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At least 163 records · Page 9

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NASA NTRS2000

Bed Rest and Orthostatic-Hypotensive Intolerance

Orthostatic tolerance may be defined as the ability of humans to maintain cerebral perfusion and consciousness upon movement from a supine or sitting position to the upright posture; for example, subjects can stand suddenly or be tilted to the head-up body position. Similar but not identical physiological responses can be induced by positive G(sub Z) (head to foot) acceleration or exposure to lower body negative pressure (LBNP). The objective is to suddenly shift blood to the lower body to determine how effectively cardiovascular and neural-hormonal compensatory responses react to maintain blood pressure. In the most precise method for measuring tolerance, individuals would be stressed until they faint (syncope). However, the potential consequences and discomforts of such a test usually prohibit such a procedure so that few investigators actually induce syncope. In a more common approach, subjects are exposed to a given level of stress, for example, head-up tilt for 15 min, and any increases in heart rate or decreases in blood pressure are interpreted as indicators of progress toward syncope. Presumably, the greater the perturbation of heart rate and blood pressure, the closer to "tolerance," i.e., point of unconsciousness. Another more appropriate approach is to induce a progressively increasing hypotensive stress until pre-determined physiological responses or pre-syncopal symptoms appear. The physiological criteria may include a sudden drop in systolic blood pressure (greater than 25 mm/min), a sudden drop in heart rate (greater than 15 beats/min), or a systolic blood pressure less than 70 mmHg. The most common pre-syncopal symptoms include lightheadedness, stomach awareness or distress, feelings of warmth, tingly skin, and light to profuse sweating. Usually a combination of physiological responses and symptoms occurs such that, on different days, the tolerance time to the same orthostatic protocol is reproducible for a given individual. The assumption is that by taking subjects to near fainting, one can determine their tolerance. This latter pre-syncopal approach is better for estimating orthostatic or hypotensive tolerance than the former measurement of heart rate and blood pressure responses to a given stress. There is considerable variability in individual responses to orthostasis. For example, some subjects are "heart-rate responders" and have a pronounced cardiovascular response similar to that when performing moderately hard aerobic exercise, whereas others may experience pre-syncopal symptoms with very little increase in heart rate. Some individuals have a slow, gradual fall in blood pressure to orthostasis, and others have little change in blood pressure until a sudden precipitous fall in pressure occurs just prior to fainting. With both tilt and LBNP tests there is a low correlation between heart-rate or blood-pressure responses to a sub-tolerance stress as a measure of pre-syncopal limited orthostatic-hypotensive tolerance.

Schneider, Suzanne M.↗

NASA NTRS1999

Cardiovascular Session Summary

It was apparent that the bed-rest and spaceflight data indicated that decreases in plasma volume and cardiac atrophy along with cardiac remodeling were fundamental changes which predisposed many astronauts to post flight orthostatic intolerance. Despite the recently acquired in-flight and post-flight muscle sympathetic nerve activity findings suggesting that the sympathetic nerve responses were appropriate there remains significant contrary data from bed-rest studies, post- flight stand tests and hind-limb unweighted rat studies that suggest that the vasoconstrictive responses were compromised at least insufficient in susceptible individuals. The key issues raised is whether a diminished increase in sympathetic activity from baseline without changes in 254 First Biennial Space Biomedical Investigators'Workshop Cardiovascular peak response or receptor adaptations is an abnormal response or is an individual variance of response to the accentuated decrease in stroke volume. Data relating autonomic neural control of heart rate were presented to suggest that the vagal and sympathetic control of heart rate was attenuated. Also, bed-rest and space flight induced attenuated baroreflex control of heart rate was shown to be restored to pre-bedrest function by one bout of maximal dynamic exercise. However, these data were confounded by relying on the use of R-R interval as a measure of efferent responses of the baroreflex during a condition in which the baseline heart rate was changed. Clearly the idea that the autonomic control of heart rate may be changed by microgravity needs further investigation. This direction is suggested despite the fact that in the triple product (HR x SV x TPR = MAP) assessment of the regulation of arterial blood pressure during orthostasis the role of the HR reflex may be less influential than that associated. with cardiac atrophy (SV changes) and aberrant sympathetic vasoconstriction (resistance) changes. Although sympathetic nerve activity responses in-flight and post-flight on neurolab appeared appropriate, enough bed-rest and post-flight stand test data, along with animal model data suggest that vasoconstriction was compromised. The mechanism of this compromised vasoconstriction needs to be delineated. Other major findings concerning microgravity and physiological regulatory systems are that: I . Thermoregulatory adaptation appear to suggest some decrements in the control of cutaneous vasodilation and sweating; 2. Calcium resorption and dietary calcium need to be defined for differing durations of spaceflight, especially as the effects of excess calcium on vasomotor function appears to be detrimental; 3. Neurohumoral mechanisms of microgravity induced changes in neural function and the regulation of plasma volume and total body water, bone resorption and autonomic neural control of the circulation need further delineation; 4. As performance of work tasks become prolonged, the mechanisms of blood pressure regulation in microgravity needs to be used in the recovery period from prolonged work tasks.

