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1.
J Am Coll Cardiol ; 51(11): 1060-5, 2008 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-18342222

RESUMO

OBJECTIVES: We conducted a randomized study to compare the effect of direct stenting (DS) and conventional stenting (CS) on post-procedural index of microcirculatory resistance (IMR) values. BACKGROUND: Direct stenting has been suggested to reduce periprocedural microcirculatory injury compared with stenting that follows pre-dilation (CS). The index of microcirculatory resistance is a sensitive invasive marker of coronary microvascular resistance. METHODS: Fifty patients admitted for elective percutaneous coronary intervention (PCI) were included. All patients had stable angina (Canadian Cardiovascular Society class 0.03 ng/ml). Patients with troponin elevation had significantly greater post-PCI IMR values than patients without troponin elevation: 24.7 +/- 13.2 versus 16.9 +/- 10.2; p = 0.04. CONCLUSIONS: In patients undergoing successful coronary stenting for stable angina, DS is associated with reduced microvascular dysfunction induced by PCI as compared with CS.


Assuntos
Angina Pectoris/terapia , Angioplastia Coronária com Balão/efeitos adversos , Circulação Coronária , Complicações Intraoperatórias/etiologia , Stents , Adenosina/farmacologia , Idoso , Cateterismo Cardíaco , Vasos Coronários/efeitos dos fármacos , Feminino , Humanos , Masculino , Microcirculação/lesões , Pessoa de Meia-Idade , Vasodilatadores/efeitos adversos , Vasodilatadores/uso terapêutico
2.
Shock ; 29(3): 384-7, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17693940

RESUMO

In response to hypoxia, an inflammatory cascade is initiated and microvascular injury ensues. Specifically, within 10 min, leukocyte adherence to the endothelium begins, and leukocyte emigration and vascular leak soon follow. Activated protein C (APC) has been reported to have both anticoagulant and anti-inflammatory properties. Activated protein C is best described in its role as a treatment for sepsis. However, it has been used, with some success, in experimental models of hypoxic injury. We hypothesized that APC would be protective against microvascular injury during systemic hypoxia. Randomized prospective animal study. Adult male Sprague-Dawley rats. To characterize the microvascular response to APC exposure during hypoxia, four rat groups were used: saline control, APC infusion alone (100 mg/kg bolus), hypoxia alone (10% O2), and simultaneous hypoxia + APC infusion. Measurements of leukocyte adherence (no. per 100-microm venule), leukocyte emigration (no. per 4,000 microm(2)), and venular leak by fluorescein isothiacyanate-labeled albumin (Fo/Fi) were performed during intravital microscopy of the intact venular bed. Leukocyte adherence decreased from 14.5 (+/-1.2) cells/100-microm venule in hypoxic rats to 4.4 (+/-1.5) cells/100-microm venule in those treated with both hypoxic gas and APC infusion (P < 0.001). Similarly, leukocyte emigration in hypoxic rats reached 12.3 (+/- 2.2) cells/4,000-microm(2) venule, but was reduced to 3.5 (+/-0.3) cells/4,000-microm(2) venule (P <.001). Venular permeability to protein was also significantly decreased in the APC-treated group from 0.82 (+/-0.14) to 0.25 (+/-0.14) (P < 0.001). The infusion of APC attenuates the inflammatory response during systemic hypoxia at the microvascular level, as evidenced by measurements of leukocyte adherence, emigration, and venular permeability. Further investigation is needed to examine the potential role of APC in the treatment of hypoxic injury.


Assuntos
Hipóxia/tratamento farmacológico , Microcirculação/efeitos dos fármacos , Microcirculação/lesões , Proteína C/farmacologia , Equilíbrio Ácido-Base/efeitos dos fármacos , Animais , Permeabilidade Capilar/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Hipóxia/patologia , Hipóxia/fisiopatologia , Leucócitos/efeitos dos fármacos , Leucócitos/patologia , Leucócitos/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley
3.
Thromb Haemost ; 98(5): 1024-30, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18000607

