| Summary: | 博士 === 臺灣大學 === 生理學研究所 === 98 === Neuronal function and innervation density is regulated by target organ-derived neurotrophic factors. The cardiovascular autonomic nerve plays an important role in modulating heart rate, blood pressure, wave conducting velocity, myocardial contraction, and relaxation. Autonomic modulation can frequently be altered in septic and critically ill patients. Although several studies have shown the change of autonomic system controlling the cardiovascualr in endotoxemic and/or septic models, little is known about the mechanism that regulates the change of autonomic dysfunction during endoxemia and sepsis.
Peptic ulcer disease represents a common disease entity and results in symptoms of a variable severity in about 10% of the patients who suffer it. Peritonitis due to gastric ulcer perforation will significantly increase the pro-inflammatory cytokines in blood and therefore encompass damage to the autonomic nerve fibers that innervate the heart and blood vessels, resulting in abnormalities in heart control and vascular dynamics. There are many techniques developed to study changes in autonomic cardiac activity in diabetic neuropathy. Heart rate (HR) variability is viewed as an index of sympathetic and parasympathetic modulation of the cardiovascular system. It has been shown that cardiovascular variability in the low-frequency (LF) band but not the high-frequency (HF) band largely reflex the integrity of the baroreflex control of both peripheral resisatnce and of heart rate in humans, in rats, and in mice. Meanwhile, the ratio of the normalized spectral powers of the LF and HF components of HR variability provides a measure of the autonomic sympatho-vagal balance in the heart control.
In the first part of our study, gastric perforation (GP) resulted in upregulation of plasma endothelin (ET) -1, cardiac nerve growth factor (NGF), growth associtated protein (GAP) 43 and tyrosine hydroxylase (Th) expression that coincided with recovery of cardiac autonomic sympatho-vagal balance. GP-induced NGF upregulation and the restoration of autonomic balance can be effectively blocked by methyprednisolone.
In the second part of this study, we investigated whether systemic inflammation can activate ET-1/NGF pathway in aorta, as it did in the heart. We further examined whether this activation is associated with aortic nerve sprouting.GP and inflammation was induced by surgery in Wistar rats. The aortic NGF expression and the GAP43 was examined by immunohistochemical staining. We found that GP resulted in upregulation of aortic NGF that coincided with aortic nerve sprouting. Methylprednisolone effectively blocked GP-induced NGF upregulation.
By using the GP animal model, we concluded that remote inflammation leads to enhanced cardiovascular expression of NGF, which coincides nerve sprouting and the change of autonomic activity. Results from this study provide an insight view of how systemic inflammation influences the cardiovascular autonomic system and the possible underlying mechanisms, which may be helpful for the clinical therapy of inflammation in the future.
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