MARCELO RODRIGUES DOS SANTOS
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- Android to gynoid fat ratio and its association with functional capacity in male patients with heart failure(2020) SANTOS, Marcelo Rodrigues Dos; FONSECA, Guilherme Wesley Peixoto da; SHERVENINAS, Leticia Pironato; SOUZA, Francis Ribeiro de; BATTAGLIA FILHO, Antonio Carlos; NOVAES, Caio Eduardo; PEREIRA, Rosa Maria Rodrigues; NEGRAO, Carlos Eduardo; BARRETTO, Antonio Carlos Pereira; ALVES, Maria-Janieire de Nazare NunesAims We studied the association between android (A) to gynoid (G) fat ratio and functional capacity (peak VO2) in male patients with heart failure with reduced ejection fraction (HFrEF). Methods and results We enrolled 118 male patients with HFrEF with left ventricular ejection fraction (LVEF) <40%. Body composition (by using dual x-ray absorptiometry) and peak VO2 (by cardiopulmonary exercise testing) were measured. Sarcopenic obesity was defined according to the Foundation for the National Institutes of Health criteria (FNIH). Blood sample for metabolic and hormonal parameters were measured. Fifteen patients (12.7%) showed sarcopenic obesity (body mass index > 25 kg/m(2) with FNIH index < 0.789). The median A/G ratio was 0.55. A/G ratio > 0.55 was detected in 60 patients. Relative peak VO2 was lower in patients with A/G ratio > 0.55 than in patients with A/G ratio <0.55 (18.7 +/- 5.3 vs. 22.5 +/- 6.1 mL/kg/min, P < 0.001). Logistic regression analysis showed A/G ratio >0.55 to be independently associated with reduced peak VO2 adjusted for age, body mass index, LVEF, presence of sarcopenia, anabolic hormones, and haemoglobin (odds ratio 3.895, 95% confidence interval 1.030-14.730, P = 0.045). Conclusions Body fat distribution, particularly android and gynoid fat composition, together with other cofactors, might have an important adverse role on functional capacity in male patients with HFrEF. Future studies are needed to address possible mechanisms involved in this relationship.
- Mechanisms of Blunted Muscle Vasodilation During Peripheral Chemoreceptor Stimulation in Heart Failure Patients(2012) ALVES, M. J. N. N.; SANTOS, Marcelo Rodrigues dos; NOBRE, Thais Simoes; MARTINEZ, Dg; BARRETTO, Antonio Carlos Pereira; BRUM, Patricia Chakur; RONDON, Maria Urbana P. B.; MIDDLEKAUFF, Holly R.; NEGRAO, Carlos EduardoWe described recently that systemic hypoxia provokes vasoconstriction in heart failure (HF) patients. We hypothesized that either the exaggerated muscle sympathetic nerve activity and/or endothelial dysfunction mediate the blunted vasodilatation during hypoxia in HF patients. Twenty-seven HF patients and 23 age-matched controls were studied. Muscle sympathetic nerve activity was assessed by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. Peripheral chemoreflex control was evaluated through the inhaling of a hypoxic gas mixture (10% O-2 and 90% N-2). Basal muscle sympathetic nerve activity was greater and basal FBF was lower in HF patients versus controls. During hypoxia, muscle sympathetic nerve activity responses were greater in HF patients, and forearm vasodilatation in HF was blunted versus controls. Phentolamine increased FBF responses in both groups, but the increase was lower in HF patients. Phentolamine and N-G-monomethyl-L-arginine infusion did not change FBF responses in HF but markedly blunted the vasodilatation in controls. FBF responses to hypoxia in the presence of vitamin C were unchanged and remained lower in HF patients versus controls. In conclusion, muscle vasoconstriction in response to hypoxia in HF patients is attributed to exaggerated reflex sympathetic nerve activation and blunted endothelial function (NO activity). We were unable to identify a role for oxidative stress in these studies. (Hypertension. 2012; 60: 669-676.) . Online Data Supplement
