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1.
J Cardiovasc Magn Reson ; 25(1): 54, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37784080

RESUMO

BACKGROUND: Macrophages play a pivotal role in vascular inflammation and predict cardiovascular complications. Fluorine-19 magnetic resonance imaging (19F MRI) with intravenously applied perfluorocarbon allows a background-free direct quantification of macrophage abundance in experimental vascular disease models in mice. Recently, perfluorooctyl bromide-nanoemulsion (PFOB-NE) was applied to effectively image macrophage infiltration in a pig model of myocardial infarction using clinical MRI scanners. In the present proof-of-concept approach, we aimed to non-invasively image monocyte/macrophage infiltration in response to carotid artery angioplasty in pigs using 19F MRI to assess early inflammatory response to mechanical injury. METHODS: In eight minipigs, two different types of vascular injury were conducted: a mild injury employing balloon oversize angioplasty only (BA, n = 4) and a severe injury provoked by BA in combination with endothelial denudation (BA + ECDN, n = 4). PFOB-NE was administered intravenously three days after injury followed by 1H and 19F MRI to assess vascular inflammatory burden at day six. Vascular response to mechanical injury was validated using X-ray angiography, intravascular ultrasound and immunohistology in at least 10 segments per carotid artery. RESULTS: Angioplasty was successfully induced in all eight pigs. Response to injury was characterized by positive remodeling with predominantly adventitial wall thickening and concomitant infiltration of monocytes/macrophages. No severe adverse reactions were observed following PFOB-NE administration. In vivo 19F signals were only detected in the four pigs following BA + ECDN with a robust signal-to-noise ratio (SNR) of 14.7 ± 4.8. Ex vivo analysis revealed a linear correlation of 19F SNR to local monocyte/macrophage cell density. Minimum detection limit of infiltrated monocytes/macrophages was estimated at approximately 410 cells/mm2. CONCLUSIONS: In this proof-of-concept study, 19F MRI enabled quantification of monocyte/macrophage infiltration after vascular injury with sufficient sensitivity. This may provide the opportunity to non-invasively monitor vascular inflammation with MRI in patients after angioplasty or even in atherosclerotic plaques.


Assuntos
Lesões do Sistema Vascular , Humanos , Animais , Camundongos , Suínos , Porco Miniatura , Valor Preditivo dos Testes , Imageamento por Ressonância Magnética/métodos , Angioplastia , Inflamação/diagnóstico por imagem , Inflamação/etiologia
2.
Clin Case Rep ; 11(4): e7137, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37006842

RESUMO

This case highlights the ECG interpretation in acute coronary syndrome absence from ST - elevation myocardial infarction. A patient with acute chest pain and biphasic T - waves or deep inverted T- waves in V2-V3 is at risk for myocardial infarction. Timely cardiological assessment and coronary angiography is required.

3.
Clin Case Rep ; 9(12): e05170, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34917378

RESUMO

Vascular complications (VCs) remain an important source of morbidity and mortality following percutaneous arterial catheterization. Vascular closure devices are popular and frequently used, but sometimes cause vessel occlusions that may require vascular surgery or complex endovascular procedures. In this case report, we describe the endovascular retrieval of an embolized Angio-Seal device causing acute limb ischemia in a severely diseased 75-year-old female patient. This case highlights the endovascular technique using a snare catheter and adds another example to the growing evidence of an endovascular approach to manage vascular access site complications in comorbid patients at risk.

4.
Vascul Pharmacol ; 141: 106925, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34619361

RESUMO

OBJECTIVES: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is standard of care in patients with peripheral artery disease (PAD) after percutaneous transluminal angioplasty (PTA). However, high on treatment platelet reactivity (HTPR) to DAPT is frequent and associated with major adverse limb events (MALE) in PAD patients. Nevertheless, association of MALE and HTPR in patients with critical limb ischemia (CLI) is not known. Moreover, comorbidities might confound response to antiplatelet medication further. Hence, in this trial we analyzed pharmacodynamic responses to DAPT and clinical events in CLI patients post PTA. METHODS: In this prospective single center pilot analysis, we included 71 CLI patients. Patients received DAPT after PTA. Antiplatelet effect were measured by light transmission aggregometry (LTA) and vasodilator-stimulated protein phosphorylation assay (VASP). MALE, major adverse cardiac and cerebrovascular events (MACCE) and BARC bleeding within 12 months follow-up were assessed. RESULTS: Mean age of patients was 73.37 ± 7.36 years and 47 (66.2%) were male. Overall HTPR appeared in 46 patients (64.8%). MALE and MACCE showed no differences between patients with and patients without HTPR. However, bleeding was higher in patients with sufficient pharmacodynamic response to DAPT (Bleeding - HTPR: 13.4% vs. no HTPR: 36.0%; log-rank HR: 0.32; 95% CI 0.1079 to 0.9396 p = 0.0217). This finding remained robust in multivariate analysis. CONCLUSION: HTPR to DAPT is frequent in CLI patients. However, bleeding was higher in patients with sufficient response to DAPT. Ischemic events did not differ. Hence, CLI patients might benefit from an alternative antithrombotic approach.