RESUMO

There is little knowledge regarding the in-vivo course of coagulation reactions in subjects with factor (F)V Leiden (G1691A, R506Q). The aim of the current study was to evaluate the effect of FV Leiden on coagulant reactions triggered by vascular injury. At the site of microvascular injury, prothrombin activation and FVa formation and inactivation have been evaluated in 16 apparently healthy subjects and 16 patients on long-term anticoagulation with acenocoumarol, with eight heterogenous carriers of FV Leiden in the healthy and in the anticoagulated group. Thrombin formation, measured by levels of thrombin-antithrombin complexes (TAT) and thrombin B-chain, proceeded at similar rates in the bleeding-time blood in carriers and non-carriers of FV Leiden. The onset and rate of FV activation did not differ significantly among the four groups. When healthy carriers of FV Leiden were compared to healthy non-carriers, the onset of FVa inactivation by activated protein C (APC) was delayed by 60 to 90 seconds (p=0.01). Anticoagulated individuals also showed the same pattern of FV Leiden associated differences in the time of occurrence of the 30 kD FVa heavy-chain fragment (p=0.021). Our results indicate that when blood clotting is triggered by microvascular injury, the heterozygous expression of FV Leiden has no effect on thrombin generation in healthy or coumadin-treated subjects. Inactivation of FVa by the APC mechanism is attenuated significantly in carriers of FV Leiden but the magnitude of this effect is smaller than that observed in most purified systems.


Assuntos
Coagulação Sanguínea , Fator V/genética , Microcirculação/lesões , Acenocumarol/farmacologia , Acenocumarol/uso terapêutico , Adulto , Testes de Coagulação Sanguínea , Estudos de Casos e Controles , Fator V/análise , Fator V/biossíntese , Fator V/metabolismo , Feminino , Genótipo , Humanos , Cinética , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Protrombina/análise , Protrombina/metabolismo
6.
Neurology ; 67(9): 1668-70, 2006 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-17101902

RESUMO

Focal areas of restricted diffusion adjacent to high-grade glioma resection cavities were detected in 70% of patients on immediate postoperative MRI studies. Follow-up studies demonstrated cystic encephalomalacia in 91% of these foci, suggesting the presence of infarction, and the infarcted tissue demonstrated enhancement in 43% of cases. New postoperative deficits correlated well with the anatomic region of infarction in six patients. Enhancement in perioperative infarcts can mimic tumor progression on follow-up imaging studies.


Assuntos
Infarto Encefálico/etiologia , Infarto Encefálico/patologia , Neoplasias Encefálicas/cirurgia , Glioblastoma/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/fisiopatologia , Infarto Encefálico/fisiopatologia , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/fisiopatologia , Artérias Cerebrais/lesões , Artérias Cerebrais/patologia , Artérias Cerebrais/fisiopatologia , Circulação Cerebrovascular/fisiologia , Confusão/etiologia , Confusão/patologia , Confusão/fisiopatologia , Imagem de Difusão por Ressonância Magnética/normas , Feminino , Glioblastoma/irrigação sanguínea , Glioblastoma/fisiopatologia , Humanos , Masculino , Microcirculação/lesões , Microcirculação/patologia , Microcirculação/fisiopatologia , Pessoa de Meia-Idade , Paresia/etiologia , Paresia/patologia , Paresia/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Valor Preditivo dos Testes
7.
Phys Med Biol ; 51(23): 6047-60, 2006 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-17110769

RESUMO

Microvascular injury is recognized as a major tissue damage mechanism of ablative cryosurgery. Endothelial cells lining the vessel wall are thought to be the initial target of freezing. However, details of this injury mechanism are not yet completely understood. In this study, ECMatrix 625 was used to mimic the tumour environment and to allow the endothelial cells cultured in vitro to form the tube-like structure of the vasculature. The influence of water dehydration on the integrity of this structure was investigated. It was found that the initial cell shape change was mainly controlled by water dehydration, dependent on the cooling rate, resulting in the shrinkage of cells in the direction normal to the free surface. As the cooling was prolonged and temperature was lowered, further cell shape change could be induced by the chilling effects on intracellular proteins, and focal adhesions to the basement membrane. Quantitative analysis showed that the freezing induced dehydration greatly enhanced the cell surface stresses, especially in the axial direction. This could be one of the major causes of the final breaking of the cell junction and cell detachment.


