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1.
Microcirculation ; 31(2): e12843, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38174616

RESUMO

INTRODUCTION: Coronary microvascular dysfunction (CMD) plays a major role in hypertrophic cardiomyopathy (HCM) physiopathology but its assessment in clinical practice remains a challenge. Nowadays, innovations in invasive and noninvasive coronary evaluation using multimodal imaging provide options for the diagnosis of CMD. The objective of the present study was to investigate if new multimodal imaging diagnosis of CMD could detect HCM patients with more impaired cardiac function by left atrioventricular coupling index (LACI). METHODS AND RESULTS: A total of 32 consecutive patients with a confirmed diagnosis of HCM (62 ± 13 years, 62% men) were prospectively screened for CMD using a multimodal imaging method. LACI was assessed by cardiovascular magnetic resonance imaging. Fifteen (47%) patients had CMD by multimodal imaging method. Patients with CMD presented a significantly higher LACI (48.5 ± 25.4 vs. 32.5 ± 10.6, p = .03). A multivariate logistic regression analysis demonstrated that CMD was independently associated with LACI (OR = 1.069, 95% CI 1.00-1.135, p = .03). CONCLUSION: Multimodal imaging diagnosis of CMD is applicable to HCM patients and is associated with more impaired cardiac function.


Assuntos
Cardiomiopatia Hipertrófica , Isquemia Miocárdica , Masculino , Humanos , Feminino , Circulação Coronária , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Imageamento por Ressonância Magnética , Imagem Multimodal
2.
Cardiovasc Ultrasound ; 22(1): 5, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745211

RESUMO

BACKGROUND: Coronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the coronary microcirculation, which may be diagnosed using invasive coronary physiology. CMD is responsible for impaired diastolic cardiac function. It has recently been suggested that left atrial strain (LASr) represents a highly sensitive tool for detecting cardiac diastolic function abnormalities. Accordingly, the aim of this study was to investigate the relationship between CMD and LASr. METHODS: Consecutively enrolled patients with non-obstructed coronary arteries (NOCA) underwent CMD and LASr evaluation by invasive thermodilution and noninvasive echocardiography, respectively. RESULTS: Forty-two (42) patients were included, out of which 26 presented with CMD. There were no significant differences between CMD-positive and negative patients in terms of clinical and echocardiographic characteristics. LASr was significantly reduced in patients with CMD (24.6% ± 6.1 vs. 30.3 ± 7.8%, p = 0.01). A moderate correlation was observed between coronary flow reserve and LAsr (r = 0.47, p = 0.002). A multivariate logistic regression analysis demonstrated that CMD was independently associated with LASr (OR = 0.88, 95%CI 0.78-0.99.135, p = 0.04). A LASr cut-off of 25.5% enabled an optimal classification of patients with or without CMD. CONCLUSION: Patients with NOCA and CMD had a significantly reduced LASr compared with patients without CMD, suggesting the early impairment of diastolic function in these patients.


Assuntos
Circulação Coronária , Vasos Coronários , Ecocardiografia , Átrios do Coração , Microcirculação , Humanos , Masculino , Feminino , Microcirculação/fisiologia , Pessoa de Meia-Idade , Circulação Coronária/fisiologia , Átrios do Coração/fisiopatologia , Átrios do Coração/diagnóstico por imagem , Ecocardiografia/métodos , Vasos Coronários/fisiopatologia , Vasos Coronários/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/complicações , Idoso , Função do Átrio Esquerdo/fisiologia , Termodiluição/métodos , Diástole
3.
J Nucl Cardiol ; 30(4): 1656-1667, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36813934

