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1.
Vasc Health Risk Manag ; 15: 375-384, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695398

RESUMO

Background: Survivors of myocardial infarction (MI) are at high risk of new major adverse cardiovascular events (MACE). Coronary flow reserve (CFR) is a strong and independent predictor of MACE. Understanding the prevalence of impaired CFR in this patient group and identifying risk markers for impaired CFR are important steps in the development of personalized and targeted treatment for high-risk individuals with prior MI. Methods: PROFLOW is a prospective, exploratory, cross-sectional open study. We used information from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) to identify high-risk patients with a history of type-1 MI. We measured CFR non-invasively in a left anterior descending artery (LAD) using transthoracic Doppler echocardiography. Coronary flow velocity was measured at rest and at maximal flow after induction of hyperemia by intravenous infusion of adenosine (140 µg/kg/min). Independent predictors of CFR were assessed with multiple linear regression. Results: We included 619 patients. The median age was 69 (IQR 65-73), and 114 (18.4%) were women. Almost one-half of the patients, 285 (46.0%) had the multi-vessel disease, and 147 (23.7%) were incompletely revascularized. The majority were on optimal standard treatment eg ASA (93.1%), statins (90.0%), ACEI/ARB (82.6%) and beta-blockers (80.8%). The majority, 547 (88.4%) had no angina pectoris, and 572 (92.2%) were in NYHA class I. Evaluation of CFR was possible in 611 (98.7%) patients. Mean CFR was 2.74 (±0.79 (mean ± SD)). A substantial number of patients (39.7%) had CFR ≤2.5. In a multiple linear regression model age, dyslipidemia, smoking, hypertension, body mass index, incomplete revascularization, and treatment with angiotensin receptor blockers were independent predictors of CFR. Conclusion: In this high-risk group of patients with prior MI, the prevalence of impaired CFR was high. Further risk stratification with CFR in addition to traditional cardiovascular risk factors may improve predictive accuracy for future MACE in this patient population.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Ecocardiografia Doppler , Reserva Fracionada de Fluxo Miocárdico , Infarto do Miocárdio/diagnóstico por imagem , Adenosina/administração & dosagem , Idoso , Velocidade do Fluxo Sanguíneo , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/terapia , Vasos Coronários/fisiopatologia , Estudos Transversais , Feminino , Humanos , Hiperemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Valor Preditivo dos Testes , Prevalência , Prognóstico , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Prevenção Secundária , Suécia/epidemiologia , Vasodilatadores/administração & dosagem
2.
Neurosurg Rev ; 42(4): 843-852, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31617125

RESUMO

To perform a systematic review of the techniques for transient circulatory arrest during intracerebral aneurysm surgery according to the PRISMA guidelines. Search of PubMed and Google Scholar using the following: ("heart arrest" OR "cardiac standstill"[All Fields]) AND ("intracranial aneurysm" OR "intracranial"[All Fields] AND "aneurysm"[All Fields]). A total of 41 original articles were retrieved, of which 17 were excluded (review articles, editorials and single-case reports). A total of 24 separate articles published between 1984 and 2018 were included in the final analysis, where the majority of patients harbored anterior circulation giant or large aneurysms. Adenosine-induced cardiac arrest gave a short, temporary asystole. The method had benefits in aneurysm with a broad neck, a thin wall, in specific localizations with narrow surgical corridors or in case of intraoperative rupture. Rapid ventricular pacing (RVP) allows a longer and more easily controlled hypotension. Its use is largely limited to elective cases. Deep hypothermic circulatory arrest required a complex infrastructure, and fatal procedure complications lead to a 11.5-30% 30-day mortality rate, limiting its application to giant or complex aneurysm of the basilar artery or to residual posterior circulation aneurysm after endovascular treatment. Adenosine and RVP are both effective options to facilitate clipping of complex aneurysms. However, their use in patient with ischemic heart disease and cardiac arrhythmias should be avoided, and their safety in the context of subarachnoid hemorrhage is yet to be determined. Today, deep hypothermic circulatory arrest is almost obsolete due to endovascular alternatives.


Assuntos
Parada Cardíaca Induzida/métodos , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adenosina/administração & dosagem , Estimulação Cardíaca Artificial/métodos , Fármacos Cardiovasculares/administração & dosagem , Parada Circulatória Induzida por Hipotermia Profunda , Humanos , Hipotensão/induzido quimicamente , Hipotensão/etiologia
3.
Mol Cell ; 76(1): 96-109.e9, 2019 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-31474572

RESUMO

Circular RNAs (circRNAs) are prevalent in eukaryotic cells and viral genomes. Mammalian cells possess innate immunity to detect foreign circRNAs, but the molecular basis of self versus foreign identity in circRNA immunity is unknown. Here, we show that N6-methyladenosine (m6A) RNA modification on human circRNAs inhibits innate immunity. Foreign circRNAs are potent adjuvants to induce antigen-specific T cell activation, antibody production, and anti-tumor immunity in vivo, and m6A modification abrogates immune gene activation and adjuvant activity. m6A reader YTHDF2 sequesters m6A-circRNA and is essential for suppression of innate immunity. Unmodified circRNA, but not m6A-modified circRNA, directly activates RNA pattern recognition receptor RIG-I in the presence of lysine-63-linked polyubiquitin chain to cause filamentation of the adaptor protein MAVS and activation of the downstream transcription factor IRF3. CircRNA immunity has considerable parallel to prokaryotic DNA restriction modification system that transforms nucleic acid chemical modification into organismal innate immunity.


