scholarly journals Safety and efficacy of omaveloxolone in patients with mitochondrial myopathy

Neurology ◽  
2020 ◽  
Vol 94 (7) ◽  
pp. e687-e698 ◽  
Author(s):  
Karen L. Madsen ◽  
Astrid E. Buch ◽  
Bruce H. Cohen ◽  
Marni J. Falk ◽  
Angela Goldsberry ◽  
...  
Keyword(s):  
Heart Rate ◽  
Mitochondrial Myopathy ◽  
Lactate Production ◽  
Primary Outcome Measure ◽  
Submaximal Exercise ◽  
Peak Exercise ◽  
Exercise Heart Rate ◽  
Double Blind ◽  
Safety And Efficacy ◽  
6Mwt Distance

ObjectiveTo investigate the safety and efficacy of escalating doses of the semi-synthetic triterpenoid omaveloxolone in patients with mitochondrial myopathy.MethodsIn cohorts of 8–13, 53 participants were randomized double-blind to 12 weeks of treatment with omaveloxolone 5, 10, 20, 40, 80, or 160 mg, or placebo. Outcome measures were change in peak cycling exercise workload (primary), in 6-minute walk test (6MWT) distance (secondary), and in submaximal exercise heart rate and plasma lactate (exploratory).ResultsNo differences in peak workload or 6MWT were observed at week 12 with omaveloxolone treatment vs placebo for all omaveloxolone dose groups. In contrast, omaveloxolone 160 mg reduced heart rate at week 12 by 12.0 ± 4.6 bpm (SE) during submaximal exercise vs placebo, p = 0.01, and by 8.7 ± 3.5 bpm (SE) vs baseline, p = 0.02. Similarly, blood lactate was 1.4 ± 0.7 mM (SE) lower vs placebo, p = 0.04, and 1.6 ± 0.5 mM (SE) lower vs baseline at week 12, p = 0.003, with omaveloxolone 160 mg treatment. Adverse events were generally mild and infrequent.ConclusionsOmaveloxolone 160 mg was well-tolerated, and did not lead to change in the primary outcome measure, but improved exploratory endpoints lowering heart rate and lactate production during submaximal exercise, consistent with improved mitochondrial function and submaximal exercise tolerance. Therefore, omaveloxolone potentially benefits patients with mitochondrial myopathy, which encourages further investigations of omaveloxolone in this patient group.Clinicaltrials.gov identifierNCT02255422.Classification of evidenceThis study provides Class II evidence that, for patients with mitochondrial myopathy, omaveloxolone compared to placebo did not significantly change peak exercise workload.

Effects of chronic beta-adrenergic blockade on exercise training in dogs

1988 ◽  
Vol 64 (5) ◽  
pp. 1960-1967 ◽  
Author(s):  
E. E. Wolfel ◽  
J. Lindenfeld ◽  
J. Smoak ◽  
L. D. Horwitz
Keyword(s):  
Heart Rate ◽  
Submaximal Exercise ◽  
Peak Exercise ◽  
Exercise Heart Rate ◽  
Adrenergic Blockade ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Exercise Time ◽  
Adrenergic Blocker

To assess the role of beta-adrenergic stimulation in cardiovascular conditioning we examined the effects of a beta-adrenergic blocker, propranolol, in mongrel dogs during an 8-wk treadmill-training program. Seven dogs were trained without a drug (NP), six were trained on propranolol 10 mg.kg-1.day-1 (P), and five served as caged controls (C). Effective beta-adrenergic blockade was documented by a decrease in peak exercise heart rate of 54 +/- 11 (SE) beats/min (P less than 0.05) and a one-log magnitude of increase in the isoproterenol-heart rate dose-response curve. Testing was performed before drug treatment or training and again after training without the drug for 5 days. Submaximal exercise heart rate decreased similarly in both NP and P (-26 +/- 4 NP vs. -25 +/- 9 beats/min P, P less than 0.05 for both) but peak heart rate decreased only with NP (-33 +/- 9 beats/min, P less than 0.05). Treadmill exercise time increased similarly in both groups: 3.4 +/- 0.6 min in NP and 3.0 +/- 0.2 min in P (both P less than 0.05). Blood volume also increased after training in both groups: 605 +/- 250 ml (26%) in NP and 377 +/- 140 ml (17%) in P (both P less than 0.05). Submaximal exercise arterial lactates were reduced similarly in both groups but peak exercise lactate was reduced more in NP (-1.4 +/- 0.3 NP vs -0.3 +/- 0.12 mmol/l P, P less than 0.05). Lactate threshold increased in both groups but the increase was greater in NP (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Diaphragm does not produce ammonia or lactate during high-intensity short-term exercise

