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Farhi, L. E.

Publications and source records attributed to Farhi, L. E..

Effects of immersion in cool water on lung-exhaled nitric oxide at rest and during exercise

Lung nitric oxide (NO) has been postulated to relax airway and vascular smooth muscle at rest and during exercise. As a cold environment is a common cause of respiratory distress, lung exhaled NO was measured during skin and core body cooling at rest and during a progressive cycle exercise. Ten healthy male subjects were immersed in water at a water temperature (Tw) which was thermal neutral (35 degrees C) at 30 degrees C Tw, at which only skin temperature is decreased; and at 20 degrees C Tw, at which the core temperature is decreased (0.05 degrees C). At rest, V(O), and V(E) increased while exhaled NO concentration [NO] and the rate of expiration of NO (V(NO)) decreased with decreased Tw. V(O2) and ventilation (V(E)) increased with workload (W) and the values at all Tw were not different, whereas, [NO] decreased with W and the values during exercise were progressively less at all Ws as Tw declined. These results indicate that lung NO output is reduced in a graded fashion during body cooling at rest and during exercise. This suggests that lower lung NO may contribute to airway obstruction in cold environments and NO may contribute to regulation of lung heat and water exchange.

Non-NASA Center↗

Pulmonary hypoxic vasoconstriction: how strong? How fast?

We have developed a minimally invasive technique for studying regional blood flow in conscious sheep, bypassing the complications of open-chest surgery, flow probes and tracer infusion. We quantitate regional perfusion continuously on the basis of regional clearance of methane (methane is produced in the sheep rumen, enters the circulation and is eliminated nearly completely (greater than 95%) in the lung). Tracheal intubation with a dual-lumen catheter isolates the gas exchange of the right apical lobe (RAL; less than 15% of the lung) from that of the remainder of the lung, which serves as a control (CL). We measure RAL and CL methane elimination by entraining expirates in constant flows, sampled continuously for methane. Results obtained with this technique and from regional oxygen uptake are in excellent agreement. We have found that hypoxic vasoconstriction is far more potent and stable during eucapnic hypoxia than during hypocapnic hypoxia. The time course of the vasoconstriction suggests that many of the data in the literature may have been obtained prior to steady state.

NASA Discipline Regulatory Physiology↗

Prolonged lobar hypoxia in vivo enhances the responsivity of isolated pulmonary veins to hypoxia

The hypoxic response of pulmonary vessels isolated from eight sheep whose right apical lobes (RAL) had inspired 100% N2 for 20 h was studied. The RAL of these conscious sheep inspired hypoxic gas and the remainder of the lung inspired air. During hypoxia, RAL perfusion was 33 +/- 3% of its air value, carotid arterial PO2 averaged 86 +/- 3 mm Hg and pulmonary perfusion pressure was not significantly different from the initial control period when the RAL inspired air. At the end of the hypoxic exposure, the sheep were killed, and pulmonary artery and vein rings (0.5 to 2 mm inner diameter) were isolated from both the RAL and the right cardiac lobe, which served as the control lobe (CL). Arteries from the RAL and CL did not contract in response to 6% O2/6% CO2/88% N2 (hypoxia). In contrast, RAL veins did contract vigorously in response to hypoxia, whereas CL veins did not contract or contracted only minimally. Rubbing of the endothelium or prior incubation of RAL veins with catalase (1,200 units/ml), indomethacin (10(-5) M), or the thromboxane A2/prostaglandin H2 (TxA2/PGH2) receptor antagonist, SQ 29,548 (3 X 10(-6) M) each significantly reduced the response to hypoxia. RAL veins were also found to be more reactive than CL veins to the prostaglandin endoperoxide analogue U46619. We conclude that prolonged lobar hypoxia in vivo increases the responsivity of isolated pulmonary veins to hypoxia. These contractions may result from an increase in reactive O2 species, which in turn modify production of, metabolism of, and/or tissue responsivity to TxA2/PGH2.

NASA Discipline Cardiopulmonary↗

Gravitational Force and the Cardiovascular System

Cardiovascular responses to changes in gravitational force are considered. Man is ideally suited to his 1-g environment. Although cardiovascular adjustments are required to accommodate to postural changes and exercise, these are fully accomplished for short periods (min). More challenging stresses are those of short-term microgravity (h) and long-term microgravity (days) and of gravitational forces greater than that of Earth. The latter can be simulated in the laboratory and quantitative studies can be conducted.

Pendergast, D. R.↗

Gravitational force and the cardiovascular system

Ground-based simulation studies have been conducted to clarify the problems of the cardiovascular adaptation to alterations in gravitational force. Simulated microgravity experiments resulted in increases in cardiac stretch, urine flow, and sodium excretion, which were accompanied by lower plasma renin, aldosterone, and ADH. There appears to be a decrease in plasma volume as well as in sympathetic tone after 2-3 days of 0 Gz. Complete adjustment to 0 Gz is found within 8 h without a decrease in plasma volume, when subjects are allowed to dehydrate mildly.

