Aviation, Space, and Environmental Medicine x Vol. 79, No. 5 x May 2008 459
REVIEW ARTICLE
LBNP: Past Protocols and Technical Considerations
for Experimental Design
Nandu Goswami , Jack A. Loeppky , and
Helmut Hinghofer-Szalkay
G OSWAMI N, L OEPPKY JA, H INGHOFER -S ZALKAY H. LBNP: past pro-
tocols and technical considerations for experimental design. Aviat
Space Environ Med 2008; 79:459 – 71.
Introduction: Lower body negative pressure (LBNP) has been used for
decades to simulate orthostatic stress and the effects of blood loss in hu-
mans. Since the defi nitive review of LBNP in 1974, new applications
have been developed and research has revealed confl icting cardiovas-
cular and neurohormonal responses during and after LBNP. Methods: A
search of the literature was conducted for 1964 – 2007 using the Web of
Science and the search terms “ cardiovascular system, ” “ orthostasis, ”
“ spacefl ight, ” and “ methodologies ” to identify publications in English
that describe human studies where LBNP was used to simulate orthosta-
sis. Publications cited in the earlier review were excluded, leaving a to-
tal of 215 articles for consideration. Results: We divided the reported
protocols into eight categories based on the pressure, pattern, and dura-
tion of the stimulus: 1) mild, constant, short; 2) mild, constant, long; 3)
mild, ramp, short; 4) mild, ramp, long; 5) moderate-to-strong, constant,
short; 6) moderate, constant, long; 7) moderate-to-strong, ramp, short;
and 8) strong, ramp, long. The review showed that these protocols stim-
ulate different refl exes and can be used to produce particular responses.
Discussion: Based on the review, we developed guidelines for using
LBNP in a predictable and reproducible manner. Variables that must be
controlled include subject characteristics, procedures, and environmen-
tal conditions as well as specifi cations for the LBNP chamber and seal
positioning. An understanding of the many technical details of such ex-
periments and the nature of elicited cardiovascular and neurohormonal
responses is required to design optimal protocols to address specifi c re-
search questions.
Keywords: orthostasis , spacefl ight , countermeasures , cardiovascular ,
LBNP methodology .
A
S EARLY AS 1834, Junod reported the use of subat-
mospheric pressure for anesthesia and draining
blood away from diseased organs ( 210 ). The lower body
negative pressure (LBNP) method was introduced into
medical research by Stevens and Lamb in 1965 and has
proven to be a useful tool to induce orthostatic stress
( 80 , 154 ), to study cardiovascular responses to hemor-
rhage ( 31 , 154 ), and to prevent cardiovascular decon-
ditioning ( 62 , 68 , 180 ). It has also proven valuable in the
study of blood pressure regulation ( 90 ), refl ex vasocon-
strictor responses ( 43 ), and the role of baroreceptors in
stabilizing vascular resistance ( 87 ). LBNP can be em-
ployed to discriminate refl exes arising from intracardiac,
aortic arch, and carotid sinus regions that detect blood
pressure changes ( 48 ).
LBNP has been successfully employed to evaluate the
effects of physiological and pharmacological interven-
tions on cardiovascular refl exes ( 38 , 39 , 42 ), in congestive
heart failure patients to simulate renal and splanchnic
adaptations ( 33 ), and to characterize reduced cardiopul-
monary functions ( 194 ). LBNP is an alternative for test-
ing autonomic function in patients, especially in those
not able to perform the Valsalva maneuver ( 142 ), and is
useful in counteracting the gait and static balance modi-
fi cations induced by bed rest ( 40 ). It increases foot-ward
loading for resistance training and creates partial foot-
ward loading for orthopedic rehabilitation such as hip
replacement ( 74 ). In surgery, it has been used to produce
dry operating fi elds ( 210 ).
LBNP partially reverses the head-ward shift of blood
and body fl uids occurring in microgravity and improves
orthostatic tolerance following bed rest, head down tilt,
or during spacefl ight ( 59 ). It has been used as a counter-
measure to spacefl ight deconditioning ( 202 ) and simu-
lates gravity during aerobic exercise in sub-gravity con-
ditions ( 60 , 61 ). LBNP has been incorporated as a unique
investigative tool during exposure to vertical accelera-
tion in high-performance aircraft ( 27 ) and has also been
used to simulate partial gravity environments, such as
on the Moon or Mars.
This review considers various applications and ad-
vantages of LBNP, provides a brief overview of physio-
logical changes induced by it, and compares it with
other models used to induce orthostasis. We propose
specifi c LBNP protocols that accentuate particular re-
fl exes and, therefore, can be used to optimize their study.
We also outline technical variables that need to be taken
into account and address their implications on the re-
sponses to LBNP. We conclude with a set of criteria/
guidelines for using LBNP, as an understanding of the
From the Institute of Physiology, Center of Physiological Medicine,
Medical University Graz, Graz, Austria (N. Goswami, H. Hinghofer-
Szalkay); the Institute of Adaptive and Spacefl ight Physiology, Graz,
Austria (H. Hinghofer-Szalkay); and the Cardiology section, VA Medi-
cal Center, Albuquerque, NM (J. A. Loeppky).
This manuscript was received for review in July 2007 . It was ac-
cepted for publication in January 2008 .
Address reprint requests to: Nandu Goswami, Institute of Physiol-
ogy, Medical University Graz, Harrachgasse 21, A-8010 Graz, Austria;
nandu.goswami@meduni-graz.at .
Reprint & Copyright © by the Aerospace Medical Association, Alex-
andria, VA.
DOI: 10.3357/ASEM.2161.2008

460 Aviation, Space, and Environmental Medicine x Vol. 79, No. 5 x May 2008
LBNP PROTOCOL CONSIDERATIONS — GOSWAMI ET AL.
technique and elicited cardiovascular and neurohor-
monal responses is helpful to design optimal protocols
for specifi c research questions.
Advantages of LBNP
LBNP is a noninvasive, easily reversible procedure
that is usually applied in the supine position. Body po-
sition changes that may infl uence fl uid distribution
during baseline ( 131 ) and stimulate the neuro-sensorial
system are unnecessary, thus removing movement arti-
facts from hemodynamic recordings ( 38 ). LBNP induces
tachycardia and hypotension similar to that caused by a
centrifuge and can be used as a less costly substitute to
study effects of G loads ( 7 , 117 , 196 ). Seated LBNP at 40
mmHg induces hemodynamic changes similar to those
during 1 2 G ( 145 ).
Use of LBNP in Spacefl ight
Manned spacefl ight is associated with orthostatic in-
tolerance ( 15 ) and LBNP can be used (until a fl ight cen-
trifuge is fl own) to assess orthostatic tolerance in fl ight.
LBNP at 80 or 90 mmHg in fl ight can simulate 1 2 G
z

heart rate responses in weightlessness ( 145 ). Also,
LBNP with treadmill exercise has been used as a coun-
termeasure to orthostatic intolerance, musculoskeletal
deconditioning and neuromotor dysfunction, and to
provide a high impact stimulus to maintain bone status
( 73 ). In the Russian space program LBNP is used at the
end of the mission as a two-step training protocol ( 99 ):
1) individualized initial training (two to six sessions) to
assess orthostatic tolerance and to prepare for intensive
LBNP exposure; and 2) two sessions to activate mecha-
nisms of cardiovascular control. Water-salt supple-
ments, in combination with LBNP (LBNP/saline ‘ soak ’ )
during the fi nal stages of spacefl ight, have been used to
counteract postfl ight orthostatic intolerance ( 18 ).
Interestingly, the leg volume response to LBNP has
been found to differ when comparing LBNP experi-
ments aboard Skylab and on Earth ( 93 ). More recently,
it has been suggested that sympathetic control and vas-
cular reactivity might be altered in spacefl ight ( 30 ).
Responses to LBNP in numerous long-term fl ights have
been summarized ( 106 ).