Assuntos
Células Endoteliais/citologia , Congelamento , Actinas/metabolismo , Fenômenos Biofísicos , Biofísica , Membrana Celular/metabolismo , Forma Celular , Células Cultivadas , Criocirurgia , Células Endoteliais/metabolismo , Endotélio Vascular/citologia , Endotélio Vascular/lesões , Endotélio Vascular/metabolismo , Humanos , Microcirculação/citologia , Microcirculação/lesões , Microcirculação/metabolismo , Modelos Biológicos , Neoplasias/irrigação sanguínea , Neoplasias/cirurgia , Tensão Superficial , Água/metabolismo
8.
Artigo em Inglês | MEDLINE | ID: mdl-16889339

RESUMO

This paper presents a detailed study of the oscillation characteristics of a bubble confined inside a deformable microvessel, whose size is comparable with the bubble size. The vessel's compliance is characterized by a nonlinear relation between the intraluminal pressure and the expansion ratio of the vessel radius, which represents the variation of the vessel stiffness with the pressure of the filling liquid. In this analysis, an initially spherical bubble evolves into an ellipsoid, and the asymmetric oscillation appears immediately after the driving pressure is applied and magnifies with oscillation cycles. Compared with the symmetric oscillation in an unconstrained environment, the vessel constraint makes the bubble contract significantly more and subsequently expand in a more violent rebound, inducing substantially larger peaks of the intraluminal pressure exerted on the vessel wall. A larger initial bubble/vessel radius ratio leads to not only a larger peak but also a higher oscillation frequency of the intraluminal pressure, which are the two most dominating parameters in determining the vessel's failure under cyclic loading. The numerical results have further shown that an increase of the vessel wall stiffness strengthens the asymmetric effect, i.e., a larger peak of the intraluminal pressure with a higher oscillation frequency, and so does a larger pre-existing pressure in the liquid filling the vessel. These findings imply that the asymmetric effect is one of the primary mechanisms for clinical injuries of capillary and small blood vessels and for the higher risk of pediatric and hypertension patients in shock wave lithotripsy.


Assuntos
Relógios Biológicos , Gases/efeitos da radiação , Litotripsia/efeitos adversos , Microcirculação/lesões , Microcirculação/efeitos da radiação , Modelos Cardiovasculares , Animais , Simulação por Computador , Relação Dose-Resposta à Radiação , Elasticidade , Humanos , Microcirculação/fisiopatologia , Pressão , Doses de Radiação , Medição de Risco/métodos , Fatores de Risco , Estresse Mecânico
9.
Artigo em Inglês | MEDLINE | ID: mdl-16787288

RESUMO

Sepsis is the result from a complex bacterial-host interaction, which is an often-fatal response when host protective molecular mechanisms designed to fight invading bacteria surpass the beneficial intensity to the point of causing injury to the host. Increasing evidences have implicated the bacterial translocation (BT) as the main source for the induction of sepsis, although the beneficial effect of BT process has been related to the development of the intestinal immune response by physiological interaction between bacteria and host. In this article, we examined evolving concepts concerning to BT and discussed about its potential role in the promotion of microcirculation injury, moreover, its possible participation in the sepsis induction. According to our data obtained from in-vivo BT animal-model, both bacterial overgrowth and bacterial pathogenic determinants seem to be major predisposing factors for the induction of BT. Besides, translocation of luminal bacteria through the lymphatic via elicits the activation of the GALT inflammatory response contributing to microcirculation injuries, and the haematological via of BT was responsible to the systemic bacterial spread. On other hand, the combination of BT process to the pre-existing host systemic infection played a crucial role in the worsening of the clinical outcome. In our understanding, studies concerning to intestinal immune response and the pathophysiology of bacterial-host interaction, under normal and disease conditions, seems to be the key elements to the development of therapeutic approaches towards sepsis.


Assuntos
Translocação Bacteriana/fisiologia , Microcirculação/lesões , Microcirculação/microbiologia , Sepse/microbiologia , Animais , Humanos , Intestinos/irrigação sanguínea , Intestinos/imunologia , Intestinos/microbiologia , Microcirculação/imunologia , Sepse/imunologia
10.
Microvasc Res ; 71(3): 175-84, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16624338

