Elevated intra-abdominal pressure limits venous return during exercise in Varanus exanthematicus
Department of Ecology and Evolutionary Biology, University of California, 321 Steinhaus Hall, Irvine, CA 92697, USA
* Author for correspondence (e-mail: smunns{at}uci.edu)
Accepted 6 September 2004
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Summary |
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Key words: exercise, hemodynamics, intra-abdominal pressure, lizard, locomotion, oxygen consumption, reptile, venous return, ventilation
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Introduction |
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Recent studies have demonstrated that ventilation is constrained during
exercise in some lizards. The laterally undulating gait employed by lizards
requires unilateral recruitment of hypaxial muscles, and costal ventilation
requires bilateral recruitment of the same hypaxial muscles. This conflict may
result in a speed-dependent constraint on ventilation
(Carrier, 1987). Thus,
effective lung ventilation may be compromised in exercising lizards by the
lateral flexions that occur during locomotion (the axial constraint
hypothesis). This constraint is overcome in varanid lizards due to the
presence of an accessory ventilatory device, called the gular pump. Gular
pumping enables varanid lizards to supplement costal ventilation during
exercise, thus maintaining oxygen consumption despite a decrease in costal
ventilation (Owerkowicz et al.,
1999
).
However, axial constraint may also have important implications for
hemodynamics. Locomotion may elevate intra-abdominal pressure as a result of
the activity of the hypaxial muscles that are recruited both during locomotion
and ventilation (Carrier,
1990; Ritter,
1996
). Elevated intra-abdominal pressures may act to compress the
large veins in the abdomen and reduce venous return. An increase in
intra-abdominal pressure and a reduction in blood flow from the caudal
portions of the body occurred during high-speed running (4 km h-1)
in Iguana iguana, and suggests that venous return may be limited
during exercise in iguanid lizards (Farmer
and Hicks, 2000
). A reduction in blood flow returning to the heart
may have important consequences for oxygen delivery to exercising muscles
because systemic venous return and ventricular preload are the major
determinants of cardiac output. Thus, in iguanid lizards, both ventilatory
(axial constraint) and circulatory (venous return) constraints may act to
limit
O2max
during exercise. Varanid lizards circumvent the ventilatory constraints
present in iguanid lizards by exploiting the gular pump; however, whether
circulatory constraints similar to those in iguanid lizards exist in varanid
lizards has not been investigated.
In mammals, venous return during exercise is the result of integration of
the cardiac, skeletal muscle and respiratory pumps. Contraction of skeletal
muscles can act as a circulatory pump in two ways: muscle contractions can
compress intramuscular venous vessels, pushing blood towards the heart, and
can reduce intramuscular venous pressure, creating an increased
arterialvenous pressure gradient that aids blood flow in the muscle
during relaxation (Rowland,
2001). Ventilation may also act to aid venous return. The negative
intra-thoracic pressures created during inspiration increase the pressure
gradient for blood flow back to the heart. During exercise, increased
ventilation causes alternating distension of intra-thoracic vessels during
inspiration and compression during expiration and may act to supplement
cardiac output during exercise (Agostini
and Butler, 1991
). Thus, the pressure gradient generated by the
heart is assisted by contraction of skeletal muscles and by the mechanical
action of ventilation during exercise. However, the degree to which the
cardiac, respiratory and skeletal muscle pumps are integrated in exercising
reptiles has not been determined.
This study aimed to investigate the effects of exercise on venous return, intra-abdominal pressure, ventilation and gas exchange in Varanus exanthematicus. In addition, intra-abdominal pressure was increased using temperature-equilibrated saline in resting lizards. Saline-induced elevations in intra-abdominal pressure were designed to simulate the elevated intra-abdominal pressures measured in exercising lizards and, thus, to determine the hemodynamic and respiratory consequences of increased intra-abdominal pressures in the absence of the confounding effects of exercise.
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Materials and methods |
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Surgical procedure, blood flow, intra-abdominal pressure and blood pressure
Lizards were lightly anesthetised by placing them in a sealed container
with gauze dampened with Isoflurane (Isoflo; Abbott laboratories, North
Chicago, IL, USA). Lizards were then intubated and artificially ventilated
(SAR-830; CWE Inc., Ardmore, PA, USA) with room air that had been passed
through a vapourizer (Dräger, Lubeck, Germany). The vapourizer was
initially set at 34%, and was then reduced to 12% for the
majority of the surgery. A 3 cm ventral incision was made in the abdomen and a
loose-fitting ultrasonic blood flow probe (2R; Transonic System Inc., Ithaca,
NY, USA) was placed around the post caval vein (homologous to the mammalian
inferior vena cava). In Varanus exanthematicus the two renal portal
veins (carrying blood from the hind limbs, tail and pubic region) fuse to form
the post caval vein just before its entry into the right lobe of the liver.
