L E Farhi

University at Buffalo, The State University of New York, Buffalo, NY, United States

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Publications (26)21.63 Total impact

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    ABSTRACT: Cardiac output (Q) is a determinant of blood pressure and O(2) delivery and is critical in the maintenance of homeostasis, particularly during environmental stress and exercise. Cardiac output can be determined invasively in patients; however, indirect methods are required for other situations. Soluble gas techniques are widely used to determine (Q). Historically, measurements during a breathhold, prolonged expiration and rebreathing to CO(2) equilibrium have been used; however, with limitations, especially during stress. Farhi and co-workers developed a single-step CO(2) rebreathing method, which was subsequently revised by his group, and has been shown to be reliable and compared closely to direct, invasive measures. V(CO2), P(ACO2), and P(VCO2) are determined during a 12-25s rebreathing, using the appropriate tidal volume, and (Q) is calculated. This method can provide accurate data in laboratory and field experiments during exercise, increased or decreased gravity, water immersion, lower body pressure, head-down tilt, altered ambient pressure or changes in inspired gas composition.
    Respiratory Physiology & Neurobiology 05/2004; 140(1):99-109. DOI:10.1016/j.resp.2003.11.006 · 1.97 Impact Factor
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    ABSTRACT: Cardiac output (Q) is a primary determinant of blood pressure and O2 delivery and is critical in the maintenance of homeostasis, particularly during environmental stress. Cardiac output can be determined invasively in patients; however, indirect methods are required for other situations. Soluble gas techniques are widely used to determine Q. Historically, measurements during a breathhold, prolonged expiration and rebreathing to CO2 equilibrium have been used; however, with limitations, especially during stress. Farhi and co-workers developed a single-step CO2 rebreathing method, which was subsequently revised by his group, and has been shown to be valid (compared to direct measures) and reliable. Carbon dioxide output (VCO2), partial pressure of arterial CO2 (PaCO2), and partial pressure of mixed venous CO2 (Pv(CO2)) are determined during 12-25 s of rebreathing, using the appropriate tidal volume, and Q is calculated. This method has the utility to provide accurate data in laboratory and field experiments during exercise, increased and micro-gravity, water immersion, lower body pressure, head-down tilt, and changes in gas composition and pressure. Utilizing the Buffalo CO2 rebreathing method it has been shown that the Q can adjust to a wide range of changes in environments maintaining blood pressure and O2 delivery at rest and during exercise.
    Arbeitsphysiologie 11/2003; 90(3-4):292-304. DOI:10.1007/s00421-003-0921-4 · 2.30 Impact Factor
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    ABSTRACT: In our previous experiments during NASA Shuttle flights SLS 1 and 2 (9-15 days) and EUROMIR flights (30-90 days) we observed that pulmonary blood flow (cardiac output) was elevated initially, and surprisingly remained elevated for the duration of the flights. Stroke volume increased initially and then decreased, but was still above 1 Gz values. As venous return was constant, the changes in SV were secondary to modulation of heart rate. Mean blood pressure was at or slightly below 1 Gz levels in space, indicating a decrease in total peripheral resistance. It has been suggested that plasma volume is reduced in space, however cardiac output/venous return do not return to 1 Gz levels over the duration of flight. In spite of the increased cardiac output, central venous pressure was not elevated in space. These data suggest that there is a change in the basic relationship between cardiac output and central venous pressure, a persistent "hyperperfusion" and a re-distribution of blood flow and volume during space flight. Increased pulmonary blood flow has been reported to increase diffusing capacity in space, presumably due to the improved homogeneity of ventilation and perfusion. Other studies have suggested that ventilation may be independent of gravity, and perfusion may not be gravity- dependent. No data for the distribution of pulmonary blood volume were available for flight or simulated microgravity. Recent studies have suggested