Overview of Physiological Changes Induced
by LBNP
LBNP elicits reproducible refl exive hemodynamic re-
sponses ( 165 ), similar to those following increased G
load ( 8 ), which tend to maintain arterial pressure and
cerebral perfusion ( 13 ). It causes pulmonary hypoperfu-
sion, a caudal shift of the diaphragm ( 210 ), and an
increase in functional residual capacity ( 210 ). Plasma
norepinephrine rises immediately ( 80 ), followed by an
activation of the renin-angiotensin-aldosterone system,
galanin, adrenomedullin, and hypothalamic-pituitary
hormones ( 80 , 81 , 158 ). Atrial natriuretic peptide is re-
duced when the presyncope level of orthostatic stress is
reached ( 60 ). LBNP release is always followed by a rapid
return of blood to the thorax from the legs, an overshoot
of arterial pressure, and bradycardia, similar to that ob-
served after termination of a Valsalva maneuver ( 210 ).
Additional Physiological Considerations in LBNP Responses
Magnitude of pressure and exposure duration: The re-
sponses to LBNP are dependent on magnitude of pres-
sure applied and exposure duration ( 128 , 210 ). LBNP re-
duces thoracic blood volume, central venous pressure
(CVP), right atrial pressure, and volume and cardiac
output, while increasing the vascular resistance, leg vas-
cular tone, and blood pooling ( 68 ). Lower body blood
pooling and the CVP decline are directly related to LBNP
intensity; LBNP of 10 and 60 mmHg reduces CVP by 3
and 7 mmHg, respectively, with an approximate slope
of 1 mmHg per 10 mmHg LBNP ( 31 ).
The onset and the magnitude of hypotension vary be-
tween subjects during LBNP exposure ( 83 ), with 500-
1000 ml fl uid displacement from central to peripheral
regions by 20-40 mmHg LBNP for 5 min ( 31 , 54 , 157 ). The
extent of pooling is also dependent on differences in in-
dividual physiological responses even when subjects
have been familiarized with the protocol and in the ab-
sence of invasive measurements ( 210 ).
LBNP magnitude has different effects on regional blood
fl ows: LBNP-induced baroreceptor unloading alters re-
gional blood fl ow ( 82 ). LBNP greater than 20 mmHg
causes differential blood fi lling in various body com-
partments ( 37 , 154 , 210 ); at 50 mmHg women pool more
blood in the pelvis than men ( 71 , 207 ). The increase in leg
volume more than doubles when LBNP is elevated from
20 to 40 mmHg ( 161 ), exclusively due to venous fi lling
( 136 ). LBNP of 50 mmHg reduces splanchnic blood fl ow
by 32% ( 159 ) and vascular conductance by 30% ( 159 ),
with a further decrease as suction pressure increases
( 45 , 92 ). However, more research is needed to under-
stand the differences of volume distribution in body
compartments during LBNP.
LBNP magnitude has variable effects on different receptors:
Specifi c LBNP pressures induce different refl ex re-
sponses due to variable effects on cardiac and arterial
baroreceptors ( 155 ): peripheral vasoconstriction (mus-
cular, cutaneous, and renal) is a result of arterial and
cardiopulmonary receptor stimulation ( 203 ), while mes-
enteric perfusion is mainly infl uenced by arterial barore-
ceptors ( 82 ). Furthermore, the cardiopulmonary low-
pressure baroreceptors (intrathoracic mechanoreceptors)
play an important role in vasodilatation responses be-
cause they inhibit sympathetic outfl ow ( 72 ).
Evolving view on specifi c receptors affected by LBNP lev-
els: LBNP of , 20 mmHg reduces CVP ( 82 ), induces
forearm vascular resistance changes ( 194 ) and periph-
eral vasoconstriction ( 31 ), and increases heart rate ( 210 )
by affecting cardiopulmonary and possibly arterial
baroreceptors ( 139 ). Higher suction affects both the arte-
rial and cardiopulmonary receptors ( 9 , 57 ), thereby re-
ducing forearm and splanchnic blood fl ow ( 82 ) and
pulse pressure ( 38 ). It has been proposed that carotid
barorefl ex function is modifi ed by changes in blood vol-
ume distribution as sensed by intrathoracic receptors