The ultrasonic blood flow probe was placed around the post caval vein,
anterior to the union of the two renal portal veins, but posterior to its
entry into the right lobe of the liver. The intestinal, lienogastric, gastric
and abdominal veins fuse to form the hepatic portal vein, which enters the
left lobe of the liver (Schaffner,
1998). Thus, the venous return measured in this study comprises
venous drainage from the hind limbs and tail, but excludes drainage from the
gastrointestinal tract, which enters the liver anterior to the location of the
blood flow probe. A pressure transducer (Millar Mikrotip; Millar Instruments
Inc., Houston, TX, USA) was sutured to connective tissue adjacent to the flow
probe. The probes were exteriorized through the lateral body wall
approximately 5 cm anterior to the pelvis and secured using 3-0 silk sutures
on the dorsal surface of the tail. In addition, the lizards used in the
resting experiments had a 23 cm piece of sterile Tygon tubing inserted
into the abdominal cavity; the remaining length of tubing (1015 cm) was
exteriorized via the same lateral incision used for the blood flow
probes. This tubing served as a port for the introduction of saline and the
direct alteration of intra-abdominal pressure.
The brachial artery was cannulated to measure arterial blood pressure. A 12 cm incision was made in the ventral surface of the upper fore limb. The brachial artery was exposed using blunt dissection techniques and the artery cannulated with polyethylene tubing (i.d. 0.023 cm, o.d. 0.038 cm; Harvard Apparatus, Inc., Holliston, MA, USA) and secured using 3-0 sutures. Blood pressure was measured using disposable pressure transducers (model MLT0670; AD Instruments, Colorado Springs, CO, USA).
In addition to the procedures detailed above, central venous pressure and right artial pressure were also measured in resting V. exanthematicus. The femoral vein was exposed using the procedure detailed above for brachial artery cannulation. A 3.5F pressure transducer (Millar Mikrotip) was introduced into the femoral vein and advanced 57 cm into the central venous circuit. Another 3.5F pressure transducer was introduced into the right atria via a 12 mm incision in the atrial wall and secured using 4-0 silk.
All incisions were closed with intermittent sutures and treated with cyanoacrylate tissue adhesive (Vetbond; 3M, St Paul, MN, USA). Artificial ventilation with room air was continued until the lizard regained consciousness and reinitiated spontaneous breathing. Intramuscular injections of the antibiotic enrofloxican (Baytril; Bayer Corporation, Shawnee Mission, KS, USA), and the analgesic flunixin meglumine (Flunixamine; Fort Dodge, Madison, NJ, USA) were given at the conclusion of surgery. Enrofloxican injections were repeated every second day after surgery. A minimum recovery period of 2 days was given before commencement of experimentation.
Lung ventilation and gas exchange
Ventilation was measured using a mask constructed from the base of a 50 ml
polypropylene centrifuge tube (Corning Inc. Life Sciences, Acton, MA, USA).
Flexible tubing was attached via two ports drilled into the mask. The
mask was attached over the lizard's nostrils and the mouth sealed closed with
a dental polyether impression material (Impregum F; 3M EPSE, St Paul, MN,
USA). Impregum is non-toxic, easily removable and non-exothermic. Fresh room
air was drawn through the mask using a sealed aquarium air pump at a constant
flow rate of between 1.2 and 1.7 l min-1 (depending on the size of
the lizard). Care was taken to ensure that the flow rate though the mask
exceeded the rate of inspiration, thus minimising the possibility of
rebreathing. Air flow through the mask was controlled with rotameters (Brooks
Instruments, Hatfield, PA, USA). Alterations in airflow due to ventilation
were measured using a pneumotachograph (8311; Hans Rudolph, Inc., Kansas City,
MO, USA) placed upstream of the mask, such that expirations caused an increase
in airflow and inspiration caused a decrease in airflow. Pressure gradients
induced by alterations in airflow across the pneumotachograph were monitored
using a Valendyne differential pressure transducer (MP-45-1-871; Validyne,
Northridge, CA, USA). The signal from the differential pressure transducer was
calibrated by injecting and withdrawing known volumes of gas from the sealed
mask and was integrated to obtain tidal volumes. Costal ventilations were
distinguished from gular pumps via visual observation of the lizards
and the absence of expirations before the low volume gular pumps. Gas from the
mask was sub-sampled and passed through Drierite (anhydrous calcium sulfate,
Sigma-Aldrich Co., Milwaulkee, WI, USA) before being passed through
CO2 (CD-3A; Applied Electrochemistry Inc., Sunnyvale, CA, USA) and
O2 (S-3A; Applied electrochemistry Inc., Sunnyvale, CA, USA)
analyzers. The rates of oxygen consumption
(O2) and carbon
dioxide production
(
CO2) were
determined using a technique described previously
(Bennett and Hicks, 2001
;
Farmer and Hicks, 2000
;
Wang et al., 1997
). Briefly,
O2 and
CO2 of single
breaths were determined as the area below
(
O2) or above
(
CO2) the
baseline signal for room air. Exhalations were simulated by injecting known
volumes of known gas mixtures (21% O2, 79% N2; 100%
N2; 15% O2, 5% CO2, 80% N2) into
the mask to establish the relationship between this area and gas exchange.