Assuntos
Isquemia Crônica Crítica de Membro , Inibidores da Agregação Plaquetária , Idoso , Idoso de 80 Anos ou mais , Angioplastia , Clopidogrel/efeitos adversos , Feminino , Humanos , Masculino , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento
5.
J Am Heart Assoc ; 10(14): e019724, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34227407

RESUMO

Background Arterial hypertension affects cardiovascular outcome in patients with peripheral artery disease (PAD). We hypothesized that angioplasty of peripheral arterial stenoses decreases aortic (aBP) and brachial blood pressure (bBP). Methods and Results In an index cohort (n=30), we simultaneously measured aBP, bBP, augmentation index (AIx), and aortic pulse wave velocity (PWV) before and after angioplasty of the iliac and femoropopliteal arteries; diagnostic angiography served as a control. In an all-comer registry cohort (n=381), we prospectively measured bBP in patients scheduled for angioplasty of the iliac, femoral, and crural arteries or diagnostic angiography. Systolic aBP decreased after iliac (Δ-25 mmHg; 95% CI, -30 to -20; P<0.0001) and femoropopliteal angioplasty (Δ-12 mmHg; 95% CI, -17 to -5; P<0.0001) as compared with diagnostic angiography. Diastolic aBP decreased after iliac (Δ-9 mmHg; 95% CI, -13 to -1; P=0.01) but not femoropopliteal angioplasty. In parallel, AIx significantly dropped, whereas PWV remained stable. In the registry cohort, systolic bBP decreased after angioplasty of the iliac (Δ-17 mmHg; 95% CI, -31 to -8; P=0.0005) and femoropopliteal arteries (Δ-10 mmHg; 95% CI, -23 to -1; P=0.04) but not the crural arteries, as compared with diagnostic angiography. Diastolic bBP decreased after iliac (Δ-10 mmHg; 95% CI, -17 to -2; P=0.01) and femoropopliteal angioplasty (Δ-9 mmHg; 95% CI, -15 to -1; P=0.04). Multivariate analysis identified baseline systolic bBP and site of lesion as determinants of systolic bBP drop after endovascular treatment. Conclusions Angioplasty of flow-limiting stenoses in patients with peripheral artery disease lowers aortic and brachial blood pressure with more pronounced effects at more proximal lesion sites and elevated baseline systolic blood pressure. These data indicate a role of endovascular treatment to acutely optimize blood pressure in patients with peripheral artery disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02728479.


Assuntos
Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Doença Arterial Periférica/fisiopatologia , Rigidez Vascular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Angioplastia/métodos , Aorta/fisiopatologia , Artéria Braquial/fisiopatologia , Constrição Patológica/diagnóstico , Constrição Patológica/fisiopatologia , Feminino , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Doença Arterial Periférica/diagnóstico , Estudos Prospectivos , Análise de Onda de Pulso
6.
Platelets ; 32(3): 391-397, 2021 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32252582

