Polyunsaturated Fatty Acid EAB-277® Supplementation Improved Heart Rate Variability and Clinical Signs in Tracheal Collapse Dogs

Introduction

Tracheal collapse is a common disease in small-breed dogs such as Pomeranians, Miniature and Toy Poodles, Yorkshire terriers, Chihuahuas, and Pugs (1). Usual clinical signs are respiratory distress, dyspnea, and harsh dry cough known as “goose-honking” which is often triggered by excitement and exercise (2). Tracheal collapse can be found in the cervical trachea and/or thoracic trachea depending on the severity (3) and is associated with the softening of hyaline cartilage rings due to a reduction of glycosaminoglycan, glycoprotein and chondroitin sulfate causing weakness and dorsoventral flattening of the tracheal rings resulting in injury to the mucosal lining of the trachea (3, 4). Moreover, in the chronic inflammatory process and mucosal change, epithelial squamous metaplasia can be found, which results in ciliary clearance dysfunction and generate coughing (1, 3).

A previous study demonstrated that the neuroendocrine pathway, the sympathetic (SNS) and the parasympathetic nervous system (PNS) are potent modulators of inflammation (5). The sympathetic nervous system can regulate both pro-inflammatory and anti-inflammatory processes by inducing the production of cytokines, whereas the parasympathetic nervous system and vagal nerve play an essential role in attenuating the inflammatory process (6). In addition, a positive correlation between oxidative stress and the inflammatory process has been reported (7, 8). Many inflammatory stimuli can induce excessive reactive oxygen species (ROS), resulting in the synthesis and secretion of pro-inflammatory cytokines such as TNF-α that play a critical role in the inflammatory process and can result in several chronic diseases (8, 9).

Heart rate variability (HRV) is a prognostic tool for evaluating sympathovagal balance and oxidative stress level (10). It has been used to evaluate the balance of the sympathetic and parasympathetic nervous systems by analyzing the variation in the beat-to-beat timing of the heart rate using portable electrocardiogram equipment or a Holter machine (11, 12). HRV has also been used as a prognostic tool for many diseases such as cardiovascular, respiratory, kidney, and neurological diseases (13–17). In addition, it can be used to monitor health status and adaptability as well as functionality related health status (5, 18). In veterinary medicine, Holter monitoring is a simple and non-invasive test that can serve many purposes, not only in cardiorespiratory disease but also in kidney diseases (19, 20). Moreover, HRV is a well-established and reliable index of cardiac vagal regulation which is inversely related to inflammatory markers and oxidative stress (6). Unfortunately, the use of HRV as a prognostic tool in tracheal collapse dogs has rarely been investigated.

Establishing priorities for tracheal collapse treatment depends on the severity of the tracheal collapse as well as other clinical signs (3). Medical management can include antitussive therapy, antibiotics, bronchodilators, and/or anti-inflammation medication, e.g., corticosteroids and NSAIDs) (21, 22). Many dogs respond to this medical therapy, but some have complications, especially with long-term use of corticosteroids which increases the risk of secondary bacterial infection, increases the respiratory rate, and induces weight loss that worsens the patient’s clinical signs (3, 23). Polyunsaturated fatty acid from Green-Lipped Mussel Blend is a safe, natural product with high antioxidant and anti-inflammation performance which is widely used to treat several diseases including as osteoarthritis in both humans and animals (24–26).

EAB-277^® is a patented nutraceutical marine-based fatty acid-containing lipid fractions from the New Zealand green-lipped mussel combined with high phospholipids extracted from krill oil (Pharmalink International Co., Ltd.,). It is composed of 91 fatty acids, including omega 3 fatty acid, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and eicosatetraenoic acid (ETA) as the key components. The patented component, EAB-277^®, has been shown to have an anti-inflammatory effect by inhibiting the COX-2 and 5-lipoxygenase (LOX) pathways resulting in a reduction in pro-inflammatory cytokine production (27, 28). Moreover, in recent studies conducted in patients with the respiratory disease, it has been found to exert a beneficial effect on asthma by reducing the inflammatory process and attenuating hyperpnea (29). In contrast, another study reported that supplementation with polyunsaturated fatty acid from Green-Lipped Mussel blend did not improve pulmonary or respiratory muscle function in non-asthmatic elite runners (24).

However, in veterinary medicine, the beneficial effects of polyunsaturated fatty acid from the Green-Lipped Mussel blend related to HRV have rarely been investigated in tracheal collapse dogs. This study aims to investigate the effect of polyunsaturated fatty acid from Green-Lipped Mussel blend (EAB-277^®) supplementation combined with standard therapy on physical examination parameters, radiographic findings, blood profile, oxidative stress, inflammatory markers, and HRV hypothesizing that EAB-277^® supplementation could improve clinical outcomes and reduce HRV impairment in tracheal collapse dogs. The findings obtained from this research help explain the effects of polyunsaturated fatty acid EAB-277^® from the Green-Lipped Mussel blend on the autonomic nervous system in tracheal collapse dogs and may also explain some of the beneficial and adverse effects of this nutraceutical on the tracheal collapse condition.