RESUMO

Endothelial phenotypes derived from different pulmonary vascular segments have markedly different permeability response to inflammatory agonists, but their responses to mechanical strain have not been characterized. Therefore, we evaluated the effect of cyclical stretch on cell shape, cell membrane wounding, and junctional beta-catenin in rat pulmonary artery (RPAEC) and microvascular (RPMVEC) endothelial cell monolayers. After 24 h of 24% uniaxial strain at 40 cycles/min, RPAEC but not RPMVEC reoriented transverse to the axis of strain. Total beta-catenin increased in RPAEC but decreased in RPMVEC. Transient plasma membrane wounding was produced by cyclical biaxial strain of 34% or by scratching of monolayers with a needle and was indicated by retention of lysine fixable fluorescent 70 kDa dextran. Junctional beta-catenin was quantified by fluorescence intensity and image analysis. beta-catenin fluorescence was significantly lower in wounded cells than in adjacent uninjured cells in both phenotypes, and the decrease was significantly greater in RPAEC compared to RPMVEC in both scratched (57% vs. 30%) and stretched (55% vs. 37%) cells. Using immunoprecipitation, VE-cadherin-associated beta-catenin decreased significantly in RPAEC (61%) but E-cadherin-associated beta-catenin was not significantly decreased in RPMVEC after 34% biaxial cyclical strain. These data suggest that RPAEC more readily remodel cell-cell adhesions during cyclical stretch than RPMVEC and that a reduced intercellular adhesion adjacent to wounded cells could serve as transvascular leak sites in both phenotypes.


Assuntos
Células Endoteliais/fisiologia , Pulmão/irrigação sanguínea , Artéria Pulmonar/fisiologia , Adaptação Fisiológica , Animais , Caderinas/metabolismo , Permeabilidade Capilar , Forma Celular , Células Endoteliais/citologia , Microcirculação/citologia , Microcirculação/lesões , Microcirculação/fisiologia , Artéria Pulmonar/citologia , Artéria Pulmonar/lesões , Ratos , Estresse Mecânico , beta Catenina/metabolismo
11.
J Thromb Haemost ; 3(9): 2015-21, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16102108

RESUMO

Fibrin (Fn) cross-linking by activated factor (F) XIII is essential for clot stability. In vitro, a common Leu34 polymorphism of the FXIIIA-subunit increases the rate of thrombin-mediated FXIII activation, but not cross-linking activity upon complete FXIII activation. The effect of FXIII Val34Leu polymorphism on fibrin(ogen) cross-linking in vivo when vascular injury triggers the blood coagulation has not been studied yet. Using quantitative immunoblotting with antibodies raised against FXIIIA-subunits, fibrinogen, and gamma-gamma-dimers, the rates of FXIIIA cleavage and fibrin(ogen) cross-link formation in the fluid phase of 30-s blood samples collected at the site of microvascular injury were compared in the Leu34-positive and -negative healthy individuals and patients on long-term oral anticoagulation. In addition to accelerated FXIII activation, in healthy subjects the presence of FXIII Leu34 allele was associated with increased soluble gamma-gamma-dimer formation by 40% (1355 +/- 17 microg L(-1) for Leu34 carriers vs. 804.3 +/- 17 microg L(-1) for Leu34 non-carriers; P = 0.028) at the site of microvascular injury. This solution phase effect was abolished in coumadin-treated patients (369.4 +/- 75.9 microg L(-1) for Leu34 carriers vs. 290.5 +/- 35.9 microg L(-1) for Leu34 non-carriers; P > 0.05). The present study indicates that the Leu34 allele affects soluble gamma-gamma-dimer formation in untreated individuals, but not in those receiving acenocoumarol. Our data may help elucidate the impact of the FXIII Val34Leu polymorphism on Fn cross-linking in vivo and its modulation by oral anticoagulants.


Assuntos
Fator XIII/genética , Microcirculação/lesões , Mutação de Sentido Incorreto , Varfarina/farmacologia , Adulto , Anticoagulantes/farmacologia , Anticoagulantes/uso terapêutico , Fator XIII/metabolismo , Feminino , Fibrina/metabolismo , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Subunidades Proteicas/metabolismo , Varfarina/uso terapêutico
12.
J Bone Joint Surg Am ; 87(7): 1464-9, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15995112

