Daniel Godoy Martinez

Effects of Long-Term Exercise Training on Autonomic Control in Myocardial Infarction Patients

Autonomic dysfunction, including baroreceptor attenuation and sympathetic activation, has been reported in patients with myocardial infarction (MI) and has been associated with increased mortality. We tested the hypotheses that exercise training (ET) in post-MI patients would normalize arterial baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA), and long-term ET would maintain the benefits in BRS and MSNA. Twenty-eight patients after 1 month of uncomplicated MI were randomly assigned to 2 groups, ET (MI-ET) and untrained. A normal control group was also studied. ET consisted of three 60-minute exercise sessions per week for 6 months. We evaluated MSNA (microneurography), blood pressure (automatic oscillometric method), heart rate (ECG), and spectral analysis of RR interval, systolic arterial pressure (SAP), and MSNA. Baroreflex gain of SAP-RR interval and SAP-MSNA were calculated using the &agr;-index. At 3 to 5 days and 1 month after MI, MSNA and low-frequency SAP were significantly higher and BRS significantly lower in MI patients when compared with the normal control group. ET significantly decreased MSNA (bursts per 100 heartbeats) and the low-frequency component of SAP and significantly increased the low-frequency component of MSNA and BRS of the RR interval and MSNA. These changes were so marked that the differences between patients with MI and the normal control group were no longer observed after ET. MSNA and BRS in the MI-untrained group did not change from baseline over the same time period. ET normalizes BRS, low-frequency SAP, and MSNA in patients with MI. These improvements in autonomic control are maintained by long-term ET. These findings highlight the clinical importance of this nonpharmacological therapy based on ET in the long-term treatment of patients with MI.

Mechanisms of Blunted Muscle Vasodilation During Peripheral Chemoreceptor Stimulation in Heart Failure Patients

We 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.

Burnt sugarcane harvesting - cardiovascular effects on a group of healthy workers, Brazil.

Background Brazil is the worlds largest producer of sugarcane. Harvest is predominantly manual, exposing workers to health risks: intense physical exertion, heat, pollutants from sugarcane burning. Design Panel study to evaluate the effects of burnt sugarcane harvesting on blood markers and on cardiovascular system. Methods Twenty-eight healthy male workers, living in the countryside of Brazil were submitted to blood markers, blood pressure, heart rate variability, cardiopulmonary exercise testing, sympathetic nerve activity evaluation and forearm blood flow measures (venous occlusion plethysmography) during burnt sugarcane harvesting and four months later while they performed other activities in sugar cane culture. Results Mean participant age was 31±6.3 years, and had worked for 9.8±8.4 years on sugarcane work. Work during the harvest period was associated with higher serum levels of Creatine Kinase – 136.5 U/L (IQR: 108.5–216.0) vs. 104.5 U/L (IQR: 77.5–170.5), (p = 0.001); plasma Malondialdehyde–7.5±1.4 µM/dl vs. 6.9±1.0 µM/dl, (p = 0.058); Glutathione Peroxidase – 55.1±11.8 Ug/Hb vs. 39.5±9.5 Ug/Hb, (p<0.001); Glutathione Transferase– 3.4±1.3 Ug/Hb vs. 3.0±1.3 Ug/Hb, (p = 0.001); and 24-hour systolic blood pressure – 120.1±10.3 mmHg vs. 117.0±10.0 mmHg, (p = 0.034). In cardiopulmonary exercise testing, rest-to-peak diastolic blood pressure increased by 11.12 mmHg and 5.13 mmHg in the harvest and non-harvest period, respectively. A 10 miliseconds reduction in rMSSD and a 10 burst/min increase in sympathetic nerve activity were associated to 2.2 and 1.8 mmHg rises in systolic arterial pressure, respectively. Conclusion Work in burnt sugarcane harvesting was associated with changes in blood markers and higher blood pressure, which may be related to autonomic imbalance.

