Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes

Bitter orange (Citrus aurantium) extract is widely used in dietary supplements for weight management and sports performance. Its primary protoalkaloid is p-synephrine. Most studies involving bitter orange extract and p-synephrine have used products with multiple ingredients. The current study assessed the thermogenic effects of p-synephrine alone and in conjunction with the flavonoids naringin and hesperidin in a double-blinded, randomized, placebo-controlled protocol with 10 subjects per treatment group. Resting metabolic rates (RMR), blood pressure, heart rates and a self-reported rating scale were determined at baseline and 75 min after oral ingestion of the test products in V-8 juice. A decrease of 30 kcal occurred in the placebo control relative to baseline. The group receiving p-synephrine (50 mg) alone exhibited a 65 kcal increase in RMR as compared to the placebo group. The consumption of 600 mg naringin with 50 mg p-synephrine resulted in a 129 kcal increase in RMR relative to the placebo group. In the group receiving 100 mg hesperidin in addition to the 50 mg p-synephrine plus 600 mg naringin, the RMR increased by 183 kcal, an increase that was statistically significant with respect to the placebo control (p<0.02). However, consuming 1000 mg hesperidin with 50 mg p-synephrine plus 600 mg naringin resulted in a RMR that was only 79 kcal greater than the placebo group. None of the treatment groups exhibited changes in heart rate or blood pressure relative to the control group, nor there were no differences in self-reported ratings of 10 symptoms between the treatment groups and the control group. This unusual finding of a thermogenic combination of ingredients that elevated metabolic rates without corresponding elevations in blood pressure and heart-rates warrants longer term studies to assess its value as a weight control agent.     

A Review of the Human Clinical Studies Involving Citrus aurantium (Bitter Orange) Extract and its Primary Protoalkaloid p-Synephrine

This review summarizes the published as well as unpublished human studies involving Citrus aurantium (bitter orange) extract and its primary protoalkaloid p-synephrine, providing information and an assessment of the safety and efficacy of these widely used products. The results of over 20 studies involving a total of approximately 360 subjects that consumed p-synephrine alone or in combination with other ingredients are reviewed and critiqued. Over 50 % of the subjects involved in these studies were overweight/obese, and approximately two-thirds of these overweight/obese subjects consumed caffeine (132-528 mg/day) in conjunction with p-synephrine (10-53 mg/day). Bitter orange/p-synephrine containing products were consumed for up to 12 weeks. Approximately 44 % of the subjects consumed a bitter orange/p-synephrine only product, while the remainder consumed a complex product that contained multiple ingredients in addition to p-synephrine. In general, bitter orange extract alone (p-synephrine) or in combination with other herbal ingredients did not produce significant adverse events as an increase in heart rate or blood pressure, or alter electrocardiographic data, serum chemistry, blood cell counts or urinalysis. p-Synephrine alone as well as in combination products were shown to increase resting metabolic rate and energy expenditure, and modest increases in weight loss were observed with bitter orange extract/p-synephrine-containing products when given for six to 12 weeks. Longer term studies are needed to further assess the efficacy of these products and affirm their safety under these conditions.     

Diabetes affects blood pressure and heart rate responses during acute hypothermia