Assuntos
Adenosina/análogos & derivados , Imunidade Inata , Melanoma Experimental/terapia , /imunologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenosina/administração & dosagem , Adenosina/imunologia , Adenosina/metabolismo , Adjuvantes Imunológicos/administração & dosagem , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Proteína DEAD-box 58/imunologia , Proteína DEAD-box 58/metabolismo , Feminino , Células HEK293 , Células HeLa , Humanos , Imunização , Fator Regulador 3 de Interferon/imunologia , Fator Regulador 3 de Interferon/metabolismo , Interferons/imunologia , Interferons/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Melanoma Experimental/imunologia , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos Endogâmicos C57BL , Poliubiquitina/imunologia , Poliubiquitina/metabolismo , Multimerização Proteica , /metabolismo , Proteínas de Ligação a RNA/imunologia , Proteínas de Ligação a RNA/metabolismo , Ubiquitinação
4.
Int J Cardiovasc Imaging ; 35(11): 2103-2112, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31273632

RESUMO

Computed tomography derived fractional flow reserve (FFRCT) and computed tomography stress myocardial perfusion imaging (CTP) are techniques to assess haemodynamic significance of coronary stenosis. To compare the diagnostic performance of FFRCT and static rest/stress CTP in detecting fractional flow reserve (FFR) defined haemodynamically-significant stenosis (FFR ≤ 0.8). Fifty-one patients (96 vessels) with suspected coronary artery disease from a single institution planned for elective invasive-angiography prospectively underwent research indicated 320-detector-CT-coronary-angiography (CTA) and adenosine-stress CTP and invasive FFR. Analyses were performed in separate core-laboratories for FFRCT and CTP blinded to FFR results. Myocardial perfusion was assessed visually and semi-quantitatively by transmural perfusion ratio (TPR). Invasive FFR ≤ 0.8 was present in 33% of vessels and 49% of patients. FFRCT, visual CTP and TPR analysis was feasible in 96%, 92% and 92% of patients respectively. Overall per-vessel sensitivity, specificity and diagnostic accuracy for FFRCT were 81%, 85%, 84%, for visual CTP were 50%, 89%, 75% and for TPR were 69%, 48%, 56% respectively. Receiver-operating-characteristics curve analysis demonstrated larger per vessel area-under-curve (AUC) for FFRCT (0.89) compared with visual CTP (0.70; p < 0.001), TPR (0.58; p < 0.001) and CTA (0.70; p = 0.0007); AUC for CTA + FFRCT (0.91) was higher than CTA + visual CTP (0.77, p = 0.008) and CTA + TPR (0.74, p < 0.001). Per-patient AUC for FFRCT (0.90) was higher than visual CTP (0.69; p = 0.0016), TPR (0.56; p < 0.0001) and CTA (0.68; p = 0.001). Based on this selected cohort of patients FFRCT is superior to visually and semi-quantitatively assessed static rest/stress CTP in detecting haemodynamically-significant coronary stenosis as determined on invasive FFR.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Reserva Fracionada de Fluxo Miocárdico , Hemodinâmica , Tomografia Computadorizada Multidetectores , Imagem de Perfusão do Miocárdio/métodos , Adenosina/administração & dosagem , Idoso , Estenose Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Vasodilatadores/administração & dosagem
5.
Insect Biochem Mol Biol ; 113: 103183, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31265905

RESUMO

Juvenile hormone (JH), synthesized by the corpora allata (CA), controls development and reproduction in mosquitoes through its action on thousands of JH-responsive genes. These JH-dependent processes can be studied using tools that increase or decrease JH titers in vitro and in vivo. Juvenile hormone acid methyl transferase (JHAMT) is a critical JH biosynthetic enzyme. JHAMT utilizes the methyl donor S-adenosyl-methionine (SAM) to methylate farnesoic acid (FA) into methyl farnesoate (MF), releasing the product S-adenosyl-L-homocysteine (AdoHcy), which inhibits JHAMT. S-adenosyl-homocysteine hydrolase (SAHH) catalyzes AdoHcy hydrolysis to adenosine and homocysteine, alleviating AdoHcy inhibition of JHAMT. 3-deazaneplanocin A (DZNep), an analog of adenosine, is an inhibitor of SAHH, and an epigenetic drug for cancer therapy. We tested the effect of DZNep on in vitro JH synthesis by CA of mosquitoes. DZNep inhibited JH synthesis in a dose-response fashion. Addition of MF, but not of FA relieved the inhibition, demonstrating a direct effect on JHAMT. In vivo experiments, with addition of DZNep to the sugar ingested by mosquitoes, resulted in a dose-response decrease in JH synthesis and JH hemolymphatic titers, as well as expression of early trypsin, a JH-dependent gene. Our studies suggest that DZNep can be employed to lower JH synthesis and titer in experiments evaluating JH-controlled processes in mosquitoes.


Assuntos
Adenosina/análogos & derivados , Aedes/genética , Proteínas de Insetos/genética , Hormônios Juvenis/biossíntese , Metiltransferases/genética , Adenosina/administração & dosagem , Aedes/metabolismo , Animais , Feminino , Proteínas de Insetos/metabolismo , Metilação , Metiltransferases/metabolismo
6.
J Cardiovasc Magn Reson ; 21(1): 33, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31230593

RESUMO

BACKGROUND: Adenosine is used in stress perfusion cardiac imaging to reveal myocardial ischemia by its vasodilator effects. Caffeine is a competitive antagonist of adenosine. However, previous studies reported inconsistent results about the influence of caffeine on adenosine's vasodilator effect. This study assessed the impact of caffeine on the myocardial perfusion reserve index (MPRI) using adenosine stress cardiovascular magnetic resonance imaging (CMR). Moreover, we sought to evaluate if the splenic switch-off sign might be indicative of prior caffeine consumption. METHODS: Semiquantitative perfusion analysis was performed in 25 patients who underwent: 1) caffeine-naïve adenosine stress CMR demonstrating myocardial ischemia and, 2) repeat adenosine stress CMR after intake of caffeine. MPRI (global; remote and ischemic segments), and splenic perfusion ratio (SPR) were assessed and compared between both exams. RESULTS: Global MPRI after caffeine was lower vs. caffeine-naïve conditions (1.09 ± 0.19 vs. 1.24 ± 0.19; p <  0.01). MPRI in remote myocardium decreased by caffeine (1.24 ± 0.19 vs. 1.49 ± 0.19; p <  0.001) whereas MPRI in ischemic segments (0.89 ± 0.18 vs. 0.95 ± 0.23; p = 0.23) was similar, resulting in a lower MPRI ratio (=remote/ischemic segments) after caffeine consumption vs. caffeine-naïve conditions (1.41 ± 0.19 vs. 1.64 ± 0.35, p = 0.01). The SPR was unaffected by caffeine (SPR 0.38 ± 0.19 vs. 0.38 ± 0.18; p = 0.92). CONCLUSION: Caffeine consumption prior to adenosine stress CMR results in a lower global MPRI, which is driven by the decreased MPRI in remote myocardium and underlines the need of abstinence from caffeine. The splenic switch-off sign is not affected by prior caffeine intake.


