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1.
World J Pediatr Congenit Heart Surg ; : 21501351241235959, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38646828

RESUMO

Background: Aortopulmonary window (APW) is a rare anomaly with variable morphology and associated cardiac anomalies. We evaluated impact of patient and operative factors on mid-term outcomes following APW repair. Methods: Twenty-nine patients underwent surgical APW repair at our institution from 1996 to 2022. Eight (28%) had simple APW, accompanied by only atrial septal defect or patent ductus arteriosus; 21 (72%) had complex APW with additional cardiovascular lesions, including nine with interrupted aortic arch. Median operative age was 19 days (range 2 days-1.5 years) via single-patch (n = 12, 41%), double-patch (n = 15, 52%), or ligation and division (n = 2, 7%). Results: The only mortality occurred in-hospital 1.4 years postoperatively following remote myocardial infarction. Factors associated with longer postoperative length of stay were complex APW (P = .003), genetic syndrome (P = .003), noncardiovascular comorbidities (P = .002), lower birth weight (P = .03), and lower operative weight (P = .03). Six patients (21%) with complex APW underwent unplanned cardiothoracic reintervention(s), including two with arch reintervention following arch advancement for interruption. Reintervention-free survival was similar for simple versus complex APW, operative age categories, and repair techniques. At median follow-up 5.5 years postoperatively, no patients had residual APW or persistent pulmonary hypertension, 1 (3%) had greater than mild ventricular dysfunction, and 25 (89% survivors) had NYHA class I functional status. Conclusions: Operative APW repair has excellent mid-term survival, durability, and functional status, regardless of operative age, cardiovascular comorbidities, or repair technique. Cardiac and noncardiac comorbidities may be associated with prolonged length of stay.

2.
Magn Reson Med ; 91(5): 1936-1950, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38174593

RESUMO

PURPOSE: Widely used conventional 2D T2 * approaches that are based on breath-held, electrocardiogram (ECG)-gated, multi-gradient-echo sequences are prone to motion artifacts in the presence of incomplete breath holding or arrhythmias, which is common in cardiac patients. To address these limitations, a 3D, non-ECG-gated, free-breathing T2 * technique that enables rapid whole-heart coverage was developed and validated. METHODS: A continuous random Gaussian 3D k-space sampling was implemented using a low-rank tensor framework for motion-resolved 3D T2 * imaging. This approach was tested in healthy human volunteers and in swine before and after intravenous administration of ferumoxytol. RESULTS: Spatial-resolution matched T2 * images were acquired with 2-3-fold reduction in scan time using the proposed T2 * mapping approach relative to conventional T2 * mapping. Compared with the conventional approach, T2 * images acquired with the proposed method demonstrated reduced off-resonance and flow artifacts, leading to higher image quality and lower coefficient of variation in T2 *-weighted images of the myocardium of swine and humans. Mean myocardial T2 * values determined using the proposed and conventional approaches were highly correlated and showed minimal bias. CONCLUSION: The proposed non-ECG-gated, free-breathing, 3D T2 * imaging approach can be performed within 5 min or less. It can overcome critical image artifacts from undesirable cardiac and respiratory motion and bulk off-resonance shifts at the heart-lung interface. The proposed approach is expected to facilitate faster and improved cardiac T2 * mapping in those with limited breath-holding capacity or arrhythmias.


Assuntos
Coração , Miocárdio , Humanos , Animais , Suínos , Coração/diagnóstico por imagem , Respiração , Suspensão da Respiração , Imagem Cinética por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Imageamento Tridimensional/métodos
3.
Clin Case Rep ; 12(1): e8454, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38268622

RESUMO

Neurocysticercosis is an infection of the central nervous system caused by the larval stage of Taenia solium. Although endemic in sub-Saharan Africa, it is neglected but remains a significant cause of preventable seizure in adults. Its diagnosis is challenging and is frequently missed due to its variable clinical manifestations and lack of diagnostic facilities in most areas of sub-Saharan Africa. This report discusses two cases of parenchymal neurocysticercosis in Ghanaians who presented to the emergency unit of a District Hospital with adult-onset seizures. The two cases highlight the need for a high index of suspicion and also underscore the important role of neuroimaging in the evaluation of patients presenting with adult-onset seizures in neurocysticercosis endemic areas. This is necessary for prompt detection and initiation of appropriate therapy in order to improve prognosis.