RESUMO

BACKGROUND: Repetitive trauma to the hand is a concern for baseball players. The present study investigated the effects of repetitive trauma and the prevalence of microvascular pathological changes in the hands of minor league professional baseball players. In contrast to previous investigators, we documented the presence of abnormalities in younger, asymptomatic individuals. METHODS: Thirty-six baseball players on active minor league rosters underwent a history and physical examination of both hands as well as additional specialized tests, including Doppler ultrasound, a timed Allen test, determination of digital brachial pressure indices, and ring sizing of fingers. Data were compared between gloved hands and throwing hands, hitters and nonhitters, and players at four different positions (catcher [nine subjects], outfielder [seven subjects], infielder [five subjects], and pitcher [fifteen subjects]). RESULTS: Digital brachial indices in the ring fingers of the gloved (p < 0.05) and throwing hands (p < 0.02) of catchers were significantly diminished compared with those in all other players. Doppler testing showed a significantly greater prevalence of abnormal flow in the ulnar artery at Guyon's canal when catchers were compared with other position players (p < 0.01). Doppler abnormalities were significantly more common in the gloved hand compared with the throwing hand (p < 0.05). Seven of nine catchers (and only catchers) were found to have index finger hypertrophy (average change, two ring sizes; p < 0.01); the hypertrophy occurred at the proximal phalanx and the proximal interphalangeal joint of the gloved hand. Catchers had a significantly higher prevalence of subjective hand symptoms (specifically, weakness in the gloved hand) compared with pitchers and infielders/outfielders (44% compared with 7% and 17%, respectively; p < 0.05). CONCLUSIONS: Microvascular changes are present in the hands of otherwise healthy professional baseball players in all positions, with a significantly higher prevalence in catchers, prior to the development of clinically important ischemia. Repetitive trauma resulting from the impact of the baseball also leads to digital hypertrophy in the index finger of the gloved hand of catchers. Gloves currently used by professional catchers do not adequately protect the hand from repetitive trauma.


Assuntos
Traumatismos em Atletas/complicações , Transtornos Traumáticos Cumulativos/diagnóstico , Dedos/irrigação sanguínea , Isquemia/etiologia , Doenças Vasculares/diagnóstico , Adulto , Beisebol/lesões , Transtornos Traumáticos Cumulativos/etiologia , Mãos/irrigação sanguínea , Humanos , Masculino , Microcirculação/lesões , Doenças Vasculares/etiologia
13.
Lasers Med Sci ; 19(4): 257-61, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15915555

RESUMO

During the process of photodynamic therapy (PDT), problems arise such as stasis or occlusion of microvasculature, tumor oxygen depletion, and photosensitizer bleaching. This study shows that the first problem could be reduced by using a lower fluence rate light source in PDT. Microvasculature damage was studied experimentally in hematoporphyrin derivative-mediated PDT against light fluence rate, and, to some extent, less microvasculature damage was induced under 75 mW/cm2 illumination than under 150 mW/cm2. Histology of vessels at the end of PDT showed that vessel damage could be observed in both groups, indicating that the microvasculature would eventually be damaged as long as the administration of light fluence was sufficient and regardless of the illuminating fluence rates. Thus microvasculature damage induced by low fluence rate illumination could also be effective in tumor control after PDT. The cell-killing experiment was performed in vitro and designed so that cell-killing rate was influenced only by light characteristics. The higher cell-killing rate caused by 75 mW/cm2 illumination indicated that lower fluence rate light could enhance the light absorbency or decrease the bleaching of photosensitizer.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Condrossarcoma/tratamento farmacológico , Neoplasias Mamárias Experimentais/tratamento farmacológico , Microcirculação/efeitos dos fármacos , Fotoquimioterapia/métodos , Animais , Neoplasias Ósseas/patologia , Morte Celular , Condrossarcoma/patologia , Contagem de Eritrócitos , Neoplasias Mamárias Experimentais/patologia , Microcirculação/lesões , Ratos , Ratos Wistar , Células Tumorais Cultivadas
14.
Kidney Int ; 67(1): 130-9, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15610236

RESUMO

BACKGROUND: The antineutrophil cytoplasmic antibody (ANCA)-positive vasculitides are characterized by a necrotizing vasculitis of small vessels with neutrophil infiltration. The reasons behind the selectivity for small vessels remain unclear, but may relate to the necessity for neutrophils to deform in order to pass through capillaries. The resistance to deformation of neutrophils largely arises from their actin cytoskeleton. It is hypothesized that ANCA, by inducing actin polymerization, increases neutrophil rigidity and contributes to their sequestration in capillaries. METHODS: To test this hypothesis, neutrophils were treated with IgG-ANCA and the following characterizations: formation of filamentous F-actin (by flow cytometry); changes in morphology (by fluorescence and electron microscopy); and the potential to obstruct microvessels (by measuring entry times into micropipettes with comparable diameters to capillaries). The neutrophil signaling mechanisms activated by IgG-ANCA were investigated using blocking antibodies to Fcgamma receptors and inhibitors of tyrosine phosphorylation. Protein tyrosine phosphorylation was examined by immunoblotting of cell lysates, and calcium fluxes were measured by spectrofluorimetry of Fura-2 pentakis (acetoxymethyl) ester (Fura 2-AM) labeled neutrophils. RESULTS: IgG-ANCA led to a significant dose-dependent actin polymerization over about 10 minutes. Over the same period, neutrophils became distorted in shape and more resistant to micropipette aspiration. Treatment with normal IgG caused less marked and delayed changes in these parameters. Actin polymerization required engagement of FcgammaRIIa receptor, tyrosine phosphorylation, and calcium fluxes. CONCLUSION: These novel findings reveal signaling mechanisms that underlie ANCA-induced actin polymerization and might explain the predilection for small vessels in IgG-ANCA-associated vasculitis.