1990 ◽  
Vol 259 (4) ◽  
pp. H1185-H1189 ◽  
Author(s):  
M. Manohar ◽  
A. S. Hassan
Keyword(s):  
Heart Rate ◽  
High Intensity ◽  
Work Of Breathing ◽  
Lactate Production ◽  
Exercise Heart Rate ◽  
Short Term ◽  
Energy Needs ◽  
Standard Procedures ◽  
O2 Extraction ◽  
Limb Muscles

To ascertain whether costal diaphragm engages in ammonia and lactate production (like limb muscles) during high-intensity short-term exercise, experiments were carried out on six healthy trained ponies in which phrenic venous catheters had been implanted 5-9 days earlier. Simultaneous anaerobically obtained blood samples from abdominal aorta and the phrenic vein at rest and during 4 min of exertion at 32 km/h and at a 7% grade were analyzed for blood-gas variables as well as lactate and ammonia concentrations using standard procedures. At rest, heart rate was 47 +/- 4 beats/min and the diaphragmatic O2 extraction was 26.5%. With exercise, heart rate rose to 218 +/- 6 beats/min, marked acidosis and hyperventilation occurred, and the diaphragmatic O2 extraction increased threefold (80.9%). Such exercise is known to dramatically increase the work of breathing as respiratory frequency and change in pleural pressure approach 138 +/- 4 breaths/min and 30 +/- 3 cmH2O, respectively. Despite the fact that phrenic-venous O2 tension of exercised ponies decreased to 15.5 +/- 0.6 Torr, the phrenic-venous lactate and ammonia concentrations did not exceed corresponding arterial values. These data thus revealed that the diaphragm is uniquely unlike limb muscles, which at high workloads readily engage in net ammonia and lactate production, and that the diaphragmatic energy needs during high-intensity short-term exercise are primarily met by aerobic metabolism.

Comparative β-Adrenoreceptor-Blocking Effects and Pharmacokinetics of Propranolol and Pindolol in Hypertensive Africans

1979 ◽  
Vol 57 (s5) ◽  
pp. 393s-396s ◽  
Author(s):  
L. A. Salako ◽  
A. O. Falase ◽  
A. Fadeke Aderounmu
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Systolic Blood Pressure ◽  
Diastolic Pressure ◽  
Exercise Heart Rate ◽  
Double Blind ◽  
Blocking Effects ◽  
The Mean ◽  
Exercise Induced ◽  
African Patients

1. The β-adrenoreceptor-blocking effects of pindolol were compared with those of propranolol and a placebo in a double-blind cross-over trial involving nine hypertensive African patients. 2. Heart rate, systolic blood pressure and diastolic blood pressure were measured at rest and immediately after exercise before and at intervals up to 6 h after oral administration of the drugs. In addition, plasma pindolol and propranolol concentrations were determined at the same intervals. 3. Pindolol diminished systolic blood pressure at rest and after exercise and antagonized exercise-induced tachycardia, but had no effect on resting heart rate. Propranolol diminished systolic blood pressure predominantly after exercise and reduced both resting and exercise heart rate. Both drugs had no effect on diastolic pressure. 4. The mean plasma concentration reached a peak at 2 h for each drug and this coincided with the interval at which maximal β-adrenoreceptor-blocking effect was observed.

scholarly journals Effect Of Endogenous Noradenaline Release On Peak Exercise Heart Rate In Subjects With Chronic Heart Failure Receiving Carvedilol Versus Metoprolol

