Persistência de distúrbios perfusionais miocárdicos após intervenção coronária percutânea com êxito: dependência de fatores microcirculatórios / Myocardial perfusion disturbances persisting after successful percutaneous coronary angioplasty: relationship to microcirculatory derangements

Introdução: A persistência transitória de defeitos perfusionais imediatamente após intervenção coronária percutânea bem sucedida para correção de estenoses coronárias é bem documentada. Método: Para testar a hipótese de que tais anormalidades perfusionais sejam associadas a distúrbios microcirculatórios causados por microembolização coronária, comparou-se a intensidade e extensão desses defeitos perfusionais detectados com cintilografia miocárdica em grupos randomicamente constituídos de pacientes tratados com angioplastia coronária por balão (AB) ou submetidos a aterectomia rotacional complementada por balão (AR + B). As características clínicas e angiográficas foram comparáveis nos dois grupos, assim como o sucesso do procedimento de angioplastia coronária. Resultados: Antes da intervenção coronária percutânea, o índice de defeito miocárdico, englobando a extensão e a gravidade da hipoperfusão, foi comparável nos dois grupos, na condição de estresse (AB = 7,72±1,91 vs AR + B = 8,61±3,38) e de repouso (AB = 3,11±1,22 vs AR + B = 2,40±1,63). Após o procedimento, o índice de defeito perfusional decresceu em ambos os grupos durante o estresse, mas com significância estatística apenas no grupo AB = 3,96±1,40 vs AR + B = 3,71 ±1,89. O contraste entre os dois grupos se acentuou na condição de repouso após a intervenção coronária: o índice de defeito decresceu de forma marginalmente significante no grupo AB para 1,46±0,66 e aumentou, embora sem significância estatística, no grupo AR + B, para 3,47±1,92. Conclusão: Esses resultados são compatíveis com o conceito de que a persistência transitória de defeitos perfusionais após angioplastia coronária bem sucedida seja dependente de distúrbios microcirculatórios associados à microembolização durante o procedimento.

Introduction: The transitory persistence of perfusion defects immediately after successful percutaneous coronary interventions to correct coronary stenosis is well known. Methods: To test the hypothesis that such perfusion abnormalities are associated with microcirculatory disorders caused by coronary microembolization we compared the intensity and extent of these perfusion defects detected using myocardial scintigraphy in groups of patients randomly assigned to coronary balloon angioplasty (BA) or to rotational atherectomy plus balloon angioplasty (RA + B). The clinical and angiography characteristics were comparable in both groups, as well as the successof the coronary angioplasty procedure. Results: Before the percutaneous coronary intervention the myocardium defect index, related to the extent and severity of hypoperfusion, was comparable for the two groups, both under stress (AB =7.72±1.91 vs. RA + B = 8.61±3.38) and at rest (AB = 3.11±1.22vs. RA + B = 2.40±1.63). After the procedure, the perfusion defect index decreased for both groups during stress, but with statistical significance only in the AB Group = 3.96±1.40 vs. RA + B = 3.71±1.89. The difference between the two groups was greater at rest after the coronary intervention procedure: the defect index decreased with marginal significance for the AB Group to 1.46±0.66 and increased, though without statistical significance, for the RA + B Group to 3.47±1.92. Conclusion: These results are compatible with the notion that transitory persistence of perfusion defects after successful coronary angioplasty are dependent on microcirculatory disorders associated to microembolization during the procedure

Retinal microvascular signs, cognitive function, and dementia in older persons: the Cardiovascular Health Study.

