Facilitation of renal autoregulation by angiotensin II is mediated through modulation of nitric oxide

Aims: This study was designed to investigate the influence of angiotensin II (Ang II) and nitric oxide (NO) on autoregulation of renal perfusion. Methods: Autoregulation was investigated in isolated perfused kidneys (IPRK) from Sprague-Dawley rats during stepped increases in perfusion pressure. Results: Ang II (75-200 pM) produced dose-dependent enhancement of autoregulation whereas phenylephrine produced no enhancement and impaired autoregulation of GFR. Enhancement by Ang II was inhibited by the AT(1) antagonist, Losartan, and the superoxide scavenger, Tempol. Under control conditions nitric oxide synthase (NOS) inhibition by 10 muM N-omega-nitro-L-arginine methyl ester (L-NAME) facilitated autoregulation in the presence of non-specific cyclooxygenase (COX) inhibition by 10 muM indomethacin. Both COX and combined NOS/COX inhibition reduced the autoregulatory threshold concentration of Ang II. Facilitation by 100 pM Ang II was inhibited by 100 muM frusemide. Methacholine (50 nM) antagonised Ang II-facilitated autoregulation in the presence and absence of NOS/COX inhibition. Infusion of the NO donor, 1 muM sodium nitroprusside, inhibited L-NAME enhancement of autoregulation under control conditions and during Ang II infusion. Conclusions: The results suggest than an excess of NO impairs autoregulation under control conditions in the IPRK and that endogenous and exogenous NO, vasodilatory prostaglandins and endothelium-derived hyperpolarizing factor (EDHF) activity antagonise Ang II-facilitated autoregulation. Ang II also produced a counterregulatory vasodilatory response that included prostaglandin and NO release. We suggest that Ang II facilitates autoregulation by a tubuloglomerular feedback-dependent mechanism through AT(1) receptor-mediated depletion of nitric oxide, probably by stimulating generation of superoxide.

Capillaries within compartments: Microvascular interpretation of dynamic positron emission tomography data

Measurement of exchange of substances between blood and tissue has been a long-lasting challenge to physiologists, and considerable theoretical and experimental accomplishments were achieved before the development of the positron emission tomography (PET). Today, when modeling data from modern PET scanners, little use is made of earlier microvascular research in the compartmental models, which have become the standard model by which the vast majority of dynamic PET data are analysed. However, modern PET scanners provide data with a sufficient temporal resolution and good counting statistics to allow estimation of parameters in models with more physiological realism. We explore the standard compartmental model and find that incorporation of blood flow leads to paradoxes, such as kinetic rate constants being time-dependent, and tracers being cleared from a capillary faster than they can be supplied by blood flow. The inability of the standard model to incorporate blood flow consequently raises a need for models that include more physiology, and we develop microvascular models which remove the inconsistencies. The microvascular models can be regarded as a revision of the input function. Whereas the standard model uses the organ inlet concentration as the concentration throughout the vascular compartment, we consider models that make use of spatial averaging of the concentrations in the capillary volume, which is what the PET scanner actually registers. The microvascular models are developed for both single- and multi-capillary systems and include effects of non-exchanging vessels. They are suitable for analysing dynamic PET data from any capillary bed using either intravascular or diffusible tracers, in terms of physiological parameters which include regional blood flow. (C) 2003 Elsevier Ltd. All rights reserved.

A model to investigate hepatic extraction of oxygen during anaesthesia in the dog

Measurement of hepatic oxygen extraction was performed on six healthy Greyhound dogs over a two hour period. The Greyhounds were anaesthetised and a right subcostal surgical incision performed. Ultrasonic flow transducers were used to measure flow rate in the hepatic artery and the portal vein. The blood oxygen tensions in arterial blood and in the portal and hepatic veins were also measured. Hepatic oxygen extraction remained stable throughout the study, despite a steady decline in arterial blood pressure. The methodology described in this study provides a direct measure of oxygen uptake by the liver in the dog and could readily be used to investigate hepatic uptake of drugs. (C) 2003 Elsevier Ltd. All rights reserved.

Endogenous angiotensin II modulates nNOS expression in renovascular hypertension

Nitric oxide (NO) influences renal blood flow mainly as a result of neuronal nitric oxide synthase (nNOS). Nevertheless, it is unclear how nNOS expression is modulated by endogenous angiotensin II, an inhibitor of NO function. We tested the hypothesis that the angiotensin II AT1 receptor and oxidative stress mediated by NADPH oxidase contribute to the modulation of renal nNOS expression in two-kidney, one-clip (2K1C) hypertensive rats. Experiments were performed on male Wistar rats (150 to 170 g body weight) divided into 2K1C (N = 19) and sham-operated (N = 19) groups. nNOS expression in kidneys of 2K1C hypertensive rats (N = 9) was compared by Western blotting to that of 2K1C rats treated with low doses of the AT1 antagonist losartan (10 mg·kg-1·day-1; N = 5) or the superoxide scavenger tempol (0.2 mmol·kg-1·day-1; N = 5), which still remain hypertensive. After 28 days, nNOS expression was significantly increased by 1.7-fold in the clipped kidneys of 2K1C rats and by 3-fold in the non-clipped kidneys of 2K1C rats compared with sham rats, but was normalized by losartan. With tempol treatment, nNOS expression increased 2-fold in the clipped kidneys and 1.4-fold in the non-clipped kidneys compared with sham rats. The changes in nNOS expression were not followed by changes in the enzyme activity, as measured indirectly by the cGMP method. In conclusion, AT1 receptors and oxidative stress seem to be primary stimuli for increased nNOS expression, but this up-regulation does not result in higher enzyme activity.

Endocardite infecciosa e acidente vascular cerebral: mecanismos fisiopatológicos e avaliação ultrassonográfica

Uma das mais graves complicações da endocardite infecciosa é o acidente vascular cerebral isquémico, responsável por uma alta taxa de mortalidade e morbilidade nos países desenvolvidos. Embora não seja o mecanismo dominante, o cardioembolismo é responsável por cerca de 20% dos enfartes cerebrais isquémicos. Sabe-se que o embolismo cerebral afeta mais de 40% dos pacientes com endocardite infecciosa, uma vez que a embolização da vegetação resultante da infeção das estruturas intracardíacas para a circulação arterial pode levar à oclusão das artérias cerebrais, dando origem, assim, a enfarte por ausência de aporte sanguíneo. O desenvolvimento de técnicas não invasivas baseadas na ultrassonografia tem potenciado um amplo estudo destas patologias, quer a nível cardíaco, quer vascular, promovendo uma melhor compreensão dos mecanismos fisiopatológicos que as envolvem. A ecocardiografia e o Doppler transcraniano detêm um papel central, respetivamente, no diagnóstico e predição do risco de fenómenos embólicos em pacientes com endocardite infecciosa e na avaliação inicial, prognóstico e follow-up de um episódio de acidente vascular cerebral.

Factors associated with arterial stiffness in children aged 9-10 years

OBJECTIVE To analyze the factors associated with stiffness of the great arteries in prepubertal children.METHODS This study with convenience sample of 231 schoolchildren aged 9-10 years enrolled in public and private schools in Vitória, ES, Southeastern Brazil, in 2010-2011. Anthropometric and hemodynamic data, blood pressure, and pulse wave velocity in the carotid-femoral segment were obtained. Data on current and previous health conditions were obtained by questionnaire and notes on the child’s health card. Multiple linear regression was applied to identify the partial and total contribution of the factors in determining the pulse wave velocity values.RESULTS Among the students, 50.2% were female and 55.4% were 10 years old. Among those classified in the last tertile of pulse wave velocity, 60.0% were overweight, with higher mean blood pressure, waist circumference, and waist-to-height ratio. Birth weight was not associated with pulse wave velocity. After multiple linear regression analysis, body mass index (BMI) and diastolic blood pressure remained in the model.CONCLUSIONS BMI was the most important factor in determining arterial stiffness in children aged 9-10 years.