Many diabetics are cold-intolerant and experience dramatic changes in normal systemic function during hypothermia. Little is known of the cardiovascular adjustments in diabetics exposed to an acute cold stress. In an effort to identify the alterations in mean arterial blood pressure (MAP) and heart rate (HR) in the diabetic during environmental cooling (10 ± 2 °C), we compared the in vivo MAP and HR responses of urethane-anaesthetized (1.5 g kg^?1), streptozotocin-diabetic (STZ, 65 mg kg^?1, n = 12) and control (CON, n = 10) rats during acute hypothermia. MAP was measured directly via an indwelling carotid artery cannula and HR was calculated from the peak systolic pressure waves. Overall, the STZ rats were more cold-intolerant than CON as evidenced by the greater rate of decline in colonic temperature (T_c) from 36 to 28 °C (STZ, 0.16 °C min^?1 vs. CON, 0.06 °C min^?1; P < 0.05). Prior to cooling, HR was significantly lower (P < 0.05) in STZ (282 ± 9 beats min^?1) than in CON rats (399 ± 24 beats min^?1); however, during the acute hypothermic period, HR displayed a similar rate of decline in both groups. With respect to MAP, both groups demonstrated similar pre-experimental pressor responses (CON, 81.7 ± 5.4 vs. STZ, 83.2 ± 5.1 mmHg, P > 0.05). During progressive hypothermia, MAP gradually increased (P < 0.05) in the CON group from baseline (T_c = 36 °C) and reached peak values (118.4 ± 2.5 mmHg) at T_c = 30 °C, while the STZ group failed to exhibit any cold pressor response. At the conclusion of the experiment (T_c = 28 °C), the STZ group pressor response to hypothermia was not different from baseline (T_c = 36 °C, 83.2 ± 5.1 vs. T_c = 28 °C, 77.4 ± 3.4 mmHg; P > 0.05). The absence of any pressor response in the diabetic group during progressive hypothermia reflects the poor overall vasoconstrictive capacity to cooling and could partially explain the rapid decline of core temperature in this group.     

Periodic variations of blood pressure and heart rate in premature neonates

Laboratory of Experimental Brain Pathology and Department of Newborn and Premature Infants, Research Institute of Pediatrics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR M. Ya. Studenikin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 3, pp. 217–219, March, 1990.     

Central apnoeas have significant effects on blood pressure and heart rate in children

Brief central apnoeas (CAs) during sleep are common in children and are not usually considered clinically significant unless associated with oxygen desaturation. CAs can occur spontaneously or following a movement or sigh. The aim of this study was to investigate acute cardiovascular changes associated with CAs in children. Beat‐by‐beat mean arterial pressure (MAP) and heart rate (HR) were analysed across CAs, and spontaneous and movement‐induced events were compared using two‐way analysis of variance with post hoc analyses. Fifty‐three children (28 male/25 female) aged 7–12 years referred for investigation of sleep‐disordered breathing (SDB) and 21 age‐matched healthy controls (8 male/13 female) were studied. Children underwent routine clinical polysomnography with continuous blood pressure (BP) recordings. Movement‐induced, but not spontaneous, CAs were more frequent in children with mild or moderate/severe obstructive sleep apnoea (OSA) compared with healthy controls (P < 0.05 for both). Movement‐induced CAs were associated with significantly larger MAP and HR changes across the event compared with spontaneous CAs. The percentage changes in MAP and HR between late‐event and post‐event were significantly greater for movement‐induced compared with spontaneous CAs (MAP 20.6 ± 2.3 versus 12.2 ± 1.8%, P < 0.01; HR 28.2 ± 2.6 versus 14.7 ± 2.5%, P < 0.001). This study demonstrates that movement‐induced CAs are more common in children with OSA, and are associated with significantly greater changes in HR and BP compared with spontaneous CAs. These data suggest that movement‐induced CAs should be considered when assessing the cardiovascular impact of SDB.     

Effects of 4-week administration of simvastatin in different doses on heart rate and blood pressure after metoprolol injection in normocholesterolaemic and normotensive rats

Introduction

Statins and β1-adrenergic antagonists are well established in cardiovascular events therapy and prevention. The previous study showed that statins might impact on β-adrenergic signalling and blood pressure in a dose-dependent manner. The aim of the study was to evaluate the impact of 4-week administration of simvastatin given at different doses on the heart rate and blood pressure after injection of metoprolol in rats.

Material and methods

The experiments were performed in normocholesterolaemic and normotensive Wistar rats. Rats received simvastatin in doses of 1, 10 and 20 mg/kg body weight (bw) for 4 weeks. The control group received 0.2% methylcellulose. For the further estimation of the heart rate and blood pressure, metoprolol at 5 mg/kg bw or 0.9% NaCl was injected intraperitoneally.

