Modified-release gliclazide acutely improves recovery but causes undesirable blood glucose decrease after a resistance exercise session in healthy adults: a pilot study for a randomized clinical trial.

Objective: Sulfonylureas have been used to improve performance in strength sports. However, this hypothetical effect has not been proven. We examined the ergogenic acute effect of gliclazide on resistance training performance and muscle recovery. Subjects and methods: We conducted a double-blind, randomized, crossover pilot study with 10 healthy resistance-trained adults (29.3 ± 4.4 years), nonusers of anabolic steroids. The participants were randomized to two exercise sessions. In the first session, five participants received placebo and the other five received gliclazide modified release, both administered 8 hours before the session. Session two was performed in a crossover fashion a week later. The volume load was calculated as the maximum number of repetitions of four sets multiplied by load (65% 1-RM). Blood samples were collected before and after exercise, as well as 24 hours and 48 hours after exercise for measurement of creatine kinase (CK-MM) and lactate dehydrogenase (LDH) activity. Blood glucose was measured with a glucometer before, during, and after the exercise sessions. Results: Gliclazide did not enhance volume load for bench press (placebo: 2,698.0 ± 923.0 kg; gliclazide: 2,675.0 ± 1,088.0 kg; p = 0.073) or leg press (placebo: 10,866.0 ± 2,671.0 kg; gliclazide: 10,817.0 ± 2,888.0 kg; p = 0.135). However, CK-MM (-27.7%; p = 0.034) and LDH (-21.1%; p = 0.021) activities were decreased with gliclazide 48 hours after exercise. There was also a decrease in blood glucose in the gliclazide compared with the placebo session (p = 0.018). Conclusion: Gliclazide did not enhance performance in a single resistance training session, but promoted faster muscle recovery. The decrease in blood glucose post-exercise with gliclazide was an undesirable effect that could lead to long-term glucose metabolism disorders. Registered in ClinicalTrials.gov under number NCT04443777.

Exercise training improves the IL-10/TNF-α cytokine balance in the gastrocnemius of rats with heart failure.

OBJECTIVE: This study examined the effects of exercise training (ExT) upon concentration of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) in the gastrocnemius of rats with heart failure (HF) induced by left coronary artery ligation. METHODS: Adult male Wistar rats submitted to myocardial infarction (MI) or sham surgery were randomly allocated into one of four experimental groups: trained HF (Tr-HF), sedentary HF (Sed-HF), trained sham (Tr-Sham) and sedentary sham (Sed-Sham). ExT protocol was performed on treadmill for a period of 8 weeks (60m/days, 5×/week, 16m/min), which started 6 weeks after MI. Cardiac hemodynamic evaluations of left ventricular end-diastolic pressure (LVEDP) and morphometric cardiac were used to characterize HF. The hemodynamic variables were recorded and gastrocnemius muscle was collected. TNF-α, IL-6 and IL-10 protein levels were determined by multiplex bead array. RESULTS: Sed-HF group presented increase of TNF-α level when compared with the Sed-Sham group (mean difference, MD 1.3; 95% confidence interval, CI -0.04 to 2.5). ExT reduced by 59% TNF-α level in Tr-HF group (MD -1.7; 95% CI -2.9 to -0.3) and increased IL-10 (MD 15; 95% CI 11-26) when compared with the Sed-HF group. Thus, the gastrocnemius muscle IL-10/TNF-α ratio was increased in Tr-HF rats (MD 15; 95% CI -8 to 47) when compared with the Sed-HF rats. CONCLUSION: These results demonstrate that ExT not only attenuates TNF-α level but also improves the IL-10 cytokine level in skeletal muscle of HF rats.

Chronic heart failure modifies respiratory mechanics in rats: a randomized controlled trial.

OBJECTIVE: To analyze respiratory mechanics and hemodynamic alterations in an experimental model of chronic heart failure (CHF) following myocardial infarction. METHOD: Twenty-seven male adult Wistar rats were randomized to CHF group (n=12) or Sham group (n=15). Ten weeks after coronary ligation or sham surgery, the animals were anesthetized and submitted to respiratory mechanics and hemodynamic measurements. Pulmonary edema as well as cardiac remodeling were measured. RESULTS: The CHF rats showed pulmonary edema 26% higher than the Sham group. The respiratory system compliance (Crs) and the total lung capacity (TLC) were lower (40% and 27%, respectively) in the CHF rats when compared to the Sham group (P<0.01). There was also an increase in tissue resistance (Gti) and elastance (Hti) (28% and 45%, respectively) in the CHF group. Moreover, left ventricular end-diastolic pressure was higher (32 mmHg vs 4 mmHg, P<0.01), while the left ventricular systolic pressure was lower (118 mmHg vs 130 mmHg, P=0.02) in the CHF group when compared to the control. Pearson's correlation coefficient showed a negative association between pulmonary edema and Crs (r=-0.70, P=0.0001) and between pulmonary edema and TLC (r=-0.67, P=0.0034). Pulmonary edema correlated positively with Gti (r=0.68, P=0.001) and Hti (r=0.68, P=0.001). Finally, there was a strong positive relationship between pulmonary edema and heart weight (r=0.80, P=0.001). CONCLUSION: Rats with CHF present important changes in hemodynamic and respiratory mechanics, which may be associated with alterations in cardiopulmonary interactions.