Raven, Peter↗

DOE OSTI2012

Detecting drug-induced prolongation of the QRS complex: New insights for cardiac safety assessment

Background: Drugs slowing the conduction of the cardiac action potential and prolonging QRS complex duration by blocking the sodium current (I{sub Na}) may carry pro-arrhythmic risks. Due to the frequency-dependent block of I{sub Na}, this study assesses whether activity-related spontaneous increases in heart rate (HR) occurring during standard dog telemetry studies can be used to optimise the detection of class I antiarrhythmic-induced QRS prolongation. Methods: Telemetered dogs were orally dosed with quinidine (class Ia), mexiletine (class Ib) or flecainide (class Ic). QRS duration was determined standardly (5 beats averaged at rest) but also prior to and at the plateau of each acute increase in HR (3 beats averaged at steady state), and averaged over 1 h period from 1 h pre-dose to 5 h post-dose. Results: Compared to time-matched vehicle, at rest, only quinidine and flecainide induced increases in QRS duration (E{sub max} 13% and 20% respectively, P < 0.01–0.001) whereas mexiletine had no effect. Importantly, the increase in QRS duration was enhanced at peak HR with an additional effect of + 0.7 ± 0.5 ms (quinidine, NS), + 1.8 ± 0.8 ms (mexiletine, P < 0.05) and + 2.8 ± 0.8 ms (flecainide, P < 0.01) (calculated as QRS at basal HR-QRS at high HR). Conclusion: Electrocardiogram recordings during elevated HR, not considered during routine analysis optimised for detecting QT prolongation, can be used to sensitise the detection of QRS prolongation. This could prove useful when borderline QRS effects are detected. Analysing during acute increases in HR could also be useful for detecting drug-induced effects on other aspects of cardiac function. -- Highlights: ► We aimed to improve detection of drug-induced QRS prolongation in safety screening. ► We used telemetered dogs to test class I antiarrhythmics at low and high heart rate. ► At low heart rate only quinidine and flecainide induced an increase in QRS duration. ► At high heart rate the effects of two out of three antiarrhythmics were enhanced. ► Detection of a drug-induced prolongation of QRS was improved at high heart rate.