BACKGROUND AND PURPOSE: Cerebral microvascular disease may be a risk factor for the development of dementia in elderly persons. We describe the association of retinal microvascular signs with cognitive function and dementia among older individuals. METHODS: In the population-based Cardiovascular Health Study, 2211 persons aged 69 to 97 years at recruitment had retinal photography. Photographs were evaluated for retinopathy (eg, microaneurysms, retinal hemorrhages), focal arteriolar narrowing, arteriovenous nicking, and retinal arteriolar and venular caliber. Cognitive status was determined from the Digit-Symbol Substitution Test and Modified Mini-Mental State Examination. Participants were also further evaluated for the presence of dementia with detailed neuropsychological testing. Persons with a prior stroke or taking antipsychotic or antidepressant medications were excluded. RESULTS: After adjusting for age, gender, race, field center, education level, internal carotid intima-media thickness, body mass index, hypertension, diabetes, and cigarette smoking status, persons with retinopathy had lower mean Digit-Symbol Substitution Test scores but not Modified Mini-Mental State Examination than those without retinopathy (39 versus 41, P=0.002). In hypertensive persons, retinopathy (multivariable-adjusted OR, 2.10; 95% CI, 1.04 to 4.24) and focal arteriolar narrowing (OR, 3.02; 95% CI, 1.51 to 6.02) were associated with dementia. These associations were not present in individuals without hypertension. CONCLUSIONS: In older persons, our study shows a modest cross-sectional association between retinopathy signs with poorer cognitive function and, in persons with hypertension, with dementia. These data support a possible role of cerebral microvascular disease in the pathogenesis of impaired cognitive function and dementia in older hypertensive persons.

Vascular development is disrupted by endothelial cell-specific expression of the anti-apoptotic protein Bcl-2.

Endothelial cell (EC) apoptosis has been detected in remodelling blood vessels in vivo, and inhibition of EC apoptosis appears to alter vascular morphogenesis in vitro, suggesting that EC apoptosis may play a role in blood vessel remodelling. However, apoptotic EC are difficult to quantify in vivo, and studies of the incidence of EC apoptosis and the sites at which it occurs in vivo have produced contradictory results. Therefore, the specific biological roles played by EC apoptosis remain unclear. Here, we have used a transgenic approach to determine the biological function of EC apoptosis in vivo. Anti-apoptotic Bcl-2 transgenes were expressed in mice under control of the EC-specific tie2 promoter. These transgenic mice died during the second half of gestation. While the development and remodelling of large vessels including aortic arch arteries and great veins proceeded normally, abnormally dense and disorganised networks of small vessels were present in the skin and internal organs. In addition, vessel organisation and lumen formation were disrupted in the placental labyrinth. This study provides direct experimental evidence that endothelial cell apoptosis plays an essential role during embryogenesis. Our results suggest that EC apoptosis plays an important role in determining the structure of the microcirculation but may be dispensable for large vessel development.

Congestive myelopathy due to cervical perimedullary arteriovenous fistula evaluated by apparent diffusion coefficient values - case report.

A 22-year-old woman presented with a cervical perimedullary arteriovenous fistula (AVF) manifesting as right upper and lower extremity weakness. T2-weighted magnetic resonance (MR) imaging showed intramedullary hyperintensity believed to be caused by venous congestion. Preoperative diffusion-weighted MR imaging showed increased apparent diffusion coefficient (ADC) value. Spinal angiography demonstrated an AVF fed mainly by the right C-5 radicular artery. Complete obliteration of AVF was achieved by endovascular embolization and microsurgical shunt occlusion. The ADC value was normalized and her neurological deficits improved after endovascular surgery, whereas T2-weighted MR imaging still demonstrated the lesion. The high preoperative ADC value probably indicated reversible vasogenic edema and immediate normalization of the ADC value suggests a good clinical outcome.

Noninvasive assessment of cutaneous vascular function in vivo using capillaroscopy, plethysmography and laser-Doppler instruments: its strengths and weaknesses.

Given that functional abnormalities of the microcirculation are one of the primary abnormalities in cardiovascular disease pathogenesis, various noninvasive clinical tools have been developed recently to assess the microvascular function, particularly at the skin. The common techniques used to assess cutaneous microvascular function in vivo include capillaroscopy, venous occlusion plethysmography, and laser-Doppler instruments (laser-Doppler fluximetry and laser-Doppler imaging). These noninvasive techniques can be used as an early measure of functional abnormalities within the microvascular tree, predominantly in population at high risk for cardiovascular events. This review discusses some underlying application principle of these techniques, including its clinical significance, method reproducibility and limitations.