Exercise during pregnancy decreases doxorubicin-induced cardiotoxic effects on neonatal hearts.

Cancer treatment with Doxorubicin (DOX) is limited due its dose-dependent cardiotoxicity, mainly related to the oxidative stress production. In experimental models of DOX treatment exercise can be used as a beneficial adjuvant therapy. This work aimed to investigate the effects of exercise during pregnancy on DOX-induced cardiotoxicity in cardiomyocytes of progeny, examining the possible intergenerational cardioprotective effects of maternal exercise. For this purpose pregnant rats were divided in control and exercise groups and pre-treated during gestational days. Hearts of newborns were used to obtain a culture of cardiomyocytes to be treated with DOX for analyses of cell viability, apoptosis and necrosis; ROS production; DNA damage; SOD and CAT activities; and Sirt6 protein expression. The results showed that exercise during pregnancy induced an increase in the viability of neonatal cardiomyocytes and a decrease in DOX-induced apoptotic and necrotic death which were correlated to the decrease in ROS production and an increase in antioxidant defenses. Exercise also protected neonatal cardiomyocytes from DOX-induced DNA damage, demonstrating a reduction in the oxidative DNA breaks. Likewise, exercise induced an increase in expression of Sirt6 in neonatal cardiomyocytes. Therefore, these results demonstrate for the first time that exercise performed by mothers protects the neonatal heart against DOX-induced toxicity. Our data demonstrate the intergenerational effect of exercise in cardiomyocytes of progeny, where the modulation of oxidative stress through antioxidant enzymes, and DNA integrity via Sirt6, were induced due to exercise in mothers, increasing the resistance of the neonatal heart against DOX toxicity.

Continuous Aerobic Training and High Intensity Interval Training Increase Exercise Tolerance in Heart Failure Patients: A Retrospective Study

Abstract Background: Conventional aerobic training is the first choice in cardiac rehabilitation for patients with chronic heart failure (CHF). However, high-intensity interval training (HIIT) may be an alternative, although it has little evidence. Objectives: To evaluate the effect of continuous aerobic training (CAT) or HIIT on exercise tolerance in CHF patients. Methods: Retrospective study with 30 patients, of both genders, members of a 10-week CAT or HIIT program. The control group (CON) consisted of patients who did not participate voluntarily in the program. Peak oxygen uptake (VO2peak), thresholds (LV1 and LV2), and ventilatory efficiency in the production of dioxide (VE/VCO2 slope), oxygen uptake efficiency (OUES), and VO2 recovery kinetics were analyzed. A two-way or repeated measures ANOVA was used, followed by Fisher's post-hoc test (p<0.05). Results: After 10 weeks of training, the CAT group increased the treadmill speed at LV1 (p=0.040), while the HIIT increased both the speed (p=0.030) and incline of the treadmill (p<0.001) for VO2peak and LV2, as well as the total time of the cardiopulmonary test. The VE/VCO2 slope was lower than that predicted for CAT (p=0.003) and HIIT (p=0.008). There was no change in VO2peak, recovery of heart rate (HR), and VO2, VE/VCO2, and OUES in both groups. Conclusions: After 10 weeks, both CAT and HIIT increased the tolerance to physical exercise. However, HIIT showed improvement in more parameters, differently from CAT.

Interval and continuous exercise enhances aerobic capacity and hemodynamic function in CHF rats.