2004 ◽  
Vol 6 (1) ◽  
Author(s):  
Timothy Vittorio ◽  
Duygu Onat ◽  
Paolo Colombo ◽  
John Stathopoulos ◽  
Cselaj Sulejman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Chronic Heart Failure ◽  
Peak Exercise ◽  
Exercise Heart Rate

Capsaicin Supplementation during High-intensity Continuous Exercise: A Double-blind Study

2020 ◽  
Vol 41 (14) ◽  
pp. 1061-1066 ◽  
Author(s):  
Camila S. Padilha ◽  
Francois Billaut ◽  
Caique Figueiredo ◽  
Valéria Leme Gonçalves Panissa ◽  
Fabrício Eduardo Rossi ◽  
...  
Keyword(s):  
Heart Rate ◽  
High Intensity ◽  
Physiological Responses ◽  
Energy Systems ◽  
Exercise Session ◽  
Exercise Heart Rate ◽  
Time To Exhaustion ◽  
Double Blind ◽  
Continuous Exercise ◽  
Significant Difference

AbstractTo investigate the effect of acute capsaicin (CAP) supplementation on time to exhaustion, physiological responses and energy systems contribution during continuous high-intensity exercise session in runners. Fifteen recreationally-trained runners completed two randomized, double-blind continuous high-intensity exercises at the speed eliciting 90% V̇O2peak (90% s V̇O2peak), 45 minutes after consuming capsaicin or an isocaloric placebo. Time to exhaustion, blood lactate concentration, oxygen consumption during and 20-min post-exercise, energy systems contribution, time to reach V̇O2peak, heart rate and the rate of perceived exertion (RPE) were evaluated. There was no significant difference between conditions for time to reach V̇O2peak (CAP:391.71±221.8 vs. PLA:298.20±174.5 sec, ES:0.58, p=0.872), peak lactate (CAP:7.98±2.11 vs. PLA:8.58±2.15 µmol, ES:−0.28, p=0.257), time to exhaustion (CAP:654.28±195.44 vs. PLA:709.20±208.44 sec, ES:−0.28, p=0.462, end-of-exercise heart rate (CAP:177.6±14.9 vs. PLA:177.5±17.9 bpm, ES:−0.10, p=0.979) and end-of-exercise RPE (CAP: 19±0.8 vs. PLA: 18±2.4, ES: 0.89, p=0.623). In conclusion, acute CAP supplementation did not increase time to exhaustion during high-intensity continuous exercise nor alter physiological responses in runners.

Sumatriptan reduces exercise capacity in healthy males: a peripheral effect of 5-hydroxytryptamine agonism?

2000 ◽  
Vol 98 (6) ◽  
pp. 643-648 ◽  
Author(s):  
Gerald P. MCCANN ◽  
Helen CAHILL ◽  
Stephen KNIPE ◽  
Douglas F. MUIR ◽  
Paul D. MACINTYRE ◽  
...  
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Exercise Capacity ◽  
Gas Analysis ◽  
Peak Oxygen Consumption ◽  
Peak Exercise ◽  
Double Blind ◽  
Peripheral Effect ◽  
Expired Gas Analysis ◽  
Exercise Induced

5-Hydroxytryptamine (5-HT; serotonin) has been implicated in the perception of exercise-induced fatigue. Sumatriptan is a selective 5-HT1B/D receptor agonist which does not cross the blood–brain barrier. The aim of the present study was to determine the effect of sumatriptan on exercise capacity. Ten healthy male subjects (mean age 28.4±10.8 years) performed a maximal treadmill exercise test according to the Bruce protocol with expired gas analysis on two occasions. Either 6 mg of sumatriptan or placebo was administered subcutaneously in a randomized, double-blind, placebo-controlled, cross-over design. Exercise time was greater after placebo compared with sumatriptan [914 and 879 s respectively; 95% confidence interval (CI) of difference 12.1 s, 59.1 s; P = 0.008]. There was no significant effect on peak oxygen consumption (placebo, 50.6±6.3 ml·min-1·kg-1; sumatriptan, 51.7±7.6 ml·min-1·kg-1). Sumatriptan administration resulted in decreases in both heart rate (sumatriptan, 188±14 beats/min, placebo, 196±12 beats/min; 95% CI of difference 12.6, 2.6; P = 0.008) and respiratory exchange ratio (sumatriptan, 1.23±0.06; placebo, 1.26±0.07; 95% CI of difference 0.05, 0.01; P = 0.01) at peak exercise. There were no significant differences in blood pressure, heart rate or submaximal oxygen consumption between sumatriptan and placebo treatments at any stage of exercise. Thus sumatriptan reduces maximal exercise capacity in normal males. The failure to demonstrate any haemodynamic or cardiorespiratory effect suggests that sumatriptan enhances perception of fatigue by a peripheral mechanism affecting 5-HT modulation.

scholarly journals Effect of Thiamine Pyrophosphate on Levels of Serum Lactate, Maximum Oxygen Consumption and Heart Rate in Athletes Performing Aerobic Activity

2008 ◽  
Vol 36 (6) ◽  
pp. 1220-1226 ◽  
Author(s):  
VM Bautista-Hernández ◽  
R López-Ascencio ◽  
M Del Toro-Equihua ◽  
C Vásquez
Keyword(s):  
Heart Rate ◽  
Oxygen Consumption ◽  
Serum Lactate ◽  
Thiamine Pyrophosphate ◽  
Exercise Heart Rate ◽  
Maximum Oxygen Consumption ◽  
Double Blind ◽  
Male Athletes ◽  
Aerobic Activity ◽  
Lactate Levels

The aim of this study was to determine the effect of thiamine pyrophosphate (TPP) on serum lactate levels, maximum oxygen consumption (Vo2max) and heart rate in male athletes performing aerobic activity. A double-blind, randomized, crossover study was performed in which lactate levels, Vo2max and heart rates in 27 male athletes were compared at rest and after exercise, following administration of placebo (sodium chloride 0.9%) or TPP (1 mg/kg). At rest, serum lactate levels after placebo or TPP were similar; however, after exercise, the levels were lower in the athletes after taking TPP than after placebo. During exercise, Vo2max in athletes on TPP was higher than on placebo. At rest, heart rate after taking placebo or TPP was similar but, after exercise, heart rate was lower after taking TPP than after placebo. It is concluded that TPP caused serum lactate levels and heart rate to be lower than placebo and Vo2max to be higher in athletes performing aerobic physical activity.

scholarly journals The Effect of AcuteRhodiola roseaIngestion on Exercise Heart Rate, Substrate Utilisation, Mood State, and Perceptions of Exertion, Arousal, and Pleasure/Displeasure in Active Men

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Michael J. Duncan ◽  
Neil D. Clarke
Keyword(s):  
Heart Rate ◽  
Energy Expenditure ◽  
Repeated Measures ◽  
Mood State ◽  
Cycling Performance ◽  
Exercise Heart Rate ◽  
Double Blind ◽  
Substrate Utilisation ◽  
Repeated Measures Analysis ◽  
Before And After

The aim of this study was to examine the effect of acuteRhodiola rosea(R. rosea) ingestion on substrate utilisation, mood state, RPE, and exercise affect. Ten males (mean age ± S.D. = 26 ± 6 years) completed two 30-minute cycling trials at an intensity of 70% ofV˙O2max⁡following ingestion of either 3 mg·kg−1body mass ofR. roseaor placebo using a double-blind, crossover design. During exercise, heart rate and RPE were recorded. Participants completed measures of mood state and exercise affect before and after exercise. Expired air samples were taken during exercise to determine substrate utilisation. Repeated measures analysis of variance indicated that RPE was significantly lower at 30 minutes into exercise versus placebo (P=0.003). Perceptions of arousal (P=0.05) and pleasure were significantly higher after exercise withR. roseacompared to placebo (P=0.003). Mood state scores for vigor were also higher inR. roseacondition compared to placebo (P=0.008). There were no significant differences in energy expenditure, carbohydrate, or fat oxidation between conditions (P>0.05). Ingestion ofR. roseafavourably influenced RPE and exercise affect without changes in energy expenditure or substrate utilization during 30-minute submaximal cycling performance.

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