Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obstructive sleep apnea (OSA) is characterised by repetitive episodes of upper airway occlusion during sleep. OSA has been shown to be associated with a variable degree of nasal inflammation, uvula mucosal congestion and airway hyperreactivity. The upper airway inflammation, whose clinical importance is uncertain, is characterised by leukocytes infiltration and interstitial oedema. In addition, recent data has shown the presence of neutrophilic inflammation in the lower airways. The current opinion is that airway inflammation is caused by the local, repeated mechanical trauma related to the intermittent airway occlusion typical of the disease. Another potential mechanism involves the intermittent nocturnal hypoxemia that through the phenomenon of the ischemia-reperfusion injury may induce the production of oxygen free radicals and therefore cause local and systemic inflammation. Finally, a state of low-grade systemic inflammation may be related to obesity per se with the pro-inflammatory mediators synthesised in the visceral adipose cells. Several authors stress the role of circulating and local inflammatory mediators, such as pro-inflammatory cytokines, exhaled nitric oxide, pentane and 8-isoprostane as the determinants of inflammation in OSA.
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PMID:Airway inflammation in patients affected by obstructive sleep apnea. 1691 81

This review summarizes the well-known clinical features of the obstructive sleep apnea-hypopnea syndrome (OSAHS) and emphasizes new research on this syndrome. Though described in the seventies, the prevalence OSAHS is known mainly in the US. A dramatic increasing in prevalence has been related to the increase prevalence of obesity, raising a substantial public health problem. Discussion continues on the proper definition of the syndrome and degrees of severity. Multiple factors are involved in the pathogenesis of sleep apnea: anatomic abnormalities, mechanical factors, nervous alterations, muscular imbalance between pharyngeal constrictor and dilator muscles or part of a metabolic syndrome? Indeed, obstructive sleep apnea with and without obesity is increasingly implicated in the initiation and progression of metabolic disorders and of cardiovascular diseases (hypertension, cardiac ischemia and probably congestive heart failure, cardiac arrhythmias and strokes). An extended literature reports the neural, humoral, thrombotic, metabolic and inflammatory mechanisms linking OSAHS to endocrinology and cardiovascular diseases. Daytime sleepiness, cognitive, memory and performance deficits with their risks are also stressed. These consequences require treating this syndrome as soon as possible. Multiple interventions (medical, mechanical-nasal positive airway pressure or oral appliances, and sometimes surgical management) can be used but nasal continuous positive airway pressure is the "gold standard" treatment in severe OSAHS. More often multiple interventions are appropriate in a given patient. Finally, there is growing evidence that genetic factors influence the expression of OSAHS. Numerous genetic studies have investigated the etiology of OSAHS with the goal of improving our understanding of its pathogenesis.
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PMID:[Obstructif sleep apnea-hypopnea syndrome: evolution of an old concept]. 1718 49

Obstructive sleep apnea is associated with increased risk for cardiovascular diseases. As obstructive sleep apnea is characterized by episodic cycles of hypoxia and normoxia during sleep, we investigated effects of intermittent hypoxia (IH) on ischemia-reperfusion-induced myocardial injury. C57BL/6 mice were subjected to IH (2 min 6% O(2) and 2 min 21% O(2)) for 8 h/day for 1, 2, or 4 wk; isolated hearts were then subjected to ischemia-reperfusion. IH for 1 or 2 wk significantly enhanced ischemia-reperfusion-induced myocardial injury. However, enhanced cardiac damage was not seen in mice treated with 4 wk of IH, suggesting that the heart has adapted to chronic IH. Ischemia-reperfusion-induced lipid peroxidation and protein carbonylation were enhanced with 2 wk of IH, while, with 4 wk, oxidative stress was normalized to levels in animals without IH. H(2)O(2) scavenging activity in adapted hearts was higher after ischemia-reperfusion, suggesting the increased antioxidant capacity. This might be due to the involvement of thioredoxin, as the expression level of this protein was increased, while levels of other antioxidant enzymes were unchanged. In the heart from mice treated with 2 wk of IH, ischemia-reperfusion was found to decrease thioredoxin. Ischemia-reperfusion injury can also be enhanced when thioredoxin reductase was inhibited in control hearts. These results demonstrate that IH changes the susceptibility of the heart to oxidative stress in part via alteration of thioredoxin.
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PMID:Effects of intermittent hypoxia on oxidative stress-induced myocardial damage in mice. 1727 4

