Endothelial mechanisms of endothelial dysfunction in patients with obstructive sleep apnea

Background  

Obstructive sleep apnea (OSA) occurs in 2% of middle-aged women and 4% of middle-aged men in the general population and the prevalence is much higher in specific patient groups. Intermittent hypoxia (IH, oxygen desaturation and re-oxygenation) cycle, a major pathophysiologic character of OSA, and the physiological responses this evokes are thought to be responsible for its association with increased cardiovascular morbidity and mortality. Endothelial dysfunction, resulting from IH and as a key early event in atherosclerosis, was demonstrated repeatedly in patients with OSA and in animal models of IH, providing an important mechanistic link between the acute cyclical IH during sleep and the increased prevalence of chronic vascular diseases.     

HDL dysfunction in obstructive sleep apnea

OBJECTIVE: HDL is anti-atherogenic and has antioxidant property. HDL dysfunction has been reported in patients with coronary heart disease and we hypothesize that HDL may also be dysfunctional in obstructive sleep apnea (OSA), a condition associated with increased oxidative stress. METHODS: 128 OSA patients and 82 controls were recruited. HDL dysfunction was determined by evaluating the ability of HDL to inhibit LDL oxidation ex vivo. Plasma HDL was incubated with native LDL in the presence of dichlorofluorescein which fluoresced upon interaction with lipid oxidation products. Plasma levels of oxidized LDL and 8-isoprostane were measured by ELISA and a specific enzyme immunoassay, respectively. RESULTS: Plasma total 8-isoprostane levels were elevated in OSA subjects (p<0.01). Despite having similar concentrations of plasma lipids and apolipoproteins as controls, OSA subjects had greater degree of HDL dysfunction (p<0.01) and increased oxidized LDL levels (p<0.05). The apnea-hypopnea index was the main determinant of HDL dysfunction in OSA, accounting for 30% of its variance, with oxidized LDL and apolipoprotein AI contributing to 8% and 5% of its variance respectively (p<0.001). CONCLUSION: HDL is dysfunctional in preventing the formation and inactivation of oxidized lipids in OSA subjects and may partly contribute to their increased cardiovascular risk.     

Myocardial perfusion imaging with contrast echocardiography

Advances in myocardial perfusion imaging have firmly established the use of noninvasive techniques capable of providing useful information over a broad range of diagnostic and therapeutic cardiovascular problems. Evaluating regional myocardial perfusion abnormalities is a cornerstone for the diagnosis of coronary artery disease, risk assessment in those with known disease, and determination of myocardial viability. The clinical use of myocardial perfusion imaging and the current limitations of existing techniques continue to promote the development of new technologies capable of assessing microvascular and capillary perfusion abnormalities on a global myocardial level. Myocardial contrast echocardiography is an emerging technique capable of rapidly assessing myocardial perfusion at the capillary level in many different clinical settings. This article focuses on myocardial contrast-enhanced ultrasound perfusion techniques, emphasizing the unique information this modality provides compared with other noninvasive perfusion imaging techniques.     

阻塞性睡眠呼吸暂停综合征与血管内皮功能障碍研究进展

阻塞性睡眠呼吸暂停综合征(obstructive sleep apnea hypopnea syndrome,OSAHS)是高血压、动脉粥样硬化等心血管疾病发病的重要危险因素之一,虽然目前机制尚未完全阐明,但与内皮功能障碍密切相关.本文就正常血管内皮功能、内皮功能障碍及评价方法 发、OSAHS与内皮功能障碍及治疗等进行综述.     

Myocardial perfusion imaging using contrast echocardiography

BACKGROUND: Intense work during the last two decades has brought forth the use of myocardial contrast echocardiography to the clinical threshold for the diagnosis and evaluation of coronary artery disease. CLINICAL USE: A number of ultrasound contrast agents have been developed that act as red blood cell tracers and display myocardial perfusion when imaged by dedicated ultrasound imaging modalities. A considerable amount of experimental and clinical research has shown that myocardial contrast echocardiography can aid in the recognition of acute and chronic myocardial infarction, viable myocardium, and functionally significant coronary stenoses. Comparison of this technique to nuclear imaging and coronary arteriography has demonstrated excellent diagnostic accuracy in the evaluation of various coronary syndromes. Optimal practice of perfusion imaging requires a thorough knowledge of microbubble characteristics and imaging modalities, as well as good experience in the method. PERSPECTIVES: The technique continues to evolve from intermittent gated examination to real-time perfusion imaging that allows evaluation of both perfusion and functional parameters. The opportunity to target sites of pathology with specially engineered microbubbles could also aid in many therapeutic applications besides diagnostic imaging.     

