Obstructive sleep apnea (OSA) adversely affects ventricular function, increasing the incidence of nocturnal death of cardiac origin and contributing to the pathogenesis of congestive heart failure. The large swings in intrathoracic pressure caused by airway occlusion increase cardiac transmural pressure, decrease preload, and increase afterload, augmenting metabolic demand at the same time as arterial oxygen content decreases. We hypothesized that repeated inspiratory occlusions, mimicking OSA, cause myocardial dysfunction and injury.
We subjected anesthetized male Sprague-Dawley rats to 3 h of repeated airway occlusion (30 s occlusion every 2 min); results were compared to sham rats.
Following occlusions, left ventricular function decreased; the peak rates of pressure generation (+dP/dt) and relaxation (-dP/dt) fell from 7820 ± 271 (SEM) to 6310 ± 623 and from -8851 ± 502 to -7121 ± 381 mmHg/s (p < 0.05), respectively. Myofibril proteins were isolated from the left ventricle for determination of Ca2+-activated myosin ATPase activity. Compared to shams, inspiratory occlusion significantly reduced maximum (97 ± 5 vs. 137 ± 9, p < 0.01) and minimum (35 ± 6 vs. 76 ± 9 nmol/min/mg, p < 0.01) ATPase activity. We detected release of cTnT into the blood in 4 of 9 occluded rats but none of the shams.
These results demonstrate for the first time that repeated inspiratory occlusions acutely impair left ventricular contractility, reduce ATPase activity of myofibril proteins, and, in some rats, cause myocardial necrosis. The mechanism(s) underlying the decrease in ATPase activity is unknown but probably reflects a post-translational modification(s) to one or more myofibril proteins.
Collectively, these results may account for the acute pathological effects of OSA.
Colleen Lynch, None.