Assuntos
Actinas/metabolismo , Anticorpos Anticitoplasma de Neutrófilos/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Actinas/química , Anticorpos Anticitoplasma de Neutrófilos/farmacologia , Biopolímeros/química , Biopolímeros/metabolismo , Sinalização do Cálcio , Forma Celular , Humanos , Imunoglobulina G/metabolismo , Imunoglobulina G/farmacologia , Técnicas In Vitro , Microcirculação/imunologia , Microcirculação/lesões , Microcirculação/metabolismo , Microscopia Eletrônica , Microscopia de Fluorescência , Neutrófilos/efeitos dos fármacos , Neutrófilos/ultraestrutura , Fosforilação , Receptores de IgG/metabolismo , Transdução de Sinais , Tirosina/química , Vasculite/etiologia , Vasculite/imunologia , Vasculite/metabolismo
15.
Lasers Med Sci ; 19(3): 150-4, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15517451

RESUMO

During the process of photodynamic therapy (PDT), problems arise such as stasis or occlusion of microvasculature, tumor oxygen depletion, and photosensitizer bleaching. This study shows that the first problem could be reduced by using a lower fluence rate light source in PDT. Microvasculature damage was studied experimentally in hematoporphyrin derivative-mediated PDT against light fluence rate, and, to some extent, less microvasculature damage was induced under 75 mW/cm(2) illumination than under 150 mW/cm(2). Histology of vessels at the end of PDT showed that vessel damage could be observed in both groups, indicating that the microvasculature would eventually be damaged as long as the administration of light fluence was sufficient and regardless of the illuminating fluence rates. Thus microvasculature damage induced by low fluence rate illumination could also be effective in tumor control after PDT. The cell-killing experiment was performed in vitro and designed so that cell-killing rate was influenced only by light characteristics. The higher cell-killing rate caused by 75 mW/cm(2) illumination indicated that lower fluence rate light could enhance the light absorbency or decrease the bleaching of photosensitizer.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Condrossarcoma/tratamento farmacológico , Neoplasias Mamárias Experimentais/tratamento farmacológico , Microcirculação/efeitos dos fármacos , Fotoquimioterapia/métodos , Animais , Neoplasias Ósseas/patologia , Morte Celular , Condrossarcoma/patologia , Contagem de Eritrócitos , Neoplasias Mamárias Experimentais/patologia , Microcirculação/lesões , Ratos , Ratos Wistar , Células Tumorais Cultivadas
16.
Int J Cardiol ; 96(3): 389-96, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15301892

RESUMO

BACKGROUND: In a significant proportion of patients with acute myocardial infarction (AMI), successful opening of the infarct related artery (IRA) does not translate into adequate perfusion at the tissue level. We hypothesised that deterioration of epicardial blood flow in early reperfusion may identify early signs of coronary microvascular injury. METHODS: In 272 consecutive patients (age 56.9+/-10.4 years) with AMI treated by primary angioplasty (PCI), coronary blood flow (Trombolysis in Myocardial Infarction (TIMI) scale and corrected TIMI frame count (cTFC)) was evaluated before [B], immediately after [O] and 15 min after [O15] opening of the IRA. The sum of ST-segment elevation in standard ECG leads (sigmaST) was measured at [B], at [O15] and 24 h after [C24]. Microvascular injury was assessed by indexes STi(O15)=sigmaST(O15)/sigmaST(B), STi(C24)=sigmaST(C24)/sigmaST(B), and by peak CK-MB release. Coronary flow deterioration (cTFC(DET)) was defined as the difference between cTFC(O15) and cTFC(O). RESULTS: TIMI-3 flow was achieved in 236 (90.8%) patients at [O]. In the early phase of reperfusion (between [O] and [O15]), TIMI flow deteriorated by >/=1 point in 19 (7.3%) patients despite angiographic optimisation of the PCI result. At [O15] 224 (86.2%) patients had TIMI-3 flow (reflow), 36 (13.8%) patients had TIMI

Assuntos
Angioplastia Coronária com Balão , Circulação Coronária/fisiologia , Microcirculação/lesões , Infarto do Miocárdio/fisiopatologia , Pericárdio/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Microcirculação/diagnóstico por imagem , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/terapia , Reperfusão Miocárdica , Pericárdio/diagnóstico por imagem , Radiografia , Fatores de Tempo
17.
Lasers Surg Med ; 34(5): 407-13, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15216534

RESUMO

BACKGROUND AND OBJECTIVES: The degree of port wine stain (PWS) blanching following pulsed dye laser (PDL) therapy remains variable and unpredictable. Because of the limitations of current PDL therapy, alternative treatment approaches should be explored. The objective was to evaluate a novel methodology for selective vascular damage, combined photodynamic (PDT) and photothermal (PDL) treatment, using the in vivo chick chorioallantoic membrane (CAM) model. STUDY DESIGN/MATERIALS AND METHODS: Thirty microliters of benzoporphyrin derivative monoacid ring A (BPD) solution was administered intraperitoneally into chick embryos at day 12 of development. Study groups were: (1) control (no BPD, no light); (2) BPD alone; (3) continuous wave irradiation (CW) alone (576 nm, 60 mW/cm2, 125 seconds); (4) CW + PDL; (5) BPD+PDL; (6) PDT (BPD+CW); (7) PDL alone (585 nm, 4 J/cm(2)); and (8) PDT+PDL (BPD + CW followed immediately by PDL). Vessels were videotaped prior to, and at 1 hour post-intervention and then assessed for damage based on the following scale: 0, no damage; 1, coagulation; 1.5, vasoconstriction; 2.0, coagulation+vasoconstriction; 2.5, angiostasis; 3.0, hemorrhage. Damage scores were weighted by vessel "order." RESULTS: PDT + PDL resulted in significantly (P < 0.01) more severe vascular damage than was observed in any other study group: 127% more than PDT, 47% more than PDL alone. CONCLUSIONS: PDT + PDL is a novel and promising approach for selective vascular damage and may offer a more effective method for treatment of PWS and other vascular skin lesions.


Assuntos
Terapia com Luz de Baixa Intensidade/efeitos adversos , Microcirculação/patologia , Fotoquimioterapia/efeitos adversos , Alantoína , Animais , Embrião de Galinha , Córion/irrigação sanguínea , Terapia Combinada , Microcirculação/efeitos dos fármacos , Microcirculação/lesões , Microcirculação/efeitos da radiação , Microscopia de Vídeo , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Verteporfina
18.
Microcirculation ; 10(5): 391-400, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14557822

RESUMO

OBJECTIVE: The hepatic toxic response to acetaminophen (APAP) is characterized by centrilobular (CL) necrosis preceded by hepatic microvascular injury and congestion. The present study was conducted to examine changes in liver microcirculation after APAP dosing. METHODS: Male C57Bl/6 mice were treated with APAP (600 mg/kg body weight) by oral gavage. The livers of anesthetized mice were examined using established in vivo microscopic methods at 0, 0.5, 1, 2, 4, 6, 12 hours after APAP. RESULTS: The levels of hepatic transaminases (i.e., alanine aminotransferase [ALT] and aspartate transaminase) increased minimally for up to 2 hours. Thereafter, their levels were significantly and progressively increased. The numbers of swollen sinusoidal endothelial cells (SECs) in periportal regions were increased (3.5-fold) from 0.5 to 6 hours, and those in CL regions were increased (4.0-fold) at 0.5 and 1 hour. The intensity of in vivo staining for formaldehyde-treated serum albumin, which is a specific ligand for SECs, was reduced from 2 to 12 hours. Erythrocytes infiltrated into the space of Disse as early as 2 hours, and the area occupied by these cells was markedly increased at 6 hours. Sinusoidal perfusion was reduced from 1 through 12 hours, with a nadir (35% decrease) at 4 and 6 hours. Phagocytic Kupffer cell activity was significantly elevated from 0.5 through 12 hours. Although gadolinium chloride minimized the changes in sinusoidal blood flow and reduced ALT levels 6 hours after APAP, it failed to inhibit endothelial swelling, extravasation of erythrocytes, and CL parenchymal necrosis. CONCLUSIONS: These results confirm that APAP-induced SEC injury precedes hepatocellular injury, supporting the hypothesis that SECs are an early and direct target for APAP toxicity. These findings also suggest that reduced sinusoidal perfusion and increased Kupffer cell activity contribute to the development of APAP-induced liver injury.


