Burn-Induced Organ Dysfunction: Vagus Nerve Stimulation Improves Cardiac Function

Andreas D. Niederbichler, MD; Stephan Papst, BS; Leif Claassen, BS; Andreas Jokuszies, MD; Kyros Ipaktchi, MD; Kerstin Reimers, PhD; Tobias Hirsch, MD; Lars Steinstraesser, MD; Theresia Kraft, PhD; Peter M. Vogt, MD


ePlasty. 2010;10:e45 

In This Article

Abstract and Introduction


Introduction: Many studies have demonstrated the existence of an anti-inflammatory, parasympathetic pathway, termed as the inflammatory reflex. Burn-induced heart failure has been investigated in many previous studies. Proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6, have been shown to play a key pathogenetic role and vagus nerve stimulation attenuates proinflammatory cytokine production. This study was designed to evaluate postburn alterations of cardiac functional parameters after vagal electrostimulation.
Material and Methods: A 30% total body surface area standardized, full-thickness rat burn model was used. Electric stimulation of the vagus nerve was performed. The following functional cardiac parameters were measured by ventricular microcatheterization: Maximal and minimal left ventricular pressure, mean left ventricular pressure, end-diastolic pressure (EDP), positive and negative pressure rise and fall (±dP/dt), cardiac contractility index, and assessment of the heart rate.
Results: Vagus nerve stimulation improved maximal and minimal left ventricular pressure values compared with burn-only animals. End-diastolic pressure was elevated significantly in stimulated animals; however, EDP values were comparable with those in sham-injured animals. Analyzing positive and negative pressure development, ±dP/dt was restored to levels measured in sham-injured animals but not to control animal levels. No variations in heart rate were found.
Conclusion: We as well as others have shown that inflammation after burn injury is a key pathogenetic element, and this study provides new evidence that cardiac function is also improved by vagus nerve stimulation. These results lead us to consider novel therapeutic options for the treatment of postburn cardiac dysfunction.


Within the last years, the multifactorial pathogenesis of burn-induced cardiac dysfunction has been experimentally evaluated. A couple of immunologic systems and mediators have been proven to play central roles in the pathogenesis of cardiac contractility deficits after thermal trauma. A parasympathetic, anti-inflammatory pathway, known as the inflammatory reflex, has been implicated to play a central role in various experimental models of inflammation.[1,2] It is known that activation of the α7 nicotinic acetylcholine receptor subunit (α7nAChR) by physical and pharmacological means attenuates the generation of multiple proinflammatory mediators.[1–3] On a cellular level, previous work by Borovikova and colleagues[1] has shown that activation of the inflammatory reflex by acetylcholine exposure blocks the release of proinflammatory mediators by macrophages. Acetylcholine exposure of α7nAChR-deficient macrophages did not change their cytokine secretion profile. Various clinical studies including patients with inflammatory diseases such as chronic inflammatory bowel diseases have revealed beneficial effects of parasympathetic stimulation.[4,5] Previous research efforts have demonstrated that burn injury leads to cardiac dysfunction, which has been attributed to functional rather than structural changes of the cardiomyocyte. Cardiodepressive mediators such as TNF-α, IL-1β, and IL-6 have been identified as key pathogenetic elements. Experimental data suggest that TNF-α, IL-1β, and IL-6 are primary cytokines that lead to the deterioration of cardiac function, either individually or in combination.[6] We have recently shown in an experimental burn trauma model that electrical stimulation of the cervical portion of the vagus nerve induces a significant reduction of circulating levels of the cytokines TNF-α, IL-1β, and IL-6.[7] Measuring the cytokine content of organ homogenates, analyses revealed markedly reduced levels after electrical vagus nerve stimulation on the organ level as well.[7] However, in experimental burn models, it is unknown whether activation of the inflammatory reflex leads to improved cardiac function. In the present study, we hypothesized that activation of the parasympathetic, anti-inflammatory pathway improves burn-induced cardiac dysfunction. The present study has been designed to evaluate whether electrical cervical vagus nerve stimulation after burn injury leads to improved cardiac function.


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