Minute ventilation and tidal volume are reported at BTPS (body
temperature and pressure, saturated) and metabolic gas values at
STPD (atmospheric temperature and pressure, dry).
Experimental protocol
Treadmill exercise
Lizards were fasted for 7 days before surgery and were held at the
experimental temperature (35°C) for 23 days before experimentation.
A mask was attached over the lizard's nostrils and the lizard was placed on
the treadmill belt. The lizard was left on the stationary treadmill belt for
at least 1 h before the treadmill was started to obtain pre-exercise `resting'
measurements. All lizards rested quietly on the treadmill during the
pre-exercise period. The exercise regime was similar to that used in the same
species by Bennett and Hicks
(2001) and consisted of a
sequential step protocol with consecutive 4 min exercise bouts at each of four
treadmill speeds: 0.5, 1.0, 1.5 or 2.0 km h-1. Locomotion was
initiated by gently tapping the treadmill belt behind the lizard or by lightly
touching the lizard's tail. All lizards completed the exercise protocol, with
exhaustion occurring between the third and forth minute of exercise at 2.0 km
h-1. Exhaustion was defined as the failure of the lizard to keep
pace with the treadmill belt despite tactile encouragement. At the lowest
treadmill speed of 0.5 km h-1, the lizard's locomotion was
intermittent, but sustained locomotion was maintained consistently at all
other treadmill speeds until exhaustion. Ventilatory and cardiovascular
parameters reached a steady state by 3 min of treadmill exercise at each
speed. To obtain blood pressure recordings that were unaffected by movement,
the treadmill was stopped for 30 s at the end of each 4 min period, after
which the treadmill was restarted at the next speed. After the exercise regime
was completed, the lizards were allowed to rest on the treadmill for up to 2 h
(termed the recovery period). Preliminary experiments suggested that venous
return and mean arterial blood pressure may increase immediately after
exercise ceased and, thus, the recovery period was included to allow
determination of cardiovascular and respiratory parameters immediately after
exercise.
Direct alteration of intra-abdominal pressure in resting lizards
Lizards were fasted for 7 days before surgery and were held at the
experimental temperature (35°C) for 23 days before experimentation.
A mask was attached over the lizard's nostrils and the lizard was placed in a
darkened plastic holding container. The lizard rested quietly for at least 1 h
before the alteration of intra-abdominal pressure. Intra-abdominal pressure
was increased by the injection of temperature equilibrated sterile saline into
the tygon port previously implanted. Intra-abdominal pressures of double and
triple resting pressures were induced separately for 5 min, followed by a
return to resting intra-abdominal pressure (by withdrawal of saline) for at
least 1 h.
Data collection, analysis and statistics
All signals were collected on a computer at 120 Hz using Acknowledge
data-acquisition software (Biopac, Goleta, CA, USA). Owing to the intermittent
and variable nature of reptilian ventilation and the low breathing frequencies
at rest, ventilatory and cardiovascular parameters, and intra-abdominal
pressure, were calculated from the last 10 min of the pre-exercise period
before commencement of treadmill exercise. Minute ventilation,
O2,
CO2,
intra-abdominal pressure (PIA) and post caval blood flow
(
PC) were calculated from
the last minute of treadmill exercise at each speed. Blood pressure and heart
rate were calculated from the first 10 s of the 30 s pause between each
treadmill speed. All recovery period data (except
PC and blood pressure) were
calculated from a 60 s window surrounding the maximal blood pressure response.
Venous return peaked earlier than maximal blood pressure (40 s vs 140
s after exercise ceased), thus the recovery
PC was calculated from a 10
s period at maximal blood flow. Blood pressure during recovery was measured
from a 10 s period at the maximal response. Mean arterial blood pressure
(
a) was calculated as:
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For experiments involving the direct manipulation of intra-abdominal pressure in resting lizards, all cardiovascular parameters were calculated from the last minute of the resting period and the last minute of the elevated intra-abdominal pressure period. Ventilatory parameters were calculated from the last 10 min of the resting period and the last minute of the elevated intra-abdominal pressure period.