RESUMO

OBJECTIVES: To assess the diagnostic performances of CZT myocardial perfusion reserve (MPR) for the detection of territories with simultaneous impaired coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients without obstructive coronary artery disease. METHODS: Patients were prospectively included before being referred for coronary angiography. All patients underwent CZT MPR before invasive coronary angiography (ICA) and coronary physiology assessment. Rest and dipyridamole-induced stress myocardial blood flow (MBF) and MPR were quantified using 99mTc-SestaMIBI and a CZT camera. Fractional flow reserve (FFR), Thermodilution CFR, and IMR were assessed during ICA. RESULTS: Between December 2016 and July 2019, 36 patients were included. 25/36 patients presented no obstructive coronary artery disease. A complete functional assessment was performed in 32 arteries. No territory presented a significant ischemia on CZT myocardial perfusion imaging. A moderate yet significant correlation was observed between regional CZT MPR and CFR (r = 0.4, P = .03). Sensitivity, specificity, positive and negative predictive value, and accuracy of regional CZT MPR versus the composite invasive criterion (impaired CFR and IMR) were 87 [47% to 99%], 92% [73% to 99%], 78% [47% to 93%], 96% [78% to 99%], and 91% [75% to 98%], respectively. All territories with a regional CZT MPR ≤ 1.8 showed a CFR < 2. Regional CZT MPR values were significantly higher in arteries with CFR ≥ 2 and IMR < 25 (negative composite criterion, n = 14) than in those with CFR < 2 and IMR ≥ 25 (2.6 [2.1 to 3.6] versus 1.6 [1.2 to 1.8]), P < .01). CONCLUSION: Regional CZT MPR presented excellent diagnostic performances for the detection of territories with simultaneously impaired CFR and IMR reflecting a very high cardiovascular risk in patients without obstructive coronary artery disease.


Assuntos
Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Imagem de Perfusão do Miocárdio , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Projetos Piloto , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Microcirculação/fisiologia , Angiografia Coronária , Perfusão , Imagem de Perfusão do Miocárdio/métodos
4.
Rev Cardiovasc Med ; 23(5): 158, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-39077613

RESUMO

Coronary physiological assessment is now widely used to assess epicardial coronary lesions in cath lab. Based on clinical evidence, fractional flow reserve (FFR) is the gold standard method to select whether epicardial coronary lesions need revascularization. While additional epicardial indexes, such as instantaneous wave-free ratio (iFR), are also used for revascularization decision-making, several indexes are now also available to explore the coronary microcirculation. Therefore, coronary physiological assessment now allows to explore the entire coronary tree and offer the potential of precision medicine for patients affected by coronary artery disease (CAD). This paper will provide review of the epicardial and microvascular indexes available for the assessment of coronary physiology. More specifically, the already demonstrated contributions of these indexes in the management of CAD and the role they could play in precision medicine will be reviewed with special emphasis on chronic coronary syndrome.

5.
Eur J Nucl Med Mol Imaging ; 49(3): 809-820, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34417856

RESUMO

PURPOSE: Coronary microvascular dysfunction (CMVD) plays a major role in the occurrence of cardiovascular events (CVE). We recently suggested the clinical potential of myocardial perfusion entropy (MPE) quantification from SPECT myocardial perfusion images (MPI) for the prognosis of CVE occurrence. We hypothesized that the quantification of MPE from SPECT MPI would allow the assessment of CMVD-related MPE variations in a preclinical model of type 2 diabetes (T2D) including treatment with the anti-diabetic incretin liraglutide (LIR). METHODS: Optimal conditions for the preclinical quantification of MPE using 201Tl SPECT MPI were determined in rats with a T2D-like condition induced by a high-fat diet and streptozotocin injection (feasibility study, n = 43). Using such conditions, echocardiography and post-mortem LV capillary density evaluation were then used in order to assess the effect of LIR and the ability of MPE to assess CMVD (therapeutic study, n = 39). RESULTS: The feasibility study identified dobutamine stress and acute NO synthase and cyclooxygenase inhibition as optimal conditions for the quantification of MPE, with significant increases in MPE being observed in T2D animals (P < 0.01 vs controls). In the therapeutic study, T2D rats were hyperglycemic (5.5 ± 0.5 vs 1.1 ± 0.3 g/L for controls, P < 0.001) and had a significantly lower left ventricular ejection fraction (LVEF) (65 ± 4% vs 74 ± 9%, P < 0.01) and LV capillary density (2400 ± 300 vs 2800 ± 600 mm-3, P < 0.05). LIR partially restored glycemia (3.9 ± 0.6 g/L, P < 0.05 vs controls and T2D), totally prevented LVEF impairment (72 ± 7%, P = NS vs CTL), with no significant effect on capillary density. MPE was significantly increased in T2D rats (7.6 ± 0.5 vs 7.1 ± 0.5, P < 0.05), with no significant improvement in T2D-LIR rats (7.4 ± 0.4, P = NS vs controls and T2D). CONCLUSION: MPE quantification allowed the preclinical noninvasive assessment of CMVD. Both MPE and capillary density quantification suggested that LIR did not improve T2D-induced CMVD. The relevance of MPE for CMVD assessment warrants further clinical investigation.


