Reduction In Vascular Volume Research Articles

Plocabulin, a novel tubulin-binding agent, inhibits angiogenesis by modulation of microtubule dynamics in endothelial cells

BackgroundVascular supply of tumors is one of the main targets for cancer therapy. Here, we investigated if plocabulin (PM060184), a novel marine-derived microtubule-binding agent, presents antiangiogenic and vascular-disrupting activities.MethodsThe effects of plocabulin on microtubule network and dynamics were studied on HUVEC endothelial cells. We have also studied its effects on capillary tube structures formation or destabilization in three-dimensional collagen matrices. In vivo experiments were performed on different tumor cell lines.ResultsIn vitro studies show that, at picomolar concentrations, plocabulin inhibits microtubule dynamics in endothelial cells. This subsequently disturbs the microtubule network inducing changes in endothelial cell morphology and causing the collapse of angiogenic vessels, or the suppression of the angiogenic process by inhibiting the migration and invasion abilities of endothelial cells. This rapid collapse of the endothelial tubular network in vitro occurs in a concentration-dependent manner and is observed at concentrations lower than that affecting cell survival. The in vitro findings were confirmed in tumor xenografts where plocabulin treatment induced a large reduction in vascular volume and induction of extensive necrosis in tumors, consistent with antivascular effects.ConclusionsAltogether, these data suggest that an antivascular mechanism is contributing to the antitumor activities of plocabulin.

PP113. NT-Pro-BNP: A predictor of adverse maternal outcomes in hypertensive gestational syndromes?

IntroductionBNP (brain-type natriuretic peptide) is released by cardiomyocytes, as a pro-hormone, in response to parietal stress augmentation and systemic endothelial dysfunction, and then Pro-BNP is cleaved into: NT-Pro-BNP and BNP fragment in 1:1 ratio. BNP is considered an important component of the adaptative mechanism that helps to reduce the load on the myocardium, through systemic vasodilatation, reduction in venous return and reduction in vascular volume. Hypertensive Gestational Syndromes (HGS) are considered to share those mechanisms, but the role of NT-Pro-BNP to evaluate maternal outcomes, is not well defined. ObjectivesEvaluate the correlation between NT-Pro-BNP: in Normotensive Pregnant Women (NPW) and HGS with established markers of adverse maternal outcomes in HGS. MethodsWe performed a transversal case–control study to analyze NT-Pro-BNP in 68 patients with HGS vs 80 NPW admitted at a private hospital, and to evaluate its correlation with established clinical and blood markers of maternal outcomes at hospital admission. Patients with renal chronic failure, previous cardiac disease and mola were excluded. We used the Pearson and Kendall correlation test for quantitative variables and the non-parametrical Mann–Whitney test for qualitative variables. ResultsThe average maternal age was: NPW 33.2 years, HGS 33.8 years; average gestational age at delivery: NPW 38.5 weeks, HGS 35.3 weeks; first pregnancy: NPW 36%, HGS 56%; birth average weight: NPW 3351.6g, HGS 2615.5g; media NT-Pro-BNP: NPW 59.7pg/ml, HGS 704.8pg/ml. None of the NPW had high levels of NT-Pro-BNP. In the HGS group: 57% had preeclampsia, 10% HELLP, 25% gestational hypertension and 8% chronic hypertension. In the HGS media values for: proteinuria 1.5g/24h, glutamic-oxalacetic transaminase 86 UI/L, platelets 231,688/mm3, glutamic-pyruvic transaminase 100 UI/L, uric acid 48mg/dl, hematocrit 33%, alkaline phosphatase 152 UI/L, lactic dehydrogenase 284 UI/L. In the HGS the following significant correlations were found: for NT-Pro-BNP relation to: proteinuria (0.34 p=0.001), glutamic–oxalacetic transaminase (0.375 p=0.001), platelets (−0.353 p=0.001), glutamic–pyruvic transaminase (0.317 p=0.001), uric acid (0.398 p=0.001), hematocrit (−0.183 p=0.048), gestational age at delivery (−0.29 p=0.002), birth average weight (−0.23 p=0.018), cardiac failure ( p=0.001), number of used anti-hypertensive drugs (0.367 p=0.004), lactic dehydrogenase (0.65 p=0.001). The media NT-Pro-BNP was: 936pg/ml in preeclampsia , 1909pg/ml in HELLP, 150pg/ml in gestational hypertension and 107pg/ml in chronic hypertension. The highest NT-Pro-BNP level was 12,386pg/ml in a patient with systolic dysfunction (LVEF: 35%) associated with preeclampsia. After delivery, 13% HGS women had persistent hypertension post-partum, and this did not correlate with the level of NT-Pro-BNP at hospital admission. ConclusionNT-Pro-BNP significantly correlates with established markers of adverse maternal outcomes in HGS, probing to be useful in routine maternal evaluation in this setting.

Plasma Concentrations of N-Terminal Pro-B-Type Natriuretic Peptide in Pregnant Women near Labor and during Early Puerperium

B-Type natriuretic peptide (BNP) is considered an important component of the adaptive mechanism that helps reduce the load on the myocardium through systemic vasodilatation, reduction in venous return, and reduction in vascular volume (1). Plasma concentrations of BNP have been shown to reflect cardiac dysfunction and volume overload in adults and children (2)(3)(4). BNP is synthesized in cardiac myocytes as a prohormone, proBNP. The active hormone, BNP, is cleaved and cosecreted from the myocyte along with its N-terminal propeptide (NT-proBNP) (5). NT-proBNP concentrations have been shown to provide information similar to BNP, and the validity of the assay as a clinical tool is well documented (3)(6)(7)(8)(9). Pregnancy represents a state of physiologic volume expansion as maternal blood volume increases ∼40%–45% above nonpregnancy volumes (10). Despite the growing data on the role of BNP in regulation of volume homeostasis, there are few studies regarding its role in pregnancy (11)(12)(13)(14). It has been shown that BNP concentrations are higher in preeclampsia and other hypertensive disorders of pregnancy than in normal pregnancy (11)(12)(14). It has also been suggested that BNP may have a role in regulation of amniotic fluid …

Effects of exercise and inactivity on intravascular volume and cardiovascular control mechanisms

Exercise, inactivity and confinement have been used as effective tools to assess the contributions of vascular volume and baroreflexes to orthostatic hypotension associated with exposure to microgravity. Prolonged exposure to bedrest, physical inactivity, or wheelchair confinement removes baroreceptor unloading caused by regular upright standing and induces attenuation of cardiovascular baroreflex responses. The magnitude of reduced baroreflex sensitivity following bedrest or wheelchair confinement is related to the degree of orthostatic hypotension. Reduction in vascular volume caused by bedrest or progressive hypovolemia does not affect carotid-cardiac baroreflex function. In contrast, intense exercise that increases arterial baroreceptor loading causes an acute increase in carotid baroreceptor sensitivity and has been associated with enhanced orthostatic stability following exposure to simulated microgravity. Endurance exercise training designed to enhance orthostatic stability was associated with increased blood volume and vasoconstrictive reserve, but no change in the carotid baroreflex response. Therefore, using models of exercise, inactivity and confinement, integrated and redundant roles for vascular volume and cardiovascular baroreflexes have been demonstrated as probable underlying mechanisms that contribute independently to the development of orthostatic hypotension following spaceflight. These data suggest that loading of arterial baroreceptors may be necessary to maintain baroreflex function.

Pulmonary Vascular Disease in Acquired and Congenital Heart Disease

This article will describe the unique behavior of the pulmonary circulation under conditions of acute and chronic stress. The four points to be described are as follows: (1) the unique nature and function of the pulmonary vascular bed; (2) the pulmonary vascular response to pulmonary venous hypertension, specifically mitral stenosis; (3) how the pulmonary vessels maintain their basic function, despite a sudden reduction of vascular volume by one half, and while having to contend with high flow, high pressure, or high pulmonary vascular resistance; and (4) the response of the pulmonary vasculature to closure of defects in congenital heart disease. Much of this information has been discussed elsewhere, with extensive bibliographic documentation. 1 PULMONARY VASCULATURE Bronchial arteries nourish the lung and mediastinal structures. The pulmonary arterial system has no metabolic function. Its main purpose is the transport of gases from the body to the pulmonary capillaries (carbon dioxide) and away

CARDIOVASCULAR DIMENSIONS

SummaryMeasurements have been made of the dimensions of the cardiovascular system, i.e., the heart volume in the prone position, the blood volume and the total amount of haemoglobin (THb). The following results are obtained:1. The blood volume is probably significantly lower (10 per cent) than that predicted from the body weight in group I and highly significantly lower in group II (21 per cent) and group III + IV (24 per cent). The mean value in adult patients in group III + IV is only 62.3 ml/kg of body weight.2. The THb is approximately normal in group I, whereas it is significantly lower (–14 per cent) than the value predicted from the body weight in group II and highly significantly lower (–17 per cent) in group III + IV.3. In Friedreich's ataxia, both inactivity and muscular atrophy contribute to a reduction in vascular volume, with a resulting decrease in blood volume and THb.4. The decrease in blood volume and THb is approximately the same in group II as in group III + IV. It is concluded that the wheel‐chair cases approach minimum values for maintenance of an adequate circulation.5. The heart volume in relation to THb is probably significantly increased in group II and significantly in group III + IV. In two wheel‐chair cases a considerable enlargement was recorded.