Periodontal microcirculatory abnormalities in patients with systemic sclerosis.

BACKGROUND: The aim of this study was to observe the differences in periodontal microcirculation between healthy patients and patients with systemic sclerosis (SSc). METHODS: Fifteen healthy patients and 15 patients with SSc were examined. Periodontal capillaroscopy was used to investigate the characteristics of microcirculation. The visibility, course, tortuosity, possible presence of microhemorrhages, average caliber of the capillary loops, and number of visible capillary loops per square millimeter were evaluated for each patient. RESULTS: The investigation was simple, non-invasive, and repeatable for each patient. In patients with SSc, it was possible to observe a reduced number of capillaries and a greater capillary diameter and tortuosity. CONCLUSIONS: Capillary alterations in patients with SSc are not limited to the nailfold bed but also occur in periodontal mucosa microcirculation. Such evidence could be extremely important in the pathogenesis and treatment of periodontal diseases in patients with SSc.

Fine structural correlates of the choroid plexus of the lateral cerebral ventricle of the human fetal brain.

The germinal matrix neuroepithelium and the choroidal fissure of the fetal choroid plexus commonly possess microvessels that are often poorly developed. There may be a reduction of type IV collagen that surrounds these fragile microvessels. During the first and second trimester of neural development, these microvessels are friable and can undergo intraventricular hemorrhage under a number of circumstances. Early subtle changes in the integrity of germinal matrix epithelium are not easily visualized by ultrasound. The current investigation employing scanning electron microscopy clearly defines subtle hemorrhagic events and tearing of the germinal matrix neuroepithelium in the brains of human fetuses. A 23-week-old fetus survived for 11 days but died from other causes. The choroid plexus of this fetus was compared with the choroid plexus and germinal matrix epithelium of a 22-week-old fetus that was the product of an elective termination due to severe anhydramnios of unknown origin and a 19-week-old male fetus from an elective termination. All tissues were autopsy material not requiring institutional review board approval.

Determination of cerebrovascular reactivity by means of FMRI signal changes in cerebral microangiopathy: a correlation with morphological abnormalities.

BACKGROUND AND PURPOSE: A reduced cerebrovascular reactivity (CR) is a risk factor of cerebrovascular disease. In this study, we implemented a protocol to assess CR by means of functional MRI (fMRI) using hyperventilation. SUBJECTS AND METHODS: In 5 patients with cerebral microangiopathy (CM/lacunar infarction and white matter degeneration), 6 healthy elderly subjects (age-matched control), and 6 young healthy subjects, the CR in response to hyperventilation was evaluated by fMRI using gradient echo-planar Imaging. The percentage signal change normalized by end-tidal CO(2) value was measured in various brain regions. RESULTS: All subjects performed hyperventilation well without adverse reaction and significant gross motion. Patients with CM showed significant qualitative and quantitative differences (p < 0.05) as compared to controls. The volume of gray matter showing significant CR was significantly reduced in patients: by 40% in comparison to the age-matched elderly control group and by 60% when compared with the young controls. The CR impairment was most pronounced in the frontal cortices with a drastically reduced magnitude of the magnetic resonance (MR) signal change in the patients (-0.62 +/- 0.2% in patients versus -2.0 +/- 0.36% in age-matched controls, p < 0.0001). A strong relation was evident between the fMRI-based CR reduction in patients with CM and the individual severity of structural MR abnormalities (p = 0.002). CONCLUSION: This study demonstrates that fMRI-based signal changes in response to hyperventilation reliably reflect cerebral vasoreactivity. The protocol is feasible in healthy young and elderly controls and patients with CM. Quantitative and qualitative assessment of the signal decrease in the T(2)-weighted MR sequence and coregistration with individual anatomical data allow the generation of an individual cerebral vasoreactivity map. Future research will address the effect of CR reduction on neuropsychological parameters in patients with CM.