Assuntos
Adenosina/administração & dosagem , Cafeína/administração & dosagem , Circulação Coronária/efeitos dos fármacos , Imagem Cinética por Ressonância Magnética , Isquemia Miocárdica/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Antagonistas de Receptores Purinérgicos P1/administração & dosagem , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Idoso , Cafeína/efeitos adversos , Feminino , Humanos , Hiperemia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologia , Valor Preditivo dos Testes , Estudos Prospectivos , Antagonistas de Receptores Purinérgicos P1/efeitos adversos , Reprodutibilidade dos Testes
7.
J Pharmacol Sci ; 140(2): 153-161, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31253430

RESUMO

A novel AMP-activated protein kinase (AMPK) activator, IMM-H007 (H007), has been reported to reduce serum lipid levels and inhibit lipid accumulation in the liver in hyperlipidemic animal models. However, how H007 ameliorates hepatic steatosis and inflammation remains unknown. In the present study, H007, at 200 mg/kg, reduced hepatic lipid levels and the levels of collagenous fiber in the liver in high-fat diet (HFD)-fed hamsters compared to those in the HFD group. Meanwhile, compared to the controls, H007 significantly inhibited sterol-regulatory element binding protein (SREBP)-1c and acetyl CoA carboxylase (ACC) expression by upregulating the AMPK activity, suppressing the saturated fatty acid accumulation and increasing polyunsaturated fatty acid synthesis in the liver. Compared to the controls, H007 treatment inhibited the expression of monocyte chemotactic protein (MCP-1) in fatty acid-treated HepG2 cells; suppressed leukocyte adherence and rolling on the liver microvasculature; and suppressed hepatic macrophage infiltration. H007 also suppressed the expression of nuclear factor-κB (NF-κB) p65 in fatty acid- and lipopolysaccharide-treated HepG2 cells compared to that in the controls by activating AMPK. These data suggested that H007 had a beneficial effect by improving the lipid composition in the liver and inhibiting inflammatory cell trafficking in the development of nonalcoholic fatty liver disease.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adenosina/análogos & derivados , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Ativadores de Enzimas/administração & dosagem , Ativadores de Enzimas/farmacologia , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/metabolismo , Leucócitos/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Adenosina/administração & dosagem , Adenosina/farmacologia , Animais , Modelos Animais de Doenças , Células Hep G2 , Humanos , Inflamação , Masculino , Mesocricetus
8.
J Trauma Acute Care Surg ; 87(3): 606-613, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31162330

RESUMO

BACKGROUND: Noncompressible torso hemorrhage is a leading cause of traumatic death. Our aim was to examine survival time and the expression of key master genes of cellular metabolism after 3% NaCl adenosine, lidocaine, and Mg (ALM) bolus and 4 hours 0.9% NaCl/ALM "drip" in a rat model of uncontrolled hemorrhagic shock. METHODS: Male Sprague-Dawley rats (425 ± 8 g) were anesthetized and randomly assigned to saline controls (n = 10) or ALM therapy (n = 10). Hemorrhage was induced by liver resection (60% left lateral lobe). After 15 minutes, a single intravenous bolus of 3% NaCl ± ALM (0.7 mL/kg) was administered (Phase 1), and after 60 minutes, a 0.9% NaCl ± ALM stabilization "drip" (0.5 mL/kg per hour) was infused for 4 hours (Phase 2) with 72 hours monitoring. Mean arterial pressure and lactate were measured. After 72 hours (or high moribund score), tissues were freeze-clamped and stored at -80°C. Total RNA was extracted in heart, brain, and liver, and the relative expressions of amp-k, mtCO3, PGC-1α, and sirt-1 genes were determined. RESULTS: Kaplan-Meier survival curves showed that controls had a mean survival time of 22.6 ± 4.5 hours, and ALM animals, 72 ± 0 hours (p < 0.05). Death in controls was accompanied by approximately sevenfold increase in lactate, while ALM animals maintained lactates similar to baseline over 72 hours. The relative expression of amp-k, PGC-1α, and sirt-1 in heart and brain was 1.5-fold and 2.7-fold higher in the ALM group compared with controls (p < 0.05), with the exception of mitochondrial encoded cytochrome C oxidase III pseudogene 1 in heart, which was 19-fold higher. In contrast, amp-k, sirt-1, and mtCO3 gene expression in liver was significantly 29-41% lower in the ALM group compared with controls, and PGC-1α was 75% lower. CONCLUSION: Small-volume ALM therapy led to 3.3-times longer survival time compared with saline controls after hemorrhagic shock. A hallmark of the ALM-survival phenotype in heart and brain was an upregulation of amp-k, PGC-1α, sirt-1, and mtCO3 to presumably "boost" mitochondrial function and ATP production, and a contrasting downregulation in liver. These central-peripheral differences in gene expression require further investigation.