60 APPLIED LIFE SCIENCES↗

NASA NTRS1996

Evidence for Increased Beta-Adrenoreceptor Responsiveness Induced by 14 Days of Simulated Microgravity in Humans

We studied hemodynamic responses to alpha and beta receptor agonists in 8 healthy men ( 38+- 2 yrs) before and after 14 days of 6 degree head-down tilt (HDT) to test the hypothesis that increased adrenergic responsiveness is induced by prolonged exposure to microgravity. Immediately following a 30-min baseline period, a steady-state infusion of isoproterenol (ISO) was used to assess beta 1- and beta 2-adrenergic responsiveness. ISO was infused at three graded constant rates of 0.005, 0.01 and 0.02 ug/kg/min. After heart rate and blood pressure had been allowed to return to baseline levels following ISO infusion graded infusion of phenylephrine (PE) was used to assess responsiveness of alpha I-vascular receptors. PE was infused at three graded constant rates of 0.25, 0.50 and 1.00 ug/kg/min. Each infusion interval for both drugs was 9 min. During the infusions, constant monitoring of beat-to-beat blood pressure and heart rate was performed and leg blood flow was measured with occlusion plethysmography at each infusion level. The slopes calculated from linear regressions between ISO and PE doses and changes in heart rate, blood pressure, and leg vascular resistance for each subject were used to represent alpha- and beta- adrenoreceptor responsiveness. Fourteen days HDT increased the slopes of heart rate (1056 +- 107 to 1553 +- 83 beats/ug/kg/min; P= 0.014) and vasodilation (-469ft +- 111 to -l446 +- 309 PRU/ug/kg/min; P =0.0224) to ISO infusion. There was no alteration in blood pressure or vascular resistance responses to PE infusion after HDT. Our results provide evidence that microgravity causes selective increases in beta 1- and beta 2-adrenergic responsiveness without affecting alpha 1-vascular responses.

CARDIOVASCULAR SYSTEM↗

DOE OSTI2013

Acute effects of a sarin-like organophosphorus agent, bis(isopropyl methyl)phosphonate, on cardiovascular parameters in anaesthetized, artificially ventilated rats

The organophosphorus compound sarin irreversibly inhibits acetylcholinesterase. We examined the acute cardiovascular effects of a sarin-like organophosphorus agent, bis(isopropyl methyl)phosphonate (BIMP), in anaesthetized, artificially ventilated rats. Intravenous administration of BIMP (0.8 mg/kg; the LD50 value) induced a long-lasting increase in blood pressure and tended to increase heart rate. In rats pretreated with the non-selective muscarinic-receptor antagonist atropine, BIMP significantly increased both heart rate and blood pressure. In atropine-treated rats, hexamethonium (antagonist of ganglionic nicotinic receptors) greatly attenuated the BIMP-induced increase in blood pressure without changing the BIMP-induced increase in heart rate. In rats treated with atropine plus hexamethonium, intravenous phentolamine (non-selective α-adrenergic receptor antagonist) plus propranolol (non-selective β-adrenergic receptor antagonist) completely blocked the BIMP-induced increases in blood pressure and heart rate. In atropine-treated rats, the reversible acetylcholinesterase inhibitor neostigmine (1 mg/kg) induced a transient increase in blood pressure, but had no effect on heart rate. These results suggest that in anaesthetized rats, BIMP induces powerful stimulation of sympathetic as well as parasympathetic nerves and thereby modulates heart rate and blood pressure. They may also indicate that an action independent of acetylcholinesterase inhibition contributes to the acute cardiovascular responses induced by BIMP. - Highlights: • A sarin-like agent BIMP markedly increased blood pressure in anaesthetized rats. • Muscarinic receptor blockade enhanced the BIMP-induced increase in blood pressure. • Ganglionic nicotinic receptor blockade attenuated the BIMP-induced response. • Blockade of α- as well as β-receptors attenuated the BIMP-induced response.

60 APPLIED LIFE SCIENCES↗

NASA NTRS1995

Spectral indices of cardiovascular adaptations to short-term simulated microgravity exposure

We investigated the effects of exposure to microgravity on the baseline autonomic balance in cardiovascular regulation using spectral analysis of cardiovascular variables measured during supine rest. Heart rate, arterial pressure, radial flow, thoracic fluid impedance and central venous pressure were recorded from nine volunteers before and after simulated microgravity, produced by 20 hours of 6 degrees head down bedrest plus furosemide. Spectral powers increased after simulated microgravity in the low frequency region (centered at about 0.03 Hz) in arterial pressure, heart rate and radial flow, and decreased in the respiratory frequency region (centered at about 0.25 Hz) in heart rate. Reduced heart rate power in the respiratory frequency region indicates reduced parasympathetic influence on the heart. A concurrent increase in the low frequency power in arterial pressure, heart rate, and radial flow indicates increased sympathetic influence. These results suggest that the baseline autonomic balance in cardiovascular regulation is shifted towards increased sympathetic and decreased parasympathetic influence after exposure to short-term simulated microgravity.