RESUMO

Objective: High on-treatment platelet reactivity (HTPR) to dual antiplatelet therapy (DAPT) predicts adverse events in coronary artery disease patients. In peripheral artery disease (PAD) patients, data concerning the clinical impact of HTPR are limited. Therefore, we evaluated the incidence of (i) HTPR to DAPT and (ii) its impact on 6 months outcome after angioplasty.Methods and results: In this prospective single center analysis, we investigated 102 consecutive patients with PAD from 2016 to 2017. All patients underwent peripheral endovascular treatment due to intermittent claudication (Fontaine IIb). Clopidogrel effects were measured using vasodilator-stimulated protein phosphorylation (VASP) assay, aspirin effects by light-transmission aggregometry (LTA). Major adverse limb events (MALE), major adverse cardiac and cerebrovascular events (MACCE) and BARC bleeding (bleeding academic research consortium classification) within 6 months were assessed. HTPR to clopidogrel (n = 37, 36%), to aspirin (n = 11, 11%) and to both (n = 11, 11%) were frequent. Compared to sufficient platelet inhibition by aspirin and clopidogrel (n = 43, 42%), patients with dual HTPR showed a higher risk of MALE at 6 months (27% vs. 7%; hazard ratio [HR]: 4.45; 95% confidence interval [CI]: 1.1 to 67.8; p = .03). This was independent of diabetes, creatinine, body mass index, and age as well as of procedural details in a multivariate logistic regression analysis. MACCE (n = 2) and BARC bleeding rates (n = 2) were low.Conclusion: In this small exploratory study, HTPR was frequent in PAD patients. Furthermore, the results are suggestive that MALE might be associated with dual HTPR. This leads to the hypothesis that optimized antithrombotic regimens post percutaneous transluminal angioplasty should be tested in clinical trials.


Assuntos
Angioplastia/efeitos adversos , Plaquetas/metabolismo , Doença Arterial Periférica/sangue , Idoso , Feminino , Humanos , Masculino , Estudos Prospectivos
7.
Eur J Med Res ; 25(1): 5, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183891

RESUMO

BACKGROUND: The prognostic implications of non-sustained ventricular tachycardia (NSVT) and their significance as therapeutic targets in patients without prior sustained ventricular arrhythmias remain undetermined. The aim of this study was to investigate the prognostic significance of asymptomatic NSVT in patients who had primary prevention implantable cardioverter-defibrillator (ICD) implantation due to ischemic or non-ischemic cardiomyopathy (ICM, NICM). METHODS: We enrolled 157 consecutive primary prevention ICD patients without previous appropriate ICD therapy (AIT). Patients were allocated to two groups depending on the presence or absence of NSVT in a 6-month period prior to enrollment. The incidence of AIT and unplanned hospitalization due to decompensated heart failure (HF) were assessed during follow-up. RESULTS: In 51 patients (32%), precedent NSVT was documented. During a median follow-up of 1011 days, AIT occurred in 36 patients (23%) and unplanned HF hospitalization was observed in 32 patients (20%). In precedent NSVT patients, the incidence of AIT and unplanned HF hospitalization was significantly higher as compared to patients without precedent NSVT (AIT: 29/51 [57%] vs. 7/106 [7%], P < 0.001, log-rank; HF hospitalization: 16/51 [31%] vs. 16/106 [15%], P = 0.043, log-rank). Cox-regression demonstrated that precedent NSVT independently predicted AIT (P < 0.0001). In subgroup analyses, precedent NSVT predicted AIT in both ICM and NICM (P < 0.0001, P = 0.020), but predicted HF hospitalization only in patients with ICM (P = 0.0030). CONCLUSIONS: Precedent non-sustained VT in patients with primary prevention ICDs is associated with subsequent appropriate ICD therapies, and is an independent predictor of unplanned heart failure hospitalizations in patients with ischemic cardiomyopathy.


Assuntos
Desfibriladores Implantáveis/estatística & dados numéricos , Insuficiência Cardíaca/complicações , Hospitalização/estatística & dados numéricos , Prevenção Primária/estatística & dados numéricos , Idoso , Feminino , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Risco
8.
Free Radic Biol Med ; 145: 78-86, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31553937

RESUMO

ß-Endorphin exerts a broad spectrum of physiological activity on mood, immune functions, pain management, reward effects, and behavioral stability. ß-Endorphin is produced in certain neurons within the central and peripheral nervous system but also in the skin, especially in response to ultraviolet radiation. In the present study we have investigated the impact of visible blue light at λ = 453 nm (BL) on ß-endorphin production of primary human skin keratinocytes (hKC) in-vitro as well as on systemic ß-endorphin formation of whole-body exposed subjects in-vivo. We found that BL irradiation significantly enhanced both keratinocytic ß-endorphin production of hKC cultures as well as systemic ß-endorphin concentrations in light exposed healthy subjects. Interestingly, in hKC cultures elevated ß-endorphin formation was paralleled by significantly increased levels of non-enzymatically generated nitric oxide (NO), whereas elevated systemic ß-endorphin values of BL-exposed subjects were accompanied by enhanced systemic concentration of bioactive NO-derivates. These findings point to a pivotal role of NO in the molecular mechanism of the observed BL-induced effects, and indeed, exogenously applied NO was able to significantly enhance ß-endorphin production in hKC cultures. Thus, our finding of BL-induced increases in systemic ß-endorphin concentration in-vivo can be plausibly explained by an event sequence comprising 1.) BL-driven non-enzymatic formation of NO in the exposed skin tissue, 2.) systemic distribution of cutaneously produced NO in the form of bioactive nitroso compounds, 3.) a subsequent NO-dependent induction of ß-endorphin synthesis in epidermal keratinocytes, and 4.) probably also a NO-dependent modulation of ß-endorphin synthesis in specialized neurons within the central and peripheral nervous system.