Assuntos
Diabetes Mellitus Tipo 2 , Imagem de Perfusão do Miocárdio , Animais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Entropia , Imagem de Perfusão do Miocárdio/métodos , Perfusão , Ratos , Roedores , Volume Sistólico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Função Ventricular Esquerda/fisiologia
6.
Catheter Cardiovasc Interv ; 99(2): 397-404, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34057279

RESUMO

BACKGROUND: Highly thrombotic coronary lesions continue to be a serious and clinically significant problem that is not effectively and completely addressed by current technology. OBJECTIVES: We aimed to investigate whether a micro-net mesh (MNM) technology covering stent could preserve the index of microcirculatory resistance (IMR) after percutaneous coronary intervention (PCI) in patients with high thrombus burden. METHODS AND RESULTS: Fifty-two patients with non-ST elevation myocardial infarction or ST Elevation Myocardial Infarction and high thrombus burden (TIMI thrombus grade ≥ 3) were randomized into two groups, PCI with a MNM covering stent (MNM group, n = 25) and PCI with any commercially available stent (DES group, n = 27). As the primary endpoint, IMR was measured immediately after PCI using a pressure-temperature sensor-tipped coronary wire. The secondary endpoint was left ventricular ejection fraction (LVEF) at 6 months of follow-up. The IMR in the MNM group was significantly lower in comparison to the DES group (33.2 [21.3, 48.9] vs. 57.2 [39.9, 98.0], p = 0.005). No significant differences were observed in baseline LVEF (54.5 ± 10.2% vs. 53.1 ± 6.87%, p = .57), while LVEF was significantly improved at follow-up in the MNM group (61.1 ± 7.1% vs. 53.9 ± 6.35%, p = .0001). CONCLUSION: MNM technology significantly improved coronary microvascular dysfunction after PCI in patient with acute coronary syndrome and appears as a useful technological option for thrombus management.


Assuntos
Intervenção Coronária Percutânea , Trombose , Humanos , Microcirculação , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Stents , Volume Sistólico , Telas Cirúrgicas , Tecnologia , Resultado do Tratamento , Função Ventricular Esquerda
7.
J Nucl Cardiol ; 29(3): 1419-1429, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33502690

