L E Farhi

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

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Publications (29)55.28 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. · 2.05 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. · 2.66 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. · 3.48 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
  • D W Sheehan, L E Farhi
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    ABSTRACT: We studied the local response of the pulmonary vasculature to combined changes in alveolar PO2 and PCO2 in the right apical lobe (RAL) of six conscious sheep. That lobe inspired an O2-CO2-N2 mixture adjusted to produce one of 12 alveolar gas compositions: end-tidal PCO2 (PETCO2) of 40, 50, and 60 Torr, each coupled with end-tidal PO2 (PETO2) of 100, 75, 50, and 25 Torr. In addition, at each of the four PETO2, the inspired CO2 was set to 0 and PETCO2 was allowed to vary as RAL perfusion changed. The remainder of the lung, which served as control (CL) inspired air. Fraction of the total pulmonary blood flow going to the RAL (%QRAL) was obtained by comparing the methane elimination from the RAL to that of the whole lung, and expressed as a percentage of that fraction at PETCO2 = 40, PETO2 = 100. Cardiac output, pulmonary vascular pressures, and CL gas tensions were unaffected or only minimally affected by changes in RAL gas composition. A drop in PO2 from 100 to 50 Torr decreased local blood flow by 60% in normocapnia and by 66% at a PCO2 of 60. At all levels of oxygenation, an increase in PCO2 from 40 to 60 reduced QRAL by nearly 50%. With these stimulus-response data, we developed a model of gas exchange, which takes into account the effects of test segment size on blood flow diversion. This model predicts that: (1) when the ventilation to one compartment of a two compartment lung is progressively decreased, PAO2 remains above 60 Torr for up to 60% reductions in alveolar ventilation, irrespective of compartment size; (2) the decrease in PAO2 that occurs at altitude is accompanied by a drop in PACO2 that limits the decrease in conductance and minimizes the pulmonary hypertension; and (3) as we stand, local blood flow control by the alveolar gas tensions halves the alveolar-arterial PO2 and PCO2 differences imposed by gravity.
    Respiration Physiology 11/1993; 94(1):91-107.
  • D W Sheehan, L E Farhi, J A Russell
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    ABSTRACT: 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.
    The American review of respiratory disease 04/1992; 145(3):640-5. · 10.19 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.
  • L E Farhi, D W Sheehan
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    ABSTRACT: Both the systemic and the pulmonary circulations respond to local hypoxia in the appropriate manner, the former by vasodilating, thereby providing more oxygen, and the latter by constricting and rerouting blood flow to areas where more O2 is available. In either case, changes in local conductance affect total conductance, and through that variable, the perfusing pressure; as a result, the effects of local vasomotion should be reduced. In the systemic circulation, arterial pressure can be prevented from falling by two important mechanisms: vasoconstriction of other vascular beds, and an increase in cardiac output. There are no similar means for protecting pulmonary arterial pressure against a rise when vessels in hypoxic areas contract; the only defense is provided by passive expansion of the vascular bed. Thus, in the lung regional circulatory readjustments conflict with the need to maintain a reasonably low pulmonary arterial pressure and local regulation (and maintenance of arterial oxygenation) may be subordinate to prevention of pulmonary hypertension.
    Advances in experimental medicine and biology 02/1990; 277:579-86. · 1.83 Impact Factor
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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. · 0.70 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. · 5.16 Impact Factor
  • J. L. Plewes, L. E. Farhi
    Anesthesiology 01/1985; 63. · 5.16 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.
  • 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
  • S Matalon, M S Nesarajah, L E Farhi
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    ABSTRACT: We have measured the effects of normobaric hyperoxia on arterial and mixed venous gas tensions, cardiac output, heart rate, right atrial, pulmonary, and aortic pressures in 12 conscious chronically instrumented sheep. Regional blood flow to brain, heart, kidney, intestines, and respiratory muscles was assessed in five sheep by injecting 15-micrometers microspheres labeled with gamma-emitting isotopes. Survival time ranged from 60 to 120 h (mean = 80 h). All variables except arterial O2 partial pressure (PaO2) and mixed venous O2 partial pressure remained at base-line level during the first 40 h of exposure, after which PaO2 decreased gradually but remained above 200 Torr at death. After this there was a progressive uncompensated respiratory acidosis with terminal arterial CO2 partial pressure values exceeding 90 Torr. There was a considerable rise in the brain blood flow, whereas flow to the other organs either remained unchanged or increased in proportion to cardiac output. Our experiments also showed that systemic hyperoxic vasoconstriction did not occur, and any local changes were not of sufficient magnitude to affect perfusion.
    Journal of applied physiology: respiratory, environmental and exercise physiology 08/1982; 53(1):110-6. · 3.73 Impact Factor
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    ABSTRACT: We used direct invasive techniques to measure the effects of hyperventilation on the pulmonary blood flow (Q) and on recirculation time of helium and of carbon dioxide in humans. The subjects hyperventilated with a tidal volume of 1.5 liters (BTPS) and a frequency of 20 or 30 breaths/min. There was no significant change in Q from control at either level of hyperventilation. Helium first appeared in the pulmonary artery within 12 s from the onset of hyperventilation and increased by approximately 0.7% of its equilibrium arterial value per second at both levels of hyperventilation. In contrast, the PVCO2 remained at base-line level until 43 s from the onset of hyperventilation. We conclude that hyperventilation at 30 or 45 l/min with constant tidal volume does not significantly affect the value of Q and that the amount of recirculation of the two gases does not result in underestimation of Q when this variable is measured by indirect respiratory rebreathing techniques.
    Journal of applied physiology: respiratory, environmental and exercise physiology 06/1982; 52(5):1161-6. · 3.73 Impact Factor
  • 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.