337 Figure 1Heart rate (HR) changes in response to sympathetic nerve stimulation (SNS) and vagus nerve stimulation (VNS). Change in HR from baseline before stimulation and after SNS (A) and VNS (C) at 5Hz and various stimulation strengths from 1-20V. Change in HR from baseline before stimulation and after SNS (B) and VNS (D) at a stimulation strength (V) that produced a heart rate 80% of the maximal response, and at various frequencies (1-20Hz). Data are presented as mean ± SEM. Male rabbits (n=6) are represented by blue lines, and female rabbits (n=4) by red lines. Statistical significance was determined using a two-way ANOVA (*P < 0.05).",
  "authors": [
    {
      "affiliations": [
        "University of Leicester, Leicester, United Kingdom"
      ],
      "name": "Katie Wilkinson"
    },
    {
      "affiliations": [
        "University of Leicester, Leicester, United Kingdom"
      ],
      "name": "Christine J Loft"
    },
    {
      "affiliations": [
        "University of Leicester, Leicester, United Kingdom"
      ],
      "name": "Bethan Roper-Jones"
    },
    {
      "affiliations": [
        "University of Leicester, Leicester, United Kingdom"
      ],
      "name": "Rachel L Sutcliffe"
    },
    {
      "affiliations": [
        "University of Leicester, Leicester, United Kingdom"
      ],
      "name": "André G Ng"
    },
    {
      "affiliations": [
        "University of Leicester, Leicester, United Kingdom"
      ],
      "name": "Reshma A Chauhan"
    }
  ],
  "title": "337 Sex differences in the autonomic regulation of cardiac electrophysiology between male and female rabbits",
  "uid": "915b1765-8033-5007-aeef-2bec8cd86750"
}