L E Farhi

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

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Publications (39)51.76 Total impact

  • [Show abstract] [Hide abstract]
    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
  • R Arieli, L E Farhi
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    ABSTRACT: The suggestion that hyperventilation caused by increased gravity is mediated by a decrease in brain perfusion has led us to propose a mathematical model based on: (1) the CO2 balance equation for the respiratory center (RC), and (2) the relationship between RC blood flow (QRC), foot-to-head acceleration (Gz) and PRCCO2, namely, QRC = [1 - a(Gz - 1)](b X PRCCO2 + c), where the coefficients a, b and c can be calculated from data in the literature. QRC is significantly affected by + GZ only at high PaCO2. The model can be used to calculate oxygen pressure in the RC; the numbers so obtained are in good agreement with measurements of jugular vein PO2 obtained by others.
    Respiration Physiology 09/1987; 69(2):237-44. DOI:10.1016/0034-5687(87)90030-2
  • Urs Boutellier, Leon E. Farhi
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    ABSTRACT: The aim of our experiment was to investigate the influence of increasing either breathing frequency or tidal volume on cardiac output (Q), in normocapnia. We measured Q with a CO2 rebreathing method in 6 men and 6 women in the sitting and the supine position, imposing different breathing patterns: in one set of experiments tidal volume was kept constant at 1 L while breathing frequency was randomly changed between 20, 30 and 40 breaths/min; in another breathing frequency was kept constant at 30 breaths/min while tidal volume was randomly altered between 1, 1.5 and 2 L. Switching from open circuit breathing to rebreathing (for measurement of Q) required no change in breathing pattern. From the beginning, CO2 was added to the inspired gas to maintain end-tidal FCO2 at 0.054, so as to obtain steady state conditions throughout the measurements. Q rose significantly when tidal volume was increased (938 ml/L rise in tidal volume when sitting, and 743 ml/L when supine). Breathing frequency had an insignificant effect (213 ml/10 breaths frequency increase when sitting and 142 ml/10 breaths when supine). The greater influence of ventilation on Q when sitting than when supine is best explained by the fact that in the latter position venous return is already high. There are no demonstrable differences in this effect between males and females.
    Respiration Physiology 12/1986; 66(2):123-33. DOI:10.1016/0034-5687(86)90066-6
  • R Arieli, U Boutellier, L E Farhi
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    ABSTRACT: We compared the cardiopulmonary physiology of eight subjects exposed to 1, 2, and 3 Gz during immersion (35 degrees C) to the heart level with control dry rides. Immersion should almost cancel the effects of gravity on systemic circulation and should leave the lung alone to gravitational influence. During steady-state breathing we measured ventilation, O2 consumption (VO2), CO2 production, end-tidal PCO2 (PACO2), and heart frequency (fH). Using CO2 rebreathing techniques, we measured cardiac output, functional residual capacity, equivalent lung tissue volume, and mixed venous O2 content, and we calculated arterial PCO2 (PaCO2). As Gz increased, ventilation, fH, and VO2 rose markedly, and PACO2 and PaCO2 decreased greatly in dry ride, but during immersion these variables changed very little in the same direction. Functional residual capacity was lower during immersion and decreased in both the dry and immersed states as Gz increased, probably reflecting closure effects. Cardiac output decreased as Gz increased in dry rides and was elevated and unaffected by Gz during immersion. We conclude that most of the changes we observed during acceleration are due to the effect on the systemic circulation, rather than to the effect on the lung itself.
    Journal of Applied Physiology 12/1986; 61(5):1686-92. · 3.43 Impact Factor
  • U Boutellier, L E Farhi
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    ABSTRACT: 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%. In this paper we 1) present theoretical and experimental data to demonstrate the effect of CO2 and O2 exchange, 2) introduce a general equation, based on N2 and Ar, which allows one to circumvent the problems created by these fluxes, and 3) show the pitfall of the back-extrapolation approach for a single tracer.
    Journal of Applied Physiology 06/1986; 60(5):1810-3. · 3.43 Impact Factor
  • Urs Boutellier, Ran Arieli, Leon E. Farhi
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    ABSTRACT: During foot-to-head acceleration (+Gz) ventilation increases despite a drop in alveolar PCO2. In order to investigate the underlying mechanisms, we measured ventilation (VE), VO2, VCO2 and PACO2, cardiac output (Q) and mixed venous CO2 concentration (CVCO2) using non-invasive techniques in 5 subjects breathing either air or a gas mixture containing 5% CO2 at +1, +2 and +3 Gz in a human centrifuge. Arterial PCO2 was calculated from Fick's equation, using CVCO2, Q and VCO2. VE increased from 8.7 to 18.0 L/min during air breathing and from 19.6 to 36.9 L/min during CO2 breathing at +1 and +3 Gz, respectively. The corresponding values for PACO2 are 37.9 vs 26.9 Torr and 47.8 vs 46.4 Torr. Q dropped from 5.9 to 4.8 L/min during air breathing and remained the same during CO2 breathing (6.7 vs 6.5 L/min). As the decrease of PaCO2 almost paralleled that of PACO2, the arterio-alveolar CO2 difference increased only slightly. The CO2 response curve shifts gradually to the left with an increase in +Gz, a fact that does not support the hypothesis that foot-to-head acceleration increases CO2 sensitivity.