OBJECTIVE: The aim of the present study was to compare the effects of continuous versus interval aerobic exercise training on hemodynamic parameters, cardiac remodeling, and maximal exercise capacity (MEC) in chronic heart failure (CHF) rats. METHOD: Twenty-four male Wistar rats were subjected to myocardial infarction (MI) surgery. Five weeks post MI, the animals were assigned to one of three groups: sedentary group (CHF-Sed, n=8), aerobic continuous training group (CHF-ACT, n=8), and aerobic interval training group (CHF-AIT, n=8). Treadmill training was performed five times a week for 8 weeks (ACT: 50 min/day at 15 m/min and AIT: 40 min/day with 8 min of warm-up at 10 m/min and exercise at 15 m/min 4×4 min interspersed with 4×4 min at 23 m/min). MEC was evaluated pre and post exercise program. RESULTS: Left ventricular end-diastolic pressure (LVEDP), left ventricular mass/body mass ratio (LVM:BM), and total collagen volume fraction were lower in the trained groups compared with the sedentary group, but no difference was found between the trained groups. Systolic ventricular pressure (SVP) and maximum positive derivative of LV pressure (+dP/dtmax) were higher in the trained groups, but CHF-ACT showed higher +dP/dt(max) compared to CHF-AIT. Both training regimens were able to increase MEC. However, the aerobic interval training was superior for improving MEC. CONCLUSION: Aerobic training is an important intervention to improve cardiac function and remodeling and physical capacity in CHF rats. Interval training is a potential strategy to maximize the results, but exercise type and intensity are still topics to be explored.

Resistance training improves hemodynamic function, collagen deposition and inflammatory profiles: experimental model of heart failure.

The role of resistance training on collagen deposition, the inflammatory profile and muscle weakness in heart failure remains unclear. Therefore, this study evaluated the influence of a resistance training program on hemodynamic function, maximum strength gain, collagen deposition and inflammatory profile in chronic heart failure rats. Thirty-two male Wistar rats submitted to myocardial infarction by coronary artery ligation or sham surgery were assigned into four groups: sedentary sham (S-Sham, n = 8); trained sham (T-Sham, n = 8); sedentary chronic heart failure (S-CHF, n = 8) and trained chronic heart failure (T-CHF, n = 8). The maximum strength capacity was evaluated by the one maximum repetition test. Trained groups were submitted to an 8-week resistance training program (4 days/week, 4 sets of 10-12 repetitions/session, at 65% to 75% of one maximum repetition). After 8 weeks of the resistance training program, the T-CHF group showed lower left ventricular end diastolic pressure (P<0.001), higher left ventricular systolic pressure (P<0.05), higher systolic blood pressure (P<0.05), an improvement in the maximal positive derivative of ventricular pressure (P<0.05) and maximal negative derivative of ventricular pressure (P<0.05) when compared to the S-CHF group; no differences were observed when compared to Sham groups. In addition, resistance training was able to reduce myocardial hypertrophy (P<0.05), left ventricular total collagen volume fraction (P<0.01), IL-6 (P<0.05), and TNF-α/IL-10 ratio (P<0.05), as well as increasing IL-10 (P<0.05) in chronic heart failure rats when compared to the S-CHF group. Eight weeks of resistance training promotes an improvement of cardiac function, strength gain, collagen deposition and inflammatory profile in chronic heart failure rats.

Aerobic exercise improves the inflammatory profile correlated with cardiac remodeling and function in chronic heart failure rats.

OBJECTIVE: The aim of the present study was to evaluate the effect of 8 weeks of aerobic exercise training on cardiac functioning and remodeling and on the plasma levels of inflammatory cytokines in chronic heart failure rats. METHODS: Wistar rats were subjected to myocardial infarction or sham surgery and assigned to 4 groups: chronic heart failure trained (n=7), chronic heart failure sedentary (n=6), sham trained (n=8) and sham sedentary (n=8). Four weeks after the surgical procedures, the rats were subjected to aerobic training in the form of treadmill running (50 min/day, 5 times per week, 16 m/min). At the end of 8 weeks, the rats were placed under anesthesia, the hemodynamic variables were recorded and blood samples were collected. Cardiac hypertrophy was evaluated using the left ventricular weight/body weight ratio, and the collagen volume fraction was assessed using histology. RESULTS: The chronic heart failure trained group showed a reduction in left ventricular end-diastolic pressure, a lower left ventricular weight/body weight ratio and a lower collagen volume fraction compared with the chronic heart failure sedentary group. In addition, exercise training reduced the plasma levels of TNF-α and IL-6 and increased the plasma level of IL-10. CONCLUSION: An 8-week aerobic exercise training program improved the inflammatory profile and cardiac function and attenuated cardiac remodeling in chronic heart failure rats.