The effect of increasing treadmill speed on all parameters was determined using paired Dunnett's tests with the rest period as the control (P<0.05). Comparisons of the recovery period to the maximal treadmill speed were performed using a paired Student's t-test (P<0.05). The effects of increased intra-abdominal pressure (via saline infusion) on all parameters were determined using paired t-tests (P<0.05). All data presented are means ± S.E.M.
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Results |
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PC increased during the
three lower treadmill speeds (0.5, 1.0 and 1.5 km h-1) from
8.76±2.27 at rest to 19.64±5.77, 20.34±5.44 and
21.63±6.11 ml min-1 kg-1, respectively
(Fig. 2). However, at the
maximum treadmill speed of 2.0 km h-1,
PC decreased to
12.30±1.21 ml min-1 kg-1 and was not
significantly different from that measured during rest. Systolic
(PS), diastolic (PD) and mean arterial
blood pressures (
a) were also
elevated during treadmill exercise; however, neither
a nor
PC showed any incremental
increase with treadmill speed (Fig.
2). This trend was also observed in the heart rate response to
exercise. Heart rate increased from 25.11±2.99 min-1 at rest
to 82.05±9.17 min-1 at 0.5 km h-1
(Fig. 2). Heart rate did not
increase between 1.0 and 2.0 km h-1 (106.12±2.50,
107.43±2.63 and 111.26±2.38 min-1, respectively).
Resting PIA (11.09± 2.14 mmHg) was variable between
individual lizards, predominantly due to body posture, degree of
gastrointestinal tract filling and exact transducer position.
PIA was not significantly different from rest at 0.5 km
h-1 (12.03± 2.88 mmHg), but increased to 15.48±2.11,
14.18±2.29 and 18.74±2.09 mmHg as treadmill speed increased from
1.0 to 2.0 km h-1 (Fig.
2). Peak PIA was measured in response to
treadmill exercise at 2.0 km h-1, representing a 43% increase in
PIA relative to that measured at 1.5 km
h-1.
|
Inspiration can occur via two methods in V. exanthematicus; costal inhalation and gular pumping. Costal ventilation initially increased in response to treadmill exercise, but as treadmill speed increased to 1.5 and 2.0 km h-1, costal ventilation decreased as a result of a decrease in tidal volume but no alteration in breathing frequency (Fig. 3). Gular pumping was not observed in resting V. exanthematicus. Gular pumping increased in response to treadmill exercise, due to increases both in gular pump volume (up to 8.3±0.4 ml kg-1) and in gular pump frequency (up to 40.5±3.3 min-1). The combined effects of treadmill exercise on costal and gular minute ventilation resulted in an increase in total ventilation, oxygen consumption and carbon dioxide production as treadmill speed increased.
|
Maximum PC and
a occurred during the recovery
period, but the time course to peak responses differed. Maximal
PC was measured at 40 s
after exercise ceased, whereas maximal
a was measured 140 s after exercise
ceased (Fig. 4).
|
The effects of increased intra-abdominal pressure in resting lizards
Increasing PIA via infusion of
temperature-equilibrated saline increased central venous pressure
(PCV), diastolic right atrial pressure
(PRA), and heart rate, but did not significantly alter
a
(Table 1). Transmural pressure
of the post cava (PTRANS) was significantly reduced at
both double and triple PIA. PTRANS
became negative when PIA was doubled due to
PIA exceeding PCV, but remained
positive when PIA was tripled due to
PCV exceeding PIA. Negative
PTRANS (at double resting PIA)
corresponded with a 52% reduction in
PC, whereas no significant
alteration in
PC occurred
when PIA was tripled and PTRANS
remained positive (Fig. 5).
Increasing PIA significantly reduced inspired tidal volume
(VTI) and increased breathing frequency
(fb), resulting in no significant alteration in minute
ventilation (
E)
(Table 1).
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Discussion |
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Elevations in PIA during treadmill exercise have also
been measured in Iguana iguana
(Farmer and Hicks, 2000) and
are probably the result of the hypaxial musculature being continuously active
during exercise, serving a role both in lung ventilation and in lateral
bending of the trunk (Carrier,
1990
; Ritter,
1996
). In Iguana iguana, treadmill exercise increased
venous return at low speeds (1.0 km h-1), but significantly reduced
venous return while increasing PIA at high speeds
(Farmer and Hicks, 2000
). High
PIA and reduced venous return during exercise may have
broad hemodynamic ramifications, potentially limiting the increase in cardiac
output and maximal oxygen consumption induced by exercise. Indeed, the
23-fold increases in venous return measured during exercise in this
study are comparable with the 23-fold increases in systemic blood flow
measured during a similar exercise regime in the same species of lizard
(Wang et al., 1997
),
highlighting the interdependence of venous return and cardiac output.
The effects of elevated PIA on hemodynamics have been
studied in only one reptile (Farmer and
Hicks, 2000), and variable results have been reported in mammals.