Results

Simvastatin at doses of 1, 10 and 20 mg/kg bw did not influence the heart rate or blood pressure as compared to the control group. Metoprolol injection statistically significantly decreased the heart rate (439.29±14.03 min⁻¹ vs. 374.41±13.32 min⁻¹; p<0.05). In rats receiving simvastatin during the 4-week period after metoprolol injection, heart rate and blood pressure (mean, systolic, diastolic) were similar as compared to the group receiving metoprolol alone.

Conclusions

Simvastatin administration during a 4-week period in different doses did not influence the heart rate or blood pressure after metoprolol injection in normocholesterolaemic and normotensive rats.     

The effect of centrally administered TRH on blood pressure,heart rate and ventilation in rat

Different doses (3, 16, 80, 400 and 2000 ng per rat) of TRH or alternatively saline were infused into the lateral ventricle of urethane-ahaesthetized rats and blood pressure, heart rate, respiration rate and tidal volume were recorded. A dose of 3 ng TRH caused a significant elevation of blood pressure and heart rate, whereas 16 ng was needed for respiration rate to be elevated. There was no change in respiratory minute volume during the experiment. We conclude that TRH has profound physiological effects and that TRH, given centrally, is a potent hypertensive, chronotropic and tachypnoeic agent.     

The effects of caffeine on ambulatory blood pressure,heart rate,and mood in coffee drinkers

The present study examined the effects of caffeine, as typically ingested through coffee, on ambulatory systolic and diastolic blood pressure (BP), heart rate, and mood. Normotensive coffee drinkers wore a BP monitor for two 24-hr periods, consuming decaffeinated coffee. Each cup was supplemented with 125 mg caffeine or cornstarch. Systolic and diastolic BPs were elevated on the day caffeine was consumed (maximum, 3.6 and 5.6 mm Hg, respectively), most notably shortly after ingestion. Heart rate was higher overnight following caffeine consumption. Negative Affectivity was also increased by caffeine, but Positive Affectivity and tiredness were unaffected.     

Nitric oxide donors dose-dependently reduce heart rate in rats against the background of blood pressure drop

The effect of nitroglycerin in increasing doses (0.2-1.0 mg/kg) and sodium nitroprusside (1 mg/kg) on the heart rate, P-Q interval of ECG, and blood pressure was studied on 53 albino rats. NO donors nitroglycerin and sodium nitroprusside directly affected vascular endothelium (the maximum decrease in blood pressure was 28.5 and 57.0%, respectively) and produced a dose-dependent negative chronotropic effect (the maximum decrease in heart rate was 13.6 and 27.0%, respectively). These drugs also affected myocytes of the cardiac conduction system: P-Q interval increased by 16.0-29.7%.     

Effect of posture on arterial baroreflex control of heart rate in humans

Summary Altered baroreflex function may contribute to the cardiovascular changes associated with weightlessness. Since central blood volume (CBV) increases during simulated weightlessness, we have examined the possibility that acute changes in CBV may modify baroreceptor function. We used graded head-up tilt (HUT) and head-down tilt (HDT) to induce changes in CBV, and neck suction to stimulte carotid baroreceptors, in 6 subjects. The increase in pulse interval induced by a negative pressure of 8.2 kPa (62 mm Hg) imposed for 10 s while supine was compared with the increase while tilted for 8 min at ± 15, ± 30 and ± 45. During HDT at 15 the pulse interval over the first 5 cardiac cycles following suction onset was 51 ± (SEM) 18 ms longer (p<0.05), at 30 it was 61±20 ms longer (p<0.05), and at 45 it was 74±35 ms longer (p<0.01), compared with supine. During HUT at 15 the pulse interval was 25±9 ms shorter (p<0.05) than when supine, but was not significantly different at 30 and 45. These responses occurred independently of changes in brachial blood pressure. Attenuation was also observed after 5 min (56±17 ms; <0.05), and after 40 min (25±9 ms; p<0.05) of 60 HUT compared with supine. We conclude that posture does modify arterial baroreflex control of heart rate. If this occurs primarily as a result of a change in CBV, then the acute effect of weightlessness may be an accentuation, not an attenuation, of baroreflex function.M. H. Harrison was a National Research Council postdoctoral research fellow on leave from the Ministry of Defence, UK     

