Acetylcholine is the main transmitter of the parasympathetic vagus nerve. According to the cholinergic anti-inflammatory pathway (CAP) concept,
acetylcholine has been shown to be important for signal transmission within the immune system and also for a variety of other functions throughout the organism. The spleen is thought to play an important role in regulating the CAP. In contrast, the existence of a "non-neuronal cardiac
cholinergic system" that influences cardiac innervation during
inflammation has been hypothesized, with recent publications introducing the heart instead of the spleen as a possible interface between the immune and nervous systems. To prove this hypothesis, we investigated whether selectively disrupting vagal stimulation of the right ventricle plays an important role in rat CAP regulation during
endotoxemia. We performed a selective resection of the right cardiac branch of the Nervus vagus (VGX) with a corresponding
sham resection in vehicle-injected and endotoxemic rats. Rats were injected with
lipopolysaccharide (LPS, 1 mg/kg
body weight, intravenously) and observed for 4 h. Intraoperative blood gas analysis was performed, and hemodynamic parameters were assessed using a left ventricular pressure-volume
catheter. Rat hearts and blood were collected, and the expression and concentration of proinflammatory
cytokines using quantitative reverse transcription polymerase chain reaction and
enzyme-linked
immunosorbent assay were measured, respectively. Four hours after injection, LPS induced a marked deterioration in rat blood gas parameters such as pH value,
potassium, base excess,
glucose, and
lactate. The mean arterial blood pressure and the end-diastolic volume had decreased significantly. Further, significant increases in blood
cholinesterases and in proinflammatory (IL-1β, IL-6, TNF-α)
cytokine concentration and gene expression were obtained. Right cardiac vagus nerve resection (VGX) led to a marked decrease in heart
acetylcholine concentration and an increase in cardiac
acetylcholinesterase activity. Without LPS, VGX changed rat hemodynamic parameters, including heart frequency, cardiac output, and end-diastolic volume. In contrast, VGX during
endotoxemia did not significantly change the concentration and expression of proinflammatory
cytokines in the heart. In conclusion we demonstrate that right cardiac vagal innervation regulates cardiac
acetylcholine content but neither improves nor worsens systemic
inflammation.