4.
Ann Thorac Surg ; 116(2): 322-329, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37150274

RESUMO

BACKGROUND: Reports using a 15-mm mechanical valve for mitral valve replacement (MMVR) in children are limited. We review our center's operative and postoperative experience with this valve. METHODS: We performed a single-center retrospective chart review identifying patients having undergone MMVRs between 2009 and 2022. We analyzed short- and long-term outcomes using descriptive statistics. RESULTS: Fifteen patients underwent 16 MMVRs with no operative deaths. The median age and weight at the time of operation was 6.2 months (interquartile range [IQR] 4.4-13.7), and 5.16 kg (IQR 4.5-6.9), respectively. Ten implants (66%) were placed in the supraannular position. Median postoperative duration of intubation was 1.5 days (IQR 1.0-3.75), cardiac intensive care unit length of stay was 6 days (IQR 3-13.5), and overall hospital length of stay was 17.0 days (IQR 12-48.5). Three patients (20%) experienced major adverse events postoperatively. Four of 13 patients discharged home (31%) required readmission within 30 days for subtherapeutic/supratherapeutic international normalized ratio values. There were no surgical mortalities and 4 late mortalities (27%). Six patients underwent subsequent MMVR at a median time to second MMVR of 6.8 (IQR 3.6-8.9) years. There are 6 patients with the original 15-mm MVR at a median time of 4.7 years since placement. CONCLUSIONS: We present the largest single-center cohort of patients having undergone 15-mm MMVR. Our experience is distinguished by a lower rate of major adverse events than previously reported, durability of the device, and a rapid postoperative recovery time. Appropriate and consistent anticoagulation is a notable challenge in this age group.


Assuntos
Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Criança , Humanos , Lactente , Implante de Prótese de Valva Cardíaca/efeitos adversos , Valva Mitral/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
5.
Antioxidants (Basel) ; 12(2)2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36829879

RESUMO

Background: Anthracyclines such as doxorubicin remain a primary treatment for hematological malignancies and breast cancers. However, cardiotoxicity induced by anthracyclines, possibly leading to heart failure, severely limits their application. The pathological mechanisms of anthracycline-induced cardiac injury are believed to involve iron-overload-mediated formation of reactive oxygen species (ROS), mitochondrial dysfunction, and inflammation. The dietary thione, ergothioneine (ET), is avidly absorbed and accumulated in tissues, including the heart. Amongst other cytoprotective properties, ET was shown to scavenge ROS, decrease proinflammatory mediators, and chelate metal cations, including Fe2+, preventing them from partaking in redox activities, and may protect against mitochondrial damage and dysfunction. Plasma ET levels are also strongly correlated to a decreased risk of cardiovascular events in humans, suggesting a cardioprotective role. This evidence highlights ET's potential to counteract anthracycline cardiotoxicity. Methods and Findings: We investigated whether ET supplementation can protect against cardiac dysfunction in mice models of doxorubicin-induced cardiotoxicity and revealed that it had significant protective effects. Moreover, ET administration in a mouse breast cancer model did not exacerbate the growth of the tumor or interfere with the chemotherapeutic efficacy of doxorubicin. Conclusion: These results suggest that ET could be a viable co-therapy to alleviate the cardiotoxic effects of anthracyclines in the treatment of cancers.

6.
Annu Rev Food Sci Technol ; 14: 323-345, 2023 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-36623925

RESUMO

This article reviews what is presently known about the biological roles of the diet-derived compound ergothioneine (ET). ET seems important to humans because it is rapidly taken up from the diet by a transporter largely or completely specific for ET, and once taken up it is retained within the body for weeks or months. The various possible functions of ET in vivo are explored. Much emphasis has been placed on the antioxidant properties of ET, but although these are well established in vitro, the evidence that antioxidant activity is the principal function of ET in vivo is weak. ET is not unique in this: The evidence for the antioxidant roles of vitamin C and polyphenols such as the flavonoids in vivo is also weak. By contrast, α-tocopherol has demonstrated in vivo antioxidant effects in humans.