Diurnal changes of blood pressure,heart rate and body temperature during sleep in the rat

We have studied diurnal changes in mean arterial pressure (MAP), heart rate (HR) and body temperature (Tb) during wake (W), non-rapid eye movement sleep (NREMS) and REM sleep (REMS) in the rat. Although HR and Tb show a similar sinusoidal diurnal variation during all vigilance states, the diurnal profile for the MAP is vigilance-state dependent. During W, MAP values are higher during the dark phase, during NREMS, no significant diurnal change is seen, and during REMS, the MAP exhibits a reversed diurnal change, being higher during the light phase. The low frequency component (0.25–0.725 Hz) in the power spectral density of the blood pressure, an index of sympathetic activity, is also higher during the light phase than the dark phase in REMS. The present findings suggest that diurnal changes in MAP in the rat result from the wake rhythm, and that the mechanism for the diurnal control of MAP may be different from that for HR or Tb.     

Effect of exercise on systemic blood pressure and heart rate in horses

Summary Carotid loops were prepared in 3 horses several months prior to the experiments. Systemic blood pressure was recorded at rest and during exercise by insertion of a plastic cannula into the carotid artery. The pressure transducer was fixed at the neck of the animal. The blood pressure signal was transmitted by telemetry.When the horses were standing under the rider, the following results were obtained: heart rate 38±5 beats · min^–1, systolic pressure 115±15, disstolic pressure 83±10, mean pressure 97±12, and pulse pressure 32±9 mm Hg. During steady gallop at a mean speed of 548±90 m · min^–1, heart rate rose to 184±23 beats · min^–1, systolic pressure to 205±23, diastolic pressure to 116±12, mean pressure to 160±20 and pulse pressure to 89±19 mm Hg. These values remained stable throughout the exercise period of 5–6 min.When the horses were exercised at stepwise increasing speed from walk through trot to gallop, both the mean arterial blood pressure and the pulse pressure rose in proportion to the running speed.     

Effect of beta-adrenomimetics on formation of blood pressure and heart rate rhythms

Chronobiological Laboratories, University of Minnesota, Minneapolis, USA. Department for Newborn and Premature Infants, Research Institute of Pediatrics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR M. Ya. Studenikin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 8, pp. 202–205, August, 1991.     

Blood pressure and heart rate response to voluntary and non-voluntary static exercise in man

6 healthy men produced static knee extension with one leg for 5 min. In one series of experiments the force was held constant at 20% of the isometric maximum voluntary contraction force. In another series of experiments the same subjects performed the same work non-voluntarily by direct percutaneous electrical stimulation. Heart rate and blood pressure was continuously recorded. Heart rate increased by 40% and systolic and diastolic blood pressure by 30% and 50% in both kind of experiments. It is concluded that receptors within the muscle has the full capacity to adjust central circulation to the muscle work performed.     

The effects of repeated occlusion measurement on blood pressure and pulse rate

We examined the effects of repeated occlusion measurement on blood pressure and pulse rate during rest and during mental arithmetic stress. Participants performed two rest-and-task sequences. We took automated blood pressure readings during each minute of one rest-and-task sequence (i.e. all-minutes measurement strategy), and during every other minute for the other sequence (i.e. odd-minutes measurement strategy). Each rest-and-task period was 5 min long and we counterbalanced the two rest-and-task sequences for order. Overall, baselines, task levels and reactivity scores were highly similar across the two measurement strategies. We did, however, find small but reliable measurement strategy effects that interacted with task novelty, particularly for DBP. Specifically, DBP levels and reactivity were lower during the all-minutes measurement strategy compared to the odd-minutes strategy, particularly during the second of two repeated tasks. We observed a similar trend for systolic blood pressure, but did not for mean arterial pressure or pulse rate. Our significant effects were small, however, and they should not overshadow the high degree of similarity of results produced by the two measurement strategies.     