RESUMO

BACKGROUND: Myocardial insulin resistance (IR) could be a predictive factor of cardiovascular events. This study aimed to introduce a new method using 123I-6-deoxy-6-iodo-D-glucose (6DIG), a pure tracer of glucose transport, for the assessment of IR using cardiac dynamic nuclear imaging. METHODS: The protocol evaluated first in rat-models consisted in two 6DIG injections and one of insulin associated with planar imaging and blood sampling. Compartmental modeling was used to analyze 6DIG kinetics in basal and insulin conditions and to obtain an index of IR. As a part of a translational approach, a clinical study was then performed in 5 healthy and 6 diabetic volunteers. RESULTS: In rodent models, the method revealed reproducible when performed twice at 7 days apart in the same animal. Rosiglitazone, an insulin-sensitizing drug, induced a significant increase of myocardial IR index in obese Zucker rats from 0.96 ± 0.18 to 2.26 ± 0.44 (P<.05) after 7 days of an oral treatment, and 6DIG IR indexes correlated with the gold standard IR index obtained through the hyperinsulinemic-euglycemic clamp (r=.68, P<.02). In human, a factorial analysis was applied on images to obtain vascular and myocardial kinetics before compartmental modeling. 1.5-fold to 2.2-fold decreases in mean cardiac IR indexes from healthy to diabetic volunteers were observed without reaching statistical significance. CONCLUSIONS: These preclinical results demonstrate the reproducibility and sensibility of this novel imaging methodology. Although this first in-human study showed that this new method could be rapidly performed, larger studies need to be planned in order to confirm its performance.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Resistência à Insulina , Animais , Glicemia , Técnica Clamp de Glucose , Humanos , Insulina , Ratos , Ratos Zucker , Reprodutibilidade dos Testes
8.
J Nucl Cardiol ; 29(4): 1647-1656, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33988809

RESUMO

AIMS: The objective of this study was to determine the accuracy of right ventricular function (RVF) assessed by Cadmium Zinc Telluride ECG-gated SPECT equilibrium radionuclide angiocardiography (CZT-ERNA). METHODS AND RESULTS: Twenty-one consecutive patients with cardiomyopathy (aged 54 ± 19 years; 62% male) were included. RV ejection fraction (EF) and volumes were analyzed by CZT-ERNA and compared with values obtained by cardiac magnetic resonance imaging (CMR). Mean values were not different between CZT-ERNA and MRI for RVEF (48.1 ± 10.4% vs 50.8 ± 10.0%; P = .23). Significant correlations (P < .0001) were observed between CZT-ERNA and MRI for RVEF, RV end-diastolic volume, and end-systolic volume (r = 0.81, r = 0.93, and r = 0.96, respectively). Bland-Altman analysis showed a mean difference (bias) between CZT-ERNA and MRI for RVEF of -2.69% (95% CI - 5.35 to - 0.42) with good agreement between the 2 techniques (limits of agreement, -14.3 to 8.99). Intraobserver and interobserver reproducibility of RVF measured by CZT-ERNA was high. CONCLUSION: CZT-ERNA provides accurate, reproducible assessment of RVF and appears as a good alternative to cardiac magnetic resonance for the evaluation of the magnitude of RVF in patients with cardiomyopathy.


Assuntos
Cardiomiopatias , Imagem do Acúmulo Cardíaco de Comporta , Cádmio , Cardiomiopatias/diagnóstico por imagem , Eletrocardiografia , Feminino , Imagem do Acúmulo Cardíaco de Comporta/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Reprodutibilidade dos Testes , Volume Sistólico , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Zinco
9.
Eur J Nucl Med Mol Imaging ; 48(6): 1813-1821, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33219463