Assuntos
Queratinócitos/metabolismo , Óxido Nítrico/química , Pele/metabolismo , beta-Endorfina/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Queratinócitos/efeitos da radiação , Luz , Óxido Nítrico/genética , Óxido Nítrico/efeitos da radiação , Pele/crescimento & desenvolvimento , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , beta-Endorfina/biossíntese
9.
Eur J Prev Cardiol ; 25(17): 1875-1883, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30196723

RESUMO

AIMS: Previous studies have shown that ultraviolet light can lead to the release of nitric oxide from the skin and decrease blood pressure. In contrast to visible light the local application of ultraviolet light bears a cancerogenic risk. Here, we investigated whether whole body exposure to visible blue light can also decrease blood pressure and increase endothelial function in healthy subjects. METHODS: In a randomised crossover study, 14 healthy male subjects were exposed on 2 days to monochromatic blue light or blue light with a filter foil (control light) over 30 minutes. We measured blood pressure (primary endpoint), heart rate, forearm vascular resistance, forearm blood flow, endothelial function (flow-mediated dilation), pulse wave velocity and plasma nitric oxide species, nitrite and nitroso compounds (secondary endpoints) during and up to 2 hours after exposure. RESULTS: Blue light exposure significantly decreased systolic blood pressure and increased heart rate as compared to control. In parallel, blue light significantly increased forearm blood flow, flow-mediated dilation, circulating nitric oxide species and nitroso compounds while it decreased forearm vascular resistance and pulse wave velocity. CONCLUSION: Whole body irradiation with visible blue light at real world doses improves blood pressure, endothelial function and arterial stiffness by nitric oxide released from photolabile intracutanous nitric oxide metabolites into circulating blood.


Assuntos
Pressão Sanguínea/efeitos da radiação , Endotélio Vascular/efeitos da radiação , Antebraço/irrigação sanguínea , Fototerapia/métodos , Rigidez Vascular/efeitos da radiação , Adulto , Biomarcadores/sangue , Estudos Cross-Over , Endotélio Vascular/metabolismo , Voluntários Saudáveis , Frequência Cardíaca/efeitos da radiação , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Fatores de Tempo , Vasodilatação/efeitos da radiação , Irradiação Corporal Total
10.
PLoS One ; 10(4): e0120961, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25875863

RESUMO

PURPOSE: Nitric oxide (NO) is constitutively produced and released from the endothelium and several blood cell types by the isoform 3 of the NO synthase (NOS3). We have shown that NO protects against myocardial ischemia/reperfusion (I/R) injury and that depletion of circulating NOS3 increases within 24 h of ischemia/reperfusion the size of myocardial infarction (MI) in chimeric mice devoid of circulating NOS3. In the current study we hypothesized that circulating NOS3 also affects remodeling of the left ventricle following reperfused MI. METHODS: To analyze the role of circulating NOS3 we transplanted bone marrow of NOS3-/- and wild type (WT) mice into WT mice, producing chimerae expressing NOS3 only in vascular endothelium (BC-/EC+) or in both, blood cells and vascular endothelium (BC+/EC+). Both groups underwent 60 min of coronary occlusion in a closed-chest model of reperfused MI. During the 3 weeks post MI, structural and functional LV remodeling was serially assessed (24 h, 4 d, 1 w, 2 w and 3 w) by echocardiography. At 72 hours post MI, gene expression of several extracellular matrix (ECM) modifying molecules was determined by quantitative RT-PCR analysis. At 3 weeks post MI, hemodynamics were obtained by pressure catheter, scar size and collagen content were quantified post mortem by Gomori's One-step trichrome staining. RESULTS: Three weeks post MI, LV end-systolic (53.2±5.9 µl; ***p≤0.001; n = 5) and end-diastolic volumes (82.7±5.6 µl; *p<0.05; n = 5) were significantly increased in BC-/EC+, along with decreased LV developed pressure (67.5±1.8 mm Hg; n = 18; ***p≤0.001) and increased scar size/left ventricle (19.5±1.5%; n = 13; **p≤0.01) compared to BC+/EC+ (ESV: 35.6±2.2 µl; EDV: 69.1±2.6 µl n = 8; LVDP: 83.2±3.2 mm Hg; n = 24; scar size/LV13.8±0.7%; n = 16). Myocardial scar of BC-/EC+ was characterized by increased total collagen content (20.2±0.8%; n = 13; ***p≤0.001) compared to BC+/EC+ (15.9±0.5; n = 16), and increased collagen type I and III subtypes. CONCLUSION: Circulating NOS3 ameliorates maladaptive left ventricular remodeling following reperfused myocardial infarction.


Assuntos
Infarto do Miocárdio/enzimologia , Traumatismo por Reperfusão Miocárdica/enzimologia , Óxido Nítrico Sintase Tipo III/fisiologia , Remodelação Ventricular/fisiologia , Animais , Cicatriz/metabolismo , Cicatriz/patologia , Colágeno/análise , Fibrose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Óxido Nítrico/fisiologia , Óxido Nítrico Sintase Tipo III/sangue , Óxido Nítrico Sintase Tipo III/deficiência , Óxido Nítrico Sintase Tipo III/genética , Quimera por Radiação , Volume Sistólico , Disfunção Ventricular Esquerda/enzimologia , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
11.
Basic Res Cardiol ; 109(1): 398, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24346018

RESUMO

Nitric oxide (NO) derived from endothelial NO synthase (NOS3) plays a central role in myocardial ischemia/reperfusion (I/R)-injury. Subsets of circulating blood cells, including red blood cells (RBCs), carry a NOS3 and contribute to blood pressure regulation and RBC nitrite/nitrate formation. We hypothesized that the circulating blood born NOS3 also modulates the severity of myocardial infarction in disease models. We cross-transplanted bone marrow in wild-type and NOS3(-/-) mice with wild-type mice, producing chimeras expressing NOS3 only in vascular endothelium (BC-/EC+) or in both blood cells and vascular endothelium (BC+/EC+). After 60-min closed-chest coronary occlusion followed by 24 h reperfusion, cardiac function, infarct size (IS), NOx levels, RBCs NO formation, RBC deformability, and vascular reactivity were assessed. At baseline, BC-/EC+ chimera had lower nitrite levels in blood plasma (BC-/EC+: 2.13 ± 0.27 µM vs. BC+/EC+ 3.17 ± 0.29 µM; *p < 0.05), reduced DAF FM associated fluorescence within RBCs (BC-/EC+: 538.4 ± 12.8 mean fluorescence intensity (MFI) vs. BC+/EC+: 619.6 ± 6.9 MFI; ***p < 0.001) and impaired erythrocyte deformability (BC-/EC+: 0.33 ± 0.01 elongation index (EI) vs. BC+/EC+: 0.36 ± 0.06 EI; *p < 0.05), while vascular reactivity remained unaffected. Area at risk did not differ, but infarct size was higher in BC-/EC+ (BC-/EC+: 26 ± 3 %; BC+/EC+: 14 ± 2 %; **p < 0.01), resulting in decreased ejection fraction (BC-/EC+ 46 ± 2 % vs. BC+/EC+: 52 ± 2 %; *p < 0.05) and increased end-systolic volume. Application of the NOS inhibitor S-ethylisothiourea hydrobromide was associated with larger infarct size in BC+/EC+, whereas infarct size in BC-/EC+ mice remained unaffected. Reduced infarct size, preserved cardiac function, NO levels in RBC and RBC deformability suggest a modulating role of circulating NOS3 in an acute model of myocardial I/R in chimeric mice.


Assuntos
Infarto do Miocárdio/sangue , Óxido Nítrico Sintase Tipo III/sangue , Disfunção Ventricular Esquerda/sangue , Animais , Western Blotting , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Óxido Nítrico/sangue , Quimeras de Transplante , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologia
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