The imbalance between oxygen demand and supply as a potential mechanism in the pathophysiology of heart failure: the role of microvascular growth and abnormalities.

In heart failure, a deficient oxygen supply often is a primary cause for myocardial dysfunction. The reverse however, may also be true; the changes that occur in the failing heart may predispose for the existence of tissue hypoxia, which further affects the function of the heart. Specifically, myocardial hypertrophy and accelerated heart rhythm enhance oxygen demand, while supply is hampered short by endothelial dysfunction and diffusion barriers (such as fibrosis, arterial hyperplasia, and myocyte hypertrophy). Another contributory factor may be deficient growth of the microvasculature that does not keep pace with the rate of myocardial hypertrophy. Fewer microvessels have been observed in many forms of cardiomyopathies. On the other hand, some distinct forms of cardiomyopathies are characterized by the compensatory growth of microvessels, or even excess angiogenesis. This review summarizes the knowledge that has been gathered on this topic thus far and discusses factors that mediate myocardial microvessel growth. Furthermore, a paradigm is presented in which the rate of microvessel growth predicts, at least in part, the degree of myocardial dysfunction. Therapies aimed at the restoration of the microcirculation are proposed to preserve and improve myocardial function.

Efeitos hemodinâmicos sistêmicos e regionais da infusão de cristalóides em modelo experimental de choque séptico hipodinâmico / Regional and systemic hemodynamics effects of crystalloids infusion in an experimental model of hypodynamic septic shock

Para estudar os efeitos hemodinâmicos sistêmicos e regionais da expansão volêmica em modelo de choque séptico, vinte e um cães anestesiados e sob ventilação mecânica receberam dose letal de E. coli vivas por via endovenosa, randomizados em três grupos: Ringer lactato 16 ou 32ml/Kg em 30min ou controle e observados 120min. A bacteremia promoveu hipotensão, redução do débito cardíaco, fluxo porta e renal, acompanhados por aumento da extração sistêmica e regional de oxigênio, acidose láctica e aumento dos gradientes veno-arterial, porta-arterial e gastro-arterial de CO2. A expansão volêmica promoveu benefícios parciais e temporários insuficientes para reverter os déficits perfusionais.To study the regional and systemic hemodynamics effects of fluid resuscitation in a model of septic shock. Twenty-one anesthetized and mechanically ventilated dogs received a lethal doses of live E. coli in blood circulation, randomized in three groups: Lactate Ringer 16 or 32ml/kg in 30 min and control and observed 120 min. The bacteremia resulted in hypotension, decrease of cardiac output, portal and renal flow, accompanied by an increase in the systemic and regional oxygen extraction, lactic acidosis and increase in venous-arterial, porto-arterial and gastro-arterial of CO2 gradients. Fluid replacement resulted in partial and temporary benefits unable to restore the perfusional deficits...

Anomalous artery directly connecting the external and internal carotid arteries.

An anomalous artery directly connecting the external with the internal carotid artery was encountered on the right side of a 68-year-old Japanese female cadaver. This anomalous artery (5 mm in diameter, 12 mm in length) branched out from the posterior aspect of the external carotid at the level of the origin of the lingual artery, ran obliquely upward posteriorly along the course of the hypoglossal nerve, and was confluent with the anterior aspect of the internal carotid artery. No other variations were found in the morphological aspects of, or in the anatomical relationships between, the carotid arteries and their surrounding structures on either side. The carotid body-like structure was observed at the carotid bifurcation and was innervated by small branches of the glossopharyngeal, the vagus and the sympathetic trunk. Embryologically, it is conceivable that this anomalous artery may have derived from the right second branchial arch artery, although there is no abnormality in other derivative structures of the second pharyngeal arch. There may have been no effect from this anomaly on the functions of the arterial blood flow and blood supply under normal circumstances in the present case, but this report may be of embryological significance and contribute some insight into the mechanisms of the formation of the carotid circulation systems.