Assuntos
Antioxidantes , Ergotioneína , Humanos , Dieta
7.
Nat Commun ; 13(1): 6394, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36302906

RESUMO

Sudden blockage of arteries supplying the heart muscle contributes to millions of heart attacks (myocardial infarction, MI) around the world. Although re-opening these arteries (reperfusion) saves MI patients from immediate death, approximately 50% of these patients go on to develop chronic heart failure (CHF) and die within a 5-year period; however, why some patients accelerate towards CHF while others do not remains unclear. Here we show, using large animal models of reperfused MI, that intramyocardial hemorrhage - the most damaging form of reperfusion injury (evident in nearly 40% of reperfused ST-elevation MI patients) - drives delayed infarct healing and is centrally responsible for continuous fatty degeneration of the infarcted myocardium contributing to adverse remodeling of the heart. Specifically, we show that the fatty degeneration of the hemorrhagic MI zone stems from iron-induced macrophage activation, lipid peroxidation, foam cell formation, ceroid production, foam cell apoptosis and iron recycling. We also demonstrate that timely reduction of iron within the hemorrhagic MI zone reduces fatty infiltration and directs the heart towards favorable remodeling. Collectively, our findings elucidate why some, but not all, MIs are destined to CHF and help define a potential therapeutic strategy to mitigate post-MI CHF independent of MI size.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Animais , Miocárdio , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Hemorragia , Coração , Insuficiência Cardíaca/etiologia , Ferro , Remodelação Ventricular , Modelos Animais de Doenças
8.
World J Pediatr Congenit Heart Surg ; 13(5): 631-636, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36053097

RESUMO

Hypoplastic left heart syndrome (HLHS) without intrinsic valvar stenosis or atresia is synonymous with the term hypoplastic left heart complex (HLHC) and is defined as a cardiac malformation at the milder end of the spectrum of HLHS with normally aligned great arteries without a common atrioventricular junction, characterized by underdevelopment of the left heart with significant hypoplasia of the left ventricle and hypoplasia of the aortic or mitral valve, or both valves, in the absence of intrinsic valvar stenosis or atresia, and with hypoplasia of the ascending aorta and aortic arch. This article describes the definitions, nomenclature, and classification of HLHC; the indications and contraindications for biventricular repair of HLHC; the surgical treatment of HLHC; and the associated outcomes.


Assuntos
Cardiopatias Congênitas , Síndrome do Coração Esquerdo Hipoplásico , Constrição Patológica , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Humanos , Síndrome do Coração Esquerdo Hipoplásico/diagnóstico por imagem , Síndrome do Coração Esquerdo Hipoplásico/cirurgia , Valva Mitral
9.
Obstet Gynecol Int ; 2022: 5129199, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847964

RESUMO

Background: Infertility impacts a lot of considerable negative social effects on the lives of infertile partners, especially females, who repeatedly experience the emotional sequelae of childlessness. The study's goal was to assess women of reproductive ages' awareness of IVF treatments, as well as their attitudes and misunderstandings about them in Cape Coast, Ghana. Methods: A total of 437 reproductive-age women in Cape Coast Metropolis were recruited using a simple random sampling approach for this Cross-Sectional Descriptive study. Data were collected with a semistructured interviewer-administered questionnaire and were analyzed using IBM SPSS version 26.0, and p ≤ 0.05 was considered significant. Results: The mean age was calculated to be 25.33 ± 0.066 years with a greater proportion, 65.7% within 15-24 years, 76.5% had no or had never had a child before. 93.4% were of the Christian faith, 66.8% were aware of IVF, and 74.8% think IVF offers hope. Although 41.4% believe it is not a natural procedure and 44.6% believe IVF children are normal but not natural. While 72.1% believe the treatment is very costly, and 40.7% believe it is not affordable or accessible. The majority believe IVF kids are legitimate (76.9%), and so should be welcomed by society (86.5%). The overall opinion of IVF service acceptability was 81.7% good. Seventy-two and three percent did not know whether IVF services are available in Cape Coast. Also, 48.1% were aware that IVF may result in pregnancy failure, with fewer than half (43.5%) believing it could be linked to genetic problems in the baby. The majority (60.4%) were willing to use IVF services, and 82.8% will utilize just their husband's sperm technique. While others may not want to undergo any form of IVF technique because they desire to conceive naturally (51.0%) and 22.4% may be unable to pay for it. Educational status and awareness of the availability of IVF services were factors that were significantly associated with their overall good perception of IVF services. Also, age, marital status, number of live children, occupation, educational status, awareness, and their overall perception were factors that are significantly associated with their preparedness to utilize IVF services. Conclusion: Overall, women's opinions of IVF and their readiness to use them were favorable, and they think it offers hope for their condition since they were well-informed about its forms and that infertility may be a result of several factors, all of which may need IVF services. It does not matter if it is difficult to obtain, expensive, or unavailable. It is recommended that the government collaborates with healthcare providers to investigate ways through the mass media in the drive to clear the misconceptions and improve the public understanding of the IVF procedure towards its utilization, thereby reducing the burden of childlessness and the resulting psychological disorders among couples, this has implications for joyful homes and societal growth.

