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Biomedical subjects

J B Charles

Publications and source records attributed to J B Charles.

61 records · Page 4Linked to original sources

Pharmacology in space. Part 1. Influence of adaptive changes on pharmacokinetics.

The topic of pharmacology in space, i.e. the administration of drugs during space flight and the subsequent pharmacokinetic handling of the pharmaceuticals, is a new field about which little is known. In a two-part series, Claire Lathers and colleagues highlight some of the current questions in this field. In this first article the physiological and biochemical changes associated with weightlessness in space are discussed. These changes induce adaptive alterations which may influence the pharmacokinetic properties of drugs. The cardiovascular system is of particular relevance here. Also discussed are the classes of pharmacological agent that are most likely to be used during space flight for medical problems and thus, by necessity, will become drugs to be examined in space to determine whether their pharmacokinetic and pharmacodynamic properties are altered. Therapy of the most common spaceflight ailment-motion sickness-will be considered next month in Part 2.

Humans↗

Pharmacology in space. Part 2. Controlling motion sickness.

In this second article in the two-part series on pharmacology in space, Claire Lathers and colleagues discuss the pharmacology of drugs used to control motion sickness in space and note that the pharmacology of the 'ideal' agent has yet to be worked out. That motion sickness may impair the pharmacological action of a drug by interfering with its absorption and distribution because of alteration of physiology is a problem unique to pharmacology in space. The authors comment on the problem of designing suitable ground-based studies to evaluate the pharmacological effect of drugs to be used in space and discuss the use of salivary samples collected during space flight to allow pharmacokinetic evaluations necessary for non-invasive clinical drug monitoring.

Humans↗

Endurance training in dogs increases vascular responsiveness to an alpha 1-agonist.

The effects of endurance training on vascular responsiveness to an alpha 1-agonist and the associated changes in baroreflex modulation of heart rate and vascular resistance were studied. Graded dosages of phenylephrine were given to eight treadmill-trained dogs and to eight untrained dogs; both groups were chronically instrumented and were sedated and resting when tested. These dosages were repeated after ganglionic blockade. Aortic pressure, cardiac output, central venous pressure, peripheral resistance, and heart rate were each averaged over 30 s before injection and 90 s after injection. The slope of the peripheral resistance-dose relationship was significantly increased in trained compared with untrained dogs in both the unblocked and blocked cases [unblocked: trained 0.89, untrained 0.47; blocked: trained 4.30, untrained 2.05 (mmHg.l-1.min)/(microgram.kg-1)]. The unblocked resistance slopes were reduced with respect to the blocked slopes by 77 (untrained) and 79% (trained). The slope of the heart rate-aortic pressure response was reduced, but not significantly, by endurance training. We conclude that 6 wk of endurance training in dogs resulted in a doubling of the vascular responsiveness to an alpha 1-agonist, with no significant change in the baroreflex regulation of resistance or heart rate.

Animals↗

Cardiovascular research in space: considerations for the design of the human research facility of the United States Space Station.

NASA has recently celebrated its 25th anniversary, and it has been over 15 years since a man first set foot upon the lunar surface. The space agency is now making plans for "permanent" human presence in space to consist of an orbiting station staffed by both career astronauts and visiting investigators. What have we learned from the experience of two and a half decades of manned space flight? How well will the human organism tolerate longer duration or repeated space flights? What physical or psychological traits will be beneficial or detrimental to future space travellers? What additional considerations or investigations should be planned on the United States Space Station? This brief review summarizes our knowledge of space physiology as it relates to the cardiovascular system. Only actual flight information is utilized; no attempt is made to include the wealth of ground based simulation data, nor are areas remote to the cardiac system discussed. Gaps in current understanding are highlighted in a manner of suggested plans for future space flight investigations.

Adaptation, Physiological↗

Cardiovascular deconditioning during space flight and the use of saline as a countermeasure to orthostatic intolerance.

Alterations in the physiology of the cardiovascular system have been noted during all exposures to the microgravity experienced in space flight. Of most importance to the operational function of Space Shuttle crewmembers is orthostatic intolerance. Although complex changes occur as a result of adaptation to weightlessness, the redistribution and loss of body fluid apparently plays a substantial role. Utilizing ground-based bed rest data as an analog to the absence of gravitational force encountered in orbital flight, a saline loading countermeasure was developed. In this study, 17 crewmembers consumed various amounts of salt and fluid prior to the reentry phase of Space Shuttle flights; 9 other astronauts served as control subjects. The countermeasure reduced the heart rate response to orthostatic stress 29% and reversed the fall in mean blood pressure. A Cardiovascular Index of Deconditioning (defined as CID = delta HR - delta SBP + delta DBP) equalled 21 in those who utilized the countermeasure, a significant improvement toward baseline (p less than 0.003) when compared to the control group CID = 49. The encouraging results of these investigations have led to the adoption of the countermeasure as an operational procedure by Shuttle crewmembers.

Blood Pressure↗

Heart rate adaptation to exercise training in cardiac-denervated dogs.

To determine the effect of cardiac denervation on the development of a training-induced decrease in heart rate at rest and during submaximal exercise, six cardiac-denervated (CD) and six sham-operated (SO) dogs were exercise trained by means of a 6-wk treadmill running program. Gastrocnemius citrate synthase activity increased significantly to the same degree in CD and SO dogs indicating that both groups were equally trained. Resting heart rates (RHR) for SO dogs decreased significantly from 64 +/- 4.8 to 51 +/- 3.2 beats/min (mean +/- SE) from pre- to posttraining. CD dogs showed no changes in RHR (95 +/- 3.5 to 96 +/- 5.3 beats/min). Heart rate responses of SO dogs to a standardized, submaximal exercise test decreased significantly from pre- to posttraining. However, CD dogs displayed no decrease in heart rate responses to the standardized, submaximal exercise test. Additionally, at pre- and posttraining, as heart rates rose in response to exercise test intensity, they increased to a significantly greater degree in SO dogs compared with CD dogs. The results indicate that in dogs, cardiac denervation prevents the decreases in resting heart rate and heart rate during submaximal exercise normally associated with endurance exercise training.

Adaptation, Physiological↗

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.

Adaptation, Physiological↗