Deep and surface hemodynamic signal from functional time resolved transcranial near infrared spectroscopy compared to skin flowmotion

The potential disturbance in the prefrontal cortex hemodynamic signal measured by functional near infrared spectroscopy (NIRS), due to forehead skin flowmotion, detected by laser Doppler flowmetry, was investigated by a standard protocol of hemodynamic challenge by Valsalva maneuver, aimed at assessing and disentangling local regulatory responses in skin vasomotion and in cerebral perfusion in presence of a strong systemic drive, and to quantify the common information in the two signals. The deep cortical NIRS signal did not appear to be affected by surface vasomotor activity, and autoregulation dynamics were dominant with respect to autonomic control of circulation.     

Different flowmotion patterns in healthy controls and patients with Raynaud's phenomenon.

Flowmotion was characterized in healthy controls and 61 Raynaud's phenomenon (RP) patients by spectral analysis of laser-Doppler perfusion monitoring (LDPM) tracings. Healthy subjects flowmotion patterns revealed a main frequency of 3 cycles per min (cpm) with another low frequency and heart rate synchronous components. A first group of RP patients presented a low frequency and heart rate frequency component but no significant difference in blood flow. The second group presented the predominating heart rate related frequency with low microvascular perfusion. The third group presented a flowmotion pattern with overlapping of heart rate and low frequency components. Patients with primary and secondary RP show specific changes in flowmotion, probably related to increased sympathetic nervous activity or vessel wall alterations causing disappearance of arteriolar tone and impairment of microvascular perfusion. The group of patients with overlapping frequency components presents an intermediate flowmotion pattern indicating a different grade of alterations in microvasculature.     

Dynamic cerebral autoregulation assessment using chaotic analysis in diabetic autonomic neuropathy

Cerebral autoregulation (CA) was assessed by chaotic analysis based on mean arterial blood pressure (MABP) and mean cerebral blood flow velocity (MCBFV) in 19 diabetics with autonomic neuropathy (AN) and 11 age-matched normal subjects. MABP in diabetics dropped significantly in response to tilting (91.6 ± 14.9 vs. 74.1 ± 13.4 mmHg, P < 0.05). Valsalva ratio of heart rate was reduced in diabetics compared to normal (1.1 ± 0.1 vs. 1.5 ± 0.2, P < 0.05). It indicated AN affects the vasomotor tone of peripheral vessels and baroreflex. Nonlinear results showed higher correlation dimension values of MABP and MCBFV in diabetics compared to normal, especially MABP (3.7 ± 2.3 vs. 2.0 ± 0.8, P < 0.05). It indicated CA is more complicated in diabetics. The lower Lyapunov exponent and the higher Kolmogorov entropy values in diabetics indicated less predictable behavior and higher chaotic degree. This study suggests impaired autoregulation would be more chaotic and less predictable.     

Vasomotion - what is currently thought?

This minireview discusses vasomotion, which is the oscillation in tone of blood vessels leading to flowmotion. We will briefly discuss the prevalence of vasomotion and its potential physiological and pathophysiological relevance. We will also discuss the models that have been suggested to explain how a coordinated oscillatory activity of the smooth muscle tone can occur and emphasize the role of the endothelium, the handling of intracellular Ca(2+) and the role of smooth muscle cell ion conductances. It is concluded that vasomotion is likely to enhance tissue dialysis, although this concept still requires more experimental verification, and that an understanding at the molecular level for the pathways leading to vasomotion is beginning to emerge.     

Absence of Kir6.1/KCNJ8 mutations in Italian patients with abnormal coronary vasomotion