Unlike mammals, reptiles do not possess a muscular diaphragm, so there is no
separation of the abdominal and thoracic compartments. However, despite the
presence of a muscular diaphragm in mammals, increases in
PIA do occur during inspiration due to descent of the
diaphragm and displacement of the abdominal viscera
(Decramer et al., 1984
;
Guyton and Adkins, 1954
;
Wexler et al., 1968
). A
PIA below 10 mmHg is considered clinically normal in
humans (Wittmann and Iskander,
2000
) and 812 mmHg is considered safe for laparoscopic
surgery, thus avoiding the serious hemodynamic complications that arise from
higher PIA (Ishizaki
et al., 1993
; Neudecker et
al., 2002
). Low PIA (<10 mmHg) and high
PIA (>20 mmHg) in combination with experimental
manipulations, such as hypervolemia, increase venous return and cardiac output
in anesthetized mammals (Kashtan et al.,
1981
; Richardson and Trinkle,
1976
). However, high PIA (>10 mmHg)
decreases inferior vena cava blood flow resulting in a decrease in venous
return (Barnes et al., 1985
;
Diamant et al., 1978
;
Ivankovich et al., 1975
;
Kashtan et al., 1981
;
Lynch et al., 1974
;
Richardson and Trinkle, 1976
).
A reduction in blood flow to the abdominal organs (renal, superior mesenteric
and celiac vasculatures) has also been demonstrated in response to elevated
PIA (Barnes et al.,
1985
; Caldwell and Ricotta,
1987
; Masey et al.,
1985
). At a PIA of 15 mmHg (a pressure
achieved during treadmill exercise in V. exanthematicus)
gastrointestinal blood flow was reduced by 2040% in anesthetised
neonatal lambs (Masey et al.,
1985
). Similar reductions in gastrointestinal blood flow were
found in anesthetised dogs at PIA between 20 and 40 mmHg
(Barnes et al., 1985
;
Caldwell and Ricotta,
1987
).
In mammals, blood flow in the inferior vena cava represents approximately
two thirds of total systemic venous return
(Kitano et al., 1999;
Scharf, 1995
). Alterations in
venous return have the potential to limit exercise performance because
systemic venous return and ventricular preload are major determinants of
cardiac output. Increases in PIA in anesthetized mammals
decrease cardiac output via decrements in stroke volume combined with
more variable changes in heart rate [decreased heart rate
(Masey et al., 1985
);
increased heart rate (Diamant et al.,
1978
; Ivankovich et al.,
1975
); no change in heart rate
(Barnes et al., 1985
)]. High
PIA of between 30 and 40 mmHg reduces cardiac output by
3040% in anesthetized mammals
(Barnes et al., 1985
;
Diamant et al., 1978
;
Lynch et al., 1974
) and the
degree of anesthesia may be responsible for the variability in heart rate
responses.
Venous return is dependent on central venous pressure
(PCV), right atrial pressure (PRA) and
venous resistance. PCV provides the upstream driving
pressure for venous return and is determined by blood volume, vascular tone
and the pressure within the tissues surrounding the small veins and venules
(capacitance vessels). PRA provides the backpressure
against venous return. Venous resistance is the hydraulic resistance of the
veins between the capacitance vessels (site of mean systemic resistance) and
the right atria. Thus, increases in PCV act to augment
venous return, while increases in PRA or venous resistance
act to decrease venous return. Large veins, such as the mammalian inferior
vena cava or the lizard post caval vein, behave like collapsible tubes in
which the cross-sectional area is largely a function of transmural pressure
(Katz et al., 1969;
Kresh and Noordergraaf, 1972
;
Moreno et al., 1970
). When
transmural pressure falls below zero, large alterations in vessel
cross-sectional area occur, causing partial or complete collapse of the vessel
and large increases in the viscous resistance to blood flow
(Badeer and Hicks, 1992
).
In resting V. exanthematicus, increasing PIA
significantly increased PRA. However, concurrent
increments in PCV resulted in no significant alteration in
the pressure gradient between the central venous circuit and the right atria
(Table 1). A twofold increase
in PIA increased PCV in resting
lizards; however, PIA exceeded PCV,
resulting in a negative PTRANS and a 52% reduction in
PC due to the collapse of
the post caval vein. The elevated PCV caused by a
threefold increase in PIA resulted in a significantly
reduced but, importantly, still positive PTRANS, thus
maintaining
PC. The high
PCV induced by a threefold increase in
PIA may be due to compression of the splanchnic veins and
movement of venous blood from the gastrointestinal capacitance vessels to the
central venous circuit. While a twofold increase in PIA
simulated the increase in PIA that occurred during
treadmill exercise, it is unclear whether threefold increases in
PIA are achieved during exercise, and these elevations in
PIA may only be physiologically relevant in certain
conditions, such as after consuming a large meal or in gravid females. While
high PCV during threefold increases in
PIA have been measured in this study, the mechanisms
underlying this increase are outside the scope of this study.
