A dynamic model of neurovascular coupling: Implications for blood vessel dilation and constriction

Neurovascular coupling in response to stimulation of the rat barrel cortex was investigated using concurrent multichannel electrophysiology and laser Doppler flowmetry. The data were used to build a linear dynamic model relating neural activity to blood flow. Local field potential time series were subject to current source density analysis, and the time series of a layer IV sink of the barrel cortex was used as the input to the model. The model output was the time series of the changes in regional cerebral blood flow (CBF). We show that this model can provide excellent fit of the CBF responses for stimulus durations of up to 16 s. The structure of the model consisted of two coupled components representing vascular dilation and constriction. The complex temporal characteristics of the CBF time series were reproduced by the relatively simple balance of these two components. We show that the impulse response obtained under the 16-s duration stimulation condition generalised to provide a good prediction to the data from the shorter duration stimulation conditions. Furthermore, by optimising three out of the total of nine model parameters, the variability in the data can be well accounted for over a wide range of stimulus conditions. By establishing linearity, classic system analysis methods can be used to generate and explore a range of equivalent model structures (e.g., feed-forward or feedback) to guide the experimental investigation of the control of vascular dilation and constriction following stimulation.

Platelet adhesion to podoplanin under flow is mediated by the receptor CLEC-2 and stabilised by Src/Syk-dependent platelet signalling

Platelet-specific deletion of CLEC-2, which signals through Src and Syk kinases, or global deletion of its ligand podoplanin results in blood-filled lymphatics during mouse development. Platelet-specific Syk deficiency phenocopies this defect, indicating that platelet activation is required for lymphatic development. In the present study, we investigated whether CLEC-2-podoplanin interactions could support platelet arrest from blood flow and whether platelet signalling is required for stable platelet adhesion to lymphatic endothelial cells (LECs) and recombinant podoplanin under flow. Perfusion of human or mouse blood over human LEC monolayers led to platelet adhesion and aggregation. Following αIIbβ3 blockade, individual platelets still adhered. Platelet binding occurred at venous but not arterial shear rates. There was no adhesion using CLEC-2-deficient blood or to vascular endothelial cells (which lack podoplanin). Perfusion of human blood over human Fc-podoplanin (hFcPDPN) in the presence of monoclonal antibody IV.3 to block FcγRIIA receptors led to platelet arrest at similar shear rates to those used on LECs. Src and Syk inhibitors significantly reduced global adhesion of human or mouse platelets to LECs and hFcPDPN. A similar result was seen using Syk-deficient mouse platelets. Reduced platelet adhesion was due to a decrease in the stability of binding. In conclusion, our data reveal that CLEC-2 is an adhesive receptor that supports platelet arrest to podoplanin under venous shear. Src/Syk-dependent signalling stabilises platelet adhesion to podoplanin, providing a possible molecular mechanism contributing to the lymphatic defects of Syk-deficient mice.

Cardiovascular actions of rattlesnake bradykinin ([Val(1), Thr(6)] bradykinin) in the anesthetized South American rattlesnake Crotalus durissus terrificus

Incubation of heat-denatured plasma from the rattlesnake Crotalus atrox with trypsin generated a bradykinin (BK) that contained two amino acid substitutions (Arg(1) --> Val and Ser(6) --> Thr) compared with mammalian BK. Bolus intra-arterial injections of synthetic rattlesnake BK (0.01-10 nmol/kg) into the anesthetized rattlesnake, Crotalus durissus terrificus, produced a pronounced and concentration-dependent increase in systemic vascular conductance (Gsys). This caused a fall in systemic arterial blood pressure (Psys) and an increase in blood flow. Heart rate and stroke volume also increased. This primary response was followed by a significant rise in Psys and pronounced tachycardia (secondary response). Pretreatment with N-G-nitro-L-arginine methyl ester reduced the NK-induced systemic vasodilatation, indicating that the effect is mediated through increased NO synthesis. The tachycardia associated with the late primary and secondary response to BK was abolished with propranolol and the systemic vasodilatation produced in the primary phase was also significantly attenuated by pretreatment, indicating that the responses are caused, at least in part, by release of cathecholamines and subsequent stimulation of beta-adrenergic receptors. In contrast, the pulmonary circulation was relatively unresponsive to BK.

Dermatophytosis: association between ABO blood groups and reactivity to the trichophytin

Os autores investigaram a relação entre dermatofitose e grupo sanguíneo ABO através da tipagem sanguínea, identificação do dermatófito isolado e resposta imune celular específica de 40 indivíduos portadores desta micose. Verificaram que o fungo Trichophyton rubrum foi isolado em 54,5% dos pacientes, sendo mais frequente em indivíduos pertencentes ao grupo sanguíneo A. A resposta imune celular, avaliada através do antígeno tricofitina, foi positiva em 25% dos pacientes estudados; a presença de reações imediatas (30 min) foi verificada em 35%. A distribuição dos grupos sanguíneos entre pacientes com dermatofitose e grupo controle foi a seguinte: 47,5% x 36% grupo A, 40% x 50% grupo O, 12,5% x 11% grupo B. Embora os autores tenham encontrado um número maior de pacientes pertencentes ao grupo sanguíneo A e infectados pelo T. rubrum, não obtiveram evidência estatística de que esses indivíduos sejam mais suscetíveis as dermatofitoses.

Efeitos hemodinâmicos e renais da injeção de doses elevadas de clonidina no espaço peridural do cão

JUSTIFICATIVA E OBJETIVOS: Não existem estudos que relatem as repercussões renais determinadas pela injeção de doses elevadas de clonidina no espaço peridural. O objetivo do estudo foi avaliar os efeitos hemodinâmicos e renais determinados pela injeção de doses elevadas de clonidina no espaço peridural do cão. MÉTODO: Vinte animais anestesiados com tiopental sódico e fentanil foram distribuídos aleatoriamente e de forma duplamente encoberta em dois grupos: Grupo 1 ou placebo (n = 10), que recebeu 0,2 mL.kg-1 de solução fisiológica, e Grupo 2 ou clonidina (n = 10), que recebeu 0,2 mL.kg-1 de uma solução contendo 50 µg.mL-1 de clonidina, no espaço peridural. Foram avaliados os seguintes parâmetros hemodinâmicos: freqüência cardíaca (FC): bat.min-1; pressão arterial média (PAM): mmHg; pressão da artéria pulmonar ocluida (PAOP): mmHg; débito cardíaco (DC): L.min-1; volume sistólico (VS): mL; também, os seguintes parâmetros da função renal foram avaliados: fluxo sangüíneo renal (FSR): mL.min-1; resistência vascular renal (RVR): mmHg.mL-1.min; volume urinário minuto (VUM): mL.min-1; depuração de creatinina (D Cr): mL.min-1; depuração de para-aminohipurato (D PAH): mL.min-1; fração de filtração (FF); depuração de sódio (D Na): mL.min-1; depuração de potássio (D K): mL.min-1; excreção fracionária de sódio (EF Na): %; excreção urinária de sódio (U NaV): µEq.min-1; excreção urinária de potássio (U K V): µEq.min-1. O experimento consistiu em três momentos de 20 minutos cada. Os dados foram coletados aos 10 minutos de cada momento e a diurese, no início e no final de cada momento. Ao término de M1, a clonidina ou a solução fisiológica foi administrada no espaço peridural. Após período de 20 minutos iniciou-se M2 e, em seguida, M3. RESULTADOS: A clonidina na dose de 10 µg.kg-1 no espaço peridural do cão promoveu alterações significativas, com diminuições da freqüência cardíaca e do débito cardíaco e aumento da relação depuração de para-aminohipurato de sódio/débito cardíaco. CONCLUSÕES: Nas condições realizadas e nas doses empregadas, pode-se concluir que a clonidina não promoveu alteração da função renal, mas diminuiu valores hemodinâmicos (freqüência e débito cardíaco).

Ecocardiografia de pacientes talassêmicos sem insuficiência cardíaca em tratamento com transfusões sanguíneas e quelação

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The role of nitric oxide in regulation of the cardiovascular system in reptiles

The roles that nitric oxide (NO) plays in the cardiovascular system of reptiles are reviewed, with particular emphasis on its effects on central vascular blood flows in the systemic and pulmonary circulations. New data is presented that describes the effects on hemodynamic variables in varanid lizards of exogenously administered NO via the nitric oxide donor sodium nitroprusside (SNP) and, preliminary data on the effects of SNP inhibition of nitric oxide synthase (NOS) by L-nitroarginine methyl ester (L-NAME). Furthermore. on hemodynamic variables in the tegu lizard are presented. The findings are compared with previously published data from Our laboratory on three other species of reptiles: pythons (Skovgaard, N., Galli, G., Taylor, E.W., Conlon, J.M., Wang.. T., 2005. Hemodynamic effects of python neuropeptide gamma in the anesthetized python, Python regius. Regul. Pept. 18, 15-26), rattlesnakes (Galli, G., Skovgaard, N., Abe, A.S., Taylor, E.W., Wang, T., 2005. The role of nitric oxide in the regulation of the systemic and the pulmonary vasculature of the rattlesnake, Crotalus durissus terrificus. J. Comp. Physiol. 175B, 201-208) and turtles (Crossley, D.A., Wang, T., Altimiras, J., 2000. Role of nitric oxide in the systemic and pulmonary circulation of anesthetized turtles (Trachemys scripta). J. Exp. Zool. 286, 683-689). These five species of reptiles possess different combinations of division of the heart and structural complexity of the lungs. Comparison of their responses to NO donors and NOS inhibitors may reveal whether the potential contribution of NO to vascular tone correlates with pulmonary complexity and/or with blood pressure. All existing studies oil reptiles have clearly established a potential role for NO in regulating vascular tone in the systemic circulation and NO may be important for maintaining basal systemic vascular tone in varanid lizards, pythons and turtles, through a continuous release of NO. In contrast., the pulmonary circulation is less responsive to NO donors or NOS inhibitors, and it was only in pythons and varanid lizards that the lungs responded to SNP. Both species have a functionally separated heart, so it is possible that NO may exert a larger role in species with low pulmonary blood pressures, irrespective of lung complexity. (C) 2005 Elsevier B.V. All rights reserved.

Heat Exchange from the Toucan Bill Reveals a Controllable Vascular Thermal Radiator

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The Heart of the South American Rattlesnake, Crotalus durissus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A mathematical model for wave propagation in elastic tubes with inhomogeneities: Application to blood waves propagation

We study the propagation of waves in an elastic tube filled with an inviscid fluid. We consider the case of inhomogeneity whose mechanical and geometrical properties vary in space. We deduce a system of equations of the Boussinesq type as describing the wave propagation in the tube. Numerical simulations of these equations show that inhomogeneities prevent separation of right-going from left-going waves. Then reflected and transmitted coefficients are obtained in the case of localized constriction and localized rigidity. Next we focus on wavetrains incident on various types of anomalous regions. We show that the existence of anomalous regions modifies the wavetrain patterns. (c) 2007 Elsevier B.V. All rights reserved.

On the cardiac control in the South American lungfish, Lepidosiren paradoxa

1. 1. The mechanisms behind cardiac control were investigated in the South American lungfish, Lepidosiren paradoxa, using fish with chronically implanted cannulae and electromagnetic flow probes. In addition, a preliminary study was made of the cardiovascular events associated with air breathing. 2. 2. The study suggests that the heart of Lepidosiren is controlled by cholinergic vagal fibres which, in some animals, exert a tonic influence in the resting fish. Cyclic changes in heart rate in association with air breaths is due to modulation of this cholinergic tonus. 3. 3. In addition to the variable cholinergic tonus, there appears to be a relatively stable adrenergic tonus on the heart, which causes an elevated heart rate. The adrenergic tonus is likely to be due to local release of catecholamines from endogenous chromaffin cells within the atrium. 4. 4. Preliminary results suggest that pulmonary arterial flow increases by about 50% immediately following an air breath. The mechanism behind this increase probably involves both an elevation of the heart rate and a redistribution of blood flow into the pulmonary circuit. © 1989.

Doppler ultrasonography principles and methods of evaluation of the reproductive tract in mares

Background: Doppler ultrasonography is a non-invasive real time pulse-wave technique recently used for the transrectal study of the reproductive system hemodynamics in large animals. This technic is based in the Doppler Effect Principle that proposes the change in frequency of a wave for an observer (red blood cells) moving relative to the source of the respective wave (ultrasonic transducer). This method had showed to be effective and useful for the evaluation of the in vivo equine reproductive tract increasing the diagnostic, monitoring, and predictive capabilities of theriogenology in mares. However, an accurate and truthful ultrasonic exam requires the previous knowledge of the Doppler ultrasonography principles. Review: In recent years, the capabilities of ultrasound flow imaging have increased enormously. The current Doppler ultrasound machines offer three methods of evaluation that may be used simultaneously (triplex mode). In B-mode ultrasound, a linear array of transducers simultaneously scans a plane through the tissue that can be viewed as a two-dimensional gray-scale image on screen. This mode is primarily used to identify anatomically a structure for its posterior evaluation using colored ultrasound modes (Color or Spectral modes). Colored ultrasound images of flow, whether Color or Spectral modes, are essentially obtained from measurements of moving red cells. In Color mode, velocity information is presented as a color coded overlay on top of a B-mode image, while Pulsed Wave Doppler provides a measure of the changing velocity throughout the cardiac cycle and the distribution of velocities in the sample volume represented by a spectral graphic. Color images conception varies according to the Doppler Frequency that is the difference between the frequency of received echoes by moving blood red cells and wave frequency transmitted by the transducer. To produce an adequate spectral graphic it is important determine the position and size of the simple gate. Furthermore, blood flow velocity measurement is influence by the intersection angle between ultrasonic pulses and the direction of moving blood-red cells (Doppler angle). Objectively colored ultrasound exam may be done on large arteries of the reproductive tract, as uterine and ovary arteries, or directly on the target tissue (follicle, for example). Mesovarium and mesometrium attachment arteries also can be used for spectral evaluation of the equine reproductive system. Subjectively analysis of the ovarian and uterine vascular perfusion must be done directly on the corpus luteum, follicular wall and uterus (endometrium and myometrium associated), respectively. Power-flow imaging has greater sensitivity to weak blood flow and independent of the Doppler angle, improving the evaluation of vessels with small diameters and slow blood flow. Conclusion: Doppler ultrasonography principles, methods of evaluation and reproductive system anatomy have been described. This knowledge is essential for the competent equipment acquisition and precise collection and analysis of colored ultrasound images. Otherwise, the reporting of inconsistent and not reproducible findings may result in the discredit of Doppler technology ahead of the scientific veterinary community.

Continuous measurement of cerebral oxygen saturation (rSO 2) for assessment of cardiovascular status during hemorrhagic shock in a swine model

Background: Early trauma care is dependent on subjective assessments and sporadic vital sign assessments. We hypothesized that near-infrared spectroscopy-measured cerebral oxygenation (regional oxygen saturation [rSO 2]) would provide a tool to detect cardiovascular compromise during active hemorrhage. We compared rSO 2 with invasively measured mixed venous oxygen saturation (SvO2), mean arterial pressure (MAP), cardiac output, heart rate, and calculated pulse pressure. Methods: Six propofol-anesthetized instrumented swine were subjected to a fixed-rate hemorrhage until cardiovascular collapse. rSO 2 was monitored with noninvasively measured cerebral oximetry; SvO2 was measured with a fiber optic pulmonary arterial catheter. As an assessment of the time responsiveness of each variable, we recorded minutes from start of the hemorrhage for each variable achieving a 5%, 10%, 15%, and 20% change compared with baseline. Results: Mean time to cardiovascular collapse was 35 minutes ± 11 minutes (54 ± 17% total blood volume). Cerebral rSO 2 began a steady decline at an average MAP of 78 mm Hg ± 17 mm Hg, well above the expected autoregulatory threshold of cerebral blood flow. The 5%, 10%, and 15% decreases in rSO 2 during hemorrhage occurred at a similar times to SvO2, but rSO 2 lagged 6 minutes behind the equivalent percentage decreases in MAP. There was a higher correlation between rSO 2 versus MAP (R =0.72) than SvO2 versus MAP (R =0.55). Conclusions: Near-infrared spectroscopy- measured rSO 2 provided reproducible decreases during hemorrhage that were similar in time course to invasively measured cardiac output and SvO2 but delayed 5 to 9 minutes compared with MAP and pulse pressure. rSO 2 may provide an earlier warning of worsening hemorrhagic shock for prompt interventions in patients with trauma when continuous arterial BP measurements are unavailable. © 2012 Lippincott Williams & Wilkins.

Ablation of the ability to control the right-to-left cardiac shunt does not affect oxygen uptake, specific dynamic action or growth in the rattlesnake Crotalus durissus

The morphologically undivided ventricle of the heart in non-crocodilian reptiles permits the mixing of oxygen-rich blood returning from the lungs and oxygen-poor blood from the systemic circulation. A possible functional significance for this intra-cardiac shunt has been debated for almost a century. Unilateral left vagotomy rendered the single effective pulmonary artery of the South American rattlesnake, Crotalus durissus, unable to adjust the magnitude of blood flow to the lung. The higher constant perfusion of the lung circulation and the incapability of adjusting the right-left shunt in left-denervated snakes persisted over time, providing a unique model for investigation of the long-term consequences of cardiac shunting in a squamate. Oxygen uptake recorded at rest and during spontaneous and forced activity was not affected by removing control of the cardiac shunt. Furthermore, metabolic rate and energetic balance during the post-prandial metabolic increment, plus the food conversion efficiency and growth rate, were all similarly unaffected. These results show that control of cardiac shunting is not associated with a clear functional advantage in adjusting metabolic rate, effectiveness of digestion or growth rates. © 2013. Published by The Company of Biologists Ltd.

Efeitos determinados pelo pneumoperitônio sobre a hemodinâmica e função renais de cães ventilados com volume e pressão controlados

Pós-graduação em Anestesiologia - FMB