conferenceObject Discriminating sarcopenia in male patients with heart failure: the influence of body mass index(2018) SANTOS, M. R. Dos; FONSECA, G. W. P.; SOUZA, F. R.; CASTRO, V. M.; TAKAYAMA, L.; PEREIRA, R. M. R.; NEGRAO, C. E.; ALVES, M. J. N. N.- MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of beta-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults(2023) PENCINA, Karol; LAVU, Siva; SANTOS, Marcello dos; BELEVA, Yusnie Memish; CHENG, Ming; LIVINGSTON, David; BHASIN, ShalenderBackground Nicotinamide adenine dinucleotide (NAD) precursors, nicotinamide mononucleotide (NMN), or nicotinamide riboside (NR) extend healthspan and ameliorate some age-related conditions in model organisms. However, early-phase trials of NAD precursors have yielded varying results and their pharmacokinetics remain incompletely understood. Here, we report the pharmacokinetics and pharmacodynamics of MIB-626, a microcrystalline unique polymorph beta NMN formulation. Methods In this double-blind, placebo-controlled study, 32 overweight or obese adults, 55-80 years, were block-randomized, stratified by sex, to 1 000-mg MIB-626 once daily, twice daily, or placebo for 14 days. NMN, NAD, and NAD metabolome were measured using liquid chromatography-tandem mass spectrometry. Results Participant characteristics were similar across groups. MIB-626 was well tolerated and frequency of adverse events was similar across groups. Blood NMN concentrations on Day 14 in MIB-626-treated groups were significantly higher compared to placebo (1.7-times and 3.7-times increase above baseline in 1 000 mg once-daily and twice-daily groups in mean AUC(last), respectively). MIB-626 treatment was associated with substantial dose-related increases in blood NAD levels. Blood levels of NAD metabolites were higher in NMN-treated participants on Days 8 and 14 than at baseline. Changes in NMN or NAD levels were not related to sex, body mass index, or age. Very little unmodified NMN was excreted in the urine. Conclusion MIB-626 1 000 mg once-daily or twice-daily regimens were safe and associated with substantial dose-related increases in blood NAD levels and its metabolome. These foundational data that were obtained using a pharmaceutical-grade beta NMN, standardized sample collection, and validated liquid chromatography-tandem mass spectrometry assays, should facilitate design of efficacy trials in disease conditions.
- Dynamic Cerebral Autoregulation Changes during Sub-Maximal Handgrip Maneuver(2013) NOGUEIRA, Ricardo C.; BOR-SENG-SHU, Edson; SANTOS, Marcelo R.; NEGRAO, Carlos E.; TEIXEIRA, Manoel J.; PANERAI, Ronney B.Purpose: We investigated the effect of handgrip (HG) maneuver on time-varying estimates of dynamic cerebral autoregulation (CA) using the autoregressive moving average technique. Methods: Twelve healthy subjects were recruited to perform HG maneuver during 3 minutes with 30% of maximum contraction force. Cerebral blood flow velocity, end-tidal CO2 pressure (PETCO2), and noninvasive arterial blood pressure (ABP) were continuously recorded during baseline, HG and recovery. Critical closing pressure (CrCP), resistance area-product (RAP), and time-varying autoregulation index (ARI) were obtained. Results: PETCO2 did not show significant changes during HG maneuver. Whilst ABP increased continuously during the maneuver, to 27% above its baseline value, CBFV raised to a plateau approximately 15% above baseline. This was sustained by a parallel increase in RAP, suggestive of myogenic vasoconstriction, and a reduction in CrCP that could be associated with metabolic vasodilation. The time-varying ARI index dropped at the beginning and end of the maneuver (p<0.005), which could be related to corresponding alert reactions or to different time constants of the myogenic, metabolic and/or neurogenic mechanisms. Conclusion: Changes in dynamic CA during HG suggest a complex interplay of regulatory mechanisms during static exercise that should be considered when assessing the determinants of cerebral blood flow and metabolism.