Pendergast, D. R.↗

Biomedical support of man in space

In its broadest sense, biomedical support of man in space must not be limited to assisting spacecraft crew during the mission; such support should also ensure that flight personnel be able to perform properly during landing and after leaving the craft. Man has developed mechanisms that allow him to cope with specific stresses in his normal habitat; there is indisputable evidence that, in some cases, the space environment, by relieving these stresses, has also allowed the adaptive mechanisms to lapse, causing serious problems after re-entry. Inflight biomedical support must therefore include means to simulate some of the normal stresses of the Earth environment. In the area of cardiovascular performance, we have come to rely heavily on complex feedback mechanisms to cope with two stresses, often combined: postural changes, which alter the body axis along which gravitational acceleration acts, and physical exercise, which increases the total load on the system. Unless the appropriate responses are reinforced continuously during flight, crew members may be incapacitated upon return. The first step in the support process must be a study of the way in which changes in g, even of short duration, affect these responses. In particular we should learn more about effects of g on the "on" and "off" dynamics, using a variety of approaches: increased acceleration on one hand at recumbency, immersion, lower body positive pressure, and other means of simulating some of the effects of low g, on the other. Once we understand this, we will have to determine the minimal exposure dose required to maintain the response mechanisms. Finally, we shall have to design stresses that simulate Earth environment and can be imposed in the space vehicle. Some of the information is already at hand; we know that several aspects of the response to exercise are affected by posture. Results from a current series of studies on the kinetics of tilt and on the dynamics of readjustment to exercise in different postures will be presented and discussed.

NASA Discipline Cardiopulmonary↗

Effect of water immersion on cardiopulmonary physiology at high gravity (+Gz)

The cardiopulmonary responses of eight male subject between 21-31 years exposed to 1, 2, and 3 Gz during immersion at 35 + or - 0.5 C to heart level and during control dry rides are studied. Ventilation, O2 consumption, the end-tidal pressure of CO2, heart frequency, cardiac output, functional residual capacity, and the arterial pressure of CO2 were measured. It is observed that as Gz increases ventilation, heart frequency, and O2 consumption increase, and the end-tidal and arterial pressures of CO2 decrease during dry rides, but are not altered during immersion. It is detected that the functional residual capacity is lower during immersion and decreases in both the dry and immersed state as Gz increases, and cardiac output decreases as Gz increases in dry rides. It is noted that changes produced by acceleration in a Gz direction are due to the effect on the systemic circulation rather than to the effect on the lungs.

Arieli, R.↗

Biomedical support of man in space

The effects of G and/or exercise on cardiopulmonary adjustments to stresses are studied. The control of the cardiopulmonary system is examined using simulated microgravity (recumbency, immersion, lower body positive pressure, and 6-deg head-down tilt) and increased acceleration. It is observed that at rest and during exercise in simulated zero-6 environments, the stroke volume and cardiac output are initially increased and then (after prolonged exposure) return to prezero-G levels. Cardiovascular responses to increased gravity (1, 2, and 3 G) at rest and during exercise are analyzed; a decrease in plasma volume resulting in decreases in stroke volume and cardiac output, and an increase in heart rate are detected.

Pendergast, D. R.↗

A fundamental problem in determining functional residual capacity or residual volume

To measure a lung volume that is not directly accessible, one often follows dilution of a single-gas tracer, present initially only in the lung or in a rebreathing bag. The final volume available to the tracer is assumed to be the sum of the two initial components. Since O2 is taken up and CO2 is eliminated during the few breaths required for mixing, the total volume changes. The error in lung volume due to this volume change can exceed 10 pct. Theoretical and experimental data is presented to demonstrate the effect of CO2 and O2 exchange. A general equation, based on N2 and Ar, which allows one to circumvent the problems created by these fluxes is introduced. The pitfall of the back-extrapolation approach for a single tracer is shown.

Boutellier, U.↗

Cardiopulmonary readjustments in passive tilt

The readjustment of cardiopulmonary variables in human volunteers at various tilt angles on a tilt board is studied. Five healthy subjects (18-31 yr) with thorough knowledge of the experimental protocol are tested, passively tilted from the supine to the upright position in 15-deg increments in random sequence. The parameters measured are cardiac output (Q), heart rate (HR), stroke volume (SV), minute and alveolar ventilation /V(E) and V(A)/, functional residual capacity (FRC), and arterial-end-tidal P(CO2) pressure difference. It is found that changes in Q and FRC are linearly related to the sine of the tilt angle, indicating that either reflexes are absent or their net effect is proportional to the effects of gravity. This is clearly not the case for other variables /HR, SV, V(E), V(A)/, where it is possible to demonstrate threshold values for the appearance of secondary changes.

Matalon, S. V.↗