The disturbances in coronary vasomotor tone have been extensively analyzed, but the exact molecular mechanisms underlying abnormal coronary vasomotion remain to be elucidated. It has been suggested that impaired coronary vasoreactivity can be the expression of a defect in vascular smooth muscle cells. A mouse model of human variant (vasospastic) angina has been recently obtained by disruption of Kir6.1/Kcnj8, a gene coding for a small pore-forming inward rectifier potassium channel. A phenotype resembling variant angina was also reported in mice lacking Sur2, the partner protein of Kir6.1. To better define the role of the smooth muscular ATP-sensitive potassium channels in the pathogenesis of abnormal coronary vasomotion, a complete mutational analysis of Kir6.1/KCNJ8 gene was performed in a series of 18 Italian patients with impaired coronary vasomotility. Polymerase chain reaction and direct sequencing of PCR products were done. No mutations were detected in the sample analyzed, thus suggesting that Kir6.1/KCNJ8 aberrations are not a common cause of abnormal coronary vasomotion in Italians. To the best of our knowledge, this study represents the first mutational analysis of Kir6.1/KCNJ8 gene in humans. Since major racial differences in the prevalence of abnormal coronary vasomotion have been described, further mutation screenings of Kir6.1/KCNJ8 gene are required to assess its role in the pathogenesis of impaired coronary vasomotility among various ethnic groups.     

Luminal ATP-induced contraction of rabbit pulmonary arteries and role of purinoceptors in the regulation of pulmonary arterial pressure

The effects of luminal ATP between rabbit pulmonary (PAs) and coronary arteries (CAs) were compared to understand the role of purinoceptors in the regulation of pulmonary arterial pressure (PAP) under hypoxia. Diameters of vessels were video analyzed under luminal perfusion. ATP-induced membrane currents and intracellular Ca²⁺ signals ([Ca²⁺]_i) were compared in pulmonary (PASMCs) and coronary myocytes (CASMCs) using patch clamp and spectrofluorimetry. PAP was measured in perfused lungs under ventilation. Luminal ATP induced constriction of rabbit PAs in the presence of endothelium. In contrast, CAs showed dilating responses to luminal ATP even in the absence of endothelium. In PASMCs, both P2X-mediated inward current and P2Y-mediated store Ca²⁺ release were consistently observed. In contrast, CASMCs showed neither P2X nor P2Y responses. In the perfused lungs, hypoxia-induced PAP increase was decreased by suramin, a purinergic antagonist. A luminal application of α,β-meATP largely increased PAP, whereas UTP decreased PAP. The combined application of P2X- and P2Y-selective agonists (α,β-meATP and UTP) increased PAP. However, the perfusion of ATP alone decreased PAP, and the ATP-induced PAP decrease was affected neither by adenosine receptor antagonist nor by nitric oxide synthase inhibitor. In summary, although the luminal ATP constricts isolated PAs and suramin attenuated the HPV of perfused lungs, the bimodal responses of PAP to purinergic agonists indicate that the luminal ATP regulates pulmonary circulation via complex signaling interactions in situ.     

Visualisation of intramural coronary vasculature by an imaging cryomicrotome suggests compartmentalisation of myocardial perfusion areas

A technique is presented for the 3D visualisation of the coronary arterial tree using an imaging cryomicrotome. After the coronary circulation of the excised heart was filled with a fluorescent plastic, the heart was frozen and mounted in the cryomicrotome. The heart was then sliced serially, with a slice thickness of 40μm, and digital images were taken from each cutting plane of the remaining bulk material using appropriate excitation and emission filters. Using maximum intensity projections over a series of images in the cutting plane and perpendicular plane, the structural organisation of intramural vessels was visualised in the present study. The branching end in the smallest visible vessels, which define tissue areas that are well delineated from each other by 1–2 mm wide bands populated only by vessels less than 40 μm in diameter. The technique presented here allows further quantification in the future of the 3D structure of the coronary arterial tree by image analysis techniques.     

Alterations in vasomotor control of coronary resistance vessels in remodelled myocardium of swine with a recent myocardial infarction

The mechanism underlying the progressive deterioration of left ventricular (LV) dysfunction after myocardial infarction (MI) towards overt heart failure remains incompletely understood, but may involve impairments in coronary blood flow regulation within remodelled myocardium leading to intermittent myocardial ischemia. Blood flow to the remodelled myocardium is hampered as the coronary vasculature does not grow commensurate with the increase in LV mass and because extravascular compression of the coronary vasculature is increased. In addition to these factors, an increase in coronary vasomotor tone, secondary to neurohumoral activation and endothelial dysfunction, could also contribute to the impaired myocardial oxygen supply. Consequently, we explored, in a series of studies, the alterations in regulation of coronary resistance vessel tone in remodelled myocardium of swine with a 2 to 3-week-old MI. These studies indicate that myocardial oxygen balance is perturbed in remodelled myocardium, thereby forcing the myocardium to increase its oxygen extraction. These perturbations do not appear to be the result of blunted β-adrenergic or endothelial NO-mediated coronary vasodilator influences, and are opposed by an increased vasodilator influence through opening of K_ATP channels. Unexpectedly, we observed that despite increased circulating levels of noradrenaline, angiotensin II and endothelin-1, α-adrenergic tone remained negligible, while the coronary vasoconstrictor influences of endogenous endothelin and angiotensin II were virtually abolished. We conclude that, early after MI, perturbations in myocardial oxygen balance are observed in remodelled myocardium. However, adaptive alterations in coronary resistance vessel control, consisting of increased vasodilator influences in conjunction with blunted vasoconstrictor influences, act to minimize the impairments of myocardial oxygen balance.     