Association of breathing movements to the variability of heart rate and blood pressure in foetal lambs

Heart rate (HR) variability and arterial blood pressure (BP) variability were analysed as functions of foetal breathing movements (FBMs) by means of power spectral analysis in seven foetal lambs during the third trimester of gestation. No evidence of FBM-related changes, either in mean HR, mean systolic or diastolic arterial pressures, were found. Mean arterial pulse pressure, HR variability, and BP variability increased during FBMs. The increase in BP variability occurred at frequencies higher than 0.35 Hz, i.e. those of FBMs. The increase in HR variability occurred at 0.07-1.0 Hz, i.e. at every frequency band except the lowest one. Thus, the increase in HR variability was not frequency-specifically related to FBMs. During FBMs the periodic variability of HR at frequencies > 0.35 Hz was only 10% of total HR variability. We suggest that the FBM-related changes of BP variability may be mediated by direct peripheral, hydraulic mechanisms. HR changes involve autonomic control systems: the vagal component of baroreflex seems to be relatively insensitive, whereas the very slow vasomotor component of HR variability is dominant.     

Comparison of blood pressure and heart rate responses to isometric exercise and passive muscle stretch in humans

The responses of mean arterial blood pressure (BP_a) and heart rate (f _c) to isometric contraction and passive stretch were compared in seven healthy male subjects at identical external forces. They were investigated in the sitting position with the hip and knee joint flexed to 90°. Each subject performed two tests, separated by a day, in which the stimuli were applied in random order. After 5 min of rest they performed either 10-min static plantar flexion of one calf (200 N) or 10 min of passive calf muscle stretch at the same load. After 5-min rest, the second stimulus was applied for a further 10 min followed by 5-min rest. The second test was identical except for the sequence of the stimuli. The BP_a was measured by a noninvasive and continuous method. Contraction of the vastus lateralis, gastrocnemius lateralis, and soleus muscles were determined by the myo-electric activity (electromyogram, EMG) by means of surface electrodes. The EMG activity of the vastus lateralis muscle remained at resting values throughout the experiments. Increases in EMG activity could only be detected for the triceps surae muscles during isometric contraction. During the initial 2 min of stimulation the BP_a and (f _c), responses to active contraction and passive stretch were comparable. Thereafter, both parameters showed significantly higher values during contraction. It was concluded that mechanical stress may have contributed to the early response of BP_a during both passive stretch and voluntary contraction but that chemical stimuli were needed to maintain the peripheral cardiovascular drive.     

Transient phase locking patterns among respiration,heart rate and blood pressure during cardiorespiratory synchronisation in humans

The interactions between respiration, heart rate and blood pressure variability (HRV, BPV), are considered to be of paramount importance for the study of the functional organisation of the autonomic nervous system (ANS). The aim of the reported study is to detect and classify the intermittent phase locking (PL) phenomena between respiration, HRV and BPV during cardiorespiratory synchronisation experiments, by using the following time-domain techniques: Poincaré maps, recurrence plots, time-space separation plots and frequency tracking locus. The experimental protocol consists of three stages, with normal subjects in paced breathing at 15, 12 and 8 breaths min⁻¹. Transient phenomena of coordination between respiration and the major rhythms of HRV and BPV (low and high frequency, LF and HF) have been detected and classified: no interaction between LF and HF rhythms at 15 breaths min⁻¹; short time intervals of stable 1∶2 frequency and phase synchronisation during the 12 breaths min⁻¹ stage; 1∶1 PL during the 8 breaths min⁻¹ stage. 1∶1 and 1∶2 PL phenomena occurred when the respiration frequency was quite close to the LF frequency or when it was about twice the LF frequency, respectively. The complex organisation of the ANS seems to provoke transient rather than permanent PL phenomena between the co-ordinating components of respiration and cardiovascular variability series.     

