Age-related changes in microvascular permeability: a significant factor in the susceptibility of children to shock?

Gamble, J.; Bethell, Delia; Day, Nicholas P. J.; Loc, Pham Phu; Phu, Nguyen Hoan; Gartside, I B; Farrar, J. F.; White, Nicholas J.

doi:10.1042/cs19990296

Cited by 92 publications

(62 citation statements)

References 16 publications

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“…It is conceivable that some of the larger vessels in this study were occluded by aggregate of smaller-sized microspheres, and/or that contiguous perfusion territories were embolized by individual microspheres, thereby perturbating the accurate relationship between the diameter of the occluded vessel and the extent of vascular permeability. In addition, we studied relatively young pigs, and vascular permeability may be partly age dependent (5,11). Nevertheless, this animal study strongly suggests that patchy occlusion of the coronary microvasculature results in enhanced extravasation of fluids and solutes.…”

Section: Discussionmentioning

confidence: 99%

Relationship between surface area of nonperfused myocardium and extravascular extraction of contrast agent following coronary microembolization

Malyar

Lerman

Gössl

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Malyar NM, Lerman LO, Gössl M, Beighley PE, Ritman EL. Relationship between surface area of nonperfused myocardium and extravascular extraction of contrast agent following coronary microembolization. Am J Physiol Regul Integr Comp Physiol 301: R430-R437, 2011. First published May 4, 2011 doi:10.1152/ajpregu.00428.2010.-Myocardial microvascular permeability and coronary sinus concentration of muscle metabolites have been shown to increase after myocardial ischemia due to epicardial coronary artery occlusion and reperfusion. However, their association with coronary microembolization is not well defined. This study tested the hypothesis that acute coronary microembolization increases microvascular permeability in the porcine heart. The left anterior descending perfusion territories of 34 anesthetized pigs (32 Ϯ 3 kg) were embolized with equal volumes of microspheres of one of three diameters (10, 30, or 100 m) and at three different doses for each size. Electron beam computed tomography (EBCT) was used to assess in vivo, microvascular extraction of a nonionic contrast agent (an index of microvascular permeability) before and after microembolization with microspheres at baseline and during adenosine infusion. A high-resolution three-dimensional microcomputed tomography (micro-CT) scanner was subsequently used to obtain ex vivo, the volume and corresponding surface area of the embolized myocardial islands within the perfusion territories of the microembolized coronary artery. EBCT-derived microvascular extraction of contrast agent increased within minutes after coronary microembolization (P Ͻ 0.001 vs. baseline and vs. control values). The increase in coronary microvascular permeability was highly correlated to the micro-CT-derived total surface area of the nonperfused myocardium (r ϭ 0.83, P Ͻ 0.001). In conclusion, myocardial extravascular accumulation of contrast agent is markedly increased after coronary microembolization and its magnitude is in proportion to the surface area of the interface between the nonperfused and perfused territories. microspheres; EBCT; micro-CT; microvascular permeability A BALANCE BETWEEN DELIVERY of vital nutrients and removal of waste products from the myocardium is pivotal for maintaining the physiological contractile function of the myocytes and for the coordinated electrical conductance along the cells' membranes. However, it has been shown that myocardial microvascular permeability can change under various pathologic and metabolic circumstances such as diabetes mellitus (24, 41), hypercholesterolemia (32), hypertension (31), and acute myocardial ischemia followed by reperfusion (29). Embolization of microscopic plaque debris into the distal coronary bed during coronary interventions is a common and frequent event (9, 10, 35) that might be associated with microinfarctions and with adverse clinical outcome (7, 10).We have previously demonstrated that experimental coronary microembolization leads to a decrease in regional myocardial contractility that is proportional to the surface...

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Section: Discussionmentioning

confidence: 99%

Relationship between surface area of nonperfused myocardium and extravascular extraction of contrast agent following coronary microembolization

Malyar

Lerman

Gössl

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Such infections can result in an acute vascular permeability syndrome known as dengue shock syndrome (DSS). The severity of DSS is age-dependent, with vascular leakage being most severe in young children, a phenomenon that is thought to be related to the intrinsic integrity of the capillaries 26,27 . In adults, primary infections with each of the four DENV serotypes, particularly with DENV-1 and -3, often results in DF.…”

Section: Dengue Virus Pathogenesismentioning

confidence: 99%

Dengue: a continuing global threat

et al. 2010

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Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral diseases. Each year, there are ~50 million dengue infections and ~500,000 individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast Asia, the Pacific and the Americas. Illness is produced by any of the four dengue virus serotypes. A global strategy aimed at increasing the capacity for surveillance and outbreak response, changing behaviours and reducing the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently under development could also make an important contribution to dengue control in the future.Dengue is the most important arthropod-borne viral infection of humans. Worldwide, an estimated 2.5 billion people are at risk of infection, approximately 975 million of whom live in urban areas in tropical and sub-tropical countries in Southeast Asia, the Pacific and the Americas 1 . Transmission also occurs in Africa and the Eastern Mediterranean, and rural Europe PMC Funders GroupAuthor Manuscript Nat Rev Microbiol. Author manuscript; available in PMC 2015 February 19. Published in final edited form as:Nat Rev Microbiol. 2010 December ; 8(12 0): S7-16. doi:10.1038/nrmicro2460. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts communities are increasingly being affected. It is estimated that more than 50 million infections occur each year, including 500,000 hospitalizations for dengue haemorrhagic fever, mainly among children, with the case fatality rate exceeding 5% in some areas [1][2][3][4] . The geographical areas in which dengue transmission occurs have expanded in recent years (FIG. 1), and all four dengue virus serotypes (DENV-1-4) are now circulating in Asia, Africa and the Americas, a dramatically different scenario from that which prevailed 20 or 30 years ago (FIG. 2). The molecular epidemiology of these serotypes has been studied in an attempt to understand their evolutionary relationships 11 .This Review will provide an update on our understanding of the pathogenesis of this successful pathogen, how we diagnose and control infection and the progress that has been made in vaccine development. Dengue virus pathogenesisDengue viruses belong to the genus flavivirus within the Flaviviridae family. DENV-1-4 evolved in non-human primates from a common ancestor and each entered the urban cycle independently an estimated 500-1,000 years ago 12 . The virion comprises a spherical particle, 40-50 nm in diameter, with a lipopolysaccharide envelope. The positive singlestrand RNA genome (FIG. 3), which is approximately 11 kb in length, has a single open reading frame that encodes three structural proteins -the capsid (C), membrane (M) and envelope (E) glycoproteins -and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5 [18][19][20] . ADE occurs when mononuclear phagocytes are infected through their Fc receptors by immune complexes that form between DE...

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“…The greater relative prevalence of DSS in children relative to adults is likely tied to their having an intrinsically more permeable vascular endothelium, as demonstrated previously by Gamble et al in healthy Vietnamese children and adults. 84 The risk for more severe outcomes in young children argues for vaccination implementation strategies to include this most vulnerable population.…”

Section: Age and Gendermentioning

confidence: 99%