The effect of atherosclerosis on the vasomotor response of coronary arteries to mental stress

BACKGROUND. Mental stress can cause angina in patients with coronary artery disease, but its effects on coronary vasomotion and blood flow are poorly understood. Because atherosclerosis affects the reactivity of coronary arteries to various stimuli, such as exercise, we postulated that atherosclerosis might also influence the vasomotor response of coronary arteries to mental stress. METHODS. We studied 26 patients who performed mental arithmetic under stressful conditions during cardiac catheterization. (An additional four patients who did not perform the mental arithmetic served as controls.) Coronary segments were classified on the basis of angiographic findings as smooth, irregular, or stenosed. In 15 of the patients without focal stenoses in the left anterior descending artery, acetylcholine (10(-8) to 10(-6) mol per liter) was infused into the artery to test endothelium-dependent vasodilation. Changes in coronary blood flow were measured with an intracoronary Doppler catheter in these 15 patients. RESULTS. The response of the coronary arteries to mental stress varied from 38 percent constriction to 29 percent dilation, whereas the change in coronary blood flow varied from a decrease of 48 percent to an increase of 42 percent. The direction and magnitude of the change in the coronary diameter were not predicted by the changes in the heart rate, blood pressure, or plasma norepinephrine level. Segments with stenoses (n = 7) were constricted by a mean (+/- SE) of 24 +/- 4 percent, and irregular segments (n = 20) by 9 +/- 3 percent, whereas smooth segments (n = 25) did not change significantly (dilation, 3 +/- 3 percent; P less than 0.0002). Coronary blood flow increased by 10 +/- 10 percent in smooth vessels, whereas the flow in irregular vessels decreased by 27 +/- 5 percent. The degree of constriction or dilation during mental stress correlated with the response to the infusions of acetylcholine (P less than 0.0003, r = 0.58). CONCLUSIONS. Atherosclerosis disturbs the normal vasomotor response (no change or dilation) of large coronary arteries to mental stress; in patients with atherosclerosis paradoxical constriction occurs during mental stress, particularly at points of stenosis. This vasomotor response correlates with the extent of atherosclerosis in the artery and with the endothelium-dependent response to an infusion of acetylcholine. These data suggest that in atherosclerosis unopposed constriction caused by a local failure of endothelium-dependent dilation causes the coronary arteries to respond abnormally to mental stress.     

冠心病患者冠状动脉侧支循环的形成与PDGF mRNA水平的关系

目的:探讨冠心病患者单核细胞血小板源性生长因子(PDGF)与冠状动脉侧支循环的关系。方法:依据选择性冠状动脉造影结果将64例患者分为对照组(非冠心病患者,n=15)、冠心病不伴侧支循环组(n=31)、冠心病伴侧支循环组(n=18),采用RT-PCR技术检测3组患者主动脉根部血液及股动脉血液中单核细胞PDGFmRNA水平。结果:(1)冠心病患者有、无侧支循环组之间的冠状脉动病变程度、不稳定心绞痛及心肌梗死发生率无显著差异(P>0.05);但无侧支循环患者心功能不全、室壁瘤的发生率显著增加(P<0.01);(2)与对照组相比,冠心病患者主动脉根部血液单核细胞PDGFmRNA水平增加(P<0.01);有侧支循环患者增加更为显著(P<0.01);而冠心病患者股动脉血液中单核细胞PDGFmRNA水平显著增加(P<0.01),有无侧支循环者之间无显著差别(P>0.05)。结论:冠状动脉侧支循环的建立可显著降低心肌梗死后心功能不全、室壁瘤的发生;PDGFmRNA水平增加与冠状动脉侧支循环形成密切相关;侧支循环形成与否可能主要取决于病变冠状动脉局部单核细胞PDGF基因水平;单核细胞PDGF基因水平可作为评价冠心病患者预后好坏的指标之一。     

