Cardiopulmonary integration: the dark side.

reported, e.g. increases in cell adhesion, coagulation and proinflammatory molecules [3, 4] . Increases in C-reactive protein have also been demonstrated [5] . In this issue of Respiration Tanriverdi et al. [6] confirm studies that demonstrated anatomical and functional changes in the blood vessels of patients with obstructive sleep apnea. They used newly developed noninvasive ultrasonographic methods to show increased aortic stiffness, increased carotid intima thickness and decreased flow-mediated vasodilatation, all signs of arteriosclerosis which occurred more frequently in the patients with obstructive sleep apnea than in the controls. There are two potential mechanisms for these pathological changes in sleep apnea. The first is repeated intermittent hypoxia and reoxygenation leading to oxygen radical formation and damage to the blood vessel endothelium [1, 7] . The second is the repeated bursts of increased sympathetic activity that occur with the frequent arousals in sleep apnea [8] . These arousals, besides causing tachycardias, make blood vessels stiffer, thus accelerating pulse wave transmission. These episodic waves of sympathetic activity arising from conventional arousals may predispose to systemic hypertension. In addition to conventional arousals that produce alpha wave desynchronization and behavioral changes, so-called ‘autonomic arousals’, commonly occuring even during normal sleep, are associated with delta wave activity and are important triggers of increased sympathetic discharge [8] . It is not yet clear if these arousals affect the quality of Normally neural and chemical mechanisms coordinate the actions of the circulatory system and the respiratory system to deliver the oxygen required by the tissues, regardless of their activity and to remove the metabolically produced carbon dioxide. But there is a dark side. The two systems are so dependent on each other that dysfunction in one pump may cause the other to fail as well. For example inadequacies in the circulation such as deficiencies in the blood supply to the brain can interfere with its operation, causing breathing to be too little or too much. Heart failure allows fluid to accumulate in the alveoli and pleural spaces so that breathing is inadequate because of poor oxygenation. More often it is the other way round, i.e. problems with breathing give rise to damaged blood vessels or pathology in the heart itself. The persistent hypoxia produced by chronic lung diseases has long been recognized as a significant cause of circulatory abnormalities and heart failure. The chronic hypoxia constricts the pulmonary vessels, raising vascular pressure, increasing the load on the right ventricle and ultimately causing heart failure (cor pulmonale). However, it seems that an even more common cause of circulatory problems is the intermittent hypoxia that occurs in both central and obstructive sleep apnea syndromes [1] . There is substantial and possibly overwhelming evidence that sleep apneas are risk factors not only for pulmonary but also for systemic hypertension and left ventricular failure [1, 2] . More recently biochemical evidence of vascular injury in sleep apnea patients has been