The hemodynamic responses to elevated PIA are the
result of complex interactions between PCV, venous
resistance and PRA. If the increase in
PIA exceeds PCV,
PTRANS becomes negative and post caval collapse will
occur, resulting in an increase in venous resistance and a decrease in venous
return. However, the effect of elevated PIA on the driving
gradient for venous return will be dependent on the interaction of
PCV and PRA. The complex interactions
of PIA, PCV, PRA
and PC have led to the use
of `abdominal vascular zone conditions' to describe the variable hemodynamic
responses to elevated PIA in mammals
(Kitano et al., 1999
;
Takata et al., 1990
). When
right atrial pressure exceeds PIA the abdominal
compartment acts as a capacitor, and increases in PIA
result in an increase in venous return in the inferior vena cava (abdominal
vascular zone 3). When PIA exceeds right atrial pressure,
the abdominal compartment acts as a Starling resistor, increases in
PIA collapse the inferior vena cava and decrease venous
return (abdominal vascular zone 2). The results of the current experiments are
consistent with the abdominal compartment acting as a Starling resistor in
lizards in response to twofold increases in PIA (induced
by either treadmill exercise or saline infusion), and as a capacitor during
threefold increases in PIA.
The relationship between venous resistance, PCV and
PRA is complicated even further during exercise due to the
increasing contributions of the skeletal muscle and respiratory pumps. During
exercise, skeletal muscle contractions compress venous vessels, forcing blood
centrally and supplementing venous return. The resulting decrement in
intramuscular venous pressure increases the arterialvenous pressure
gradient and aids arterial inflow into the muscle
(Madger, 1995;
Rowland, 2001
). Fluctuations
in intrathoracic and intra-abdominal pressures also affect venous return due
to their effects on the inferior vena cava.
In mammals, the vigorous inhalations associated with exercise distend the
inferior vena cava, supplementing venous return and cardiac output during
exercise (Rowland, 2001).
Collapse of the inferior vena cava due to elevated PIA
would limit the increase in venous return associated with increasingly
negative intra-thoracic pressures during vigorous breathing
(Amoore and Santamore, 1994
).
In V. exanthematicus, the phasic fluctuations in
PIA causes by ventilation and the tonically elevated
PIA induced by exercise had different effects on venous
return. Exhalation caused an increase, and inspiration caused a decrease, in
PIA and
PC
(Fig. 1). In contrast, exercise
was associated with tonically elevated PIA, which
suppressed
PC. The sudden
increase in
PC at the
cessation of exercise correlated with a decrease in PIA
(Fig. 2) and an increase in
venous return from the peripheral circulation. Concurrently, ventilation
increased during the recovery period (Fig.
3), thus increasing the supplementary action of expiration on
venous return. These results suggest that exercise-induced increases in
PIA reduce venous return to the heart and cause both a
pooling of blood in the peripheral circulation as well as an increase in
cardiac afterload. The combined effects of increasing cardiac afterload and
decreasing cardiac preload during exercise may act to decrease stroke volume
by increasing end-systolic volume and decreasing end-diastolic volume,
respectively. Stroke volume was not measured directly in this study, however,
arterial pulse pressure decreased during maximal exercise
(Fig. 2),suggesting a decrease
in stroke volume (assuming that arterial compliance was unchanged).
In V. exanthematicus, maximal heart rate was achieved at 1.0 km
h-1 (106.1±2.5 beats min-1). Comparable maximal
heart rates have been measured in response to treadmill exercise in V.
mertensi (rest 74±9; exercise 120±14 beats
min-1; Frappell et al.,
2002a) and V. exanthematicus (rest 45.5±3.6;
exercise 99.4±5.7 beats min-1;
Wang et al., 1997
); (rest 50
beats min-1, exercise 105110 beats min-1;
Gleeson et al., 1980
), despite
these studies recording higher resting heart rates than the present study
(rest 25.1±3.0 beats min-1). Further increments in treadmill
speed elicited no additional increase in heart rate in this or previous
studies (Gleeson et al., 1980
;
Wang et al., 1997
).
Progressive increments in treadmill speed also failed to elicit graded
increases in systemic blood flow (Wang et
al., 1997
) and venous return (present study) nor any increment in
stroke volume (Frappell et al.,
2002a
). Thus, in contrast to the graded respiratory response to
exercise in varanid lizards, the cardiovascular response may be `all or
nothing', with maximal cardiac output, systemic blood flow, heart rate and
venous return reached at relatively low exercise intensities. The `all or
nothing' response of
PC at
the three lowest treadmill speeds, combined with the maintenance of
O2 at the
highest treadmill speed (despite a decrease in
PC) may suggest that lung
perfusion may be in excess at low treadmill speeds. The maintenance of
O2 despite a
decrease in
PC may be the
result of alterations in cardiac or intrapulmonary shunting, decreases in
perfusion to areas of the lung with low ventilationperfusion ratios, or
may simply reflect a reduction in the over-perfusion of the lungs present at
lower treadmill speeds.