10.
FEBS Lett ; 596(10): 1241-1251, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35486429

RESUMO

The dietary thione-thiol, ergothioneine (ET), accumulates in human and animal tissues and may play important roles in disease prevention. ET biosynthesis has only been described in fungi and certain bacteria, and humans and animals are widely assumed to accumulate ET solely from diet. However, a recent study suggested that Lactobacillus/Limosilactobacillus reuteri, a commensal gut bacterium, may produce ET, thereby protecting the host against social defeat stress and sleep disturbances. Upon our further investigation, no evidence of ET biosynthesis was observed in L. reuteri when a heavy-labelled histidine precursor was administered. Instead, we discovered that L. reuteri avidly accumulates ET. This observation may indicate a possible mechanism by which the gut microbiota could influence tissue levels of ET in the host.


Assuntos
Ergotioneína , Microbioma Gastrointestinal , Limosilactobacillus reuteri , Probióticos , Animais , Bactérias , Dieta , Corpo Humano , Humanos
12.
Expert Opin Drug Saf ; 21(8): 1121-1126, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35196183

RESUMO

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening skin reactions. Colistin is a last resort antibiotic with a historically poor safety profile. The association between colistin and SJS/TEN has not been previously quantified. RESEARCH DESIGN AND METHODS: We identified colistin and SJS/TEN adverse event reports from the Food and Drug Administration Adverse Event Reporting System (FAERS) and calculated effect estimates using OpenEpi. RESULTS: From January 2013 through March 2021, 964 adverse events were reported for colistin. Colistin was listed as a secondary suspect drug in 13 SJS/TEN adverse event reports (1.3%), with a reporting odds ratio of 29.6 (95% confidence interval [CI] 17.1-51.1), and proportional reporting ratio of 29.2 (95% CI 17.0-50.2). Limitations of any FAERS study include the voluntary nature of reporting, unclear causal relationship between drug and adverse reaction, underreporting, and wide confidence intervals for rare adverse events like SJS/TEN. CONCLUSIONS: Colistin was not the primary suspect drug in any SJS/TEN adverse event reports. We did identify a statistically significant safety signal for SJS/TEN with colistin as a secondary suspect drug. SJS/TEN is not currently included in the colistin product label. This association should be further explored in other pharmacoepidemiologic drug safety studies.


Assuntos
Síndrome de Stevens-Johnson , Sistemas de Notificação de Reações Adversas a Medicamentos , Colistina/efeitos adversos , Humanos , Farmacovigilância , Estudos Retrospectivos , Síndrome de Stevens-Johnson/epidemiologia , Síndrome de Stevens-Johnson/etiologia
13.
J Am Coll Cardiol ; 79(1): 35-48, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34991787

RESUMO

BACKGROUND: Reperfusion therapy for acute myocardial infarction (MI) is lifesaving. However, the benefit of reperfusion therapy can be paradoxically diminished by reperfusion injury, which can increase MI size. OBJECTIVES: Hemorrhage is known to occur in reperfused MIs, but whether hemorrhage plays a role in reperfusion-mediated MI expansion is not known. METHODS: We studied cardiac troponin kinetics (cTn) of ST-segment elevation MI patients (n = 70) classified by cardiovascular magnetic resonance to be hemorrhagic (70%) or nonhemorrhagic following primary percutaneous coronary intervention. To isolate the effects of hemorrhage from ischemic burden, we performed controlled canine studies (n = 25), and serially followed both cTn and MI size with time-lapse imaging. RESULTS: CTn was not different before reperfusion; however, an increase in cTn following primary percutaneous coronary intervention peaked earlier (12 hours vs 24 hours; P < 0.05) and was significantly higher in patients with hemorrhage (P < 0.01). In hemorrhagic animals, reperfusion led to rapid expansion of myocardial necrosis culminating in epicardial involvement, which was not present in nonhemorrhagic cases (P < 0.001). MI size and salvage were not different at 1 hour postreperfusion in animals with and without hemorrhage (P = 0.65). However, within 72 hours of reperfusion, a 4-fold greater loss in salvageable myocardium was evident in hemorrhagic MIs (P < 0.001). This paralleled observations in patients with larger MIs occurring in hemorrhagic cases (P < 0.01). CONCLUSIONS: Myocardial hemorrhage is a determinant of MI size. It drives MI expansion after reperfusion and compromises myocardial salvage. This introduces a clinical role of hemorrhage in acute care management, risk assessment, and future therapeutics.