The effects of clinical support surfaces on pressure as a risk factor in the development of pressure ulcers, from a radiographical perspective: a narrative literature review

Purpose: Pressure ulcers are a high cost, high volume issue for health and medical care providers, having a detrimental effect on patients and relatives. Pressure ulcer prevention is widely covered in the literature, but little has been published regarding the risk to patients in the radiographical setting. This review of the current literature is to identify findings relevant to radiographical context. Methods: Literature searching was performed using Science Direct and Medline databases. The search was limited to articles published in the last ten years to remain current and excluded studies containing participants less than 17 years of age. In total 14 studies were acquired; three were excluded as they were not relevant. The remaining 11 studies were compared and reviewed. Discussion: Eight of the studies used ‘healthy’ participants and three used symptomatic participants. Nine studies explored interface pressure with a range of pressure mat technologies, two studies measured shear (MRI finite element modelling, and a non-invasive instrument), and one looked at blood flow and haemoglobin oxygenation. A range of surfaces were considered from trauma, nursing and surgical backgrounds for their ability to reduce pressure including standard mattresses, high specification mattresses, rigid and soft layer spine boards, various overlays (gel, air filled, foam). Conclusion: The current literature is not appropriate for the radiographic patient and cannot be extrapolated to a radiologic context. Sufficient evidence is presented in this review to support the need for further work specific to radiography in order to minimise the development of PU in at risk patients.

Automatic sleep apnea detection and sleep classification using the ECG and the SpO2 signals

Dissertation for a Masters Degree in Computer and Electronic Engineering

Imaging in neurological and vascular brain diseases (SPECT and SPECT/CT)

Since the first in vivo studies of cerebral function with radionuclides by Ingvar and Lassen, nuclear medicine (NM) brain applications have evolved dramatically, with marked improvements in both methods and tracers. Consequently it is now possible to assess not only cerebral blood flow and energy metabolism but also neurotransmission. Planar functional imaging was soon substituted by single-photon emission computed tomography (SPECT) and positron emission tomography (PET); it now has limited application in brain imaging, being reserved for the assessment of brain death.

Radiopharmaceuticals for myocardial perfusion imaging: SPECT & PET

Myocardial perfusion imaging (MPI) is used on a daily basis to access coronary blood flow in patients that are suspected or have known Coronary Artery Disease (CAD). A Single Photon Emission Computed Tomography (SPECT) or and Positron Emission Tomography (PET) scan are used to access regional blood flow quantification either at rest or stress, the imaging acquisition is connected to an Electrocardiogram (ECG) and it is able to determine and quantify other myocardial parameters like myocardial wall thickness and wall motion. PET is not used so broadly due to its high procedure cost, the proximity with cyclotron, where are produced the majority of radiopharmaceuticals used in PET, due to their shor thalf-life. This work is intended to carry out a review of the tests relating to radiopharmaceuticals that are used in clinical practice in SPECT or PET for assessment of myocardial perfusion, also focusing very promising radiopharmaceuticals that are under investigation or in clinical trials with great potential for conventional nuclear medicine or PET, proceeding to a comparative analysis of both techniques and respective radiopharmaceuticals used.

Functional studies on magnetic resonance

Dissertation submitted in Faculdade de Ciências e Tecnologia of Universidade Nova de Lisboa for the degree of Master in Biomedical Engineering

Cardiac Angiosarcoma. A Review

Based on a case of a patient with angiosarcoma (AS) of the right atrium with superior vena cava syndrome associated with urticaria and polyarthralgias, who died soon after surgery, the authors present a brief review of the subject of cardiac AS, an extremely rare pathology, usually diagnosed late due to its non-specific symptomatology. Several topics are discussed, including mechanisms of clinical manifestations caused by blood flow obstruction and valve dysfunction, local invasion with arrhythmias and pericardial effusion, embolic phenomena and constitutional symptoms. Imaging and histopathologic methods of diagnosis are considered, as well as references to cytogenetic analysis. Surgery is the first treatment choice, but heart AS are frequently not completely resectable and concomitant metastases at the time of surgery are common, both usually leading to a dismal prognosis. Chemotherapy, radiotherapy and even heart transplantation do not substantially improve the survival of these patients. Urticaria is not generally assumed by most authors to be associated with malignancy, but there are rare reports of its association with some malignant tumors.

Disturbed Correlation Between Arterial Resistance and Pulsatility in Glaucoma Patients

PURPOSE: (i) To investigate whether pulsatility index (PI) and mean flow velocities (MFV) are altered in glaucoma patients. (ii) To evaluate the significance of PI in retrobulbar autoregulation capacity. METHODS: Patients with primary open-angle glaucoma (POAG; n = 49), normal tension glaucoma (NTG; n = 62) and healthy controls (n = 48) underwent colour Doppler imaging measurements of the retrobulbar vasculature. Kruskal-Wallis test was used to compare variables between the three diagnostic groups. Restricted cubic splines were used to determine nonlinearities between the resistive index (RI) and PI correlations. RESULTS: Mean flow velocities (MFV) were lower in both short posterior ciliary arteries (SCPA) and central retinal arteries (CRA) from the two glaucoma groups (p < 0.04 versus healthy controls). No differences were detected in RI or PI in any arteries of the three diagnostic groups (p > 0.08). In healthy individuals, correlations between RI and PI were linear in all arteries. In both POAG and NTG patients, CRA presented a nonlinear curve with a cutpoint at RI 0.77 (p < 0.001) and 0.61 (p = 0.03), respectively, above which the slope increased nearly five- and tenfold (POAG: 1.96 to 10.06; NTG: -0.46-4.06), respectively. A nonlinear correlation in the ophthalmic artery was only observed in NTG patients, with a cutpoint at RI 0.82 (p < 0.001), above which the slope increased from 3.47 to 14.03. CONCLUSIONS: Glaucoma patients do not present the linear relationships between RI and PI observed in healthy individuals. Their nonlinear relations may be indicative of an altered autoregulation and suggest a possible threshold RI could be determined above which autoregulatory disturbances become more relevant.

Lack of Spontaneous Venous Pulsation: Possible Risk Indicator in Normal Tension Glaucoma?

PURPOSE: Recently, the absence of spontaneous venous pulsation (SVP) has been suggested as a vascular risk factor for primary open-angle glaucoma (POAG). As the mechanism behind this phenomenon is still unknown, the authors have studied this vascular component using colour Doppler imaging (CDI). METHODS: A total of 236 patients were divided into three diagnostic groups: healthy controls (81), POAG (86) and normal tension glaucoma (NTG; 69). All subjects were submitted to CDI studies of the retrobulbar circulation, intraocular pressure measurements and assessment of SVP existence. Mann-Whitney, chi-square contingency tables and Spearman correlations were used to explore differences and correlations between variables in the diagnostic groups. RESULTS: Eighty-two percent of healthy controls had SVP (66/81), while a smaller numbers were registered in both glaucoma groups: POAG - 50% (43/86); NTG - 51% (35/69). In NTG patients, but not in POAG patients, the prevalence of the SVP phenomenon decreases with increased glaucoma damage (p = 0.04; p = 0.55, respectively). Overall glaucoma patients from both groups had lower central retinal vein (CRV) velocities than the healthy controls (p < 0.05). NTG patients with SVP had less severe visual field defects (mean defect -6.92 versus -11.1, p < 0.05), higher [correction added after online publication 21 September 2012; the word 'higher' has been inserted to replace the word 'lower'] peak systolic and mean flow velocities in the central retinal artery (p < 0.01; p < 0.05, respectively) as well as higher [correction added after online publication 21 September 2012; the word higher has been inserted to replace the word lower] maximal velocities and RI of the CRV (p < 0.02; p < 0.05, respectively). CONCLUSIONS: Glaucoma patients have a decrease in CRV velocities. SVP is less prevalent in glaucoma patients than in healthy individuals. This phenomenon apparently reflects different hemodynamic patterns in the central retinal vessels. This variable may be of particular importance in NTG patients, where it may be associated with more advanced functional damage.

Anesthesia for Ex Utero Intrapartum Treatment: Renewed Insight on a Rare Procedure

The ex utero intrapartum treatment is a rare surgical procedure performed in cases of expected postpartum fetal airway obstruction. The technique lies on a safe establishment of a patent airway during labor in anticipation of a critical respiratory event, without interrupting maternal-fetal circulation. Anesthetic management is substantially different from that regarding standard cesarean delivery and its main goals include uterine relaxation, fetal anesthesia and preservation of placental blood flow. We present the case of an ex utero intrapartum treatment procedure performed on a fetus with a large cervical lymphangioma and prenatal evidence of airway compromise. Modifications to the classic ex utero intrapartum treatment management strategies were successfully adopted and will be discussed in the following report.