Cardiac Hemodynamics,Coronary Circulation and Interventional Cardiology

Microcirculation is the functional end of the coronary circulation and it plays a key role in the regulation of coronary blood flow, both on the local and global scales. A good understanding of its function under physiological and pathophysiological conditions is crucial but, because of its micro-scale, access to this part of the coronary circulation is extremely difficult and requires a considerable amount of innovation and new technologies. Dynamics of the coronary circulation provide the true vehicle by which blood supply reaches the myocardium- coronary vasculature is only the conducting component of that vehicle. It is highly unlikely that the pulsatile nature of the flow, the capacitance of the conducting vessels and the constant pounding of coronary vasculature by surrounding tissue are not part of the design, regulation, and function of the coronary circulation. Interventions, whether to assess or to correct coronary stenosis, continue to be the main clinical avenue to dealing with coronary heart disease. Clinical decisions rely heavily on the ability to determine the true morphology of an occlusive lesion, to predict the future course of that lesion and to assess the functional toll on coronary blood supply which it will inflict at each stage.     

Spontaneous contractions of isolated rat portal vein under temperature perturbations

We studied nonlinear dynamics underlying spontaneous rhythmical contractions of isolated rat portal vein. The signals were acquired at four different temperatures important in isolated blood vessels preparations: 4, 22, 37 and 40°C. To characterize the system’s nonlinearity, we calculated the largest Lyapunov exponent, sample entropy and scaling exponents. Evidence for nonlinearity was provided by analysis of surrogate data generated from the phase-randomized Fourier transform of the original sequences. Positive values of the largest Lyapunov exponent were obtained for the time series recorded under applied conditions, indicating that the system preserves its chaotic deterministic nature even far from the physiological temperature range. Scaling exponents revealed three distinctive regions with different correlation properties. The calculated measures that characterize the time series obtained at 4°C were significantly different from those derived from data obtained at higher temperatures. System’s dynamics becomes more complex or less predictable as temperature approaches physiological value. The computation of the largest Lyapunov exponent, sample entropy and correlation measures gave an insight into the complex dynamics of the isolated blood vessels rhythmicity. We identified different modes of rhythmical contractions of isolated rat portal vein which could improve understanding of possible control mechanisms in vivo.     

A comparative analysis of chaotic particle swarm optimizations for detecting single nucleotide polymorphism barcodes

ObjectiveEvolutionary algorithms could overcome the computational limitations for the statistical evaluation of large datasets for high-order single nucleotide polymorphism (SNP) barcodes. Previous studies have proposed several chaotic particle swarm optimization (CPSO) methods to detect SNP barcodes for disease analysis (e.g., for breast cancer and chronic diseases). This work evaluated additional chaotic maps combined with the particle swarm optimization (PSO) method to detect SNP barcodes using a high-dimensional dataset.Methods and materialNine chaotic maps were used to improve PSO method results and compared the searching ability amongst all CPSO methods. The XOR and ZZ disease models were used to compare all chaotic maps combined with PSO method. Efficacy evaluations of CPSO methods were based on statistical values from the chi-square test (χ²).ResultsThe results showed that chaotic maps could improve the searching ability of PSO method when population are trapped in the local optimum. The minor allele frequency (MAF) indicated that, amongst all CPSO methods, the numbers of SNPs, sample size, and the highest χ² value in all datasets were found in the Sinai chaotic map combined with PSO method. We used the simple linear regression results of the gbest values in all generations to compare the all methods. Sinai chaotic map combined with PSO method provided the highest β values (β ≥ 0.32 in XOR disease model and β ≥ 0.04 in ZZ disease model) and the significant p-value (p-value < 0.001 in both the XOR and ZZ disease models).ConclusionThe Sinai chaotic map was found to effectively enhance the fitness values (χ²) of PSO method, indicating that the Sinai chaotic map combined with PSO method is more effective at detecting potential SNP barcodes in both the XOR and ZZ disease models.     

冠心患者与健康人同步12导联ECG信号的李雅普诺夫指数谱比较研究

本研究首次计算了60名具有窦性心率的冠心患者(Coronary atrery disease:CAD)和60名健康老年人的同步12导联心电图信号的李雅普诺夫指数谱.发现对同一个人,从不同导联得出的Lyapunov指数是不同的,具有明显的空间分布特性.所有导联的ECG信号的最大Lyapunov指数L1均为正数,其余指数为负,心电信号表现出明显的混沌特征.同一导联相比较,冠心患者的最大Lyapunov指数L1低于健康正常人的最大Lyapunov指数L1,提示在心肌缺血的情况下,心电信号的混沌程度下降了,重构相空间中ECG信号的奇异吸引子的动力学复杂性降低了.结果表明,在估算Lyapunov指数时,有必要指明导联的位置.在Lyapunov指数谱中,最大Lyapunov指数可以将冠心患者与健康正常人区分开来,在心脏疾病诊断中具有潜在的应用价值.     

Parametric analysis of flow in the intramyocardial circulation

A simple mathematical model of the intramyocardial circulation has been utilized to provide a better understanding of coronary blood flow. The model includes three myocardial layers, each characterized by a three-parameter windkessel with one capacitance and two resistances. The effects of the beating heart are taken into account by means of an intramyocardial pump and the possible collapse of the vessels by an elevated backpressure. The three basic parameters that govern the flow are a normalized time constant, , the total resistance, R_t, and a parameter, α, which specifies the resistance distribution in the intramyocardial circulation. Both the normal beating heart and prolonged diastole have been investigated analytically as well as numerically. It is shown that each of these parameters has its own special significance. Calculated pressure-flow relationships and zero-flow pressures for the case of prolonged diastole show a high sensitivity to and α.     

Coronary sinus outflow and O2 content in anterior cardiac vein blood at different levels of right ventricle performance

Summary Previous investigations have demonstrated that 60–70% of myocardial venous blood returns from the coronary sinus and that this percentage increases by experimentally raising right ventricle systolic pressure.The experiments described were performed in anesthetized open chest dogs and showed that the increase in coronary sinus outflow is not due to a change in the distribution of venous blood between the coronary sinus and the deep venous system, but is secondary to the increased left coronary artery inflow.A possible explanation of this might be that the increase in intramyocardial right ventricular pressure brings about some release of certain catecholamines which may induce a persisting increase in coronary artery inflow. Beta-blockade can in effect prevent any change in coronary blood flow arising from overdistension of the right ventricle.The O₂ content of the coronary sinus blood (returning mainly from the left ventricle) is constantly lower than that of the anterior cardiac and Thebesius veins (flowing mainly out of the right ventricle). This difference is very probably the result of mechanical factors which play an active role in regulating coronary flow. As is well known, total coronary resistances are the sum of two components i.e., a) extravascular compression during ventricular systole and b) active vasomotor tone in the coronary bed.Vasomotility in the right and left coronary arteries is virtually identical, whereas myocardial compression is considerably lower in the right side of the heart than in the left. Right coronary flow is therefore less impaired than the flow in the left coronary artery; the ratio between coronary flow and O₂ myocardial extraction should thus be better in the right than in the left ventricle.     

Application of the ARMA method to acoustic detection of coronary artery disease

To further explore the application of advanced signal processing techniques to the noninvasive detection of coronary artery disease, 30 patients (10 angioplasty and 20 normal or abnormal) were tested using autoregressive moving average (ARMA) modelling of the disastolic heart sound data. It is during diastole that coronary blood flow is maximum and sounds associated with turbulent blood flow through partially occluded coronary arteries would be loudest. Model parameters (the power spectral density (PSD) functions and the poles of the ARMA method) were used to separate the normal patients from the abnormal patients in the normal/ abnormal study, or to decide whether the recordings were made before or after angioplasty in the angioplasty study. The decisions were made ‘blind’, without knowledge of the actual disease states of the patients for the normal/abnormal study and without prior knowledge of whether a given recording was made before or after angioplasty for the angioplasty study. Results from the angioplasty and the normal/abnormal studies showed that pre- and post-angioplasty records were correctly distinguished in 8 out of 10 cases, and normal and abnormal records were correctly distinguished in 17 of 20 cases. These results also confirmed that high frequency energy above 400 Hz is probably associated with coronary stenosis.     

Identification of canine coronary resistance and intramyocardial compliance on the basis of the waterfall model

This study was performed to elucidate the effects of cardiac contraction on coronary pressure-flow relations. On the basis of the waterfall mechanism, a lumped model of the coronary arterial system is presented consisting of a proximal (epicardial) compliance, a coronary resistance, and an intramyocardial compliance. A “back”-pressure, assumed to be proportional (constant k) to left ventricular pressure, impedes flow. From steady-state measurements of circumflex coronary artery flow and inflow pressure, together with left ventricular pressure, the values of the three model parameters and the constant k have been estimated. In the control condition proximal compliance is found to be 1.7×10⁻¹² m⁴s²kg⁻¹, intramyocardial compliance 110×10⁻¹²m⁴s²kg⁻¹, and resistance 7.5×10⁹kgm⁻⁴s⁻¹. The proportionality constant k is close to unity. Effects of changes in left ventricular pressure and inflow pressure and the effect of vasoactive drugs on the parameters are also investigated. Changes in coronary resistance are always opposite to changes in intramyocardial compliance. Sensitivity analysis showed that epicardial compliance plays its major role during isovolumic contraction and relaxation; resistance plays a role throughout the cardiac cycle but is more important in diastole than in systole, whereas intramyocardial compliance plays a role in systole and in early diastole.     

老年冠心病人脑循环动力学的改变

目的：心脑血管疾病在当今疾病死亡率中占第一位,如何早期防治,减少死亡率,对其相应研究内容非常之多。本文侧重研究心功能基本正常的老年冠心病患者,其脑循环动力学的改变。方法：６０例老年冠心病患者及６８例正常对照组间的心功能参数及脑循环动力参数的比较。结果：本组冠心病患者心功能８个指标中,唯有主动脉内径减小有显著性差异外,余项均在正常范围内。但脑循环动力参数已有显著性改变。主要表现在颈内动脉最大血流速、最小血流速均减小、颈内动脉直径减小、搏动指数、阻力指数均增高。脑血管阻力、特性阻抗增高。脑血管功能已受到明显损害。提示早期防治脑血管疾病的重要性。结论：虽然老年冠心病人没有任何脑部症状和体征,但他们的脑血管功能早已发生变化。因此,对冠心病人早期防治脑血管疾患,减少脑血管疾病对病人带来的危害是十分重要的。     

Vasomotor changes in isolated coronary arteries from diabetic rats

Contractile responses to prostaglandin F2 alpha, serotonin, noradrenaline, and potassium were examined in isolated intramyocardial arteries of Wistar rats 8 weeks after the induction of diabetes mellitus by administration of streptozotocin (STZ). The concentration-response curves obtained were compared with those noted in vessels both from age- and from weight-matched control rats. Light and electron microscopy did not reveal any major change in coronary artery wall thickness or morphology. There was no difference in the pattern of vasomotor responses between the two control groups. Contractile responses to prostaglandin F2 alpha, and potassium were significantly reduced, while contractile responses to serotonin and noradrenaline were unaltered in coronary arteries from diabetic rats. The vasomotor responses to noradrenaline and potassium showed a biphasic pattern in control vessels, i.e. contraction noted at high agonist concentrations was preceded by slight, but reproducible relaxation at lower concentrations. In diabetic vessels these relaxant responses were absent. The contraction produced by noradrenaline was markedly enhanced by the presence of propranolol in both diabetic and control vessels. Dilator responses to verapamil, diltiazem, nifedipine, papaverine and magnesium were studied in serotonin-precontracted coronary arteries; the concentration-response curves obtained by verapamil and diltiazem were shifted to the right in diabetic vessels. It appears justified to use vessels from age-matched rats as controls when vasomotor reactivity in coronary arteries from STZ-diabetic rats is investigated. The reduction in contractile responses to prostaglandin F2 alpha and potassium, and the reduction or lack of relaxant responses to noradrenaline, potassium, verapamil and diltiazem, in diabetic coronary arteries, indicate a selective modification of the coronary circulation by the diabetic disease.