Assuntos
Hemorragia/diagnóstico por imagem , Traumatismo por Reperfusão Miocárdica/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Animais , Modelos Animais de Doenças , Cães , Humanos , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Necrose , Intervenção Coronária Percutânea , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Terapia de Salvação , Tempo para o Tratamento , Troponina/sangue
14.
J Cardiovasc Magn Reson ; 23(1): 104, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34587984

RESUMO

BACKGROUND: T2* cardiovascular magnetic resonance (CMR) is commonly used in the diagnosis of intramyocardial hemorrhage (IMH). For quantifying IMH with T2* CMR, despite the lack of consensus studies, two different methods [subject-specific T2* (ssT2*) and absolute T2* thresholding (aT2* < 20 ms)] are interchangeably used. We examined whether these approaches yield equivalent information. METHODS: ST elevation myocardial infarction (STEMI) patients (n = 70) were prospectively recruited for CMR at 4-7 days post revascularization and for 6-month follow up (n = 43). Canines studies were performed for validation purposes, where animals (n = 20) were subject to reperfused myocardial infarction (MI) and those surviving the MI (n = 16) underwent CMR at 7 days and 8 weeks and then euthanized. Both in patients and animals, T2* of IMH and volume of IMH were determined using ssT2* and aT2* < 20 ms. In animals, ex-vivo T2* CMR and mass spectrometry for iron concentration ([Fe]Hemo) were determined on excised myocardial sections. T2* values based on ssT2* and absolute T2* threshold approaches were independently regressed against [Fe]Hemo and compared. A range of T2* cut-offs were tested to determine the optimized conditions relative to ssT2*. RESULTS: While both approaches showed many similarities, there were also differences. Compared to ssT2*, aT2* < 20 ms showed lower T2* and volume of IMH in patients and animals independent of MI age (all p < 0.005). While T2* determined from both methods were highly correlated against [Fe]Hemo (R2 = 0.9 for both), the slope of the regression curve for ssT2* was significantly larger as compared to aT2* < 20 ms (0.46 vs. 0.32, p < 0.01). Further, slightly larger absolute T2* cut-offs (patients: 23 ms; animals: 25 ms) showed similar IMH characteristics compared to ssT2*. CONCLUSION: Current quantification methods have excellent capacity to identify IMH, albeit the T2*of IMH and volume of IMH based on aT2* < 20 ms are smaller compared to ssT2*. Thus the method used to quantify IMH from T2* CMR may influence the diagnosis for IMH.


Assuntos
Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio com Supradesnível do Segmento ST , Animais , Cães , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Miocárdio , Valor Preditivo dos Testes , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem
15.
Can J Cardiol ; 37(7): 1117-1120, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33434611

RESUMO

Robotic cardiac surgery addressing the mitral and tricuspid valves is a highly developed field offering multiple potential advantages regarding postoperative complications, valve repair rates, hospital length of stay, and rapid functional recovery compared with the conventional sternotomy approach for select patients. The unparalleled stereoscopic view within the heart and precision of robotic arms make robotic surgery a highly attractive minimally invasive approach, facilitating repair of even the most complex valvular pathology. Careful candidate selection and surgical planning are paramount to optimising the outcomes of those who undergo robotic valve surgery. As a team's experience grows, the technique can be applied to a wider range of patients that may derive even greater benefit, such as those with significant comorbid conditions, ventricular dysfunction, and previous sternotomy. The goal of this review is to provide clinicians with a practical overview of the factors influencing a patient's candidacy for robotic valve surgery. We discuss key issues such as preoperative diagnostic assessment, concerns regarding demographics and surgical pathology, and additional considerations relating to surgical exposure, cardiopulmonary bypass, and myocardial protection. Diligent patient assessment and a strong team-based approach are paramount to developing and maintaining a successful robotic valve surgery program, with the most seasoned teams being able to safely offer the technique to the vast majority of patients referred for mitral or tricuspid valve repair or replacement.


