Mechanical work of the left ventricle of the human heart

By means of the echocardiographic techniques, morphometric and functional parameters of the heart left ventricle (HLV) were studied in male humans aged 20 to 23, in resting and under the effect of a physical load. The total ventricle work was found to be about 1 J, the relative one (per 100 g of the LV mass)--0.6 J. The total working power was found to be about 70 Watt, the relative one--about 40 Watt. The physical load resulted in increase of the LV mechanical work parameters due to the heart rate and systolic arterial pressure.     

A severe vicious cycle in uncontrolled subarachnoid hemorrhage: the effects on cerebral blood flow and hemodynamic responses upon intracranial hypertension

In subarachnoid hemorrhage (SAH), Cushing postulated that the increase in systemic arterial pressure (SAP) in response to elevation of intracranial pressure (ICP) was beneficial to cerebral perfusion. However, in uncontrolled SAH, the increased SAP may cause more bleeding into the subarachnoid space and further increase the ICP. We created an animal model to simulate SAH by connecting a femoral arterial catheter to the subarachnoid space. The global cerebral blood flow (CBF) was measured with a venous outflow method. The purposes were to observe the CBF change under the simulated SAH, and to evaluate the effects of an adrenergic blocker and a vasodilator. In addition, spectral analysis of the aortic pressure and flow was employed for the analysis of hemodynamic changes at various ICP levels. When the femoral arterial blood was allowed to flow into the subarachnoid space, the ICP was elevated. The Cushing response to increased ICP caused an increase in SAP. A vicious cycle was generated between ICP and SAP. The CBF under the vicious cycle was greatly depressed. The dog developed pulmonary edema (PE) within 5 mins. An alpha-adrenergic blocker (phentolamine) and a vasodilator (nitroprusside) were beneficial to the reduction of SAP and ICP, improvement of CBF, and prevention of PE. Hemodynamic analysis revealed that graded increases in ICP caused increases in SAP, total peripheral resistance, arterial impedance, and pulse reflection with decreases in stroke volume, cardiac output and arterial compliance. The hemodynamic changes may contribute to acute left ventricular failure that leads to pressure and volume loading in the lung circulation, and finally acute PE.     

The effect of craniotomy on the intracranial hemodynamics and cerebrospinal fluid dynamics in humans

The goal of the research was to study the effect of the trephination of the human cranial cavity on the intracranial hemodynamics and cerebrospinal fluid (CSF) dynamics. The sample comprised 15 patients of a neurosurgical clinic in whom a trephine opening in the cranial bones was made for medical indications. In these patients, at rest and during an appropriate functional load, we recorded pulse changes in blood circulation (by transcranial Doppler sonography) and in the ratio between the pulse fluctuations in the blood and CSF volumes (by rheoencephalography) before and after surgery. Simultaneous recording of these parameters followed by computer pattern and phase analyses allowed evaluation of the complex biomedical compliance of the cranium during successive phases of the cardiac rhythm: the inflow of arterial blood, the redistribution of blood/CSF volumes, and the outflow of venous blood. Analysis of the results showed a beneficial influence of craniotomy on the intracranial hemodynamics and CSF dynamics. This was reflected in an increase in the cranial compliance, which increased the pulse increment in the volume of the arterial blood in the skull almost twofold. After craniotomy, the cross-flow of CSF between the cranial and spinal cavities decreased significantly, giving way to volumetric compensatory translocations of blood and CSF within the cranial cavity per se during the cardiac cycle, which increased the intracranial utilization of the energy of the cardiac output and contributed to the outflow of venous blood from the cranium. The results suggest a beneficial effect of craniotomy on the physiological mechanisms of the circulatory and metabolic maintenance of the brain activity.     