NASA Discipline Cardiopulmonary↗

DOE OSTI2012

A less stressful alternative to oral gavage for pharmacological and toxicological studies in mice

Oral gavage dosing can induce stress and potentially confound experimental measurements, particularly when blood pressure and heart rate are endpoints of interest. Thus, we developed a pill formulation that mice would voluntarily consume and tested the hypothesis that pill dosing would be significantly less stressful than oral gavage. C57Bl/6 male mice were singly housed and on four consecutive days were exposed to an individual walking into the room (week 1, control), a pill being placed into the cage (week 2), and a dose of water via oral gavage (week 3). Blood pressure and heart rate were recorded by radiotelemetry continuously for 5 h after treatment, and feces collected 6–10 h after treatment for analysis of corticosterone metabolites. Both pill and gavage dosing significantly increased mean arterial pressure (MAP) during the first hour, compared to control. However, the increase in MAP was significantly greater after gavage and remained elevated up to 5 h, while MAP returned to normal within 2 h after a pill. Neither pill nor gavage dosing significantly increased heart rate during the first hour, compared to control; however, pill dosing significantly reduced heart rate while gavage significantly increased heart rate 2–5 h post dosing. MAP and heart rate did not differ 24 h after dosing. Lastly, only gavage dosing significantly increased fecal corticosterone metabolites, indicating a systemic stress response via activation of the hypothalamic–pituitary–adrenal axis. These data demonstrated that this pill dosing method of mice is significantly less stressful than oral gavage. -- Highlights: ► Developed a novel oral dosing method using a pill that mice will readily consume. ► Assessed stress by blood pressure, heart rate, and fecal corticosterone metabolites. ► Demonstrated that pill dosing is significantly less stressful than oral gavage.

60 APPLIED LIFE SCIENCES↗

NASA NTRS1972

'Diving reflex' in man - Its relation to isometric and dynamic exercise.

To test the influence of physical activity on the diving reflex, 10 normal men held their breath with their faces immersed in 15 C water during rest, bicycle exercise, and sustained isometric handgrip contraction. At all conditions, a slight but statistically significant elevation of blood pressure and a marked decrease in heart rate occurred during each dive. During moderate bicycle exercise heart rate fell more rapidly than at rest and the final level of bradycardia approached that achieved at rest, despite the fact that predive heart rates were much higher during exercise. When diving occurred in combination with isometric exercise, bradycardia was less severe than during resting dives and final heart rates could be represented as the sum of the expected responses to each intervention alone. In all conditions apnea without face immersion caused bradycardia that was less severe than during wet dives.

Bergman, S. A., Jr.↗

NASA NTRS2002

Baroreflex modulation of muscle sympathetic nerve activity during cold pressor test in humans

The purpose of this project was to test the hypothesis that baroreceptor modulation of muscle sympathetic nerve activity (MSNA) and heart rate is altered during the cold pressor test. Ten subjects were exposed to a cold pressor test by immersing a hand in ice water for 3 min while arterial blood pressure, heart rate, and MSNA were recorded. During the second and third minute of the cold pressor test, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.005) during the cold pressor test (-244.9 +/- 26.3 units x beat(-1) x mmHg(-1)) when compared with control conditions (-138.8 +/- 18.6 units x beat(-1) x mmHg(-1)), whereas no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that baroreceptors remain capable of modulating MSNA and heart rate during a cold pressor test; however, the sensitivity of baroreflex modulation of MSNA is elevated without altering the sensitivity of baroreflex control of heart rate.