Obstructive Sleep Apnea Impairs Postexercise Sympathovagal Balance in Patients with Metabolic Syndrome

STUDY OBJECTIVES The attenuation of heart rate recovery after maximal exercise (ΔHRR) is independently impaired by obstructive sleep apnea (OSA) and metabolic syndrome (MetS). Therefore, we tested the hypotheses: (1) MetS + OSA restrains ΔHRR; and (2) Sympathetic hyperactivation is involved in this impairment. DESIGN Cross-sectional study. PARTICIPANTS We studied 60 outpatients in whom MetS had been newly diagnosed (ATP III), divided according to apnea-hypopnea index (AHI) ≥ 15 events/h in MetS + OSA (n = 30, 49 ± 1.7 y) and AHI < 15 events/h in MetS - OSA (n = 30, 46 ± 1.4 y). Normal age-matched healthy control subjects (C) without MetS and OSA were also enrolled (n = 16, 46 ± 1.7 y). INTERVENTIONS Polysomnography, microneurography, cardiopulmonary exercise test. MEASUREMENTS AND RESULTS We evaluated OSA (AHI - polysomnography), muscle sympathetic nerve activity (MSNA - microneurography) and cardiac autonomic activity (LF = low frequency, HF = high frequency, LF/HF = sympathovagal balance) based on spectral analysis of heart rate (HR) variability. ΔHRR was calculated (peak HR minus HR at first, second, and fourth minute of recovery) after cardiopulmonary exercise test. MetS + OSA had higher MSNA and LF, and lower HF than MetS - OSA and C. Similar impairment occurred in MetS - OSA versus C (interaction, P < 0.01). MetS + OSA had attenuated ΔHRR at first, second, and at fourth minute than did C, and attenuated ΔHRR at fourth minute than did MetS - OSA (interaction, P < 0.001). Compared with C, MetS - OSA had attenuated ΔHRR at second and fourth min (interaction, P < 0.001). Further analysis showed association of the ΔHRR (first, second, and fourth minute) and AHI, MSNA, LF and HF components (P < 0.05 for all associations). CONCLUSIONS The attenuation of heart rate recovery after maximal exercise is impaired to a greater degree where metabolic syndrome (MetS) is associated with moderate to severe obstructive sleep apnea (OSA) than by MetS with no or mild or no OSA. This is at least partly explained by sympathetic hyperactivity.

Increased peripheral vascular resistance in male patients with traumatic lower limb amputation: one piece of the cardiovascular risk puzzle.

AimThe increased morbidity and mortality in traumatic lower limb amputees can be explained by the development of risk factors, among which high blood pressure plays an important role. However, the possible mechanisms underlying increased blood pressure levels observed in this population remain unclear. Thus, we aimed to test the hypothesis that peripheral vascular resistance is increased at rest in patients with traumatic lower limb amputation. Patients and methodsIn a cross-sectional study, eight patients with traumatic unilateral lower limb amputation (amputee group) and eight healthy individuals without amputation (control group) were included. Resting blood pressure, heart rate, and forearm blood flow were recorded simultaneously and thus, forearm vascular resistance was calculated. ResultsThe amputee group showed higher systolic (126±2 vs. 118±5 mmHg, P<0.01), diastolic (78±2 vs. 63±3 mmHg, P<0.01), mean blood pressure (94±2 vs. 81±3 mmHg, P<0.01), and heart rate (74±5 vs. 65±8 bpm, P=0.02) compared with the control group. Despite the similar forearm blood flow response between groups, patients with traumatic lower limb amputation presented increased peripheral vascular resistance at rest compared with the control group (31.3±3.8 vs. 25.7±6.5 U, P=0.05). ConclusionPatients with traumatic amputation present increased peripheral vascular resistance. Our findings clarify one possible mechanism underlying the higher blood pressure levels observed in this population.

Abnormal muscle vascular responses during exercise in myocardial infarction patients

[1] Charra B, Calemard E, Ruffet M, et al. Survival as an index of adequacy of dialysis. Kidney Int 1992;41:1286–91. [2] Wizemann V, Wabel P, Chamney P, et al. The mortality risk of overhydration in haemodialysis patients. Nephrol Dial Transplant 2009;24:1574–9. [3] Solomon SD, Dobson J, Pocock S, et al. For the Candesartan in Heart failure— Assessment of Reduction in Mortality and morbidity (CHARM) investigators. Influence of nonfatal hospitalization for heart failure on subsequent mortality in patients with chronic heart failure. Circulation 2007;116:1482–7. [4] Kataoka H. A new monitoring method for the estimation of body fluid status by digital weight scale incorporating bioelectrical impedance analyzer in definite heart failure patients. J Card Fail 2009;15:410–8. [5] Kataoka H. Novel monitoring method for management of heart failure: combined measurement of body weight and bioimpedance index of body fat percentage. Future Cardiol 2009;5:541–6. [6] Kataoka H. Detection of preclinical body fluid retention in established heart failure patients during follow-up by a digital weight scale incorporating a bioelectrical impedance analyzer. Congest Heart Fail 2012;18:37–42. [7] Stall SH, Ginsberg NS, DeVita MV, et al. Comparison of five body-composition methods in peritoneal dialysis patients. Am J Clin Nutr 1996;64:125–30. [8] Deurenberg P, Andreoli A, Borg P, et al. The validity of predicted body fat percentage from bodymass index and from impedance in samples of five European populations. Eur J Clin Nutr 2001;55:973–9. [9] Schroeder KL, Sallustio JE, Ross EA. Continuous haematocrit monitoring during intradialytic hypotention: precipitous decline in plasma refill rates. Nephrol Dial Transplant 2004;19:652–6. [10] Booth J, Pinney J,DavenportA.Dochanges in relativebloodvolumemonitoringcorrelate to hemodialysis-associated hypotension? Nephron Clin Pract 2011;117:c179–83. [11] Boyle A, Sobotka PA. Redefining the therapeutic objective in decompensated heart failure: hemoconcentration as a surrogate for plasma refill rate. J Card Fail 2006;12:247–9. [12] Kataoka H. Short-term dynamic changes in hematologic and biochemical tests during follow-up of definite heart failure patients. Int J Cardiol 2010;144:441–4. [13] Packer M, Abraham WT, Mehra MR, et al. For the Prospective Evaluation and Identification of Cardiac Decompensation by ICG Test (PREDICT) Study Investigators and Coordinators. Utility of impedance cardiography for the identification of shortterm risk of clinical decompensation in stable patients with chronic heart failure. J Am Coll Cardiol 2006;47:2245–52. [14] Tang WHW, Tong W. Measuring impedance in congestive heart failure: current options and clinical applications. Am Heart J 2009;157:402–11. [15] Kraemer M, Rode C, Wizemann V. Detection limit of methods to assess fluid status changes in dialysis patients. Kidney Int 2006;69:1609–20.

Neurovascular control during exercise in acute coronary syndrome patients with Gln27Glu polymorphism of β2-adrenergic receptor

Background Gln27Glu (rs1042714) polymorphism of the β2-adrenergic receptor (ADRB2) has been association with cardiovascular functionality in healthy subjects. However, it is unknown whether the presence of the ADRB2 Gln27Glu polymorphism influences neurovascular responses during exercise in patients with acute coronary syndromes (ACS). We tested the hypothesis that patients with ACS homozygous for the Gln allele would have increased muscle sympathetic nerve activity (MSNA) responses and decreased forearm vascular conductance (FVC) responses during exercise compared with patients carrying the Glu allele (Gln27Glu and Glu27Glu). In addition, exercise training would restore these responses in Gln27Gln patients. Methods and results Thirty-days after an ischemic event, 61 patients with ACS without ventricular dysfunction were divided into 2 groups: (1) Gln27Gln (n = 35, 53±1years) and (2) Gln27Glu+Glu27Glu (n = 26, 52±2years). MSNA was directly measured using the microneurography technique, blood pressure (BP) was measured with an automatic oscillometric device, and blood flow was measured using venous occlusion plethysmography. MSNA, mean BP, and FVC were evaluated at rest and during a 3-min handgrip exercise. The MSNA (P = 0.02) and mean BP (P = 0.04) responses during exercise were higher in the Gln27Gln patients compared with that in the Gln27Glu+Glu27Glu patients. No differences were found in FVC. Two months of exercise training significantly decreased the MSNA levels at baseline (P = 0.001) and in their response during exercise (P = 0.02) in Gln27Gln patients, but caused no changes in Gln27Glu+Glu27Glu patients. Exercise training increased FVC responses in Gln27Glu+Glu27Glu patients (P = 0.03), but not in Gln27Gln patients. Conclusion The exaggerated MSNA and mean BP responses during exercise suggest an increased cardiovascular risk in patients with ACS and Gln27Gln polymorphism. Exercise training emerges as an important strategy for restoring this reflex control. Gln27Glu polymorphism of ADRB2 influences exercise-induced vascular adaptation in patients with ACS.