Sex differences in intracranial arterial bifurcations

Background: Subarachnoid hemorrhage (SAH) is a serious condition, occurring more frequently in females than in males. SAH is mainly caused by rupture of an intracranial aneurysm, which is formed by localized dilation of the intracranial arterial vessel wall, usually at the apex of the arterial bifurcation. The female preponderance is usually explained by systemic factors (hormonal influences and intrinsic wall weakness); however, the uneven sex distribution of intracranial aneurysms suggests a possible physiologic factor—a local sex difference in the intracranial arteries.Objective: The aim of this study was to explore sex variation in the bifurcation anatomy of the middle cerebral artery (MCA) and internal carotid artery (ICA), and the subsequent hemodynamic impact.Methods: Vessel radii and bifurcation angles were measured in patients with MCA and ICA bifurcations. Data from a previously published study of 55 patients undergoing diagnostic cerebral digital subtraction angiography at Dalcross Private Hospital in Sydney, Australia, between 2002 and 2003, were available for analysis. The measurements were used to create idealized, averaged bifurcations of the MCA and ICA for females and males. Computational fluid dynamics simulations were performed to calculate hemodynamic forces in the models.Results: The vessel radii and bifurcation angles of 47 MCA and 52 ICA bifurcations in 49 patients (32 females, 17 males; mean age, 53 years; age range, 14–86 years) were measured. Statistically significant sex differences were found in vessel diameter (males larger than females; P < 0.05), but not in bifurcation angle. Computational fluid dynamics simulations revealed higher wall shear stress in the female MCA (19%) and ICA (50%) bifurcations compared with the male bifurcations.Conclusions: This study of MCA and ICA bifurcations in female and male patients suggests that sex differences in vessel size and blood flow velocity result in higher hemodynamic forces acting on the vessel wall in females. This new hypothesis may partly explain why intracranial aneurysms and SAH are more likely to occur in females than in males.     

Digital Subtraction Angiography Imaging Characteristics of Patients with Extra–Intracranial Atherosclerosis and Its Relationship to Stroke

To investigate the angiographic characteristics and clinical features in patients with suspected extra–intracranial atherosclerosis in a large cohort of Chinese population. On the basis of digital subtraction angiography characteristics, pathological morphology of extra–intracranial atherosclerosis was divided into tortuosity, kinking, coiling, and stenosis in 2,218 individuals aged 45–89 years. The degree of stenosis was further divided into low-grade (<30 %), intermediate-grade (30–69 %), and high-grade stenosis (≥70 %). Clinical manifestations were divided into transient ischemic attack, cerebral infarction and cerebral hemorrhage. The prevalence of tortuosity and stenosis were significantly higher in the extracranial arterial system than that of intracranial arterial system. The prevalence of tortuosity and kinking were significantly higher on the left side than the right side. The prevalence of mild and moderate stenosis in the internal carotid artery was significantly higher in the left side than the right side. The incidence of cerebral infarction was significantly higher in the internal carotid arterial (ICA) system than the vertebrobasilar arterial (VBA) system. Tortuosity is a common carotid abnormality in the Chinese population. The prevalence of ICA tortuosity is higher than that of VBA. The incidence of cerebral infarction in each atherosclerosis group was significantly higher in ICA than that of VBA. The prevalence of stroke is higher in the ICA system than the VBA system. Kinkings and coilings may not have a clinical significance if these lesions are not associated with atheromatous plaques or carotid stenosis.     

Fluid–structure interaction (FSI) simulation for studying the impact of atherosclerosis on hemodynamics,arterial tissue remodeling,and initiation risk of intracranial aneurysms

The biomechanical and hemodynamic effects of atherosclerosis on the initiation of intracranial aneurysms (IA) are not yet clearly discovered. Also, studies for the observation of hemodynamic variation due to atherosclerotic stenosis and its impact on arterial remodeling and aneurysm genesis remain a controversial field of vascular engineering. The majority of studies performed are relevant to computational fluid dynamic (CFD) simulations. CFD studies are limited in consideration of blood and arterial tissue interactions. In this work, the interaction of the blood and vessel tissue because of atherosclerotic occlusions is studied by developing a fluid and structure interaction (FSI) analysis for the first time. The FSI presents a semi-realistic simulation environment to observe how the blood and vessels' structural interactions can increase the accuracy of the biomechanical study results. In the first step, many different intracranial vessels are modeled for an investigation of the biomechanical and hemodynamic effects of atherosclerosis in arterial tissue remodeling. Three physiological conditions of an intact artery, the artery with intracranial atherosclerosis (ICAS), and an atherosclerotic aneurysm (ACA) are employed in the models with required assumptions. Finally, the obtained outputs are studied with comparative and statistical analyses according to the intact model in a normal physiological condition. The results show that existing occlusions in the cross-sectional area of the arteries play a determinative role in changing the hemodynamic behavior of the arterial segments. The undesirable variations in blood velocity and pressure throughout the vessels increase the risk of arterial tissue remodeling and aneurysm formation.