- Nutritional status and its effects on muscle wasting in patients with chronic heart failure: insights from Studies Investigating Co-morbidities Aggravating Heart Failure(2016) SAITOH, Masakazu; SANTOS, Marcelo Rodrigues dos; EBNER, Nicole; EMAMI, Amir; KONISHI, Masaaki; ISHIDA, Junichi; VALENTOVA, Miroslava; SANDEK, Anja; DOEHNER, Wolfram; ANKER, Stefan D.; HAEHLING, Stephan vonInadequate nutritional status has been linked to poor outcomes in patients with heart failure (HF). Skeletal muscle wasting affects about 20% of ambulatory patients with HF. The impact of nutritional intake and appetite on skeletal muscle wasting has not been investigated so far. We sought to investigate the impact of nutritional status on muscle wasting and mortality in ambulatory patients with HF. We studied 130 ambulatory patients with HF who were recruited as a part of the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) program. Muscle wasting was defined according to criteria of sarcopenia, i.e., appendicular skeletal muscle mass two standard deviations below the mean of a healthy reference group aged 18-40 years. Nutritional status was evaluated using the Mini-Nutritional Assessment-Short Form (MNA-SF). Functional capacity was assessed as peak oxygen consumption (peak VO2) by cardiopulmonary exercise testing, 6aEurominute walk testing, and the Short Physical Performance Battery (SPPB). At baseline, 19 patients (15%) presented with muscle wasting. Patients with muscle wasting had significantly lower values of peak VO2, 6aEurominute walk distance, SPPB, and MNA-SF score than patients without (all p < 0.05). In multivariate analysis, MNA-SF remained an independent predictor of muscle wasting after adjustment for age and New York Heart Association class (odds ratio [OR] 0.66; confidence interval [CI] 0.50-0.88; p < 0.01). A total of 16 (12%) patients died during a mean follow-up of 21 months. In Cox regression analysis, MNA-SF (OR 0.80, CI 0.64-0.99, p = 0.04), left ventricular ejection fraction (OR 0.93, CI 0.86-0.99, p = 0.05), and peak VO2 (OR 0.78, CI 0.65-0.94, p = 0.008) were predictors of death. MNA-SF is an independent predictor of muscle wasting and mortality in ambulatory patients with HF. Nutritional screening should be included as a fundamental part of the overall assessment of these patients.
- Diminished cholesterol efflux mediated by HDL and coronary artery disease in young male anabolic androgenic steroid users(2019) SOUZA, Francis Ribeiro de; SANTOS, Marcelo Rodrigues Dos; PORELLO, Rafael Armani; FONSECA, Guilherme Wesley Peixoto da; SAYEGH, Ana Luiza Carrari; LIMA, Thais Pinheiro; FERREIRA, Fabiana Dias; OLIVEIRA, Tiago Franco de; YONAMINE, Mauricio; TAKAYAMA, Liliam; PEREIRA, Rosa Maria Rodrigues; NEGRAO, Carlos Eduardo; PASSARELLI, Marisa; ROCHITTE, Carlos Eduardo; ALVES, Maria Janieire de Nazare NunesBackground and aims: Anabolic androgenic steroids (AAS) have been associated with coronary artery disease (CAD). AAS abuse leads to a remarkable decrease in high-density lipoprotein (HDL) plasma concentration, which could be a key factor in the atherosclerotic process. Moreover, not only the concentration of HDL, but also its functionality, plays a pivotal role in CAD. We tested the functionality of HDL by cholesterol efflux and antioxidant capacity. We also evaluated the prevalence of CAD in AAS users. Methods: Twenty strength-trained AAS users (AASU) age 29 +/- 5 yr, 20 age-matched strength-trained AAS nonusers (AASNU), and 10 sedentary controls (SC) were enrolled in this cross-sectional study. Functionality of HDL was evaluated by C-14-cholesterol efflux and the ability of HDL in inhibiting LDL oxidation. Coronary artery was evaluated with coronary computed tomography angiography. Results: Cholesterol efflux was lower in AASU compared with AASNU and SC (20 vs. 23 vs. 24%, respectively, p < 0.001). However, the lag time for LDL oxidation was higher in AASU compared with AASNU and SC (41 vs 13 vs 11 min, respectively, p < 0.001). We found at least 2 coronary arteries with plaques in 25% of AASU. None of the AASNU and SC had plaques. The time of AAS use was negatively associated with cholesterol efflux. Conclusions: This study indicates that AAS abuse impairs the cholesterol efflux mediated by HDL. Long-term AAS use seems to be correlated with lower cholesterol efflux and early subclinical CAD in this population.