Myocardial perfusion abnormality induced by right ventricular pacing: real-time myocardial contrast echocardiography study

BACKGROUND AND OBJECTIVES: False positive findings of coronary stenosis are frequently detected by exercise stress myocardial scintigraphy in patients with left bundle branch block (LBBB). We investigated the relationship between regional wall motion abnormality and myocardial perfusion abnormality at high right ventricular (RV) pacing rate in the region of the RV pacing (the ventricular septum) and the control region (the lateral wall) assuming exercise stress in patients with LBBB. METHODS: RV pacing was performed in 7 open chest canines. Real time myocardial contrast echocardiography of the left right ventricular short-axis view was examined by Toshiba Aplio during infusion of the ultrasound contrast agent (Definity). The examination was performed at baseline without pacing and at high RV pacing. Replenishment curve of the myocardial opacification was obtained and fit to the equation of y = A (1 - e (-betat)) in the regions of the ventricular septum and the lateral wall. Wall thickening ratio (%WT) was calculated in both regions. RESULTS: Dyssynchronous motion was observed during high RV pacing, but no wall motion abnormality was seen in control conditions. Although %WT, A-value and beta-value were almost identical between both regions at baseline, %WT and beta decreased in the ventricular septum at high RV pacing. The value did not differ between two regions. CONCLUSIONS: We concluded that perfusion abnormality occurs with regional wall motion abnormality at high RV pacing based on real time myocardial contrast echocardiography.     

Myocardial perfusion echocardiography and coronary microvascular dysfunction

Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation, but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography (MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction, respectively, and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall, MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice, but the approval of regulatory authorities is lacking.     

Endothelial dysfunction in obstructive sleep apnea patients

Sleep and Breathing - Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular diseases. The aim of the study was to assess the influence of OSAS on endothelial...     

Quantifying myocardial perfusion using contrast echocardiography

There is a complex relation between what can be seen using perfusion imaging techniques, and what can be measured.     

Myocardial contrast echocardiography: relation between on-line and off-line assessment of myocardial perfusion

Background: Quantitative assessment of myocardial perfusion by myocardial contrast echocardiography has been made possible by the use of custom-made off-line video-intensity programs. A standardized program that could be used by all investigators would improve the reproducibility of results and enhance its clinical utility. Methods and Results: The purpose of this study was to determine if the assessment of myocardial perfusion by contrast echocardiography using a new commercially available, quantitative on-line software program correlates with an off-line custom-made video-intensity program previously validated by our laboratory and with radiolabeled microspheres, under various experimental myocardial perfusion conditions. Two of the measured myocardial contrast echocardiographic parameters (peak intensity, area under the time-intensity curve {area}) correlated well among on-line and off-line methods and radiolabeled microspheres, especially when the data were "normalized" by comparing percent change from baseline or a ratio of ischemic to nonischemic myocardium. The third myocardial contrast echocardiographic parameter examined, half-time of the peak intensity on the washout limb of the curve (t 1/2), correlated only when the percent change from baseline was compared between the two methods or when the off-line method was compared with radiolabeled microspheres. Conclusion: The results of this investigation add further support to the potential use of myocardial contrast echocardiography to evaluate serial changes in myocardial perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular subclinical dysfunction associated with myocardial deformation changes in obstructive sleep apnea patients estimated by real-time 3D speckle-tracking echocardiography

Background

Previous studies have demonstrated that patients with obstructive sleep apnea (OSA) may develop left ventricular (LV) diastolic dysfunction. We aimed to study whether OSA patients have LV regional systolic dysfunction with myocardial deformation changes, despite a normal LV ejection fraction, using real-time 3D speckle-tracking echocardiography (Rt3D-STE).

Methods

Seventy-eight patients with OSA and no comorbidities were studied. They were divided into the following three groups according to the apnea–hypopnea index (AHI): 5~15/h as group I (mild OSA, 26 cases), 15~30/h as group II (moderate OSA, 29 cases), and ≥30/h as group III (severe OSA, 23 cases). Thirty gender–age-matched normal subjects were included as controls. The parameters of LV diastolic function were acquired with traditional echocardiography. The LV myocardial deformation parameters were obtained, including the longitudinal (LS), circumferential (CS), radial (RS), and area (AS) strains, with Rt3D-STE.