RESUMO

PURPOSE: Risk stratification of patients with type 2 diabetes mellitus (T2D) remains suboptimal. We hypothesized that myocardial perfusion entropy (MPE) quantified from SPECT myocardial perfusion images may provide incremental prognostic value in T2D patients independently from myocardial ischemia. METHODS: T2D patients with very high and high cardiovascular risk were prospectively included (n = 166, 65 ± 12 years). Stress perfusion defect was quantified by visual evaluation of SPECT MPI. SPECT MPI was also used for the quantification of rest and stress MPE. The primary end point was major adverse cardiac events (MACEs) defined as cardiac death, myocardial infarction (MI), and myocardial revascularization > 3 months after SPECT. RESULTS: Forty-four MACEs were observed during a 4.6-year median follow-up. Significant differences in stress MPE were observed between patients with and without MACEs (4.19 ± 0.46 vs. 3.93 ± 0.40; P ≤ .01). By Kaplan-Meier analysis, the risk of MACEs was significantly higher in patients with higher stress MPE (log-rank P ≤ 01). Stress MPE and stress perfusion defect (SSS ≥ 4) were significantly associated with the risk of MACEs (hazard ratio 2.77 and 2.06, respectively, P < .05 for both) after adjustment for clinical and imaging risk predictors as identified from preliminary univariate analysis. MPE demonstrated incremental prognostic value over clinical risk factors, stress test EKG and SSS as evidenced by nested models showing improved Akaike information criterion (AIC), reclassification (global continuous net reclassification improvement [NRI]: 63), global integrated discrimination improvement (IDI: 6%), and discrimination (change in c-statistic: 0.66 vs 0.74). CONCLUSIONS: Stress MPE provided independent and incremental prognostic information for the prediction of MACEs in diabetic patients. TRIAL REGISTRATION NUMBER: NCT02316054 (12/12/2014).


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Imagem de Perfusão do Miocárdio , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Entropia , Teste de Esforço , Humanos , Perfusão , Prognóstico , Medição de Risco , Fatores de Risco , Tomografia Computadorizada de Emissão de Fóton Único
10.
Eur J Nucl Med Mol Imaging ; 46(10): 2042-2050, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31321484

RESUMO

PURPOSE: To determine whether the assessment of regional wall thickening (WT) in addition to myocardial perfusion from stress supine acquisitions could compensate for the lack of prone acquisition and the corresponding decrease in the diagnostic performance of SPECT myocardial perfusion imaging (MPI) in patients with known or suspected coronary artery disease (CAD). METHODS: The study group comprised 41 patients (123 vessels) with known or suspected CAD prospectively recruited for systematic prone and supine 201Tl stress SPECT MPI. The diagnostic performance of SPECT MPI was determined for various image sets including nongated supine images (supine NG), nongated combined prone and supine images (prone and supine NG) and gated supine images, allowing WT evaluation from NG images in addition to perfusion (supine NG + WT) using invasive coronary angiography and fractional flow reserve as the gold standards. RESULTS: The rate of false positives was significantly higher among the supine NG images (20.8%) than among either the prone and supine NG or the supine NG + WT images (3.3% and 2.7%, respectively, P < 0.05 vs. supine NG). Consequently, specificity was higher for the prone and supine NG images than for the supine NG images (96.1% vs. 76.1%, P < 0.01) and was highest for the supine NG + WT images (96.8%, P not significant vs. prone and supine NG), without significant differences in sensitivity (80.0%, 86.6% and 73.3%, respectively, P not significant for all comparisons). CONCLUSION: The diagnostic performance of supine stress SPECT MPI is improved when WT assessment of ischaemic segments is used as an additional diagnostic criterion to values not significantly different from those with combined prone and supine acquisitions.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Posicionamento do Paciente/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio/instrumentação , Imagem de Perfusão do Miocárdio/normas , Posicionamento do Paciente/normas , Valor Preditivo dos Testes , Decúbito Ventral , Compostos Radiofarmacêuticos , Semicondutores , Decúbito Dorsal , Radioisótopos de Tálio , Tomografia Computadorizada de Emissão de Fóton Único/instrumentação , Tomografia Computadorizada de Emissão de Fóton Único/normas
11.
J Nucl Cardiol ; 26(4): 1269-1279, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-29380286

RESUMO

BACKGROUND: The aim of this study was to determine the diagnostic accuracy of stress thallium-201/rest technetium-99m-sestamibi sequential dual-isotope high-speed myocardial perfusion imaging (DI-HS-MPI) against invasively determined fractional flow reserve (FFR). METHODS: Fifty-four consecutive patients prospectively underwent DI-HS-MPI before invasive coronary angiography. Perfusion was scored visually by summed stress score on a patient and coronary territory basis. Significant coronary artery disease (CAD) was defined by the presence of ≥ 90% stenosis/occlusion or fractional flow reserve ≤ 0.80 for coronary stenosis ≥ 50%. RESULTS: FFR was measured in 69 of 162 coronary vessels, with 1.28 ± 0.56 vessels assessed/patient. Sensitivity, specificity, and diagnostic accuracy of MPI for the detection of significant CAD were 92.8%, 69.2%, and 81.4%, on a patient basis, and 83.7%, 90.4%, and 88.8% by coronary territory. CONCLUSIONS: DI-HS-MPI accurately detects functionally significant CAD as defined by using FFR.