     

A functional variant of the collagen type III alpha1 gene modify risk of sporadic intracranial aneurysms

Abnormalities in type III collagen in the arterial walls cause certain familial intracranial aneurysms (IAs); however, it remains unknown whether COL3A1 variants contribute to the risk of sporadic IAs. To study whether COL3A1 variants are associated with sporadic IAs, the association of COL3A1 variants with sporadic IAs was tested in 298 cases and 488 controls, replicated in an independent population of 192 cases and 1,690 controls, and further verified in 633 patients with intra-cerebral hemorrhage, 1,074 hypertensives, and 1,883 controls. We found that allele A of SNP rs1800255 conferred a 1.71-fold increased risk for IAs (adjusted odds ratio: OR = 1.71, 95% confidence interval: CI 1.19-2.45, P = 0.004) and results in an amino acid change of Ala698Thr, which led to a lower thermal stability of the peptide. These results were confirmed in the independent study. The associations were independent of the presence of hemorrhagic stroke and hypertension. These results support the view that the functional variant of COL3A1 is genetic risk factors for IAs in the Chinese population.     

Cerebral hemodynamics during arterial and CO(2) pressure changes: in vivo prediction by a mathematical model

The aim of this work was to analyze changes in cerebral hemodynamics and intracranial pressure (ICP) evoked by mean systemic arterial pressure (SAP) and arterial CO(2) pressure (Pa(CO(2))) challenges in patients with acute brain damage. The study was performed by means of a new simple mathematical model of intracranial hemodynamics, particularly aimed at routine clinical investigation. The model was validated by comparing its results with data from transcranial Doppler velocity in the middle cerebral artery (V(MCA)) and ICP measured in 44 tracings on 13 different patients during mean SAP and Pa(CO(2)) challenges. The validation consisted of individual identification of 6 parameters in all 44 tracings by means of a best fitting algorithm. The parameters chosen for the identification summarize the main aspects of intracranial dynamics, i.e., cerebrospinal fluid circulation, intracranial elastance, and cerebrovascular control. The results suggest that the model is able to reproduce the measured time patterns of V(MCA) and ICP in all 44 tracings by using values for the parameters that lie within the ranges reported in the pathophysiological literature. The meaning of parameter estimates is discussed, and comments on the main virtues and limitations of the present approach are offered.     

Conditional gene expression in human intracranial xenograft tumors

In an initial effort to determine the effect of expressing potentially therapeutic gene products on the growth properties of glioma tumor xenografts, we describe the development of cell lines that can conditionally express beta-galactosidase (beta-gal). To achieve this, we generated stable cell lines that express the modified tetracycline repressor molecule (rtTA) and the beta-gal gene under control of tetracycline-responsive cis-elements. The resulting cell lines express functional beta-gal following treatment with the tetracycline analog doxycyclin (Dox). These cells were then used to form intracranial tumors after injection into the brain using an implantable guide-screw system. The xenografts were found to express beta-gal when the animals were fed drinking water containing Dox. From these studies, we conclude that the expression of a target gene in a human xenograft growing in the brain of a living mouse can be conditionally regulated.     

The neurohypophyseal capillary bed. I. Anatomy and arterial supply.

Vascular casts of the pituitary-median eminence complex of mice,rats, dogs, sheep and monkeys were examined with the scanning electron microscope. Microfil-injected specimens of the rabbit and monkey pituitary-median eminence complex were examined by light microscopy after intracranial internal carotid artery occlusion. In each species a common neuropophyseal capillary network was found uniting infundibulum (median eminence), infundibular stem and infundibular process. This capillary bed is supplied from above by superior hypophyseal arteries and from below by inferior hypophyseal arteries. An artery to the infundibular stem was found in some species. With occlusion of the intracranial internal carotid arteries, flow through superior hypophyseal arteries did not occur. Yet the entire neurohypophyseal capillary bed filled upon injection with Microfil. These observations suggest the concept of a restricted arterial supply to the median eminence with drainage to the underlying adenohypophsis on one hand and to the infundibular process with drainage to the systemic circulation on the other must be modifed and that blood flow within the neurohypophyseal capillary bed (between infundibular process and median eminence) occurs.     