that the pulmonary vascular tree is influenced by sympathetic tone in a manner similar to that of the systemic system. This implies that the pulmonary circulation is dilated during microgravity and that the distribution of blood flow and volume may be influenced more by vascular control than by gravity. The cerebral circulation is influenced by sympathetic tone similarly to that of the systemic and pulmonary circulations; however its effects are modulated by cerebral autoregulation. Thus it is difficult to predict if cerebral perfusion is increased and if there is edema in space. Anecdotal evidence suggests there may be cerebral edema early in flight. Cerebral artery velocity has been shown to be elevated in simulated microgravity. The elevated cerebral artery velocity during simulated microgravity may reflect vasoconstriction of the arteries and not increased cerebral blood flow. The purpose of our investigations was to evaluate the effects of alterations in simulated gravity (+/-), resulting in changes in cardiac output (+/-), and on the blood flow and volume distribution in the lung and brain of human subjects. The first hypothesis of these studies was that blood flow and volume would be affected by gravity, but their distribution in the lung would be independent of gravity and due to vasoactivity changing vascular resistance in lung vessels. The vasodilitation of the lung vasculature (lower resistance) along with increased "compliance" of the heart could account for the absence of increased central venous pressure in microgravity. Secondly, we postulate that cerebral blood velocity is increased in microgravity due to large artery vasoconstriction, but that cerebral blood flow would be reduced due to autoregulation.
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    ABSTRACT: Cardiac output (Q), heart rate (HR), blood pressure, and oxygen consumption (VO2) were measured repeatedly both at rest and at two levels of exercise in six subjects during microgravity exposure. Exercise was at 30 and 60% of the workload producing the individual's maximal VO2 in 1 G. Three of the subjects were on a 9-day flight, Spacelab Life Sciences-1, and three were on a 15-day flight, Spacelab Life Sciences-2. We found no temporal differences during the flights. Thus we have combined all microgravity measurements to compare in-flight values with erect or supine control values. At rest, Q in flight was 126% of Q erect (P < 0.01) but was not different from Q supine, and HR in flight was 81% of HR erect (P < 0.01) and 91% of HR supine (P < 0.05). Thus resting stroke volume (SV) in flight was 155% of SV erect (P < 0.01) and 109% SV supine (P < 0.05). Resting mean arterial blood pressure and diastolic pressure were lower in flight than erect (P < 0.05). Exercise values were considered as functions of VO2. The increase in Q with VO2 in flight was less than that at 1 G (slope 3.5 vs. 6.1 x min-1.l-1.min-1). SV in flight fell with increasing VO2, whereas SV erect rose and SV supine remained constant. The blood pressure response to exercise was not different in flight from erect or supine. We conclude that true microgravity causes a cardiovascular response different from that seen during any of its putative simulations.
    Journal of Applied Physiology 08/1996; 81(1):26-32. · 3.43 Impact Factor
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    ABSTRACT: The cardiovascular effects of supine lower body negative pressure (LBNP, 0 mm Hg, -8 mm Hg, -15 mm Hg, -25 mm Hg, -35 mm Hg, and -45 mm Hg) were studied in humans (n = 10). The LBNP's were applied in a random order (three per session) for 20 min, with 15 min between each LBNP. Leg blood flow, cardiac output (Q), stroke volume (SV) and estimated lung blood volume were significantly reduced at -15 mm Hg. Increasing LBNP to -35 mm Hg did not result in further changes. When the LBNP was increased to -45 mm Hg, Q and SV were lower than comparable values at -15 mm Hg. Heart rate was unchanged up to -25 mm Hg, after which it increased proportionally to the LBNP. Systolic blood pressure was maintained throughout. Diastolic blood pressure was unchanged below -45 mm Hg, but was significantly elevated at -45 mm Hg. Mean arterial pressure was maintained up to LBNP's of -35 mm Hg by increased vascular resistance, in spite of reduced thoracic blood volume, as indicated by reduced central venous pressure and Q. Greater levels of LBNP were outside the physiological adjustment range and blood pressure dropped progressively.