TIE1 and TIE2 receptor tyrosine kinases inversely regulate embryonic angiogenesis by the mechanism of intussusceptive microvascular growth.

As shown previously, TIE1 and TIE2 receptor tyrosine kinases are specifically expressed in endothelial cells during embryonic angiogenesis. A detailed analysis of the vascular malformations of homozygous mice for a targeting mutation of both receptors was performed at the histological and cellular level. The data demonstrate that the TIE1 and TIE2 receptor inversely and concomitantly mediate interactions between endothelial cells with their extracellular matrix and with surrounding mesenchymal cells. These interactions are obviously crucial for normal endothelial cell motility and/or attachment and also for recruitment of periendothelial cells. The analysis of the TIE2-deficient embryos demonstrates how these cell/cell- and cell/matrix interactions subsequently influence the formation of normally structured tissue folds that divide the vessel lumen. They are also essential for the formation of vessel loops that compose a new vascular network and for the development of the ventricle in the heart. Fold and loop formation follow the principles of intussusceptive microvascular growth. The localization of the cardiovascular malformations corresponds to the temporal and spatial expression pattern of the TIE2 receptor. Angiopoietin-1, a ligand that activates the TIE2 receptor, is expressed in mesenchymal cells surrounding the endothelium. This local relationship is indicative of a paracrine regulation.

Suspected microscopic hepatic arteriovenous fistulae in a young dog.

Portal hypertension can develop from any disorder that obstructs portal blood flow and may cause ascites in young dogs. Anomalous hepatic arteriovenous (AV) connections are rare but should be suspected in any young dog with portal hypertension or ascites. All previous reports of dogs with hepatic AV fistulae have documented macroscopic connections between the arterial and venous systems. Identical clinical signs and histopathologic findings can develop in dogs in which a macroscopic hepatic AV connection cannot be detected. Microscopic AV connections may be responsible for clinical signs in these dogs.

Intestinal vascular anomalies in children.

Vascular anomalies are an uncommon cause of gastrointestinal bleeding in childhood. Confusing nomenclature has made objective comparisons of published cases difficult and has interfered with an established consensus regarding diagnosis and therapeutic modalities. The purpose of this study was to clarify the situation by reviewing the records of all children who had intestinal vascular anomalies who were referred to our institution from 1975 to 1995. Thirteen lesions were identified in nine children (five boys and four girls). The median age at clinical onset was 8 years. Only two patients presented with a complex syndrome (Klippel-Trenaunay, 1; Osler-Rendu-Weber, 1). Diagnosis, location, and extension of these anomalies was only possible by angiography, which indicated that seven patients had isolated venous malformations and two had arteriovenous malformations. Because the lesions did not involve the serosa, intraoperative localization was a major problem. The main findings were a few slightly dilated mesenteric veins. Treatment was conservative in four children and surgical in five. Pathological findings on resected bowel demonstrated dilated and abnormal veins in the mucosa and submucosa. Selective angiography should not be delayed in patients with gastrointestinal bleeding if results of all other investigations are negative. Because these lesions are rarely recognizable on operative inspection, precise preoperative angiographic localization of intestinal vascular anomalies is essential to allow for a safe and limited resection of the involved bowel segment. Based on a better understanding of the natural history of these lesions, a classification of vascular anomalies of intestines in children is proposed.

Characterization of hepatoportal microvascular dysplasia in a kindred of cairn terriers.