In contrast to the `all or nothing' cardiovascular response elicited by
exercise, the cardiovascular response to digestion in reptiles is graded,
showing progressive increases in heart rate, stroke volume and cardiac output
during the first 2448 h after feeding
(Hicks et al., 2000;
Secor et al., 2000
). Thus, the
cardiovascular response in varanid lizards, like the respiratory response,
appears to be state dependent and flexible, and not stereotyped as previously
suggested (Hicks et al.,
2000
). The conclusion of a previous study that the cardiovascular
response to exercise was graded and, therefore, similar to the graded
responses induced by digestion (Hicks et
al., 2000
) was probably the result of applying a linear regression
analysis to non-linear data. The original data presented
(Wang et al., 1997
) and
interpreted by Hicks et al.
(2000
) for heart rate and
relative change in cardiac output show no increase in either parameter at the
three highest treadmill speeds, thus demonstrating a curvilinear, rather than
a linear, response. Thus, the cardiovascular responses to exercise measured in
Wang et al. (1997
) and the
present study are in agreement, and together with the cardiovascular response
to digestion measured by Hicks et al.
(2000
) suggest that the
cardiovascular response in varanid lizards is plastic.
Resting respiratory parameters measured in this study (minute ventilation,
total tidal volume, breathing frequency,
O2,
CO2) were
comparable to those measured at rest in the same species
(Hicks et al., 2000
). In
contrast, studies on the same or closely related species reported fivefold
higher resting minute ventilations and fourfold higher breathing frequencies
resulting from shorter pre-exercise equilibration times
(Frappell et al., 2002a
;
Wang et al., 1997
). Treadmill
exercise increased total minute ventilation and costal breathing frequency by
24-fold and 10.5-fold, respectively, in this study, matching the magnitude of
responses shown previously in the same species
(Bennett and Hicks, 2001
), but
exceeding the magnitude of change reported in studies with elevated resting
minute ventilations and breathing frequencies (47-fold and 2.5-fold,
respectively; Frappell et al.,
2002a
; Wang et al.,
1997
). In the present study, minute ventilation, breathing
frequency and tidal volume were analyzed in terms of the contributions made by
costal ventilation and gular pumping. At rest, gular pumping did not occur and
costal ventilation was the sole contributor to total minute ventilation. As
treadmill speed increased, the frequency of gular pumping increased up to 40
min-1 and gular pump volume increased up to 8.3 ml kg-1.
The progressive increments both in gular pump volume and in frequency enabled
overall minute ventilation to increase in response to increasing treadmill
speed, despite the reduction in costal tidal volume and costal minute
ventilation measured at high treadmill speeds. These results support the
hypothesis that gular pumping supplements costal ventilation during exercise
and compensates for the speed-dependent axial constraint present during
high-speed running in lizard species that laterally undulate
(Owerkowicz et al., 1999
).
Reductions in costal tidal volume were also associated with elevated
PIA in resting V. exanthematicus
(Table 1). Minute ventilation
was maintained during elevated PIA due to an increase in
breathing frequency. These results suggest that costal tidal volume may be
limited during exercise due to the demands placed on the hypaxial musculature
and as a direct result of elevated PIA.
The recovery from exercise was marked with an increase in
PC, peaking 40 s after the
cessation of exercise, and an increase in
a, peaking at 140 s
(Fig. 4). The difference in the
time course of these two responses may be due to their underlying causes.
During recovery, PIA and its compressive effect on the
post caval vein decreases immediately. This sudden decrement allows blood
pooled in the peripheral circulation to return to the heart, thus causing an
increase in venous return. The movement of blood from the venous to the
arterial compartment increases effective blood volume, thus driving up
a. At the same time, pulse pressure
increases with no concurrent change in heart rate, suggesting that any
alterations in cardiac output during the recovery period are produced by
increments in stroke volume alone.
Exercise increased PIA up to 18.74±2.09 mmHg in V. exanthematicus. Similar PIA in resting mammals induce broad hemodynamic alterations including decrements in splanchnic blood flow, heart rate, stroke volume and cardiac output. In this study, increments in PIA suppress venous return from the hind limbs and tail, potentially limiting the increase in cardiac output that can be achieved during exercise. The limitation of venous return during exercise by elevated PIA demonstrates that despite circumventing the respiratory constraints present in iguanid lizards, cardiovascular constraints do still exist in varanid lizards. Understanding the integration of the cardiac, respiratory and skeletal muscle pumps during exercise, as well as the impact of elevated PIA, may provide insight into factors that determine cardiac output, maximal oxygen consumption and endurance performance in reptiles.