NASA Discipline Cardiopulmonary↗

DOE OSTI2018

Association between human and animal thermal comfort indices and physiological heat stress indicators in dairy calves

Warm summer episodes have a significant effect on the overall health and well-being of young cattle; however, it is not known which temperature measure should be used for estimating heat stress in dairy calves. In this study, generalized linear mixed-effects models were used to estimate the relationships between thermal comfort indices and animal-based heat stress indicators in sixteen Holstein bull calves that were housed in individual calf hutches. Data were collected under continental weather characteristics over a 5-day period: day 1 (lower-temperature day), days 2 and 3 (heat stress days), and a 2-day post-stress period. Relative humidity, ambient temperature, the heat index, the humidex and five different temperature–humidity indices (THI) were used as thermal indices. Physiological variables monitored included respiratory rate, rectal temperature, ear skin temperature and heart rate. The heat index and the humidex measuring human thermal comfort were more closely associated with physiological measures than were the ambient temperature or the THIs (in case of heat index: R{sup 2} = 0.87 for respiratory rate, R{sup 2} = 0.63 for rectal temperature, R{sup 2} = 0.70 for ear skin temperature, and R{sup 2} = 0.78 for heart rate, respectively; in case of humidex: R{sup 2} = 0.85 for respiratory rate, R{sup 2} = 0.60 for rectal temperature, R{sup 2} = 0.68 for ear skin temperature, and R{sup 2} = 0.75 for heart rate, respectively). Based on our results, parameters of human outdoor comfort seem better to estimate heat stress in dairy calves in a continental region than those of THIs or ambient temperature.

54 ENVIRONMENTAL SCIENCES↗

NASA NTRS2001

Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes

The autonomic nervous system drives variability in heart rate, vascular tone, cardiac ejection, and arterial pressure, but gender differences in autonomic regulation of the latter three parameters are not well documented. In addition to mean values, we used spectral analysis to calculate variability in arterial pressure, heart rate (R-R interval, RRI), stroke volume, and total peripheral resistance (TPR) and measured circulating levels of catecholamines and pancreatic polypeptide in two groups of 25 +/- 1.2-yr-old, healthy men and healthy follicular-phase women (40 total subjects, 10 men and 10 women per group). Group 1 subjects were studied supine, before and after beta- and muscarinic autonomic blockades, administered singly and together on separate days of study. Group 2 subjects were studied supine and drug free with the additional measurement of skin perfusion. In the unblocked state, we found that circulating levels of epinephrine and total spectral power of stroke volume, TPR, and skin perfusion ranged from two to six times greater in men than in women. The difference (men > women) in spectral power of TPR was maintained after beta- and muscarinic blockades, suggesting that the greater oscillations of vascular resistance in men may be alpha-adrenergically mediated. Men exhibited muscarinic buffering of mean TPR whereas women exhibited beta-adrenergic buffering of mean TPR as well as TPR and heart rate oscillations. Women had a greater distribution of RRI power in the breathing frequency range and a less negative slope of ln RRI power vs. ln frequency, both indicators that parasympathetic stimuli were the dominant influence on women's heart rate variability. The results of our study suggest a predominance of sympathetic vascular regulation in men compared with a dominant parasympathetic influence on heart rate regulation in women.

Non-NASA Center↗

NASA NTRS1999

Cardiac interbeat interval dynamics from childhood to senescence : comparison of conventional and new measures based on fractals and chaos theory