Assuntos
Adenosina/uso terapêutico , Hidratação/métodos , Lidocaína/uso terapêutico , Magnésio/uso terapêutico , Choque Hemorrágico/terapia , Adenosina/administração & dosagem , Animais , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Perfilação da Expressão Gênica , Lidocaína/administração & dosagem , Magnésio/administração & dosagem , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/metabolismo , Choque Hemorrágico/mortalidade , Fatores de Tempo
9.
Am J Emerg Med ; 37(8): 1604.e1-1604.e2, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31155170

RESUMO

Supraventricular Tachycardias are the most common cardiac rhythm disturbances in pregnant patients. Adenosine is the recommended medication to treat these arrhythmias in part because the medication is projected to be metabolized prior to crossing the placenta and producing any fetal effects. Reported here is a case of a pregnant patient treated with adenosine in which the fetal heart activity was monitored through point of care ultrasonography with documentation of no fetal impact from this medication. This is the first documentation of a lack of fetal effect from adenosine.


Assuntos
Adenosina/administração & dosagem , Antiarrítmicos/administração & dosagem , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Taquicardia Supraventricular/tratamento farmacológico , Administração Intravenosa , Adulto , Eletrocardiografia , Feminino , Monitorização Fetal/métodos , Frequência Cardíaca Fetal , Humanos , Testes Imediatos , Gravidez , Ultrassonografia Pré-Natal
10.
Kardiol Pol ; 77(6): 610-617, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31241047

RESUMO

BACKGROUND: Achievement of maximal hyperemia is mandatory for an accurate calculation of fractional flow reserve (FFR) and it is obtained with adenosine given either as an intravenous infusion or as an intracoronary bolus. AIMS: The purpose of this study was to compare the infusion of adenosine with intracoronary adenosine bolus dose escalation in the optimal assessment of peak FFR. METHODS: We enrolled consecutive patients with borderline coronary lesions that were assessed by FFR with the use of adenosine intracoronary boluses (100, 200, 400 and 600 µg) and intravenous infusion of 140 µg/kg/min and 280 µg/kg/min. FFR values were assessed and compared. RESULTS: Fifty patients with 125 borderline coronary artery stenoses were enrolled. Physiological severity assessed with: intravenous adenosine infusion at 140 µg/kg/min was mean 0.82 ± 0.09; infusion at 280 µg/kg/min - 0.81 ± 0.09; intracoronary bolus of 100 µg, 200 µg, 400 µg and 600 µg - 0.83 ± 0.09; 0.83 ± 0.09, 0.83 ± 0.09; and 0.83 ± 0.09, respectively. There was a strong linear correlation between FFR values obtained from 140 µg/kg/min infusion and adenosine intracoronary 100, 200, 400 and 600 µg bolus injection (r = 0.989, r = 0.99, r = 0.993, r = 0.994, respectively, p < 0.001 for all). CONCLUSIONS: FFR values achieved with intracoronary boluses of adenosine are very similar, but not identical to those obtained using intravenous adenosine administration. The values of FFR may vary between escalating doses of intracoronary boluses and intravenous infusion.


Assuntos
Adenosina/administração & dosagem , Doença da Artéria Coronariana/diagnóstico por imagem , Circulação Coronária , Estenose Coronária/diagnóstico por imagem , Hiperemia/induzido quimicamente , Idoso , Feminino , Reserva Fracionada de Fluxo Miocárdico , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Vasodilatadores/administração & dosagem
11.
Int J Cardiovasc Imaging ; 35(7): 1319-1325, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31093894

RESUMO

To demonstrate the potential for differentiating normal and diseased myocardium without Gadolinium using rest and stress T1-mapping. Patients undergoing 1.5T magnetic resonance imaging (MRI) as part of clinical work-up due to suspicion of coronary artery disease (CAD) were included. Adenosine stress perfusion MRI and late gadolinium enhancement (LGE) imaging were performed to identify ischemic and infarcted myocardium. Patients were retrospectively categorized into an ischemic, infarct and control group based on conventional acquisitions. Patient with both ischemic and infarcted myocardium were excluded. A total of 64 patients were included: ten with myocardial ischemia, 15 with myocardial infarction, and 39 controls. A native Modified Look-Locker Inversion Recovery (MOLLI) T1-mapping acquisition was performed at rest and stress. Pixel-wise myocardial T1-maps were acquired in short-axis view with inline motion-correction. Short-axis T1-maps were manually contoured using conservative septal sampling. Regions of interest were sampled in ischemic and infarcted areas detected on perfusion and LGE images. T1 reactivity was calculated as the percentage difference in T1 values between rest and stress. Remote myocardium was defined as myocardium without defects in the ischemic and infarcted group whereas normal myocardium is found in the control group only. Native T1-values were significantly higher in infarcted myocardium in rest and stress [median 1044 ms (interquartile range (IQR) 985-1076) and 1053 ms (IQR 989-1088)] compared to ischemic myocardium [median 961 ms (IQR 939-988) and 958 ms (IQR 945-988)]. T1-reactivity was significantly lower in ischemic and infarcted myocardium [median 0.00% (IQR - 0.18 to 0.16) and 0.41% (IQR 0.09-0.86)] compared to remote myocardium [median 3.54% (IQR 1.48-5.78) and 3.21% (IQR 1.95-4.79)]. Rest-stress T1-mapping is able to distinguish between normal, ischemic, infarcted and remote myocardium using native T1-values and T1-reactivity, and holds potential as an imaging biomarker for tissue characterization in MRI.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Isquemia Miocárdica/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Miocárdio/patologia , Adenosina/administração & dosagem , Idoso , Meios de Contraste/administração & dosagem , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária , Diagnóstico Diferencial , Feminino , Gadolínio DTPA/administração & dosagem , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Isquemia Miocárdica/patologia , Isquemia Miocárdica/fisiopatologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Sobrevivência de Tecidos , Vasodilatadores/administração & dosagem
12.
Pharmacol Biochem Behav ; 181: 110-116, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31054946

