title: Mild Chronic Intermittent Hypoxia in Wistar Rats Evokes Significant Cardiovascular Pathophysiology but No Overt Changes in Carotid Body-Mediated Respiratory Responses.
abstract: Models of chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnoea (OSA), have demonstrated dysregulation of the cardiovascular and respiratory systems resulting in hypertension, cardiac hypertrophy and alterations in the hypoxic ventilatory response (HVR) due to changes in sympathetic and respiratory control by the carotid body. In the UK, treatment of OSA is only offered to patients with an apnoea-hypopnoea index (AHI) >15, we investigated whether mild CIH produced significant pathophysiological changes, which might inform treatment guidelines.Rats were exposed to CIH (6 h(-1), 8 h day(-1), 5 % O(2) nadir) for 2 weeks and then arterial blood pressure (ABP), heart rate (HR) and ventilation were recorded in these and normoxic control rats (N) under Alfaxan anaesthesia, at baseline and in response to Dejours test, graded hypoxia and hypercapnia. Hearts were analysed post-mortem.CIH induced significant increases in baseline ABP (142 ± 5 vs 122 ± 2 mmHg), HR (448 ± 9 vs 412 ± 5 bpm) and cardiac mass (3.5 ± 0.1 vs 2.7 ± 0.1 g kg body mass(-1)) as a result of a selective left ventricular hypertrophy (1.6 ± 0.1 vs 1.3 ± 0.08 g kg body mass(-1); FCSA 464 ± 32 μm(2) vs 314 ± 9 μm(2)). There was no significant difference between N and CIH in baseline respiration or the response to Dejours test, graded hypoxia and hypercapnia.These results demonstrate that mild CIH can induce the significant cardiovascular changes associated with OSA without overt changes in respiratory function. Given evidence that CIH changes carotid body sensory activity, a possible explanation for these results is that there is differential integration of chemoreceptor input with respiratory and cardiac sympathetic outputs.
authors: School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK, c.j.ray@bham.ac.uk.
authors: Clare J
authors: CJ
authors: Ray
authors: Ben
authors: B
authors: Dow
authors: Prem
authors: P
authors: Kumar
authors: Andrew M
authors: AM
authors: Coney
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002344:Carotid Body / Q000502:physiology*; D002908:Chronic Disease; D006339:Heart Rate; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration