Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/terapia , Terapia por Ultrassom , Ultrassonografia , Bioengenharia , Doenças Cardiovasculares/diagnóstico por imagem , Sistema Cardiovascular , Comunicação , Congressos como Assunto , Ecocardiografia/normas , Ecocardiografia/tendências , Ecocardiografia Doppler , Desenho de Equipamento , Humanos , Imageamento Tridimensional , Relações Interprofissionais , Sistema de Registros , Pesquisa , Software , Avaliação da Tecnologia Biomédica , Terapia Trombolítica/métodos , Ultrassonografia/tendências , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: During coronary stenosis, flow reserve in the adjacent nonstenotic bed decreases, but the microvascular mechanisms are unknown. Because myocardial contrast echocardiography (MCE) assesses microvascular physiology, we used it to relate flow reserve to intramyocardial blood volume in the adjacent bed. METHODS AND RESULTS: A noncritical left anterior descending (LAD) stenosis was created in 10 dogs. MCE was performed and myocardial blood flow was measured with neutron-activated microspheres and flow probes. Data were collected at baseline, hyperemia, and hyperemia and stenosis. Hyperemia was induced with an A2A receptor agonist. MCE acoustic intensity in the LAD and left circumflex (LCx) regions were fit to the following: y=A(1-e(-beta t)), where A, beta, and A x beta reflect intramyocardial blood volume, red cell velocity, and flow, respectively. During hyperemia alone, LCx probe and microsphere flows and MCE-derived red cell velocity increased from baseline (30+/-14 versus 125+/-62 mL/min, P<0.0005; 1.5+/-0.5 versus 6.6+/-2.0 mL x min(-1) x g(-1), P<0.0005; and 0.53+/-0.14 versus 0.96+/-0.45 second(-1), P=0.030, respectively); intramyocardial blood volume was unchanged. LAD stenosis during hyperemia decreased LCx probe flow (125+/-62 versus 110+/-57 mL/min; P<0.05), microsphere flow (6.6+/-2.0 versus 4.2+/-2.1 mL x min(-1) x g(-1); P<0.0005), and MCE-derived flow (0.57+/-0.29 versus 0.45+/-0.33 second(-1); P=0.032). LCx bed intramyocardial blood volume concurrently increased (0.61+/-0.14 versus 0.70+/-0.15; P<0.01). CONCLUSIONS: Coronary stenosis impairs flow reserve in the adjacent nonstenotic bed, in which intramyocardial blood volume increases. MCE suggests compensatory recruitment of microvascular anastomotic collateral networks that augment stenotic bed flow reserve, but at the expense of the adjacent bed. Adjacent bed collateral microcirculation thus participates in the regulation of collateral flow and appears functionally significant during coronary stenosis.
Assuntos
Circulação Colateral , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/fisiopatologia , Reserva Fracionada de Fluxo Miocárdico , Animais , Cães , Ecocardiografia/métodos , Hiperemia/diagnóstico por imagem , Hiperemia/fisiopatologia , Microcirculação , Modelos CardiovascularesRESUMO
An ultrasound-based molecular imaging technique capable of detecting endothelial cell markers of inflammation may allow early, non-invasive assessment of vascular disease. Clinical application of targeted, acoustically-active microbubbles requires optimization of microbubble-endothelial adhesion strength to maximize image signal-to-noise ratio, as well as the ability to discern the degree of inflammation along a continuum of dysfunction. Accordingly, we hypothesized that adhesion of intercellular adhesion molecule-1 (ICAM-1)-targeted microbubbles is dependent on the degree of endothelial inflammation, and that microbubbles multi-targeted to both ICAM-1 (via anti-ICAM-1 antibodies) and selectins (via sialyl Lewisx) demonstrate greater adhesion strength than microbubbles targeted to either inflammatory marker alone. In a radial flow chamber, microbubbles were perfused across endothelial cells activated with interleukin-1beta to four different levels of inflammation, as assessed by quantitative ICAM-1 expression. ICAM-1-targeted microbubble adhesion strength increased with increasing degree of inflammation, with a relationship that was both positive and linear (r > 0.99). Microbubble adhesion strength was significantly higher for the multi-targeted microbubbles than either of the single-targeted microbubbles. These data thus demonstrate that multi-targeting of contrast microbubbles may offer improved adhesion characteristics, allowing for greater sensitivity to inflammation. Furthermore, the adhesion strength of targeted microbubbles is linearly dependent on the degree of inflammation, suggesting that targeted ultrasound imaging may offer differentiation between various degrees of endothelial dysfunction, and thus detect not only the presence, but also the severity of inflammatory disease processes.