Hypoxia is an important topic both physiologically and clinically. Traditionally, physiology research has been focusing on the effect of acute and chronic sustained hypoxia and human adaptive response to high altitude. In the past 20 years, genetic studies by many have expanded our understanding of hypoxia to the molecular level. However, in contrast to our extensive knowledge about acute and chronic sustained hypoxia, we know relatively little about the effect of chronic intermittent hypoxia (CIH). In recent years, CIH has attracted more research attention because of the increasing prevalence of obesity and obstructive sleep apnea (OSA) in the western countries. Clinically, CIH is commonly seen in patients with sleep-disordered breathing including OSA, Cheyne-Stokes respiration and nocturnal hypoventilation. It was estimated that for OSA of at least mild severity prevalence estimates range from 3 to 28% in the general population. OSA is characterized by recurrent upper airway collapse during sleep leading to intermittent nocturnal hypoxia and sleep fragmentation. OSA is associated with significant mortality and morbidity including neurocognitive dysfunction, hypertension, many cardiovascular disorders and metabolic disorders such as diabetes and metabolic syndrome. The intermittent hypoxia in OSA closely mimics what is seen in the ischemia-reperfusion injury. Experimentally, there is no universally accepted definition for CIH. Laboratory protocols vary greatly in duration of hypoxia exposure, numbers of hypoxia episodes per day and the total number of days of exposure. Despite the lack of a uniform definition, recent data suggest that CIH may lead to multiple long-term pathophysiologic consequences similar to what we see in patients with OSA. Recent evidences also demonstrate that there are remarkable differences in the response of the physiologic systems to sustained hypoxia and intermittent hypoxia. This review is aimed to briefly discuss the clinical significance of sleep-disordered breathing and our current understanding of CIH.
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PMID:Obstructive sleep apnea and chronic intermittent hypoxia: a review. 1729 31

Obstructive sleep apnea (OSA) is associated with cardiovascular diseases such as hypertension through mechanisms involving intermittent hypoxia (IH). However, it is not yet clear whether IH directly affects the heart. In a mouse model of OSA, we found that IH causes time-dependent alterations of the susceptibility of the heart to oxidative stress. Acute IH can exert preconditioning-like cardioprotection, in part, through the transcriptional activation of genes such as bcl-x(L) and gata4. We cloned the mouse gata4 promoter and identified an IH-responsive region. The exposure of mice to prolonged IH results in the increased susceptibility of the heart to ischemia-reperfusion injury by increasing the oxidative stress status. This might resemble conditions of OSA patients. In our mouse model, further exposure to prolonged IH allowed reversal of the enhancement of myocardial damage. Understanding the complex effects of IH on the heart should help ultimately to develop therapeutic strategies against OSA-induced complications.
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PMID:Effects of intermittent hypoxia on the heart. 1751 87

The aim of this study was to establish cardiac damage related to nocturnal ischemia using heart type fatty acid binding protein (h-fabp), which reaches detectable levels in plasma after being released from myocytes in case of ischemia in obstructive sleep apnea syndrome (OSAS) patients without coronary artery disease (CAD). Fifty patients diagnosed with OSAS in our sleep laboratory with polysomnographic analysis (PSG), who did not have any previous history of cardiac disease and in whom CAD was ruled out with myocardium perfusion scintigraphy, were included in the study. Control group comprised 19 volunteers without history of cardiac disease and risk factors in whom OSAS was excluded with PSG analysis. Blood samples were drawn from the patients to examine h-fabp, creatine kinase (CK), creatine kinase-MB (CK-MB), aspartate aminotransferase (AST), troponin I levels before and after sleep. No significant difference was found in CK, CK-MB, AST, Troponin I, and h-fabp levels before and after sleep in patient and control groups (p > 0.05). No significant difference was found between groups in terms of CK, CK-MB, AST, and Troponin I levels before and after sleep, while a significant difference was found between them with regard to h-fabp levels before (p = 0.006) and after sleep (p = 0.022). When arithmetical mean of the fabp levels before and after sleep was taken in the patient group, it was found that mean value of h-fabp was associated with the desaturated period in sleep which was under 80% (p = 0.04). H-fabp seems to be a marker that will enable the detection of cardiac injury in the early asymptomatic period in OSAS patients before development of disease that can be detected by imaging methods. Further studies are required to investigate the relation between the value of h-fabp and the development of cardiac dysfunction in the long term.
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PMID:Evaluation of the relationship between heart type fatty acid binding protein levels and the risk of cardiac damage in patients with obstructive sleep apnea syndrome. 1823 25

