Coronary blood flow becomes uncoupled from myocardial work during obstructive sleep apnea in the presence of endothelial dysfunction

Abstract

Study Objectives: Patients with obstructive sleep apnea (OSA) and coronary artery disease have a poor long-term prognosis. It is unknown whether the coronary blood flow (CBF) response to OSA is appropriate for myocardial metabolic requirements. Therefore, CBF was assessed during OSA, before and after the development of coronary artery endothelial dysfunction. Setting: University Hospital Animal Laboratory. Patients or Participants: Newborn lambs. Interventions: Lambs were surgically instrumented for invasive hemodynamic monitoring and sleep-wake EEG recordings. A tracheostomy was inserted to control the upper airway and model OSA during sleep. Coronary artery endothelial dysfunction was created using infusions of lipopolysaccharide (LPS). The CBF response during OSA was assessed and compared to changes in myocardial work (rate-pressure product [RPP]), O2 saturation, and cortical arousal, before and after the LPS infusions. Measurements and Results: During OSA, CBF increased by 8.6% ± 2.4% above baseline in the pre-LPS condition and 8.8% ± 1.9% post-LPS, peaking following termination of the respiratory event. Pre-LPS, change in CBF post-apnea was independently correlated with change in RPP (R2 = 0.50), minimum SpO2 (R2 = 0.11) and the presence of cortical arousal (R2 = 0.04) (P < 0.01, forward stepwise regression analysis). Following LPS, the only predictor of CBF was degree of O2 desaturation (R2 = 0.14, P < 0.05). Conclusion: Under baseline conditions, CBF correlates well with myocardial work following the termination of apnea in lambs. After the creation of coronary artery endothelial dysfunction with LPS, there is uncoupling of the normal CBF-myocardial work relationship.