Assuntos
Acetaminofen/toxicidade , Fígado/irrigação sanguínea , Fígado/lesões , Acetaminofen/administração & dosagem , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/patologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microcirculação/efeitos dos fármacos , Microcirculação/lesões , Microcirculação/patologia , Fatores de Tempo
19.
Shock ; 18(5): 423-7, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12412620

RESUMO

The generation of oxygen radicals during leukocyte-endothelial cell interaction is considered to represent one of the fundamental steps of microvascular injury following ischemia and reperfusion. Indirect evidence also suggests that this relationship may be important following hemorrhagic shock. The purpose of this study was to characterize the temporal changes of reactive oxygen species (ROS) in the mesenteric microvascular endothelium, in vivo, as a consequence of hemorrhagic shock and reperfusion, and to correlate this ROS production to leukocyte adherence. Following a control period, blood was withdrawn to reduce the mean arterial pressure to 40 mmHg for 1 h in urethane-anesthetized rats. Mesenteric venules in a transilluminated segment of small intestine were examined to quantitate changes in ROS generation and leukocyte adherence. Sprague-Dawley rats were injected with dihydrorhodamine 123, a hydroperoxide-sensitive fluorescent probe that is trapped within viable cells as a nonfluorescent form and then converted to the mitochondrion-selective form rhodamine 123 by hydroperoxides. The fluorescent light emission from rhodamine 123 was recorded with digital microscopy and downloaded to a computerized image analysis program. Our results demonstrated an 80% increase in ROS generation beginning within 5 min into resuscitation and a 10-fold increase in leukocyte adherence that occurred at 10 min after resuscitation. Both ROS generation and leukocyte adherence were attenuated with pre-shock administration of platelet activating factor (PAF) antagonist, WEB 2086, and the CD11/CD18a antibody, anti-LFA-1beta. Our findings suggest that ROS production in endothelial cells is increased during reperfusion following hemorrhagic shock and that the mechanism of expression is mediated in part by both PAF expression and subsequent leukocyte adherence.


Assuntos
Endotélio Vascular/patologia , Leucócitos/patologia , Espécies Reativas de Oxigênio/metabolismo , Choque Hemorrágico/metabolismo , Choque Hemorrágico/patologia , Animais , Azepinas/farmacologia , Adesão Celular , Corantes Fluorescentes , Antígeno-1 Associado à Função Linfocitária/fisiologia , Masculino , Microcirculação/lesões , Microcirculação/metabolismo , Microcirculação/patologia , Fator de Ativação de Plaquetas/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Ressuscitação , Rodaminas , Triazóis/farmacologia
20.
Eur J Med Res ; 6(6): 231-4, 2001 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-11432795

RESUMO

We report on the use of OPS imaging to visualize the microcirculation in a burn wound. This novel technique produces high quality images of the microcirculation and quantitative analysis of functional capillary density (FCD) was possible. FCD measured at day 3 following the injury was 11.2 +/- 4.6 (n/mm superset2; mean +/- SEM). During the initial phase of healing microcirculatory changes were characterized by a moderate but steady increase of FCD, which showed marked increase beginning from day 12 following the burn (16.6 +/- 6.9). Maximal FCD measured at day 23 (48.2 +/- 19.7) decreased from this point in time to finally reach 25.2 +/- 10.3 n/mm superset2 at the end of observation. OPS imaging allows for direct in vivo visualization and quantification of the microcirculation in burned skin. Our results of the use of OPS imaging in assessing the microcirculation in a burn wound appear promising, and we hope that this novel technique will allow to improve the knowledge of the dynamics of the microcirculation in the pathophysiology of thermal injury.


Assuntos
Queimaduras/fisiopatologia , Microcirculação/lesões , Microscopia de Polarização/métodos , Adulto , Queimaduras/diagnóstico , Queimaduras/patologia , Queimaduras/cirurgia , Humanos , Masculino , Microcirculação/patologia , Microcirculação/fisiopatologia , Microscopia de Polarização/instrumentação
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