Assuntos
Estenose Coronária/diagnóstico por imagem , Imagem de Perfusão do Miocárdio , Compostos Radiofarmacêuticos , Tecnécio Tc 99m Sestamibi , Radioisótopos de Tálio , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Angiografia Coronária , Estenose Coronária/fisiopatologia , Teste de Esforço , Feminino , Reserva Fracionada de Fluxo Miocárdico , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
12.
J Nucl Cardiol ; 25(3): 1017-1022, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29209950

RESUMO

Coronary microvascular dysfunction has recently emerged as a major independent prognostic factor and can be invasively assessed by coronary flow reserve (CFR) and the index of microvascular resistance (IMR). The incremental prognostic value of myocardial ischemia from SPECT myocardial perfusion imaging (MPI) over clinical characteristics, cardiac risk factors, and stress test data for the prediction of hard cardiac events (myocardial infarction and cardiac death) has been well demonstrated over the last two decades regardless of the absence or presence of epicardial CAD. Recently developed semi-conductor, cardiac-dedicated cameras allow for decreased acquisition times and systematic procubitus and decubitus acquisitions thereby limiting the occurrence of false positives historically attributable to artefactual motion, attenuation, and digestive artifacts. It is therefore likely that pathophysiological causes rather than acquisition artifacts might underlie SPECT perfusion abnormalities. Here, we report four representative examples of patients presenting with ischemia in the setting of no obstructive CAD and normal fractional flow reserve together with elevated IMR and low CFR. The results indicate that ischemia from SPECT MPI could result from microvascular dysfunction in patients without obstructive CAD and should be considered as a prognostic factor for hard cardiac events.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/etiologia , Imagem de Perfusão do Miocárdio , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária/fisiologia , Feminino , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Humanos , Masculino , Microcirculação/fisiologia , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologia
13.
J Nucl Cardiol ; 25(2): 483-491, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-27572925

RESUMO

BACKGROUND: Sympathetic system abnormalities have been reported in sepsis-related cardiac dysfunction. The present study aimed at evaluating the potential of the norepinephrine radiolabeled analogue [123I]-meta-iodobenzylguanidine (123I-MIBG) for the noninvasive assessment of modifications in cardiac sympathetic activity occurring in lipopolysaccharide (LPS)-induced experimental acute sepsis by single-photon emission computed tomographic imaging (SPECT). METHODS AND RESULTS: Sepsis was induced in male Wistar rats by intraperitoneal injection of 10 mg·kg-1 lipopolysaccharide (n = 16), whereas control animals (n = 7) were injected with vehicle (NaCl 0.9%). Echocardiography in LPS-injected animals (n = 8) demonstrated systolic and diastolic cardiac dysfunction. 123I-MIBG was injected 1 hour after LPS or vehicle administration (n = 8 and 7, respectively), and in vivo SPECT imaging was performed early and late (20 and 180 minutes) after tracer injection prior to animal euthanasia and ex vivo assessment of 123I-MIBG biodistribution. Global and 17-segment SPECT image analysis indicated that early 123I-MIBG activity was not affected by LPS treatment, whereas late cardiac tracer activity was significantly decreased in LPS-treated animals. Consequently, the cardiac washout of 123I-MIBG was significantly higher in LPS-treated (63.3% ± 4.0%) than that in control animals (56.7% ± 5.8%) (P < .05). CONCLUSION: Sepsis-induced modifications in cardiac sympathetic nervous system activity were evidenced by noninvasive in vivo 123I-MIBG SPECT imaging.


