Introduction: Parasympathetic dysfunction after myocardial infarction (MI) predisposes to arrhythmias and heart failure. Mechanisms behind this dysfunction are unclear. It is known that cardiac sensory afferent neurons in the vagal ganglia sense beat-to-beat changes at the level of the heart. This vagal afferent signaling/activation then increases central cardiac vagal efferent drive. Hypothesis: We hypothesized that MI causes a functional reduction in vagal afferent signaling that subsequently decreases efferent vagal tone, resulting in parasympathetic dysfunction. Methods: A transgenic mouse line was created by crossing mice expressing excitatory vesicular glutamate transporter 2, VGlut-ires-cre, with those expressing channel rhodopsin 2 EYFP (ChR2), resulting in mice with VGlut and ChR2 expression in afferent-specific vagal neurons and fibers. MI was created by left anterior descending artery ligation. Sham animals underwent thoracotomy only. Control animals did not undergo a thoracotomy. Two weeks post-MI or sham, the left cervical vagus nerve was isolated and optically stimulated in vivo using blue light laser (473 nm, 20 Hz, 10 & 20 msec). Heart rate (HR), respiratory rate (RR), and time to activation of efferent vagal effects (time to nadir HR/RR) were assessed. Results: In response to optical stimulation, MI animals (n=5) demonstrated significantly reduced HR responses vs. sham (n=4) and control (n=7) animals at both 10 ms and 20 ms, figure. Time to nadir HR was also increased in MI animals (P<0.05 vs. sham/control). RR decreased in all animals, without significant differences between groups. Conclusions: MI is associated with decreased efferent vagal responses to similar levels of parasympathetic afferent activation. These results suggests that mechanisms behind decreased vagal tone post-MI may be due altered vagal afferent neurotransmission and signaling capabilities. MI selectively affects cardiac, not respiratory, neural responses.

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