BACKGROUND: New methods of R-R interval variability based on fractal scaling and nonlinear dynamics ("chaos theory") may give new insights into heart rate dynamics. The aims of this study were to (1) systematically characterize and quantify the effects of aging from early childhood to advanced age on 24-hour heart rate dynamics in healthy subjects; (2) compare age-related changes in conventional time- and frequency-domain measures with changes in newly derived measures based on fractal scaling and complexity (chaos) theory; and (3) further test the hypothesis that there is loss of complexity and altered fractal scaling of heart rate dynamics with advanced age. METHODS AND RESULTS: The relationship between age and cardiac interbeat (R-R) interval dynamics from childhood to senescence was studied in 114 healthy subjects (age range, 1 to 82 years) by measurement of the slope, beta, of the power-law regression line (log power-log frequency) of R-R interval variability (10(-4) to 10(-2) Hz), approximate entropy (ApEn), short-term (alpha(1)) and intermediate-term (alpha(2)) fractal scaling exponents obtained by detrended fluctuation analysis, and traditional time- and frequency-domain measures from 24-hour ECG recordings. Compared with young adults (<40 years old, n=29), children (<15 years old, n=27) showed similar complexity (ApEn) and fractal correlation properties (alpha(1), alpha(2), beta) of R-R interval dynamics despite lower spectral and time-domain measures. Progressive loss of complexity (decreased ApEn, r=-0.69, P<0.001) and alterations of long-term fractal-like heart rate behavior (increased alpha(2), r=0.63, decreased beta, r=-0.60, P<0.001 for both) were observed thereafter from middle age (40 to 60 years, n=29) to old age (>60 years, n=29). CONCLUSIONS: Cardiac interbeat interval dynamics change markedly from childhood to old age in healthy subjects. Children show complexity and fractal correlation properties of R-R interval time series comparable to those of young adults, despite lower overall heart rate variability. Healthy aging is associated with R-R interval dynamics showing higher regularity and altered fractal scaling consistent with a loss of complex variability.

NASA Discipline Cardiopulmonary↗

NASA NTRS1984

Inflight evaluation of four measures of pilot workload

Four measures of pilot workload were tested in the NASA C-141 Kuiper Airborne Observatory. The measured included a communications analysis, subjective ratings of workload, subjective ratings of additional factors related to workload, and heart rate. Data were collected for 11 flights, each of which lasted approximately seven hours. Heart rate was found to be significantly higher for the pilot who was flying than for the pilot who was not flying and it varied significantly across flight segments, peaking during landing and take off, particularly for the pilot in the left seat who was resonsible for aircraft control. For both left and right seats, the subjective assessment of stress rather than the subjective assessment of workload was significantly correlated with variation in heart rate. Frequencies of different types of communications varied significantly across segments of flight, however, they were not correlated with subjective ratings of workload. There was a significant difference between the left and right seats in the types of activities that contributed to their workload, however, workload was considered to be equivalent for the two.

Hart, S. G.↗

NASA NTRS1973

Ergometer

An ergometer is described that has a pedal driven direct current motor as a load and includes a frame for supporting the body of a person in either a sitting or a prone position. The pedals may be operated by either the feet or the hands. The electrical circuitry of the ergometer includes means for limiting the load applied to the pedals as a function of work being performed, heart rate, and increases in heart rate.

Gause, R. L.↗

NASA NTRS1989

Ventilation loss and pressurization in the NASA launch/entry suit: Potential for heat stress

The potential of the NASA Launch/Entry Suit (LES) for producing heat stress in a simulated Space Shuttle cabin environment was studied. The testing was designed to identify potential heat stress hazards if the LES were pressurized or if ventilation were lost. Conditions were designed to simulate an extreme pre-launch situation with chamber temperatures maintained at dry bulb temperature = 27.2 +/- 0.1 C, globe temperature = 27.3 +/- 0.1 C, and wet bulb temperature = 21.1 +/- 0.3 C. Two females and two males, 23 to 34 years of age, were employed in this study, with two subjects having exposures in all 3 conditions. Test durations in the ventilated (V) and unventilated (UV) conditions were designed for 480 minutes, which all subjects achieved. Pressurized runs (Pr) were designed for 45 minutes, which all subjects also achieved. While some significant differences related to experimental conditions were noted in rectal and mean skin temperatures, evaporation rates, sweat rates, and heart rate, these differences were not thought to be physiologically significant. The results indicate that the LES garment, in either the Pr or UV state, poses no danger of inducing unacceptable heat stress under the conditions expected within the Space Shuttle cabin during launch or reentry.