Assuntos
3-Iodobenzilguanidina/farmacocinética , Coração/diagnóstico por imagem , Choque Séptico/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Tomografia Computadorizada de Emissão de Fóton Único , Animais , Lipopolissacarídeos/química , Masculino , Norepinefrina/sangue , Prognóstico , Ratos , Ratos Wistar , Receptores Adrenérgicos/metabolismo , Distribuição Tecidual
16.
Int J Mol Sci ; 16(11): 27730-40, 2015 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-26610471

RESUMO

Maurocalcine (MCa) is the first natural cell penetrating peptide to be discovered in animal venom. In addition to the fact that it represents a potent vector for the cell penetration of structurally diverse therapeutic compounds, MCa also displays several distinguishing features that make it a potential peptide of choice for clinical and biotechnological applications. The aim of the present study was to gain new information about the properties of MCa in vivo in order to delineate the future potential applications of this vector. For this purpose, two analogues of this peptide with (Tyr-MCa) and without (Lin-Tyr-MCa) disulfide bridges were synthesized, radiolabeled with (125)I, and their in vitro stabilities were first evaluated in mouse blood. The results indicated that (125)I-Tyr-MCa was stable in vitro and that the disulfide bridges conferred a competitive advantage for the stability of peptide. Following in vivo injection in mice, (125)I-Tyr-MCa targeted peripheral organs with interesting quantitative differences and the main route of peptide elimination was renal.


Assuntos
Peptídeos Penetradores de Células/farmacocinética , Venenos de Escorpião/farmacocinética , Animais , Peptídeos Penetradores de Células/administração & dosagem , Peptídeos Penetradores de Células/síntese química , Cromatografia Líquida de Alta Pressão , Estabilidade de Medicamentos , Marcação por Isótopo , Camundongos , Tomografia por Emissão de Pósitrons , Venenos de Escorpião/administração & dosagem , Venenos de Escorpião/síntese química , Distribuição Tecidual , Microtomografia por Raio-X
17.
Circ Res ; 110(7): 927-37, 2012 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-22461363

RESUMO

RATIONALE: A noninvasive tool allowing the detection of vulnerable atherosclerotic plaques is highly needed. By combining nanomolar affinities and fast blood clearance, nanobodies represent potential radiotracers for cardiovascular molecular imaging. Vascular cell adhesion molecule-1 (VCAM1) constitutes a relevant target for molecular imaging of atherosclerotic lesions. OBJECTIVE: We aimed to generate, radiolabel, and evaluate anti-VCAM1 nanobodies for noninvasive detection of atherosclerotic lesions. METHODS AND RESULTS: Ten anti-VCAM1 nanobodies were generated, radiolabeled with technetium-99m, and screened in vitro on mouse and human recombinant VCAM1 proteins and endothelial cells and in vivo in apolipoprotein E-deficient (ApoE(-/-)) mice. A nontargeting control nanobody was used in all experiments to demonstrate specificity. All nanobodies displayed nanomolar affinities for murine VCAM1. Flow cytometry analyses using human human umbilical vein endothelial cells indicated murine and human VCAM1 cross-reactivity for 6 of 10 nanobodies. The lead compound cAbVCAM1-5 was cross-reactive for human VCAM1 and exhibited high lesion-to-control (4.95±0.85), lesion-to-heart (8.30±1.11), and lesion-to-blood ratios (4.32±0.48) (P<0.05 versus control C57Bl/6J mice). Aortic arch atherosclerotic lesions of ApoE(-/-) mice were successfully identified by single-photon emission computed tomography imaging. (99m)Tc-cAbVCAM1-5 binding specificity was demonstrated by in vivo competition experiments. Autoradiography and immunohistochemistry further confirmed cAbVCAM1-5 uptake in VCAM1-positive lesions. CONCLUSIONS: The (99m)Tc-labeled, anti-VCAM1 nanobody cAbVCAM1-5 allowed noninvasive detection of VCAM1 expression and displayed mouse and human cross-reactivity. Therefore, this study demonstrates the potential of nanobodies as a new class of radiotracers for cardiovascular applications. The nanobody technology might evolve into an important research tool for targeted imaging of atherosclerotic lesions and has the potential for fast clinical translation.