conferenceObject Coronary inflammation by computed tomography pericoronary fat attenuation in young male anabolic androgenic steroid users(2022) SOUZA, F.; ROCHITTE, C. E.; SILVA, D. C.; GOMES, A. M. R.; SANTOS, M. R.; FONSECA, G. W. P.; BATTAGLIA, A. C. B. F.; CORREA, K. T. S.; YONAMINE, M.; PEREIRA, R. M. R.; NEGRAO, C. E.; ALVES, M. J. N. N.- Sympatho-Vagal Imbalance is Associated with Sarcopenia in Male Patients with Heart Failure(2019) FONSECA, Guilherme Wesley Peixoto da; SANTOS, Marcelo Rodrigues dos; SOUZA, Francis Ribeiro de; COSTA, Marcel Jose A. da; HAEHLING, Stephan von; TAKAYAMA, Liliam; PEREIRA, Rosa Maria R.; NEGRAO, Carlos Eduardo; ANKER, Stefan D.; ALVES, Maria Janieire de Nazare NunesBackground: Resting sympathetic hyperactivity and impaired parasympathetic reactivation after exercise have been described in patients with heart failure (HF). However, the association of these autonomic changes in patients with HF and sarcopenia is unknown. Objective: The aim of this study was to evaluate the impact of autonomic modulation on sarcopenia in male patients with HF. Methods: We enrolled 116 male patients with HF and left ventricular ejection fraction < 40%. All patients underwent a maximal cardiopulmonary exercise testing. Maximal heart rate was recorded and delta heart rate recovery (Delta HRR) was assessed at 1st and 2nd minutes after exercise. Muscle sympathetic nerve activity (MSNA) was recorded by microneurography. Dual-energy X-ray absorptiometry was used to measure body composition and sarcopenia was defined by the sum of appendicular lean muscle mass (ALM) divided by height in meters squared and handgrip strength. Results: Sarcopenia was identified in 33 patients (28%). Patients with sarcopenia had higher MSNA than those without (47 [41-52] vs. 40 [34-48] bursts/min, p = 0.028). Sarcopenic patients showed lower Delta HRR at 1st (15 [10-21] vs. 22 [16-30] beats/min, p < 0.001) and 2nd min (25 [19-39] vs. 35 [24-48] beats/min, p = 0.017) than non-sarcopenic. There was a positive correlation between ALM and HRR at 1st (r = 0.26, p = 0.008) and 2nd min (r = 0.25, p = 0.012). We observed a negative correlation between ALM and MSNA (r = -0.29, p = 0.003). Conclusion: Sympatho-vagal imbalance seems to be associated with sarcopenia in male patients with HF. These results highlight the importance of a therapeutic approach in patients with muscle wasting and increased peripheral sympathetic outflow.
conferenceObject Impaired Baroreflex Sensitivity in Anabolic Steroid Users(2012) SANTOS, Marcelo Rodrigues dos; PORELLO, Rafael Armani; SAYEGH, Ana L. C.; HONG, Valeria; TOSCHI-DIAS, Edgar; BORTOLOTTO, Luiz A.; YONAMINE, Mauricio; NEGRAO, Carlos E.; ALVES, Maria-Janieire N. N.Purpose: Exacerbated sympathetic nerve activity and increased blood pressure have been documented in anabolic androgenic steroid users (AASU). We tested the hypothesis that arterial baroreflex sensitivity (BRS) and carotid distensibility would be reduced in AASU. Methods: Ten AASU and 10 age-paired anabolic androgenic steroid nonusers (AASNU) were studied. Both groups were involved in strength training (90% 1MR) and AASU were self-administered anabolic steroids for at least 2 years. The use of AAS was proved by urine. Heart rate (HR) was evaluated by EKG and blood pressure non-invasively on a beat to beat. BRS was analyzed by time domain through spontaneous fluctuations between systolic blood pressure (SBP) and HR. Carotid artery distensibility was measured by doppler (M-mode). Results: HR was higher in AASU compared to AASNU (69±3 vs. 59±3 bpm, P≤0.05). Systolic (123±4 vs. 118±2 mmHg, P=0.29), diastolic (72±2 vs. 67±2 mmHg, P=0.12) and mean blood pressure (90±3 vs. 85±2 mmHg, P=0.15) were not different between groups. BRS for increases (14.2±2 vs. 22.8±3 msec/mmHg, P=0.05) and decreases (13.3±1 vs. 19.2±2 msec/mmHg, P=0.04) were lower in AASU. Carotid distensibility was reduced in AASU (7±1 vs. 9±1 %, P≤0.05). Conclusion: Impaired BRS and reduced carotid distensibility may prematurely lead to increased cardiovascular risk in AASU.