    Aviation Space and Environmental Medicine 08/1994; 65(7):615-20. · 0.78 Impact Factor
  • B E Shykoff, L E Farhi
    The Physiologist 03/1992; 35(1 Suppl):S177-9.
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    ABSTRACT: 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.
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    ABSTRACT: 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.
    Acta Astronautica 02/1988; 17(2):187-93. DOI:10.1016/0094-5765(88)90021-5 · 0.82 Impact Factor
  • J L Plewes, L E Farhi
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    ABSTRACT: Cardiovascular responses to acute hemodilution and controlled hypotension were studied in mongrel dogs anesthetized with halothane and paralyzed with pancuronium. Regional blood flows were determined by microsphere injections. Hemodilution to an hematocrit of 23% was produced by removal of whole blood and simultaneous infusion of Ringer's lactate solution. Subsequently, hypotension to a mean arterial pressure of 55 mmHg was produced for 90 min by intravenous infusion of trimethaphan. The hypotension resulted entirely from a 55% decrease in total peripheral resistance. Thirty minutes after initiation of controlled hypotension, there were significant increases in blood flow to the brain, liver, skeletal muscles, and diaphragm. However, at 30 min, calculated oxygen delivery had decreased to brain (-16%), renal cortex (-51%), heart (-45%), and retina (-44%). By 90 min, retinal, adrenal, and renal cortical blood flows were decreased significantly relative to control, and cerebral blood flows had returned to control levels. Absence of changes in acid-base status during the period of hemodilution and hypotension may indicate that whole body oxygen delivery was maintained at adequate levels. However, major decreases in calculated oxygen delivery after 90 min to critical tissue beds such as renal cortex (-67%) and retina (-78%) indicate that extension of the procedure past 30 min may involve risks that are not warranted by the benefits.
    Anesthesiology 03/1985; 62(2):149-54. DOI:10.1097/00000542-198502000-00010 · 6.17 Impact Factor
  • J. L. Plewes, L. E. Farhi
    Anesthesiology 01/1985; 63. DOI:10.1097/00000542-198509001-00026 · 6.17 Impact Factor
  • J L Plewes, L E Farhi
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    ABSTRACT: Acute hyperoxia (1 atm) in anesthetized dogs produced a 14% decrease in cardiac output relative to that observed with FIo2 = 0.21 and was associated with 7% decreases in heart rate and stroke volume. Changes in the distribution of peripheral blood flow during hyperoxia, as measured with radioactive labeled microspheres, included decreases in renal cortical flow (-20%), retinal blood flow (-27%), and blood flow to the caudate nucleus, mesencephalon, hippocampus, and cerebellum. Absolute blood flow to intestinal viscera, to respiratory and skeletal muscle, and to fat were unchanged. Simulation of these changes in cardiac output and distribution of blood flow using a digital computer model show a minimal change in the pattern of nitrogen gas elimination, with nitrogen partial pressures in the "slowest" body compartment within 1% of control by 60 min.
    Undersea biomedical research 07/1983; 10(2):123-9.
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    The Physiologist 05/1983; 26(2):93-5.
  • J L Plewes, A J Olszowka, L E Farhi
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    ABSTRACT: Carbonic anhydrase in lung tissue might play a role in speeding the movement of CO2 between blood and alveolus. To test this hypothesis, we measured the transpleural diffusion rate of CO2 and compared it to that of oxygen, argon, and nitrogen, before and after inhibition of carbonic anhydrase activity with acetazolamide. Experiments were performed in exsanguinated dog lungs, which allowed study of CO2 dynamics in the absence of carbonic anhydrase activity from erythrocytes. The relative rate of movement of CO2 and the other gases into and out of the lung, agreed with that predicted solely on the basis of molecular weight and solubility. We conclude that there is no evidence for facilitated diffusion of CO2 across the pleural tissue.
    Respiration Physiology 06/1981; 44(2):187-94. DOI:10.1016/0034-5687(81)90037-2
  • H K Chang, Leon E. Farhi
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    ABSTRACT: An experimentally verified mathematical model of non-equimolar ternary gas diffusion is applied to simulate the conditions existing in the alveolar spaces. When a fictitious gas film is erected a certain distance away from the alveolar membrane, and when the compositions at the two boundaries of the film are, respectively, the alveolar gas composition and a proportional mixture of inspired gas with the alveolar gas, the resulting fluxes of O2 and CO2 are essentially linearly related to their respective partial pressure gradients. From the slopes of these flux lines, effective diffusion coefficients are obtained. Ramifications of the effective diffusion coefficients approach are discussed.
    Respiration Physiology 06/1980; 40(2):269-79. DOI:10.1016/0034-5687(80)90098-5
  • Ronald C. Tai, H K Chang, Leon E. Farhi
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    ABSTRACT: Previous studies of multicomponent gas diffusion, using mathematical and physical models, have dealt with equimolar diffusion in closed systems. To simulate respiratory gas transport more faithfully, we have investigated ternary gas diffusion in open systems, which allow non-equimolar diffusion to occur. Theoretical results showed the effects of gas composition on the induced fluxes. A unique state in which the diffusion system satisfies both the equimolar and non-equimolar conditions was found for gas systems in which the net flux changes as the composition varies. To verify the non-equimolar film theory, we conducted experiments with a diffusion cell apparatus. Diffusional fluxes across a porous membrane were obtained for N2-O2-SF6, N2-O2-Ne, and N2-O2-He combinations. The experimental results agreed with the predicted values, validating the theoretical film approach.
    Respiration Physiology 06/1980; 40(2):253-67. DOI:10.1016/0034-5687(80)90097-3
  • Leon E. Farhi, Dag Linnarsson
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    ABSTRACT: Six normal male volunteers, aged 25 to 34, suspended vertically in a harness that allowed them to completely relax their postural muscles, were studied in four randomly ordered conditions, namely in air at 28 degrees C, and immersed in water at 35 degrees C to the level of the hips, the xiphoid, or the chin. In each situation, several variables were measured by noninvasive techniques. Cardiac output rose from 5.11 min-1 (air) to 8.31-min-1 (chin), the increase in each of the three steps being significant at the 0.001 level. Heart rate dropped from 76 to 68 min-1 (P less than 0.001) from air to xiphoid immersion, but appeared to rise again (P less than 0.02) during chest immersion. Functional residual capacity decreased marginally during lower limb submergence, and considerably in each of the following stages. Pulmonary capillary blood volume rose significantly only during abdomen immersion. The arterial-endtidal PCO2 difference was minimally reduced as water reached hip level and then remained steady. Mixed venous PO2 increased during abdomen submergence, and PVCO2, was unaltered throughout. Analysis of the step-to-step changes demonstrates that some variables are set by a combination of processes which may counteract each other, and explains the difference between results obtained by previous investigators.
    Respiration Physiology 07/1977; 30(1-2):35-50. DOI:10.1016/0034-5687(77)90020-2
  • J L Plewes, A J Olszowka, L E Farhi
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    ABSTRACT: The slope of the lung tissue CO2 dissociation curve and the rate of storage of CO2 in the lung tissue were studied at 22 degrees C and at 37 degrees C in 21 isolated, bloodless dog lungs with a total of 465 separate observations. Results at the two temperatures were similar. The slope of the tissue dissociation curve of lung tissue at a PCO2 of 40 torr was approximately 0.3 ml CO2 X 100 g wet tissue-1 X torr-1. Normally, this storage was 90% complete in about 5 seconds. After carbonic anhydrase inhibition by acetazolamide, the total storage capacity was unchanged, but the rate at which storage occurred decreased significantly, so that it took about 25 seconds for 90% of the storage to be completed.