Chronic heart failure modifies respiratory mechanics in rats: a randomized controlled trial

ABSTRACT Objective To analyze respiratory mechanics and hemodynamic alterations in an experimental model of chronic heart failure (CHF) following myocardial infarction. Method Twenty-seven male adult Wistar rats were randomized to CHF group (n=12) or Sham group (n=15). Ten weeks after coronary ligation or sham surgery, the animals were anesthetized and submitted to respiratory mechanics and hemodynamic measurements. Pulmonary edema as well as cardiac remodeling were measured. Results The CHF rats showed pulmonary edema 26% higher than the Sham group. The respiratory system compliance (Crs) and the total lung capacity (TLC) were lower (40% and 27%, respectively) in the CHF rats when compared to the Sham group (P<0.01). There was also an increase in tissue resistance (Gti) and elastance (Hti) (28% and 45%, respectively) in the CHF group. Moreover, left ventricular end-diastolic pressure was higher (32 mmHg vs 4 mmHg, P<0.01), while the left ventricular systolic pressure was lower (118 mmHg vs 130 mmHg, P=0.02) in the CHF group when compared to the control. Pearson’s correlation coefficient showed a negative association between pulmonary edema and Crs (r=–0.70, P=0.0001) and between pulmonary edema and TLC (r=–0.67, P=0.0034). Pulmonary edema correlated positively with Gti (r=0.68, P=0.001) and Hti (r=0.68, P=0.001). Finally, there was a strong positive relationship between pulmonary edema and heart weight (r=0.80, P=0.001). Conclusion Rats with CHF present important changes in hemodynamic and respiratory mechanics, which may be associated with alterations in cardiopulmonary interactions.

Interval and continuous exercise enhances aerobic capacity and hemodynamic function in CHF rats

OBJECTIVE: The aim of the present study was to compare the effects of continuous versus interval aerobic exercise training on hemodynamic parameters, cardiac remodeling, and maximal exercise capacity (MEC) in chronic heart failure (CHF) rats.METHOD: Twenty-four male Wistar rats were subjected to myocardial infarction (MI) surgery. Five weeks post MI, the animals were assigned to one of three groups: sedentary group (CHF-Sed, n=8), aerobic continuous training group (CHF-ACT, n=8), and aerobic interval training group (CHF-AIT, n=8). Treadmill training was performed five times a week for 8 weeks (ACT: 50 min/day at 15 m/min and AIT: 40 min/day with 8 min of warm-up at 10 m/min and exercise at 15 m/min 4×4 min interspersed with 4×4 min at 23 m/min). MEC was evaluated pre and post exercise program.RESULTS: Left ventricular end-diastolic pressure (LVEDP), left ventricular mass/body mass ratio (LVM:BM), and total collagen volume fraction were lower in the trained groups compared with the sedentary group, but no difference was found between the trained groups. Systolic ventricular pressure (SVP) and maximum positive derivative of LV pressure (+dP/dtmax) were higher in the trained groups, but CHF-ACT showed higher +dP/dtmax compared to CHF-AIT. Both training regimens were able to increase MEC. However, the aerobic interval training was superior for improving MEC.CONCLUSION: Aerobic training is an important intervention to improve cardiac function and remodeling and physical capacity in CHF rats. Interval training is a potential strategy to maximize the results, but exercise type and intensity are still topics to be explored.

Aerobic exercise improves the inflammatory profile correlated with cardiac remodeling and function in chronic heart failure rats

OBJECTIVE: The aim of the present study was to evaluate the effect of 8 weeks of aerobic exercise training on cardiac functioning and remodeling and on the plasma levels of inflammatory cytokines in chronic heart failure rats. METHODS: Wistar rats were subjected to myocardial infarction or sham surgery and assigned to 4 groups: chronic heart failure trained (n = 7), chronic heart failure sedentary (n = 6), sham trained (n = 8) and sham sedentary (n = 8). Four weeks after the surgical procedures, the rats were subjected to aerobic training in the form of treadmill running (50 min/day, 5 times per week, 16 m/min). At the end of 8 weeks, the rats were placed under anesthesia, the hemodynamic variables were recorded and blood samples were collected. Cardiac hypertrophy was evaluated using the left ventricular weight/body weight ratio, and the collagen volume fraction was assessed using histology. RESULTS: The chronic heart failure trained group showed a reduction in left ventricular end-diastolic pressure, a lower left ventricular weight/body weight ratio and a lower collagen volume fraction compared with the chronic heart failure sedentary group. In addition, exercise training reduced the plasma levels of TNF-α and IL-6 and increased the plasma level of IL-10. CONCLUSION: An 8-week aerobic exercise training program improved the inflammatory profile and cardiac function and attenuated cardiac remodeling in chronic heart failure rats. .