Abstract

Background: Neuropeptide Y (NPY) and its receptors, NPY1R, NPY2R, and NPY5R, Substance P (SP) and its receptor Neurokinin 1R (NK1R) and calcitonin gene related peptide (CGRP), are important regulators of cardiac physiology, including: vasomodulation, cardiomyocyte hypertrophy, ischemia-induced angiogenesis, modulation of Protein Kinase C activity and calcium homeostasis.[[Unable to Display Character: ]] Objective: To determine the relationship between cardiac function and neuropeptide expression in human subjects. Methods: 38 consecutive patients undergoing elective, on pump, coronary artery bypass surgery (CABG) for coronary artery occlusive disease were studied. A Transesophageal Echo was performed immediately following induction of anesthesia and Left Ventricular Ejection Fraction (LVEF) was determined by AHA criteria as Normal, >55% (NLVEF, n = 26) or Low, <50% (LLVEF, n = 12). Patients with HbA1c>6.0 were considered diabetic. Right atrial tissue was obtained at the time of cannulation and the mRNA expression of Pre-Pro-NPY, NPY1R, NPY2R, NPY5R, Pre-Pro-SP, NK1R and CGRP was determined with qRT-PCR. Data are expressed as fold change relative to the NLVEF group. Results: The results of this study are summarized in the table below. Conclusions: 1. There is a strong association of LLVEF with diminished expression of SP, NK1R and NPY5R, with a similar trend for NPY2R. 2. LLVEF was not associated with HbA1c or diabetes status. 3. The consequences of diminished cardiac neuropeptide expression, the mechanisms involved, the relationship to cardiac autonomic neuropathy, with or without diabetes, warrant priority as an investigational initiative.

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