    Respiration Physiology 01/1977; 28(3):359-69. DOI:10.1016/0034-5687(76)90030-X
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    ABSTRACT: Normal human subjects inspired various volumes of a normoxic argon mixture containing low concentrations of several biologically inert tracer gases with markedly different diffusivities (helium, neon, and sulfur hexafluoride). The behavior of Ne, Ar, and SF6 could be predicted on the basis of axial dispersion due to differences in diffusivity. For example, neon, having the highest diffusivity of the three, was more uniformly distributed within the bronchial tree than either argon or SF6. The behavior of helium, however, was not consistent with predictions based solely on axial diffusion. Contrary to expectation, the early portion of expiration was helium enriched while gas assumed to come from the alveolar regions contained relatively less helium than the other gases. Results of this study suggest that radial diffusion during convective bulk flow may play a significant role in intrapulmonary gas transport if relative diffusivity is extremely large. We conclude that diffusion gradients do exist within the bronchial tree during normal quiet breathing and that these gradients become less significant as inspired volume increases.
    Respiration Physiology 12/1976; 28(2):217-25. DOI:10.1016/0034-5687(76)90040-2
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    ABSTRACT: We have developed a rebreathing technique for measuring cardiac output in resting or exercising subjects. The data needed are the subject's CO2 dissociation curve, the initial volume and CO2 fraction of the rebreathing bag, and a record of CO2 at the mouth during the maneuver. From these one can obtain all the values required to solve the Fick equation. The combined error due to inaccuracy in reading the tracings and to the simplifying assumptions was found to be small (mean = 0.5%, SD ;.5%). Cardiac output values determined with this technique in normal subjects were on the average 2% higher than those obtained simultaneously with an acetylene rebreathing method (n = 49, SD = 11%). Among the advantages of the technique are that it requires analysis of a single gas, takes less than thirty seconds per determination, allows one to obtain repeated measurements at rapid intervals, is not affected by the ability of lung tissue to store CO2, and eliminates many of the assumptions usually made in non-invasive measurements of cardiac output.
    Respiration Physiology 11/1976; 28(1):141-59. DOI:10.1016/0034-5687(76)90091-8
  • H I Modell, Leon E. Farhi
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    ABSTRACT: The purpose of these experiments was to compare diffusive gas movement in a two-gas system with that in a three-gas system. Gas mixtures of different compositions were placed initially on either side of a removable partition dividing a cylindrical lucite diffusion chamber, filled with 3 mm glass beads. This served to slow diffusion, minimize convective currents generated by removing the partition, and stabilize temperature within the chamber. In two-gas systems, after the partition was removed, oxygen equilibrated between the two parts of the chamber more rapidly in a helium environment than in a nitrogen environment, conforming with predictions based on binary gas laws. Results obtained with a three-gas system differed significantly from those obtained with the binary system. With 21% oxygen in belium initially in one half of the chamber and 21% oxygen in nitrogen in the other, PO2 rose transiently in the He-O2 side of the chamber. Qualitatively, similar results were obtained when the O2-N2 mixture was replaced by 100% nitrogen. Pressure in the system remained essentially constant. The possible mechanisms responsible for the PO2 rise were studied using a computer model of the system. This showed that movement of a given gas may be affected significantly by movement of other gases in the system. Hence, application of binary gas diffusion laws to systems containing more than two gases may lead to significant errors.
    Respiration Physiology 08/1976; 27(1):65-71. DOI:10.1016/0034-5687(76)90018-9

Publication Stats

296 Citations
21.63 Total Impact Points


  • 1973–1994
    • University at Buffalo, The State University of New York
      • • School of Medicine and Biomedical Sciences
      • • Department of Medicine
      • • Department of Anesthesiology
      Buffalo, NY, United States
  • 1980
    • McGill University
      • Department of Biomedical Engineering
      Montréal, Quebec, Canada