Effects of Fluid Overload on the Genioglossus Activity in Urethane-Anesthetized Rat Model

 Sabetian, Parisa 1 ; Yadollahi, Azadeh 1, 3 ; Yoo, Paul 1, 2  

1. Institute of Biomaterials and Biomedical Engineering, University of Toronto; 2. Department of Electrical and Computer Engineering, University of Toronto; 3. Toronto Rehabilitation Institute, University Health Network

Introduction: Although the precise cause of obstructive sleep apnea (OSA) remains unknown, various anatomical or structural factors (e.g., obesity) are considered as contributing factors in upper airway collapse. Recent clinical studies show that OSA is frequently observed among patients with fluid-retaining states, such as chronic heart or renal failure, and post-surgical recovery. A factor common to these patients is fluid overload [1].  These findings are consistent with previous studies that rostral fluid shift during sleep exacerbated OSA. It is important to note that a cause-effect relationship is not yet established, and our understanding of the effects of fluid overload is limited.

Objective: The goal of this study was to develop an animal model that can characterize the physiological changes that occur in response to fluid overload.

Method: Non-survival experiments were conducted in 8 Sprague Dawley rats (male, weight= 500-800g). The protocol was approved by the Animal Care Committee at the University of Toronto and in accordance with the regulations of the Ontario Animal Research Act. Rats were initially anesthetized by inhaled isoflurane (5% in 100% O2) while both the femoral vein and carotid artery (blood pressure) were cannulated. A pair of stainless steel wires was implanted into the genioglossus muscle (Electromyogram, EMG). Anesthesia was then gradually transitioned to urethane (initial SQ bolus: 1.5–1.9 g/kg body weight followed by supplemental doses of 0.4 - 0.5 ml). All physiological measurements were recorded before, during and following IV infusion of saline (infusion rate= 22ml/kg, duration = 30 mins).

Results: Our preliminary results in urethane-anesthetized rats indicate that acute ‘fluid overloading’ results in a notable and consistent decrease in genioglossus muscle activity (i.e., 40% decreases between pre – and post – infusion periods). This change in upper airway dilator function also occurs persisted after saline infusion has stopped (~90 mins after stopping infusion). Blood Pressure increased significantly (~20%) in response to IV saline infusion, but returned back to baseline within 15 mins after stopping infusion. Saline infusion did not cause changes heart rate.

Conclusion: The preliminary results of this study indicate that induction of fluid overload can cause significant prolonged change in genioglossus muscle activity. Further work is needed to examine the validity of this animal model.

Reference: [1] Braunwald E. Edema. In: Kasper DL, Braunwald E, Fauci A, Hauser S, editors. Harrison’s principles of internal medicine, 16th ed. New York: McGraw-Hill; 2005. p. 212–216.