More than two thirds of stroke patients suffer from sleep apnea. A recent study showed that mirtazapine reduced the respiratory disturbance index (RDI) of a stroke patient by 80%. These promising results prompted us to offer mirtazapine to non-depressed stroke patients who suffered from sleep apnea and refused treatment with a continuous positive airway pressure (CPAP) device. Polysomnography was performed between 2200 and 0600 hours. We examined ten inpatients [nine male, one female; mean age of 68.7 +/- 1.5 years +/- SE; body mass index of 26.1 +/- 1.2 kg/m(2), basal ganglia bleeding (n = 3), middle cerebral artery ischemia (n = 4), basal ganglia ischemia (n = 1), cerebellar bleeding (n = 2)] in the Neurologic Clinic's sleep laboratory. The mean duration of illness before the first polysomnography was 52.6 +/- 11.4 days. Mirtazapine effectively consolidated sleep in all patients, i.e., sleep efficiency significantly increased from 63.1 +/- 4.8% to 75.7 +/- 5.0%. A moderate increase in RDI (137.4 +/- 15.3% of baseline) occurred during initial mirtazapine administration (intake duration 15.8 +/- 5.5 days). After 51.9 +/- 8.4 days, the RDI was either reduced (51.9% in "responders" who were identified arbitrarily by a reduction in RDI >or= 25% at any time point of the investigation) or increased (154.4% in "non-responders"). Mirtazapine administration was stopped in the four patients with increased RDI. Mirtazapine may be a probably effective treatment in stroke survivors with obstructive sleep apnea who refuse nasal CPAP treatment. As it may worsen central and mixed sleep apnea, patients who receive mirtazapine to alleviate sleep apnea or to control post-stroke depression with sleep disturbances should be monitored for changes in breathing parameters during sleep.
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PMID:Success and failure of mirtazapine as alternative treatment in elderly stroke patients with sleep apnea-a preliminary open trial. 1836 72

Recurrent and intermittent nocturnal hypoxia is characteristic of several diseases including chronic obstructive pulmonary disease, congestive heart failure, obesity-hypoventilation syndrome, and obstructive sleep apnea. The contribution of hypoxia to cardiovascular morbidity and mortality in these disease states is unclear, however. To investigate the impact of recurrent nocturnal hypoxia on hemodynamics, sympathetic activity, and vascular tone we evaluated 10 normal volunteers before and after 14 nights of nocturnal sustained hypoxia (mean oxygen saturation 84.2%, 9 h/night). Over the exposure, subjects exhibited ventilatory acclimatization to hypoxia as evidenced by an increase in resting ventilation (arterial Pco(2) 41.8 +/- 1.5 vs. 37.5 +/- 1.3 mmHg, mean +/- SD; P < 0.05) and in the isocapnic hypoxic ventilatory response (slope 0.49 +/- 0.1 vs. 1.32 +/- 0.2 l/min per 1% fall in saturation; P < 0.05). Subjects exhibited a significant increase in mean arterial pressure (86.7 +/- 6.1 vs. 90.5 +/- 7.6 mmHg; P < 0.001), muscle sympathetic nerve activity (20.8 +/- 2.8 vs. 28.2 +/- 3.3 bursts/min; P < 0.01), and forearm vascular resistance (39.6 +/- 3.5 vs. 47.5 +/- 4.8 mmHg.ml(-1).100 g tissue.min; P < 0.05). Forearm blood flow during acute isocapnic hypoxia was increased after exposure but during selective brachial intra-arterial vascular infusion of the alpha-blocker phentolamine it was unchanged after exposure. Finally, there was a decrease in reactive hyperemia to 15 min of forearm ischemia after the hypoxic exposure. Recurrent nocturnal hypoxia thus increases sympathetic activity and alters peripheral vascular tone. These changes may contribute to the increased cardiovascular and cerebrovascular risk associated with clinical diseases that are associated with chronic recurrent hypoxia.
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PMID:Ventilatory, hemodynamic, sympathetic nervous system, and vascular reactivity changes after recurrent nocturnal sustained hypoxia in humans. 1853 53

Obstructive sleep apnea (OSA), a highly prevalent breathing disorder in sleep, characterized by intermittent and recurrent pauses in respiration, has emerged as an independent risk factor for cardiovascular morbidity and mortality. Accumulated evidence implicates Leukocyte-endothelial cell activation and adhesion as critical components that induce inflammation and injury to the vasculature resulting in the development of cardiovascular complications. Similar cellular interactions were described in conditions of ischemia/reperfusion, and various components of the metabolic syndrome as hypercholesterolemia and hypertension. The hallmark of sleep apnea--the multiple cycles of hypoxia/reoxygenation--promote oxidative stress and inflammation. These facilitate increased interactions of blood cells with endothelial cells, resulting in endothelial cell injury and dysfunction. Such events can promote atherosclerosis and the development of cardiovascular morbidities in OSA. However, inter-individual differences in response to intermittent hypoxia and activation of anti-inflammatory cytokine profiles in T lymphocytes can serve as protective mechanisms.
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PMID:Biology of peripheral blood cells in obstructive sleep apnea--the tip of the iceberg. 1894 85

Endothelial activation and inflammation are important mediators of accelerated atherogenesis and consequent increased cardiovascular morbidity in obstructive sleep apnea (OSA). Repetitive episodes of hypoxia/reoxygenation associated with transient cessation of breathing during sleep in OSA resemble ischemia/reperfusion injury and may be the main culprit underlying endothelial dysfunction in OSA. Additional factors such as repetitive arousals resulting in sleep fragmentation and deprivation and individual genetic susceptibility to vascular manifestations of OSA contribute to impaired endothelial function in OSA. The present review focuses on possible mechanisms that underlie endothelial activation and inflammation in OSA.
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PMID:Mechanisms of endothelial dysfunction in obstructive sleep apnea. 1933 46


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