Hepatoportal microvascular dysplasia (MVD), a congenital disorder of the hepatic vasculature, is described in a kindred of Cairn Terrier dogs. Cairn Terrier dogs (n = 165) were evaluated using the serum bile acid test. Affected dogs, identified by abnormal fasting or postprandial serum bile acid concentrations, were divided into 2 groups. Group 1 dogs (n = 147) were used for pedigree analysis. Group 2 dogs (n = 18) were characterized on the basis of history, physical examination, clinicopathologic studies, diagnostic imaging of the liver and portal circulation, and hepatic histopathology. Group 2 contained control dogs (n = 2), dogs with hepatoportal MVD (n = 11), and dogs with macroscopic portosystemic vascular anomalies (PVSA) (n = 5). With the exception of high serum bile acid concentrations, dogs with hepatoportal MVD were indistinguishable from control dogs on the basis of history, physical examination, clinicopathologic findings, survey abdominal radiography, abdominal ultrasound, or transcolonic scintigraphy. Contrast portography in dogs with MVD revealed abnormalities of terminal twigs of the portal vasculature with out large intrahepatic or extrahepatic shunting vessels. Histopathologic abnormalities in dogs with hepatoportal MVD were similar to those reported for dogs with PSVA. Pedigree analysis suggested an autosomal inheritance for MVD. Dogs with MVD had high serum bile acid concentrations, abnormal indocyanine green clearance, and hepatic pathology suggestive of PSVA, but they lacked characteristic clinical findings of PSVA. The clinical significance of MVD is unclear. Dogs with MVD were clinically normal when evaluated but long-term follow-up is not yet available. Dogs with hepatoportal MVD should be identified at an early age to avoid confusion in future diagnostic evaluations.

Deterioro de la microcirculación en la sustancia negra como causa de la enfermedad de Parkinson / Microcirculation deterioration in the substantia nigra caused by Parkinson's disease

Presentamos nuevos conceptos relativos a la etiología de la Enfermedad de Parkinson (EP). Basado en los hallazgos sobre la angio-arquitectura, relaciones neurono-vasculares y actividad metabólica de la zona compacta de la sustancia negra normal y parkinsoniana, nosotros creemos que una reducción subóptima en el flujo sanguíneo y su persistencia crónica a al sustancia negra, puede ser la clave en la patogénesis de la EP. Por el contrario, suponiendo que nuestra hipótesis es correcta, una revascularización de la sustancia negra podría detener o mejorar esta enfermedad.

[The diagnosis of vascular micromalformations in the brain]. / Diagnostika sosudistykh mikromal'formatsii golovnogo mozga.

Ninety cases with cerebrovascular micro-malformations were analyzed. These abnormalities amount to 5.3% of the total number of patients with arteriovenous malformation. These include various vascular defects from 0.5 to 1.0 cm. Most of them run as strokes (80%); the others have a pseudotumorous course. Angiography reveals 60.5% of cerebrovascular micro-malformations. In other cases they are undetectable or their identification requires functional and gross angiography. Computed tomography and magnetic resonance tomography reveal intracranial hemorrhages from cerebrovascular micro-malformations, without identifying the latter. They cannot differentiate a tumor from parenchymatous hemorrhages from cerebrovascular micro-malformations in 37.7%. The greater diagnostic difficulties arise in subtentorial cerebrovascular micro-malformations having a pseudotumorous course. In these cases they are angiographically invisible, and CT (MRT) diagnosis prior to surgery is a volumetric brain formation, providing no specification of the process.

Abnormalities of cutaneous microcirculation in atopic eczematics.

There are signs of abnormal microcirculation in atopics, yet reliable methods for its non-invasive measurement are scarce so far. Since the phenomenon of dermographism (D) elicited by blunt stroking of the skin reflects the functional response of cutaneous vessels to pressure, we studied the haemodynamics of D using laser-Doppler microfluxometry (LDF) and infrared thermography (IR-TH) in patients with atopic eczema (n = 23) and in healthy controls (n = 21) under standardized investigative conditions. Only in-patients not treated with corticoids were selected. LDF values showed a marked reduction in the intensity of hyperaemia in the patients as compared with the controls, according to the visual degree of the dermographic blanching effect (white, delayed white, indifferent; pink). A reduction of the radiating skin temperature vis-à-vis the controls was measured by IR-TH. These results yield evidence that dermographic pallor of atopic skin depends on the strength of local vasoconstriction, possibly including altered blood flow in cutaneous shunt vessels.