    Respiration Physiology 12/1985; 62(2):141-51. DOI:10.1016/0034-5687(85)90110-0
  • R Arieli, L E Farhi
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    ABSTRACT: We studied the effect of cyclic lung perfusion - fast cycle in synchrony with heart beats and slow cycle in synchrony with ventilation - on gas exchange in a lung model. There was almost no effect in the fast cycle. In a homogeneous single-lung unit, arterial PO2 increased, and the (A - a)DO2 decreased (by approximately 0.5 Torr), as the amplitude of the slow cyclic lung perfusion (TIP) increased. The calculated (A - a)DO2 and (a - A)DCO2 were negative. Maximal PaO2 was found when peak lung perfusion was delayed with respect to ventilation by 0.2 of a cycle. In a non-homogeneous nine-unit lung, cyclic lung perfusion caused an increase in PaO2 and a decrease in (A - a)DO2 by 2 Torr as compared to steady perfusion. No apparent negative (A - a)DO2 was found, but apparent negative (a - A)DCO2 was calculated at no pulmonary shunt and also with 5% shunt. The correlation of cyclic lung perfusion to the reduced (A - a)DO2 in dense-gas breathing - where large swings of pleural pressure are expected - and its effect on the diffusion capacity of the lung are discussed. Non-steady perfusion of the lung as caused by ventilatory movements expanded our understanding of gas exchange and shed some light on a few controversial experimental findings, such as the negative (a - A)DCO2, the decreased (A - a)DO2 while breathing dense gas, and the effects of gas density on diffusion capacity of the lung.
    Respiration Physiology 07/1985; 60(3):295-309. DOI:10.1016/0034-5687(85)90059-3
  • 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
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    ABSTRACT: We have studied the effects of severe acute hypoxemia (PaO2 = 25 torr) on cardiac output (Q), heart rate (HR), left ventricular contractility ((dP/dt)max/P), intravascular pressures and blood flow to the heart, brain, abdominal viscera, skin and respiratory and non-respiratory muscles in twelve conscious ewes that breathed a mixture of 8% O2 and 92% N2 for 20 min. Q, HR, (dP/dt)max/P) and systemic and pulmonary arterial pressures increased. Total peripheral resistance decreased while pulmonary vascular resistance remained unchanged. Coronary, cerebral, respiratory and nonrespiratory muscle and adrenal flows increased, in association with a decrease in regional vascular resistances, while the flows to the kidney and other abdominal viscera remained unchanged. The concentration of total plasma catecholamines doubled, indicating that the sympathetic nervous system plays a major role in the hemodynamic response to this level of hypoxia. Increased oxygen delivery to the heart (31%) and respiratory muscles (44%) were brought about by increases in both the magnitude and the redistribution of Q, the latter being the more important of the two mechanisms. In contrast, both mechanisms contributed equally to the amount of oxygen delivered to the brain and nonrespiratory muscles. We concluded that in acute hypoxemia, both the increase in Q and its regional redistribution contribute to the delivery of oxygen to the various tissues.
    Respiration Physiology 09/1983; 53(2):161-72. DOI:10.1016/0034-5687(83)90064-6
  • 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.
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    ABSTRACT: We studied the cardiorespiratory effects of acute hypercapnia in 10 unanesthetized sheep. After a 15-min exposure to either 7.3 or 10% CO2 in air, we measured arterial blood gases, minute ventilation (VE), O2 consumption (VO2), cardiac output (Q), heart rate (HR), an index of left ventricular contractility [(dP/dt)/P], and vascular pressures. In addition, regional flows to all major organs were determined by injecting 15-microns radiolabeled microspheres into the left heart. Exposure to 7.3% CO2 (arterial CO2 partial pressure, PaCO2, 58 Torr) resulted in increased VE, (dP/dt)/P, and higher blood flows to the brain and respiratory muscles. All other variables remained unchanged. Exposure to 10% CO2 (PaCO2 75 Torr) resulted in a further augmentation of VE and a 48% increase in Q, which was associated with a tachycardia, a decrease in systemic vascular resistance, and an increase in VO2. Coronary and respiratory muscle flows increased, but all other variables remained unchanged. Thus the hemodynamic effects of hypercapnia are not related linearly to the level of PaCO2.
    Journal of applied physiology: respiratory, environmental and exercise physiology 04/1983; 54(3):803-8. · 3.73 Impact Factor

Publication Stats

445 Citations
51.76 Total Impact Points

Institutions

  • 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