RESUMO

Repetitive behaviors are diagnostic for autism spectrum disorder (ASD) and commonly observed in other neurodevelopmental disorders. Currently, there are no effective pharmacological treatments for repetitive behavior in these clinical conditions. This is due to the lack of information about the specific neural circuitry that mediates the development and expression of repetitive behavior. Our previous work in mouse models has linked repetitive behavior to decreased activation of the subthalamic nucleus, a brain region in the indirect and hyperdirect pathways in the basal ganglia circuitry. The present experiments were designed to further test our hypothesis that pharmacological activation of the indirect pathway would reduce repetitive behavior. We used a combination of adenosine A1 and A2A receptor agonists that have been shown to alter the firing frequency of dorsal striatal neurons within the indirect pathway of the basal ganglia. This drug combination markedly and selectively reduced repetitive behavior in both male and female C58 mice over a six-hour period, an effect that required both A1 and A2A agonists as neither alone reduced repetitive behavior. The adenosine A1 and A2A receptor agonist combination also significantly increased the number of Fos transcripts and Fos positive cells in dorsal striatum. Fos induction was found in both direct and indirect pathway neurons suggesting that the drug combination restored the balance of activation across these complementary basal ganglia pathways. The adenosine A1 and A2A receptor agonist combination also maintained its effectiveness in reducing repetitive behavior over a 7-day period. These findings point to novel potential therapeutic targets for development of drug therapies for repetitive behavior in clinical disorders.


Assuntos
Agonistas do Receptor A1 de Adenosina/uso terapêutico , Agonistas do Receptor A2 de Adenosina/uso terapêutico , Adenosina/análogos & derivados , Comportamento Compulsivo/tratamento farmacológico , Fenetilaminas/uso terapêutico , Comportamento Estereotipado/efeitos dos fármacos , Adenosina/administração & dosagem , Adenosina/química , Adenosina/uso terapêutico , Agonistas do Receptor A1 de Adenosina/administração & dosagem , Agonistas do Receptor A1 de Adenosina/química , Agonistas do Receptor A2 de Adenosina/administração & dosagem , Agonistas do Receptor A2 de Adenosina/química , Análise de Variância , Animais , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/metabolismo , Comportamento Animal/efeitos dos fármacos , Corpo Estriado/citologia , Quimioterapia Combinada , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Neurônios/metabolismo , Óleo de Amendoim/química , Óleo de Amendoim/farmacologia , Fenetilaminas/administração & dosagem , Fenetilaminas/química , Fenótipo , Proteínas Proto-Oncogênicas c-fos/metabolismo
13.
Int J Cancer ; 145(11): 3064-3077, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31032902

RESUMO

Myofibroblasts are a population of highly contractile fibroblasts that express and require the activity of the transcription factor Snail1. Cancer-associated fibroblasts (CAFs) correlate with low survival of cancer patients when present in the stroma of primary tumors. Remarkably, the presence of myofibroblastic CAFs (which express Snail1) creates mechanical properties in the tumor microenvironment that support metastasis. However, therapeutic blockage of fibroblast activity in patients with cancer is a double-edged sword, as normal fibroblast activities often restrict tumor cell invasion. We used fibroblasts depleted of Snail1 or protein arginine methyltransferases 1 and 4 (PRMT1/-4) to identify specific epigenetic modifications induced by TGFß/Snail1. Furthermore, we analyzed the in vivo efficiency of methyltransferase inhibitors using mouse models of wound healing and metastasis, as well as fibroblasts isolated from patients with idiopathic pulmonary fibrosis (IPF). Mechanistically, TGFß-induced Snail1 promotes the epigenetic mark of asymmetrically dimethylated arginine. Critically, we found that inhibitors of methyltransferases prevent myofibroblast activity (but not regular fibroblast activity) in the extracellular matrix, both in cell culture and in vivo. In a mouse breast cancer model, the inhibitor sinefungin reduces both the myofibroblast activity in the tumor stroma and the metastatic burden in the lung. Two distinct inhibitors effectively blocked the exacerbated myofibroblast activity of patient-derived IPF fibroblasts. Our data reveal epigenetic regulation of myofibroblast transdifferentiation in both wound healing and in disease (fibrosis and breast cancer). Thus, methyltransferase inhibitors are good candidates as therapeutic reagents for these diseases.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Inibidores Enzimáticos/administração & dosagem , Fibrose Pulmonar Idiopática/tratamento farmacológico , Neoplasias Pulmonares/secundário , Metiltransferases/antagonistas & inibidores , Miofibroblastos/efeitos dos fármacos , Fatores de Transcrição da Família Snail/genética , Adenosina/administração & dosagem , Adenosina/análogos & derivados , Adenosina/farmacologia , Animais , Neoplasias da Mama/enzimologia , Fibroblastos Associados a Câncer/citologia , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/metabolismo , Linhagem Celular Tumoral , Transdiferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Epigênese Genética , Feminino , Deleção de Genes , Humanos , Fibrose Pulmonar Idiopática/enzimologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/enzimologia , Metiltransferases/genética , Camundongos , Miofibroblastos/citologia , Miofibroblastos/enzimologia , Fatores de Transcrição da Família Snail/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Indian Heart J ; 71(1): 74-79, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31000187

RESUMO

OBJECTIVE: Fractional flow reserve (FFR) using adenosine has been the gold standard in the functional assessment of intermediate coronary stenoses in the catheterization laboratory. We aim to study the correlation of adenosine-free indices such as whole cycle Pd/Pa [the ratio of mean distal coronary pressure (Pd) to the mean pressure observed in the aorta (Pa)], instantaneous wave-free ratio (iFR), and contrast-induced submaximal hyperemia (cFFR) with FFR. METHODS: This multicenter, prospective, observational study included patients with stable angina or acute coronary syndrome (>48 h since onset) with discrete intermediate coronary lesions (40-70% diameter stenosis). All patients underwent assessment of whole cycle Pd/Pa, iFR, cFFR, and FFR. We then evaluated the correlation of these indices with FFR and assessed the diagnostic efficiencies of them against FFR ≤0.80. RESULTS: Of the 103 patients from three different centers, 83 lesions were included for analysis. The correlation coefficient (r value) of whole cycle Pd/Pa, iFR, and cFFR in relation to FFR were +0.84, +0.77, and +0.70 (all p values < 0.001), respectively, and the c-statistic against FFR ≤0.80 were 0.92 (0.86-0.98), 0.89(0.81-0.97), and 0.91 (0.85-0.97) (all p values < 0.001), respectively. The best cut-off values identified by receiver-operator characteristic curve for whole cycle Pd/Pa, iFR, and cFFR were 0.94, 0.90, and 0.88, respectively, for an FFR ≤0.80. By the concept of "adenosine-free zone" (iFR = 0.86-0.93), 59% lesions in this study would not require adenosine. CONCLUSION: All the three adenosine-free indices had good correlation with FFR. There is no difference in the diagnostic accuracies among the indices in functional evaluation of discrete intermediate coronary stenoses. However, further validation is needed before adoption of adenosine-free pressure parameters into clinical practice.


Assuntos
Adenosina/administração & dosagem , Cateterismo Cardíaco/métodos , Estenose Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Hiperemia/induzido quimicamente , Angiografia Coronária , Estenose Coronária/diagnóstico , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/efeitos dos fármacos , Feminino , Humanos , Hiperemia/fisiopatologia , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Vasodilatadores/administração & dosagem
15.
J Trauma Acute Care Surg ; 87(1): 68-75, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30985476

RESUMO

BACKGROUND: Adenosine, lidocaine, and magnesium (ALM) is a cardioplegic agent shown to improve survival by improving cardiac function, tissue perfusion, and coagulopathy in animal models of shock. We hypothesized prehospital ALM treatment in hemorrhagic shock would improve survival compared to current Tactical Combat Casualty Care (TCCC) resuscitation beyond the golden hour. METHODS: Swine were randomized to: (1) TCCC, (2) 2 mL·kg vehicle control (VC), (3) 2 mL·kg ALM + drip, (4) 4 mL·kg ALM + drip, 5) 4 mL·kg ALM + delayed drip at 0.5 mL·kg·h, 6) 4 mL/kg VC, 7) 4 mL·kg ALM for 15 minutes + delayed drip at 3 mL·kg·h. Animals underwent pressure controlled hemorrhage to mean arterial pressure (MAP) of 30 mm Hg (S = 0). Treatment was administered at T = 0. After 120 minutes of simulated prehospital care (T = 120) blood product resuscitation commenced. Physiologic variables were recorded and laboratories were drawn at specified time points. RESULTS: Tactical Combat Casualty Care demonstrated superior survival to all other agents. The VC and ALM groups had lower MAPs and systolic blood pressures compared with TCCC. Except for the VC groups, lactate levels remained similar with correction of base deficit after prehospital resuscitation in all groups. Kidney function and liver function remained comparable across all groups. Compared with baseline values, TCCC demonstrated significant hypocoagulability. CONCLUSION: Adenosine, lidocaine, and magnesium, as administered in this study, are inferior to current Hextend-based resuscitation for survival from prolonged hemorrhagic shock in this model. In survivors, ALM groups had lower systolic blood pressures and MAPs, but provided a protective effect on coagulopathy as compared to TCCC. Adenosine, lidocaine, and magnesium do not appear to be a suitable low volume replacement to current TCCC resuscitation. The reduced coagulopathy compared to TCCC warrants future studies of ALM, perhaps as a therapeutic adjunct.


Assuntos
Adenosina/uso terapêutico , Soluções Cardioplégicas/uso terapêutico , Serviços Médicos de Emergência/métodos , Lidocaína/uso terapêutico , Magnésio/uso terapêutico , Medicina Militar/métodos , Ressuscitação/métodos , Choque Hemorrágico/terapia , Ferimentos e Lesões/terapia , Adenosina/administração & dosagem , Animais , Soluções Cardioplégicas/administração & dosagem , Modelos Animais de Doenças , Lidocaína/administração & dosagem , Magnésio/administração & dosagem , Masculino , Ressuscitação/mortalidade , Choque Hemorrágico/mortalidade , Suínos , Ferimentos e Lesões/mortalidade
16.
Int J Mol Sci ; 20(6)2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30875759

RESUMO

Cordyceps species are known to contain numerous bioactive compounds, including cordycepin. Extracts of Cordyceps militaris (CME) are used in diverse medicinal purposes because of their bioactive components. Cordycepin, one of the active components of CME, exhibits anti-proliferative, pro-apoptotic, and anti-inflammatory effects. Cordycepin structurally differs from adenosine in that its ribose lacks an oxygen atom at the 3' position. We previously reported that cordycepin suppresses Epstein⁻Barr virus (EBV) gene expression and lytic replication in EBV-associated gastric carcinoma (EBVaGC). However, other studies reported that cordycepin induces EBV gene expression and lytic reactivation. Thus, it was reasonable to clarify the bioactive effects of CME bioactive compounds on the EBV life cycle. We first confirmed that CME preferentially induces EBV gene expression and lytic reactivation; second, we determined that adenosine in CME induces EBV gene expression and lytic reactivation; third, we discovered that the adenosine A1 receptor (ADORA1) is required for adenosine to initiate signaling for upregulating BZLF1, which encodes for a key EBV regulator (Zta) of the EBV lytic cycle; finally, we showed that BZLF1 upregulation by adenosine leads to delayed tumor development in the EBVaGC xenograft mouse model. Taken together, these results suggest that adenosine is an EBV lytic cycle inducer that inhibits EBVaGC development.


Assuntos
Desoxiadenosinas/administração & dosagem , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Herpesvirus Humano 4/fisiologia , Receptor A1 de Adenosina/metabolismo , Neoplasias Gástricas/virologia , Transativadores/genética , Adenosina/administração & dosagem , Adenosina/farmacologia , Animais , Linhagem Celular Tumoral , Desoxiadenosinas/química , Desoxiadenosinas/farmacologia , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Herpesvirus Humano 4/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Humanos , Camundongos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Regulação para Cima , Ativação Viral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
17.
J Biol Chem ; 294(17): 6888-6898, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-30872404

RESUMO

Virus-inhibitory protein, endoplasmic reticulum-associated, interferon-inducible (viperin) is a radical SAM enzyme that plays a multifaceted role in the cellular antiviral response. Viperin has recently been shown to catalyze the SAM-dependent formation of 3'-deoxy-3',4'-didehydro-CTP (ddhCTP), which inhibits some viral RNA polymerases. Viperin is also implicated in regulating Lys-63-linked polyubiquitination of interleukin-1 receptor-associated kinase-1 (IRAK1) by the E3 ubiquitin ligase tumor necrosis factor receptor-associated factor 6 (TRAF6) as part of the Toll-like receptor-7 and -9 (TLR7/9) innate immune signaling pathways. In these pathways, the poly-ubiquitination of IRAK1 by TRAF6 is necessary to activate IRAK1, which then phosphorylates downstream targets and ultimately leads to the production of type I interferons. That viperin is a component of these pathways suggested that its enzymatic activity might be regulated by interactions with partner proteins. To test this idea, we have reconstituted the interactions between viperin, IRAK1, and TRAF6 by transiently expressing these enzymes in HEK 293T cells. We show that IRAK1 and TRAF6 increase viperin activity ∼10-fold to efficiently catalyze the radical-mediated dehydration of CTP to ddhCTP. Furthermore, we found that TRAF6-mediated ubiquitination of IRAK1 requires the association of viperin with both IRAK1 and TRAF6. Ubiquitination appears to depend on structural changes in viperin induced by SAM binding, but, significantly, does not require catalytically active viperin. We conclude that the synergistic activation of viperin and IRAK1 provides a mechanism that couples innate immune signaling with the production of the antiviral nucleotide ddhCTP.


Assuntos
Antivirais/metabolismo , Citidina Trifosfato/biossíntese , Imunidade Inata , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Proteínas/metabolismo , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/metabolismo , Adenosina/administração & dosagem , Adenosina/análogos & derivados , Células HEK293 , Meia-Vida , Humanos , Fosforilação , Ligação Proteica , S-Adenosilmetionina/metabolismo , Ubiquitinação
18.
Neurotox Res ; 36(1): 193-203, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30927242

RESUMO

The metabolism of adenosine (ADO) and nitric oxide (NO) in brain tissues is closely associated with the change of oxygen content. They have contrary effects in the onset of hyperbaric oxygen (HBO)-induced central nervous system oxygen toxicity (CNS OT): ADO can suppress the onset, while NO promotes it. We adopted the ADO-augmenting measure and NO-inhibiting measure in this study and found the combined use had a far superior preventive and therapeutic effect in protecting against CNS OT compared with the use of either measure alone. So we hypothesized that there is an interaction between ADO and NO which has an important impact on the onset of CNS OT. On this basis, we administered ADO-augmenting or ADO-inhibiting drugs to rats. After exposure to HBO, the onset of CNS OT was evaluated, followed by the measurement of NO content in brain tissues. In another experiment, rats were administered NO-augmenting or NO-inhibiting drugs. After exposure to HBO, the onset of CNS OT was evaluated, followed by measurement of the activities of ADO metabolism-related enzymes in brain tissues. The results showed that, following ADO augmentation, the content of NO and its metabolite was significantly reduced, and the onset of CNS OT significantly improved. After ADO inhibition, just the opposite was observed. NO promotion resulted in a decrease in the activity of ADO-producing enzyme, an increase in the activity of ADO-decomposing enzyme, and an aggravation in CNS OT. The above results were all reversed after an inhibition in NO content. Studies have shown that exposure to HBO has a significant impact on the content of ADO and NO in brain tissues as well as their biological effects, and ADO and NO might have an intense interaction, which might generate an important effect on the onset of CNS OT. The prophylaxis and treatment effects of CNS OT can be greatly enhanced by augmenting ADO and inhibiting NO.


Assuntos
Adenosina/metabolismo , Córtex Cerebral/metabolismo , Óxido Nítrico/metabolismo , Oxigênio/toxicidade , Adenosina/administração & dosagem , Adenosina Quinase/metabolismo , Animais , Indazóis/administração & dosagem , Pulmão/patologia , Masculino , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Ratos Sprague-Dawley
19.
Cardiovasc Diabetol ; 18(1): 22, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30819191

RESUMO

BACKGROUND: Patients with type 2 diabetes mellitus are at an increased risk of adverse cardiovascular events compared to those without diabetes. The timing, relative to disease onset, and degree of glycemic control that reduces the risk of adverse cardiovascular events remains uncertain. Coronary microvascular dysfunction is prevalent in patients with type 2 diabetes mellitus and is linked to adverse cardiovascular events. We assessed the association between endothelial-dependent and endothelial-independent coronary microvascular dysfunction and glycemic control in patients presenting with chest pain and nonobstructive coronary disease at angiography. METHODS: Patients presenting with chest pain and found to have non-obstructive CAD (stenosis < 40%) at angiography underwent an invasive assessment of endothelial-independent and endothelial -dependent microvascular function. Endothelial-independent microvascular function was assessed by comparing the coronary flow velocity, measured using a Doppler guidewire, in response to intracoronary infusion of adenosine to calculate the coronary flow reserve ratio in response to adenosine (CFRAdn Ratio). A CFRAdn Ratio ≤ 2.5 was considered abnormal. Endothelial-dependent microvascular function was assessed by measuring the percent change in coronary blood flow in response to intracoronary infusions of acetylcholine (%ΔCBFAch), and microvascular endothelial dysfunction defined as a %ΔCBFAch of ≤ 50%. Patients were classified by normal versus abnormal CFRAdn Ratio and %ΔCBFAch. Measurements of HbA1c and fasting serum glucose were obtained prior to catheterization and compared between groups. RESULTS: Between 1993 and 2012, 1469 patients (mean age 50.4 years, 35% male) underwent coronary angiography and invasive testing for coronary microvascular dysfunction, of which 129 (8.8%) had type 2 diabetes. Fifty-one (39.5%) had an abnormal %ΔCBFAch and 49 (38.0%) had an abnormal CFRAdn Ratio. Conventional cardiovascular risk factors and cardiovascular or diabetic medication use did not vary significantly between groups. Females with an abnormal CFRAdn Ratio or abnormal %ΔCBFAch had a significantly higher HbA1c compared to patients with a normal CFRAdn Ratio or %ΔCBFAch respectively: HbA1c % (standard deviation) 7.4 (2.1) vs. 6.5 (1.1), p = 0.035 and 7.3 (1.9) vs. 6.4 (1.2), p = 0.022, respectively. Female patients with an abnormal CFRAdn Ratio had significantly higher fasting serum glucose concentrations compared to those with a normal CFRAdn Ratio: fasting serum glucose mg/dL (standard deviation) 144.4 (55.6) vs. 121.9 (28.1), p = 0.035. This was not observed in men. Amongst female diabetics, a higher HbA1c was significantly associated with any coronary microvascular dysfunction both in a univariate and multivariate analysis: odds ratio (95% confidence interval) 1.69 (1.01-2.86) p = 0.049; and a fasting serum glucose > 140 mg/dL was significantly associated with an abnormal CFRAdn Ratio, 4.28 (1.43-12.81). CONCLUSION: Poor glycemic control is associated with coronary microvascular dysfunction amongst female diabetics presenting with chest pain and non-obstructive CAD. These findings highlight the importance of sex specific risk stratification models and treatment strategies when managing cardiovascular risk amongst diabetics. Further studies are required to identify additional risk prevention tools and therapies targeting microvascular dysfunction as an integrated index of cardiovascular risk.


Assuntos
Angina Pectoris/fisiopatologia , Glicemia/metabolismo , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Microvasos/fisiopatologia , Acetilcolina/administração & dosagem , Adenosina/administração & dosagem , Adulto , Idoso , Angina Pectoris/diagnóstico por imagem , Angina Pectoris/epidemiologia , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/epidemiologia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/efeitos dos fármacos , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Ecocardiografia Doppler , Feminino , Reserva Fracionada de Fluxo Miocárdico , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Microcirculação , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Minnesota/epidemiologia , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Vasoconstritores/administração & dosagem , Vasodilatadores/administração & dosagem
20.
J Cardiovasc Comput Tomogr ; 13(2): 86-91, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30718182

RESUMO

BACKGROUND: Myocardial CT perfusion imaging with dual energy (DE-CTP) can produce myocardial iodine perfusion maps. This study evaluated the accuracy of first pass myocardial iodine concentration in DE-CTP compared to CT derived dynamic myocardial blood flow (MBF) to determine regional myocardial ischemia in an animal model of coronary stenosis using invasive Fractional Flow Reserve (FFR). METHODS: Seven anaesthetised pigs (mean weight 51 ±â€¯4 kg) had a graded coronary artery stenosis produced in six vessels (plus one control animal) using a methacrylate plug with FFR recorded in the target artery (ischemia = FFR<0.80). During adenosine vasodilation, dynamic myocardial CTP and DE-CTP imaging was performed. Using vendor supplied applications, matching regions of interest (ROIs) were drawn in myocardial segments supplied by the target coronary artery to compare the two techniques. RESULTS: FFR correlated strongly to MBF (r = 0.81) and modestly to myocardial iodine concentration (r = 0.65) and myocardial CT attenuation (r = 0.62) (p < 0.0001 each). The correlation to FFR was stronger using relative ratios (absolute value/reference value of normal segments) than absolute values for MBF (r = 0.86), myocardial iodine concentration (r = 0.80) and CT number (r = 0.79) (p < 0.0001 each). Comparing normal and ischaemic territories there were significant differences in MBF (96 ±â€¯14 vs. 27 ±â€¯18 ml/100 ml of tissue/min, p < 0.0001), myocardial iodine concentration (3.5 ±â€¯1 vs. 1.0 ±â€¯0.7 mg/ml, p < 0.0001) and myocardial CT number (89 ±â€¯9 vs. 73 ±â€¯14 HU, p = 0.002). Myocardial iodine concentration had 91% sensitivity and 98% specificity for detecting FFR <0.8. CONCLUSION: Quantified myocardial iodine content from first pass DE-CTP correlates with CT derived myocardial blood flow and FFR and accurately discriminates ischemic territories in a porcine model. The accuracy and utility of myocardial iodine content in DE-CTP warrants further investigation in a clinical population with FFR as a reference standard.


Assuntos
Meios de Contraste/metabolismo , Estenose Coronária/diagnóstico por imagem , Reserva Fracionada de Fluxo Miocárdico , Iodo/metabolismo , Imagem de Perfusão do Miocárdio/métodos , Miocárdio/metabolismo , Tomografia Computadorizada por Raios X , Adenosina/administração & dosagem , Animais , Meios de Contraste/administração & dosagem , Estenose Coronária/metabolismo , Estenose Coronária/fisiopatologia , Modelos Animais de Doenças , Feminino , Valor Preditivo dos Testes , Interpretação de Imagem Radiográfica Assistida por Computador , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Sus scrofa , Vasodilatadores/administração & dosagem
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