Kaufman, Jonathan W.↗

NASA NTRS1993

MAC to VAX Connectivity: Heartrate Spectral Analysis System

The heart rate Spectral Analysis System (SAS) acquires and analyzes, in real-time, the Space Shuttle onboard electrocardiograph (EKG) experiment signals, calculates the heartrate, and applies a Fast Fourier Transformation (FFT) to the heart rate. The system also calculates other statistical parameters such as the 'mean heart rate' over specific time period and heart rate histogram. This SAS is used by NASA Principal Investigators as a research tool to determine the effects of weightlessness on the human cardiovascular system. This is also used to determine if Lower Body Negative Pressure (LBNP) is an effective countermeasure to the orthostatic intolerance experienced by astronauts upon return to normal gravity. In microgravity, astronauts perform the LBNP experiment in the mid deck of the Space Shuttle. The experiment data are downlinked by the orbiter telemetry system, then processed and analyzed in real-time by the integrated Life Sciences Data Acquisition (LSDS) - Spectral Analysis System. The data system is integrated within the framework of two different computer systems, VAX and Macintosh (Mac), using the networking infrastructure to assist the investigators in further understanding the most complex machine on Earth--the human body.

Rahman, Hasan H.↗

NASA NTRS1975

Cardiorespiratory responses to orthostasis and the effects of propranolol

Cardiac output and gas exchange were determined serially using the single-breath method of Kim et al. before, during, and after orthostasis on six subjects after beta-adrenergic blockage and in duplicate controls. In the latter, heart rate increased and pulse pressure dropped immediately on tilting to 60 deg and remained stable while cardiac output and stroke volume declined gradually over 21 min upright. On propranolol, heart rate was 10 bpm lower supine and 20 bpm less at 60 deg but cardiac output was only slightly lower before and following tilt-up. However, after 15 min upright, stroke volume and cardiac output recovered on propranolol exceeding the controls after 21 min without change in heart rate. Returning to supine, heart rate dropped in all tests with a transitory increase in stroke volume, cardiac output and arteriovenous O2 difference. At the same time, apparent O2 uptake increased temporarily, reflecting the return of pooled venous blood to the lungs. Orthostatic tolerance did not appear to be affected by beta-adrenergic blockade.

Loeppky, J. A.↗

DOE OSTI2012

Physiological effects following administration of Citrus aurantium for 28 days in rats

Background: Since ephedra-containing dietary supplements were banned from the US market, manufacturers changed their formulations by eliminating ephedra and replacing with other botanicals, including Citrus aurantium, or bitter orange. Bitter orange contains, among other compounds, synephrine, a chemical that is chemically similar to ephedrine. Since ephedrine may have cardiovascular effects, the goal of this study was to investigate the cardiovascular effects of various doses of bitter orange extract and pure synephrine in rats. Method: Female Sprague–Dawley rats were dosed daily by gavage for 28 days with synephrine from two different extracts. One extract contained 6% synephrine, and the other extract contained 95% synephrine. Doses were 10 or 50 mg synephrine/kg body weight from each extract. Additionally, caffeine was added to these doses, since many dietary supplements also contain caffeine. Telemetry was utilized to monitor heart rate, blood pressure, body temperature and QT interval in all rats. Results and conclusion: Synephrine, either as the bitter orange extract or as pure synephrine, increased heart rate and blood pressure. Animals treated with 95% synephrine showed minimal effects on heart rate and blood pressure; more significant effects were observed with the bitter orange extract suggesting that other components in the botanical can alter these physiological parameters. The increases in heart rate and blood pressure were more pronounced when caffeine was added. None of the treatments affected uncorrected QT interval in the absence of caffeine.

60 APPLIED LIFE SCIENCES↗