Assuntos
Anuloplastia da Valva Cardíaca , Doenças das Valvas Cardíacas , Implante de Prótese de Valva Cardíaca , Seleção de Pacientes , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Robóticos , Anuloplastia da Valva Cardíaca/efeitos adversos , Anuloplastia da Valva Cardíaca/instrumentação , Anuloplastia da Valva Cardíaca/métodos , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/instrumentação , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Valva Mitral/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Valva Tricúspide/cirurgia
17.
NPJ Aging Mech Dis ; 6: 6, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32566245

RESUMO

Caloric restriction (CR) is one of the most effective interventions to prolong lifespan and promote health. Recently, it has been suggested that hydrogen sulfide (H2S) may play a pivotal role in mediating some of these CR-associated benefits. While toxic at high concentrations, H2S at lower concentrations can be biologically advantageous. H2S levels can be artificially elevated via H2S-releasing donor drugs. In this study, we explored the function of a novel, slow-releasing H2S donor drug (FW1256) and used it as a tool to investigate H2S in the context of CR and as a potential CR mimetic. We show that exposure to FW1256 extends lifespan and promotes health in Caenorhabditis elegans (C. elegans) more robustly than some previous H2S-releasing compounds, including GYY4137. We looked at the extent to which FW1256 reproduces CR-associated physiological effects in normal-feeding C. elegans. We found that FW1256 promoted healthy longevity to a similar degree as CR but with fewer fitness costs. In contrast to CR, FW1256 actually enhanced overall reproductive capacity and did not reduce adult body length. FW1256 further extended the lifespan of already long-lived eat-2 mutants without further detriments in developmental timing or fertility, but these lifespan and healthspan benefits required H2S exposure to begin early in development. Taken together, these observations suggest that FW1256 delivers exogenous H2S efficiently and supports a role for H2S in mediating longevity benefits of CR. Delivery of H2S via FW1256, however, does not mimic CR perfectly, suggesting that the role of H2S in CR-associated longevity is likely more complex than previously described.

18.
Radiology ; 295(1): 82-93, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32096705

RESUMO

Background Despite advances, blood oxygen level-dependent (BOLD) cardiac MRI for myocardial perfusion is limited by inadequate spatial coverage, imaging speed, multiple breath holds, and imaging artifacts, particularly at 3.0 T. Purpose To develop and validate a robust, contrast agent-unenhanced, free-breathing three-dimensional (3D) cardiac MRI approach for reliably examining changes in myocardial perfusion between rest and adenosine stress. Materials and Methods A heart rate-independent, free-breathing 3D T2 mapping technique at 3.0 T that can be completed within the period of adenosine stress (≤4 minutes) was developed by using computer simulations, ex vivo heart preparations, and dogs. Studies in dogs were performed with and without coronary stenosis and validated with simultaneously acquired nitrogen 13 (13N) ammonia PET perfusion in a clinical PET/MRI system. The MRI approach was also prospectively evaluated in healthy human volunteers (from January 2017 to September 2017). Myocardial BOLD responses (MBRs) between normal and ischemic myocardium were compared with mixed model analysis. Results Dogs (n = 10; weight range, 20-25 kg; mongrel dogs) and healthy human volunteers (n = 10; age range, 22-53 years; seven men) were evaluated. In healthy dogs, T2 MRI at adenosine stress was greater than at rest (mean rest vs stress, 38.7 msec ± 2.5 [standard deviation] vs 45.4 msec ± 3.3, respectively; MBR, 1.19 ± 0.08; both, P < .001). At the same conditions, mean rest versus stress PET perfusion was 1.1 mL/mg/min ± 0.11 versus 2.3 mL/mg/min ± 0.82, respectively (P < .001); myocardial perfusion reserve (MPR) was 2.4 ± 0.82 (P < .001). The BOLD response and PET MPR were positively correlated (R = 0.67; P < .001). In dogs with coronary stenosis, perfusion anomalies were detected on the basis of MBR (normal vs ischemic, 1.09 ± 0.05 vs 1.00 ± 0.04, respectively; P < .001) and MPR (normal vs ischemic, 2.7 ± 0.08 vs 1.7 ± 1.1, respectively; P < .001). Human volunteers showed increased myocardial T2 at stress (rest vs stress, 44.5 msec ± 2.6 vs 49.0 msec ± 5.5, respectively; P = .004; MBR, 1.1 msec ± 8.08). Conclusion This three-dimensional cardiac blood oxygen level-dependent (BOLD) MRI approach overcame key limitations associated with conventional cardiac BOLD MRI by enabling whole-heart coverage within the standard duration of adenosine infusion, and increased the magnitude and reliability of BOLD contrast, which may be performed without requiring breath holds. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Almeida in this issue.


Assuntos
Técnicas de Imagem Cardíaca/métodos , Frequência Cardíaca , Coração/diagnóstico por imagem , Imageamento Tridimensional , Imageamento por Ressonância Magnética/métodos , Oxigênio/sangue , Tomografia por Emissão de Pósitrons , Adenosina , Adulto , Amônia , Animais , Meios de Contraste , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/fisiopatologia , Cães , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio , Radioisótopos de Nitrogênio , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Adulto Jovem
20.
JACC Cardiovasc Imaging ; 12(4): 693-703, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29680356

RESUMO

OBJECTIVES: This study sought to determine whether T2 cardiac magnetic resonance (CMR) can stage both hemorrhagic and nonhemorrhagic myocardial infarctions (MIs). BACKGROUND: CMR-based staging of MI with or without contrast agents relies on the resolution of T2 elevations in the chronic phase, but whether this approach can be used to stage both hemorrhagic and nonhemorrhagic MIs is unclear. METHODS: Hemorrhagic (n = 15) and nonhemorrhagic (n = 9) MIs were created in dogs. Multiparametric noncontrast mapping (T1, T2, and T2*) and late gadolinium enhancement (LGE) were performed at 1.5- and 3.0-T at 5 days (acute) and 8 weeks (chronic) post-MI. CMR relaxation values and LGE intensities of hemorrhagic, peri-hemorrhagic, nonhemorrhagic, and remote territories were measured. Histopathology was performed to elucidate CMR findings. RESULTS: T2 of nonhemorrhagic MIs was significantly elevated in the acute phase relative to remote territories (1.5-T: 39.8 ± 12.8%; 3.0-T: 27.9 ± 16.5%; p < 0.0001 for both) but resolved to remote values by week 8 (1.5-T: -0.0 ± 3.2%; p = 0.678; 3.0-T: -0.5 ± 5.9%; p = 0.601). In hemorrhagic MI, T2 of hemorrhage core was significantly elevated in the acute phase (1.5-T: 17.7 ± 10.0%; 3.0-T: 8.6 ± 8.2%; p < 0.0001 for both) but decreased below remote values by week 8 (1.5-T: -8.2 ± 3.9%; 3.0-T: -5.6 ± 6.0%; p < 0.0001 for both). In contrast, T2 of the periphery of hemorrhage within the MI zone was significantly elevated in the acute phase relative to remote territories (1.5-T: 35.0 ± 16.1%; 3.0-T: 24.2 ± 10.4%; p < 0.0001 for both) and remained elevated at 8 weeks post-MI (1.5-T: 8.6 ± 5.1%; 3.0-T: 6.0 ± 3.3%; p < 0.0001 for both). The observed elevation of T2 in the peri-hemorrhagic zone of MIs and the absence of T2 elevation in nonhemorrhagic MIs were consistent with ongoing or absence of histological evidence of inflammation, respectively. CONCLUSIONS: Hemorrhagic MIs are associated with persisting myocardial inflammation and edema, which can confound staging of hemorrhagic MIs when T2 elevations alone are used to discriminate between acute and chronic MI. Moreover, given the poor prognosis in patients with hemorrhagic MI, CMR evidence for myocardial hemorrhage with persistent edema may evolve as a risk marker in patients after acute MI.


Assuntos
Hemorragia/diagnóstico por imagem , Imageamento por Ressonância Magnética , Infarto do Miocárdio/diagnóstico por imagem , Animais , Meios de Contraste/administração & dosagem , Modelos Animais de Doenças , Cães , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Reperfusão Miocárdica , Valor Preditivo dos Testes
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