List of abbreviations
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Acknowledgments |
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References |
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Agostini, P. and Butler, J. (1991). Cardiopulmonary interactions in exercise. In Exercise: Pulmonary Physiology and Pathophysiology (ed. K. Wasserman), pp.221 -252. New York, USA: Marcel Dekker Inc.
Altimiras, J., Franklin, C. and Axelsson, M.
(1998). Relationship between blood pressure and heart rate in the
saltwater crocodile Crocodylus porosus. J. Exp. Biol.
201,2235
-2242.
Amoore, J. and Santamore, W. (1994). Venous collapse and the respiratory variability in systemic venous return. Cardiovasc. Res. 28,472 -479.[Medline]
Badeer, H. and Hicks, J. (1992). Hemodynamics of vascular `waterfall': is the analogy justified? Resp. Physiol. 87,205 -221.[CrossRef][Medline]
Barnes, G., Laine, G., Giam, P., Smith, E. and Granger, H. (1985). Cardiovascular responses to elevation of intra-abdominal hydrostatic pressure. Am. J. Physiol. 248,R208 -R213.[Medline]
Bennett, A. F. (1994). Exercise performance of reptiles. Adv. Vet. Sci. Comp. Med. 38B,113 -138.[Medline]
Bennett, A. F. and Hicks, J. (2001). Postprandial exercise: prioritization or additivity of the metabolic responses? J. Exp. Biol. 204,2127 -2132.[Medline]
Caldwell, C. and Ricotta, J. (1987). Changes in visceral blood flow with elevated intraabdominal pressure. J. Surg. Res. 43,14 -20.[Medline]
Carrier, D. R. (1987). The evolution of locomotor stamina in tetrapods: circumventing a mechanical constraint. Paleobiology 13,326 -341.
Carrier, D. R. (1990). Activity of the hypaxial muscles during walking in the lizard Iguana iguana. J. Exp. Biol. 152,453 -470.[Abstract]
Decramer, M., DeTroyer, A., Kelly, S., Zocchi, L. and Macklem,
P. T. (1984). Regional differences in abdominal pressure
swings in dogs. J. Appl. Physiol.
57,1682
-1687.
Diamant, M., Benumof, J. and Saidman, L. (1978). Hemodynamics of increased intra-abdominal pressure: interaction with hypovolemia and halothane anesthesia. Anesthesiology 48,23 -27.[Medline]
Farmer, C. G. and Hicks, J. W. (2000).
Circulatory impairment induced by exercise in the lizard Iguana iguana.J. Exp. Biol. 203,2691
-2697.
Frappell, P., Schultz, T. and Christain, K.
(2002a). Oxygen transfer during aerobic exercise in a varanid
lizard Varnus mertensi is limited by the circulation. J.
Exp. Biol. 205,2725
-2736.
Frappell, P., Schultz, T. and Christain, K. (2002b). The respiratory system in varanid lizards: determinants of O2 transfer. Comp. Biochem. Physiol. A 133,239 -258.
Gleeson, T., Mitchell, G. and Bennett, A. F. (1980). Cardiovascular responses to graded activity in the lizards Varanus and Iguana. Am. J. Physiol. 239,R174 -R179.[Medline]
Guyton, A. C. and Adkins, L. H. (1954). Quantitative aspects of the collapse factor in relation to venous return. Am. J. Physiol. 177,R523 -R527.
Hicks, J., Wang, T. and Bennett, A. F. (2000).
Patterns of cardiovascular and ventilatory response to elevated metabolic
states in the lizard Varanus exanthematicus. J. Exp.
Biol. 203,2437
-2445.
Hoppler, H. and Weibel, E. (1998). Limits for
oxygen and substrate transport in mammals. J. Exp.
Biol. 201,1051
-1064.
Ishizaki, Y., Bandai, Y., Shinomura, K., Abe, H., Ohtomo, Y. and Idezuki, Y. (1993). Safe intra-abdominal pressure of carbon dioxide pneumoperitoneum during laparoscopic surgery. Surgery 114,549 -554.[Medline]
Ivankovich, A., Miletich, D., Albrecht, R., Heyman, H. and Bonnnet, R. (1975). Cardiovascular effects of intraperitoneal insufflaion with carbon dioxide and nitrous oxide in the dog. Anesthesiology 42,281 -287.[Medline]
Kashtan, J., Green, J., Parsons, E. and Holcroft, J. (1981). Hemodynamic effect of increased abdominal pressure. J. Surg. Res. 30,249 -255.[Medline]
Katz, A., