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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxemia and decreased intrathoracic pressure have been postulated as contributing causes of cardiovascular morbidity in obstructive sleep apnea syndrome (OSAS). Because of the difficulty of manipulating experimental conditions in humans, we developed an anesthetized closed-chest dog model, simulating the periodic airway occlusions of OSAS by periodic occlusions of the endotracheal tube (PUO). Using a periodicity of 60 s occluded, followed by 60 s ventilation for five to seven cycles, we measured heart rate (HR), cardiac output (CO), arterial pressure (Pa); left ventricular (LV) end-diastolic and end-systolic transmural pressure; dp/dt of LV pressure; left anterior descending (LAD) coronary blood flow (CBF), and regional myocardial contractility and intramyocardial pH. Four experimental conditions were studied: room air (RA) breathing (PO2 = 40); 100% O2 breathing (O2), and RA and O2 breathing with critical LAD stenosis (CS). Under all conditions PUO produced decreases in CO (10 to 30%) and proportional decreases in Pa. HR decreased, and in all but RA conditions stroke volume was unchanged. During the obstructed phase, indices of LV preload decreased. Indices of LV afterload also decreased except for LAD-perfused myocardium under RACS conditions. This latter was shown to be associated with regional ischemia (decreased regional pH and shortening). Regional ischemia was also demonstrated in two of nine dogs even under O2CS conditions. Among our major conclusions: (1) decreased Pa during PUO is due to decreased CO; (2) LV afterload does not increase during PUO; (3) with limited coronary flow reserve (CS), PUO can lead to myocardial ischemia. This is mostly but not solely due to hypoxia.
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PMID:Cardiovascular effects of periodic occlusions of the upper airways in dogs. 148 19

The case of an obese patient who developed massive centrilobular liver cell necrosis, severe coagulopathy, acute renal failure, and encephalopathy is presented. Hypovolemia and heart failure were absent, but the acute liver disease was associated with severe arterial hypoxemia due to obstructive sleep apnea that was shown by the nocturnal blood oxygen desaturation, the results of the polysomnographic study, and normal baseline pulmonary function tests. In this obese patient, liver cell necrosis was caused by severe liver cell hypoxia secondary to severe arterial hypoxemia as a consequence of obstructive sleep apnea associated with a Pickwickian syndrome. This observation is consistent with the hypothesis that liver ischemia was directly related to severe arterial hypoxemia.
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PMID:Ischemic hepatitis due to obstructive sleep apnea. 755 54

Cardiac and circulatory failure are the main causes of hypoxic hepatitis. In a prospective study of 142 cases of hypoxic hepatitis collected during a 10-year period, we encountered two cases resulting from extreme arterial hypoxemia without congestive heart failure, cor pulmonale, or circulatory failure. Both patients were morbidly obese women admitted to the intensive care unit for carbonarcosis. Oxygen arterial saturation was very low, less than 35% in both patients, but there was no history of cardiac or respiratory failure and no clinical evidence of circulatory failure. Cardiac function, evaluated by isotopic scintigraphy, was normal. After the episode of hypoxic hepatitis, a diagnosis of obstructive sleep apnea was made clinically and confirmed by performing nocturnal oximetry, which showed multiple episodes of oxygen desaturation in both patients. Polysonography could be performed in one case and was typical of obstructive sleep apnea. Liver ischemia is the main mechanism leading to hypoxic hepatitis. More recently, the role of passive congestion of the liver has been emphasized. Arterial hypoxemia, however, is generally considered to be a minor factor. Our two cases support the hypothesis that severe arterial hypoxemia may lead to hypoxic hepatitis even in the absence of cardiac and circulatory failure.
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PMID:Hypoxic hepatitis caused by severe hypoxemia from obstructive sleep apnea. 925 50

Because chronic obstructive pulmonary disease (COPD) is well known to induce peripheral neuropathy and resistance to ischemic nerve conduction failure (RICF), we performed a case-control study examining peripheral nerve function during ischemia in 17 patients with severe obstructive sleep apnea (OSA) without daytime hypoxemia and 10 control subjects. Median nerve conduction was studied before, during, and after a 30-min period of ischemia. Preischemic sensory and mixed nerve potential amplitudes and sensory conduction velocity were lower in OSA patients than in control subjects despite higher supramaximal stimulation. During ischemia, seven OSA patients manifested RICF (OSA-RICF), whereas both the other 10 patients, who were nonresistant to ischemic conduction failure (OSA-NR), and control subjects did not. OSA-RICF patients had the lowest initial nerve-potential amplitude, whereas OSA-NR patients had a response intermediate between that of control subjects and OSA-RICF patients. OSA-RICF patients had a lower mean nocturnal SaO2 and a higher body mass index (BMI) and duration of SaO2 < 70% than did OSA-NR patients. Seven patients (four OSA-RICF and three OSA-NR) were reevaluated after at least 2 mo of treatment with nasal continuous positive airway pressure (nCPAP). RICF disappeared in all OSA-RICF patients, whereas preischemic nerve conduction parameters were unchanged in both OSA-RICF and OSA-NR patients. Thus OSA patients have peripheral nerve dysfunction whose severity is partly related to the level of nocturnal hypoxemia. Abnormal preischemic nerve conduction suggests axonal lesions, whereas RICF, which appears to be a sensitive but nonspecific tissue marker of the severity of hypoxemia, may result from adaptative mechanisms.
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PMID:Peripheral neuropathy in sleep apnea. A tissue marker of the severity of nocturnal desaturation. 987 41

Patients with obstructive sleep apnea (OSA) have been reported to have an augmented pressor response to hypoxic rebreathing. To assess the contribution of the peripheral vasculature to this hemodynamic response, we measured heart rate, mean arterial pressure (MAP), and forearm blood flow by venous occlusion plethysmography in 13 patients with OSA and in 6 nonapneic control subjects at arterial oxygen saturations (Sa(O(2))) of 90, 85, and 80% during progressive isocapnic hypoxia. Measurements were also performed during recovery from 5 min of forearm ischemia induced with cuff occlusion. MAP increased similarly in both groups during hypoxia (mean increase at 80% Sa(O(2)): OSA patients, 9 +/- 11 mmHg; controls, 12 +/- 7 mmHg). Forearm vascular resistance, calculated from forearm blood flow and MAP, decreased in controls (mean change -37 +/- 19% at Sa(O(2)) 80%) but not in patients (mean change -4 +/- 16% at 80% Sa(O(2))). Both groups decreased forearm vascular resistance similarly after forearm ischemia (maximum change from baseline -85%). We conclude that OSA patients have an abnormal peripheral vascular response to isocapnic hypoxia.
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PMID:Patients with obstructive sleep apnea have an abnormal peripheral vascular response to hypoxia. 1048 89

There is emerging evidence linking obstructive sleep apnea (OSA) to vascular disease, including hypertension. This relationship may be independent of co-morbidity, such as obesity. Even apparently healthy OSA patients have evidence of subtle functional vascular abnormalities that are known to occur in patients with hypertension and atherosclerosis. Untreated OSA may possibly contribute to the initiation and/or progression of pathophysiologic mechanisms involved in hypertension, heart failure, cardiac ischemia and stroke. This brief commentary will examine the evidence and mechanisms linking OSA to vascular disease.
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PMID:Obstructive sleep apnea and vascular disease. 1173 28

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, however, nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS) play an important role as regulatory mediators in signaling processes. Many of the ROS-mediated responses actually protect the cells against oxidative stress and reestablish "redox homeostasis." Higher organisms, however, have evolved the use of NO and ROS also as signaling molecules for other physiological functions. These include regulation of vascular tone, monitoring of oxygen tension in the control of ventilation and erythropoietin production, and signal transduction from membrane receptors in various physiological processes. NO and ROS are typically generated in these cases by tightly regulated enzymes such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. In a given signaling protein, oxidative attack induces either a loss of function, a gain of function, or a switch to a different function. Excessive amounts of ROS may arise either from excessive stimulation of NAD(P)H oxidases or from less well-regulated sources such as the mitochondrial electron-transport chain. In mitochondria, ROS are generated as undesirable side products of the oxidative energy metabolism. An excessive and/or sustained increase in ROS production has been implicated in the pathogenesis of cancer, diabetes mellitus, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and other diseases. In addition, free radicals have been implicated in the mechanism of senescence. That the process of aging may result, at least in part, from radical-mediated oxidative damage was proposed more than 40 years ago by Harman (J Gerontol 11: 298-300, 1956). There is growing evidence that aging involves, in addition, progressive changes in free radical-mediated regulatory processes that result in altered gene expression.
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PMID:Free radicals in the physiological control of cell function. 1177 9

Sleep apnea is associated with several cardiovascular disease conditions. A causal relationship between sleep apnea and each of these diseases is likely, but remains to be proven. The clearest evidence implicating OSA in the development of new cardiovascular disease involves data that show an increased prevalence of new hypertension in patients with OSA followed over 4 years [3]. Circumstantial evidence and data from small study samples suggest that OSA, in the setting of existing cardiovascular disease, may exacerbate symptoms and accelerate disease progression. The diagnosis of OSA always should be considered in patients with refractory heart failure, resistant hypertension, nocturnal cardiac ischemia, and nocturnal arrhythmias, especially in individuals with risk factors for sleep apnea (e.g., central obesity, age, and male gender). Treating sleep apnea may help to achieve better clinical control in these diseases and may improve long-term cardiovascular prognosis.
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PMID:Cardiovascular consequences of obstructive sleep apnea. 1280 Jul 78

Chronic intermittent hypoxia (CIH), as occurs in obstructive sleep apnea (SA), is associated with substantial cortico-hippocampal damage leading to impairments of neurocognitive, respiratory and cardiovascular functions. Previous studies in a rat model have shown that CIH increases brain cortical neuronal cell death. However, the molecular events leading to CIH-mediated neuronal cell death remain largely undefined. The oscillation of O2 concentrations during CIH remarkably mimics the processes of ischemia/re-oxygenation and could therefore increase cellular production of reactive oxygen species (ROS). We extended the CIH paradigm to a mouse model of SA to identify the molecular mechanisms underlying cortical neuronal cell death. A significant increase of ROS production in mouse brain cortex and cortical neuronal cells was detected by fluorescent oxidation assays upon exposure of mice to CIH, followed by increased expression of oxidative stress response markers, c-Fos, c-Jun and NF-kappaB in mouse brain cortex, as revealed by immunohistochemical and LacZ reporter assays respectively. Long-term exposure of mice to CIH increased the levels of protein oxidation, lipid peroxidation and nucleic acid oxidation in mouse brain cortex. Furthermore, exposure of mice to CIH induced caspase-3 activation and increased some cortical neuronal cell apoptosis. On the other hand, transgenic mice overexpressing Cu,Zn-superoxide dismutase exposed to CIH conditions had a lower level of steady-state ROS production and reduced neuronal apoptosis in brain cortex compared with that of normal control mice. Taken together, these findings suggest that the increased ROS production and oxidative stress propagation contribute, at least partially, to CIH-mediated cortical neuronal apoptosis and neurocognitive dysfunction.
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PMID:Increased oxidative stress is associated with chronic intermittent hypoxia-mediated brain cortical neuronal cell apoptosis in a mouse model of sleep apnea. 1520 49

Coronary heart disease is frequently associated with obstructive sleep apnea syndrome and treating obstructive sleep apnea appears to significantly improve the outcome in coronary heart disease. Thus we have developed a rat model of chronic intermittent hypoxia (IH) to study the influence of this condition on myocardial ischemia-reperfusion tolerance and on functional vascular reactivity. Wistar male rats were divided in three experimental groups (n = 12 each) subjected to chronic IH (IH group), normoxia (N group), or control conditions (control group). IH consisted of repetitive cycles of 1 min (40 s with inspired O(2) fraction 5% followed by 20 s normoxia) and was applied for 8 h during daytime, for 35 days. Normoxic cycles were applied in the same conditions, inspired O(2) fraction remaining constant at 21%. On day 36, mean arterial blood pressure (MABP) was measured before isolated hearts were submitted to an ischemia-reperfusion protocol. The thoracic aorta and left carotid artery were also excised for functional reactivity studies. MABP was not significantly different between the three experimental groups. Infarct sizes (in percent of ventricles) were significantly higher in IH group (46.9 +/- 3.6%) compared with N (26.1 +/- 2.8%) and control (21.7 +/- 2.1%) groups. Vascular smooth muscle function was similar in aorta and carotid arteries from all groups. The endothelium-dependent relaxation in response to acetylcholine was also similar in aorta and carotid arteries from all groups. Chronic IH increased heart sensitivity to infarction, independently of a significant increase in MABP, and did not affect vascular reactivity of aorta and carotid arteries.
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PMID:Chronic intermittent hypoxia increases infarction in the isolated rat heart. 1561 17


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