Effect of combining traction and vibration on back muscles,heart rate and blood pressure

Eighty-five percent of the population has experienced low back pain (LBP), which may result in decreasing muscle strength and endurance, functional capacity of the spine, and so on. Traction and vibration are commonly used to relieve the low back pain. The effect of the combing traction and vibration on back muscles, heart rate (HR) and blood pressure (BP) was investigated in this study. Thirty healthy subjects participated in 12 trials lying supine on the spine-combing bed with different tilt angle (0°, 10°, 20° and 30°) and vibration modes (along with the sagittal and coronal axis with 0 Hz, 2 Hz and 12 Hz separately). EMG was recorded during each trial. Power spectral frequency analysis was applied to evaluate muscle fatigue by the shift of median power frequency (MPF). Pulse pressure (PP) was calculated from BP. HR and PP were used to estimate the effect of the combination of traction and vibration on the cardio-vascular system. It was shown that vibration could increase HR and decrease PP. The combination of traction and vibration (2 Hz vibration along Z-axis and 12 Hz vibration along Y-axis) had no significant effect on the cardio-vascular system. The MPF of lumbar erector spinae (LES) and upper trapezius (UT) decreased significantly when the angle reached 20° under the condition of 2 Hz vibration along Z-axis compared with it of 0°. Furthermore, the MPF also decreased significantly compared with it of static mode at 20° for LES and at 30° for UT. However at 12 Hz vibration along Y-axis, the MPF had significant increase when the angle reached 20° in LES and 30° in UT compared to 0°. For LES, the MPF also had significant difference when the angle was increased from 10° to 20°. Therefore, combining 2 Hz vibration along Z-axis and traction (tilt angles that less than 20°) may to reduce muscle fatigue both for LES and UT compared with either vibration or traction alone. The combination of 12 Hz vibration along Y-axis and traction (tilt angles greater than 10° for LES and more than 20° for UT) could provide good treatment of lower muscle fatigue for back pain compared with either vibration or traction alone. It is helpful to provide biomechanical quantitative basis for the selection of the clinical treatment methods.     

Mixed group of Rhizobiales microbes in lung and blood of a patient with fatal pulmonary illness

We examined the microbial composition in the diseased lung and early-phase microbial cultures from the blood of a patient with a rapidly progressing fatal pulmonary illness. Although no microbes could be isolated from such cultures during the initial study, the HTS-microbiome study revealed the presence of a unique mixture of alphaproteobacteria, composed mainly of different families of Rhizobiales microbes. Microbial 16S rDNA sequences matching closely to Afipia cberi were identified mainly in the patient’s diseased lung tissue, but only rarely in the early-phase blood cultures. Conversely, the high abundance of sequences found in early-phase blood cultures of different broth media matched closely with those of the families Methylobacteriaceae, Phyllobacteriaceae and Sphingomonadaceae. The two species that successfully adapted to grow in a laboratory culture system were A. cberi and Mesorhizobium hominis, which eventually were isolated from a previously cryopreserved blood culture of SP4 broth. Many other species, including members of the Bradyrhizobiaceae and Phyllobacteriaceae families, and all members of the Methylobacteriaceae and Sphingomonadaceae families identified by HTS remained non-cultivated. We developed specific PCR primers and FISH probes, which detected the target Rhizobiales microbes in former blood cultures and autopsy lung tissues. It is unclear what role these Rhizobiales microbes might have played in the patient’s complex disease process. However, the above mentioned assays should help in rapidly detecting and identifying these previously unrecognized Rhizobiales microbes in patients.