Cardiac Autonomic Dysfunction in Offspring of Hypertensive Parents During Exercise

Offspring of hypertensive parents present autonomic dysfunction at rest and during physiological maneuvers. However, the cardiac autonomic modulation during exercise remains unknown. This study tested whether the cardiac autonomic modulation would be reduced in offspring of hypertensive parents during exercise. Fourteen offspring of hypertensive and 14 offspring of normotensive individuals were evaluated. The groups were matched by age (24.5±1.0 vs. 26.6±1.5 years; p=0.25) and BMI (22.8±0.6 vs. 24.2±1.0 kg/m2; p=0.30). Blood pressure and heart rate were assessed simultaneously during 3 min at baseline followed by 3-min isometric handgrip at 30% of maximal voluntary contraction. Cardiac autonomic modulation was evaluated using heart rate variability. Primary variables were subjected to two-way ANOVA (group vs. time). P value<0.05 was considered statistically significant. Blood pressure and heart rate were similar between groups during exercise protocol. In contrast, offspring of hypertensive subjects showed a reduction of SDNN (Basal=34.8±3.5 vs. 45.2±3.7 ms; Exercise=30.8±3.3 vs. 41.5±3.9 ms; p group=0.01), RMSSD (Basal=37.1±3.7 vs. 52.0±6.0 ms; Exercise=28.6±3.4 vs. 41.9±5.3 ms; p group=0.02) and pNN50 (Basal=15.7±4.0 vs. 29.5±5.5%; Exercise=7.7±2.4 vs. 18.0±4.3%; p group=0.03) during the exercise protocol in comparison with offspring of normotensive parents. We concluded that normotensive offspring of hypertensive parents exhibit impaired cardiac autonomic modulation during exercise.

Different times of day do not change heart rate variability recovery after light exercise in sedentary subjects: 24 hours Holter monitoring

ABSTRACT Incidence of cardiovascular events follows a circadian rhythm with peak occurrence during morning. Disturbance of autonomic control caused by exercise had raised the question of the safety in morning exercise and its recovery. Furthermore, we sought to investigate whether light aerobic exercise performed at night would increase HR and decrease HRV during sleep. Therefore, the aim of this study was to test the hypothesis that morning exercise would delay HR and HRV recovery after light aerobic exercise, additionally, we tested the impact of late night light aerobic exercise on HR and HRV during sleep in sedentary subjects. Nine sedentary healthy men (age 24 ± 3 yr; height 180 ± 5 cm; weight 79 ± 8 kg; fat 12 ± 3%; mean±SD) performed 35 min of cycling exercise, at an intensity of first anaerobic threshold, at three times of day (7 a.m., 2 p.m. and 11 p.m.). R-R intervals were recorded during exercise and during short-time (60 min) and long-time recovery (24 hours) after cycling exercise. Exercise evoked increase in HR and decrease in HRV, and different times of day did not change the magnitude (p < 0.05 for time). Morning exercise did not delay exercise recovery, HR was similar to rest after 15 minutes recovery and HRV was similar to rest after 30 minutes recovery at morning, afternoon, and night. Low frequency power (LF) in normalized unites (n.u.) decreased during recovery when compared to exercise, but was still above resting values after 60 minutes of recovery. High frequency power (HF-n.u.) increased after exercise cessation (p < 0.05 for time) and was still below resting values after 60 minutes of recovery. The LF/HF ratio decreased after exercise cessation (p < 0.05 for time), but was still different to baseline levels after 60 minutes of recovery. In conclusion, morning exercise did not delay HR and HRV recovery after light aerobic cycling exercise in sedentary subjects. Additionally, exercise performed in the night did change autonomic control during the sleep. So, it seems that sedentary subjects can engage physical activity at any time of day without higher risk.

Blunted muscle vasodilatory response during mental stress in predialysis nondiabetic patients: a cross-sectional study

Hypertension 2014; 63:925–933. 6 Liu M, Li Y, Wei FF, Zhang L, Han JL, Wang JG. Is blood pressure load associated, independently of blood pressure level, with target organ damage? J Hypertens 2013; 31:1812–1818. 7 Triantafyllidi H, Trivilou P, Ikonomidis I, Kontsas K, Tzortzis S, Pavlidis G, Lekakis J. Is arterial hypertension control enough to improve aortic stiffness in untreated patients with hypertension? A 3-year follow-up study. Angiology 2015; 66:759–765. 8 Parati G, Stergiou G, O’Brien E, Asmar R, Beilin L, Bilo G, et al. European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring. J Hypertens 2014; 32:1359–1366.