Assuntos
Aterosclerose/diagnóstico , Aterosclerose/metabolismo , Endotélio Vascular/metabolismo , Imagem Molecular/métodos , Traçadores Radioativos , Molécula 1 de Adesão de Célula Vascular/metabolismo , Animais , Apolipoproteínas E/deficiência , Apolipoproteínas E/genética , Aterosclerose/patologia , Biomarcadores/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Endotélio Vascular/patologia , Feminino , Humanos , Técnicas In Vitro , Camundongos , Camundongos Knockout , Radioimunodetecção/métodos , Compostos Radiofarmacêuticos , Tecnécio
18.
J Nucl Cardiol ; 21(5): 984-92, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24875578

RESUMO

BACKGROUND: The great clinical potential of myocardial ß-AR imaging has been shown by recent studies evaluating the ß-AR-specific, non-selective agent [(11)C]-CGP12177 in the setting of idiopathic-dilated cardiomyopathy, and myocardial infarction. However, the short half-life of (11)C hampers the potential of [(11)C]-CGP12177 for routine clinical use. AMI9 is an analog of the ß-adrenoceptor ligand practolol that can readily be labeled using radioactive isotopes of iodine. The present study was aimed at characterizing the in vitro, ex vivo, and in vivo ß-AR binding properties of [(125)I]-AMI9. METHODS AND RESULTS: Newborn rat cardiomyocytes were used for saturation and kinetic binding assays as well as for displacement and competition experiments. Isolated perfused rat hearts were used to evaluate the pharmacological activity of AMI9. The in vivo kinetics of [(125)I]-AMI9 were studied using biodistribution experiments in mice. [1(25)I]-AMI9 displayed high specific affinity for ß-AR with no ß-AR subtype selectivity (K D, 5.6 ± 0.3 nM; B max, 231 ± 7 fmol·(mg protein)(-1)). AMI9 potently inhibited the inotropic effects of isoproterenol. The early in vivo cardiac and lung activities of [(125)I]-AMI9 compared favorably with those of the clinically validated tracer CGP12177. CONCLUSION: Iodine-labeled AMI9 is a promising agent for the molecular imaging of myocardial ß-AR density.


Assuntos
Imagem Molecular/métodos , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Practolol/análogos & derivados , Practolol/farmacocinética , Receptores Adrenérgicos beta/metabolismo , Antagonistas de Receptores Adrenérgicos beta 1/química , Antagonistas de Receptores Adrenérgicos beta 1/farmacocinética , Animais , Animais Recém-Nascidos , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos , Coração/diagnóstico por imagem , Radioisótopos do Iodo/química , Radioisótopos do Iodo/farmacocinética , Marcação por Isótopo/métodos , Taxa de Depuração Metabólica , Camundongos , Miócitos Cardíacos/diagnóstico por imagem , Especificidade de Órgãos , Cintilografia , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Distribuição Tecidual
20.
Diagnostics (Basel) ; 13(11)2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37296830

RESUMO

Advances in computer technology and image processing now allow us to obtain from angiographic images a large variety of information on coronary physiology without the use of a guide-wire as a diagnostic information equivalent to FFR and iFR but also information allowing for the performance of a real virtual percutaneous coronary intervention (PCI) and finally the ability to obtain information to optimize the results of PCI. With specific software, it is now possible to have a real upgrading of invasive coronary angiography. In this review, we present the different advances in this field and discuss the future perspectives offered by this technology.

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