Results

LV global systolic function was normal in all patients, but diastolic function was impaired in groups II and III (E/E′ was 9.6?±?2.8 and 10.4?±?2.5, respectively, p?<?0.0001). The global LS and AS were significantly reduced in groups II and III compared with the controls and group I (LS 15.9?±?1.4 % and 14.8?±?1.5 % vs 18.2?±?1.7 % and 17.8?±?1.5 %; AS 27.4?±?1.8 % and 24.9?±?2.3 % vs 33.4?±?2.2 % and 32.7?±?2.9 %, respectively, p?<?0.0001), but the global CS and RS were significantly reduced only in group III (17.3?±?1.4 % and 43.1?±?6.5 % vs 19.6?±?1.6 % and 55.4?±?4.0 %, respectively, <0.0001). The severity of OSA was significantly associated with the LV global AS value (r?=??0.80, p?<?0.0001), LS (r?=??0.64, p?<?0.0001), CS (r?=??0.51, p?<?0.0001), and RS (r?=??0.62, p?<?0.0001).

Conclusions

Patients with moderate and severe OSA tended to have both LV diastolic dysfunction and abnormalities in regional systolic function with myocardial deformation changes, in spite of the normal LV ejection fraction. Myocardial strains of the LV were negatively correlated with the AHI. Rt-3DST had important clinical significance in the early evaluation of cardiac dysfunction in OSA patients.

     

Myocardial contrast echocardiography in acute myocardial infarction

PURPOSE OF REVIEW: Myocardial contrast echocardiography (MCE) has evolved into an important clinical tool for imaging coronary microcirculation. It can be used to delineate the spectrum of perfusion derangements that characterize acute myocardial infarction. RECENT FINDINGS: Presently, MCE uses microcirculatory perfusion as the basis to distinguish myocardial necrosis and viability in the post-infarct stage. Its future role may expand to image cellular integrity, inflammation, and angiogenesis, all of which contribute to the pathophysiology of the myocardial infarction. SUMMARY: This review provides an update of the current role and future clinical applications of MCE in acute myocardial infarction.     

Endothelial cell apoptosis in obstructive sleep apnea: a link to endothelial dysfunction

RATIONALE: Patients with obstructive sleep apnea (OSA) are at increased risk for cardiovascular diseases. Injury of endothelial cells has been advanced as an initial trigger to atherosclerosis. OBJECTIVES: To study the association between circulating apoptotic endothelial cells and vasomotor dysfunction as a function of sleep apnea. METHODS: Brachial artery flow-mediated dilation was determined in 14 subjects with documented OSA and 10 healthy control subjects at baseline and 8 weeks after continuous positive airway pressure (CPAP) therapy. Quantification of circulating apoptotic endothelial cells (CD146(+) Annexin V(+)) was performed by flow cytometry. MEASUREMENTS AND MAIN RESULTS: Compared with healthy subjects, patients with OSA had higher numbers of circulating CD146(+) Annexin V(+) cells (39.2 +/- 13.6 cells/mL and 17.8 +/- 9.4, respectively; p < 0.001). Increased apoptotic endothelial cells correlated moderately with abnormal vascular function (r = -0.61; p = 0.001). A significant correlation was observed between CD146 Annexin V(+) cells and the apnea-hypopnea index (r = 0.56; p = 0.004). After 8 weeks of treatment with CPAP, the numbers of circulating apoptotic endothelial cells were reduced significantly from 39.2 +/- 13.6 to 22.3 +/- 12.9 apoptotic cells per milliliter (p < 0.001) and correlated with improvement in endothelium-dependent vasodilation (r = 0.49; p = 0.07). CONCLUSIONS: In patients with OSA, impairment of endothelial-dependent vasodilation correlated with the degree of endothelial cell apoptosis. CPAP therapy led to significant decline in circulating apoptotic endothelial cells. These findings provide an additional mechanism for the predisposition of patients with OSA to premature vascular disease.     

睡眠呼吸障碍引起的间断低氧血症与呼吸功能衰竭

OSAHS是一种常见的睡眠呼吸障碍性疾病,成人发生率为2%～4%.由于睡眠中反复发生上气道部分或完全阻塞而表现为夜间间断低氧和高碳酸血症、反复觉醒、睡眠结构紊乱,临床上常引起心、脑、肾等多器官损害.越来越多的证据表明,OSAHS并发高血压、冠心病、肺动脉高压、心力衰竭、卒中的危险性增高,是心脑血管疾病的独立危险因素[1].未经治疗的重度OSAHS患者5年病死率高达1l%～13%,死亡的主要原因是心脑血管并发症.由于这些并发症与内皮功能密切相关,内皮功能紊乱又是动脉粥样硬化的始动因素,因此OSAHS与血管内皮功能的关系逐渐引起了人们的关注.