Vasopressor responses and hypoxemia with acutely increased intracranial pressure

We studied anesthetized dogs subjected to graded increases in intracranial pressure (ICP) to assess the role of the systemic vasopressor (Cushing) response in the arterial hypoxemia associated with increased ICP. The arterial PO2 decrement was significantly greater with rapidly increased ICP compared to slowly increased ICP (P less than 0.01). Systemic vasopressor responses generated in cats by direct electrical stimulation of the vasomotor center resulted in arterial hypoxemia during controlled ventilation. Therefore, arterial hypoxemia was coincident with increased systemic blood pressure produced by either elevation of ICP or electrical stimulation of the vasomotor center.     

Iatrogenic Chlamydia infection-associated damage in the basilar arterial wall of the rat

A random finding of intracranial vascular Chlamydia sp. infection in Wistar rats and its associated damage of the component tissues of the basilar arterial wall are described as seen with transmission electron microscopy. The pathological changes observed showed no apparent specificity except for "striding" of the endothelial cells on the elastic lamina, the phenomenon observed in all five rats with basilar arterial Chlamydia infection, and in only two out of 13 rats with no proof of the infection. No atherosclerotic changes were found in the infected artery in rats sacrificed 8 or 26 weeks after the presumed infection.     

Cerebral Strokes Associated with Pregnancy and the Puerperium

Thirty-one cases of ischaemic cerebral stroke occurring in association with childbirth were fully investigated. The pathological basis of non-haemorrhagic carotid territory strokes in pregnant or puerperal women proved to be similar to that in non-pregnant women of the same age group. Over 70% were due to occlusive cerebral arterial disease or ischaemic lesions unrelated to thrombosis of the intracranial venous system. Comparisons are made with some other reported series in which only a minority of the patients were investigated by angiography, but in which intracranial venous occlusion was assumed to be the primary lesion. It seems likely that many of these patients may also have suffered arterial rather than venous lesions.     

基于蛋白质互作网络的COVID-19对肺动脉高压的影响机制

通过构建肺动脉高压差异基因和冠状病毒侵入人体后免疫反应相关基因的互作网络,探索COVID-19对肺动脉高压的影响机制。首先通过Meta分析挖掘肺动脉高压相关差异表达基因;其次通过SARS-CoV侵染人体后的基因表达数据,挖掘主要功能通路;最后构建肺动脉高压差异表达基因和冠状病毒主要功能通路基因的互作网络,挖掘网络的显著功能模块。发现肺动脉高压与血管平滑肌细胞、成纤细胞、T/B细胞免疫过程、转录调节因子通路、Toll样信号通路等密切相关,互作网络发现ITGAM、HBB、VCAM1、IL1R2等基因是COVID-19感染肺动脉高压患者的重要调节基因。通过肺动脉高压与冠状病毒感染机体后蛋白质互作网络探索了COVID-19对肺动脉高压的影响机制,为肺动脉高压感染COVID-19的研究及治疗提供了新思路。     

Normal physiological values for conscious pigs used in biomedical research

Although the domestic pig is rapidly becoming an animal of choice in certain areas of biomedical research requiring a large animal model, effective utilization of the species is often encumbered by a lack of reference values for common functional variables. To address this problem, normal data for over 100 physiologic or related variables were collected from conscious chronically instrumented animals that were maintained under near basal conditions. Included were measurements of body composition, fluid volumes, blood physical and biochemical characteristics, blood gas and acid-base status, plasma hormone levels, energy metabolism, renal function, hemodynamics and pulmonary function. Most porcine values were similar to those collected under comparable conditions from humans. Compared to adult man, however, pigs had higher values for extracellular space, plasma volume, arterial pH, plasma bicarbonate, cardiac output, arterial pressure, expired ventilation, heat production, and core temperature, and lower values for red cell volume, hemoglobin level, plasma osmotic and oncotic pressure, arterial O2 content, renal blood flow and glomerular filtration rate. Many of these deviations were due to immaturity. Nevertheless, we have found pigs to be an excellent large animal model for a variety of functional studies.     

Brain microvascular and intracranial artery resistance to atherosclerosis is associated with heme oxygenase and ferritin in Japanese quail

Oxidative stress and increased oxidation of low-density lipoprotein (oxLDL) through free radical-mediated tissue injury may be important factors in the development of extracranial atherosclerotic lesions. However, the roles of oxidative stress and hypercholesterolemia in intracranial atherosclerosis is less established. The induction of heme oxygenase (HO) is a cellular response to oxidative stress, and inducible HO (HO-1) may protect against oxidized lipids such as those produced by oxidative stress. We investigated the effects of oxLDL on cell and tissue viability, HO-1 and ferritin expression in extracranial and intracranial endothelial cells, and the arteries of cholesterol-induced atherosclerosis (CIA) Japanese quail. We report that cultured microvascular endothelial cells from the brain (QBMEC) and carotid (QCEC) differ in their response to oxidative stress. The QCECs are less responsive than QBMECs to oxidative stress induced by oxLDL, as evident by lower expression of HO-1 mRNA, HO activity, and ferritin levels. Furthermore, the higher levels of catalytic iron, thiobarbituric acid reactive substances, and lactate dehydrogenase released in QCECs indicated that these cells are more susceptible to oxidative stress than QBMECs. We also investigated the relationship between extent of atherosclerotic plaque deposition and the extracranial and intracranial arterial expression of HO-1 in quail. The common carotid and vertebral (extracranial) arteries had higher tissue cholesterol levels (starting at 2 weeks of cholesterol-supplementation) and a greater atherosclerotic plaque score (starting at 4 weeks of cholesterol-supplementation) compared with middle cerebral and basilar (intracranial) arteries, and this may be relevant to the effect of aging on the process of atherogenesis. The extracranial arteries also had early and greater levels of lipid peroxidation and catalytic iron coupled with lower expression of HO-1 protein, HO activity, and ferritin compared to the intracranial vessels. These observations suggest that the extracranial and intracranial arterial walls respond differently to oxidation of lipoproteins, and support the feasibility of increased HO-1 expression as a means of protection against oxidant injury.     

Isolation and Controlled Perfusion of the Canine Brain

Experiments were carried out to evaluate the adequacy of internal carotid perfusion of the isolated canine brain and the application of a perfusion apparatus which was designed to facilitate environmental control for the isolated functioning organ. Anatomic considerations and the surgical isolation of the cerebral vasculature are presented in detail. Intact animals were used to provide physiologic arterial blood which was pumped under pressure control to six brains which were maintained at simulated low, normal and high intracranial pressures. Good electrocortical activity has been preserved for up to eight hours in the preparation.The methods provide a useful model for the future investigation of cerebral circulation, metabolism and function under normal and various pathophysiologic conditions.     

Hippocampal signal complexity in mesial temporal lobe epilepsy: a noisy brain is a healthy brain

Patients with mesial temporal lobe epilepsy (mTLE) show structural and functional abnormalities in hippocampus and surrounding mesial temporal structures. Brain signal complexity appears to be a marker of functional integrity or capacity. We examined complexity in 8 patients with intracranial hippocampal electrodes during performance of memory tasks (scene encoding and recognition) known to be sensitive to mesial temporal integrity. Our patients were shown to have right mesial temporal seizure onsets, permitting us to evaluate both epileptogenic (right) and healthy (left) hippocampi. Using multiscale entropy (MSE) as a measure of complexity, we found that iEEG from the epileptogenic hippocampus showed less complexity than iEEG from the healthy hippocampus. This difference was reliable for encoding but not for recognition. Our results indicate that both functional integrity and cognitive demands influence hippocampal signal complexity.     

Outcome of Investigation of Patients with Presenile Dementia

Of 106 patients admitted for investigation to a neurological hospital with a presumptive diagnosis of dementia, 84 were confirmed to have intellectual impairment or loss of learning and memory function or both. A possible aetiology for the dementia was found in 36 of these 84 patients; the commonest causes discovered were intracranial mass lesions, arterial disease, and alcoholism. Fifteen of the 106 patients were found not to be demented but to have some other illness, most commonly depression. Of the whole series some 15% of the patients suffered from conditions that were amenable to treatment.     

Effect of the new anti-arrhythmia preparation Bonnecor on the hemodynamics and activity of the ischemic heart

The effect of newly-developed anti-arrhythmia drug Bonnecor compared to that of ethacizin and lidocaine has been studied on anesthetized rats under acute myocardial ischemia. The drugs injected intravenously prior to coronary artery occlusion have been shown to prevent to a great degree the appearance of hemodynamic and functional disturbances of the heart. When compared to control, less reduction in systemic arterial pressure, systolic discharge cardiac output, contractility and heart power were observed. In addition, Bonnecor has been found to have certain advantages over reference drugs.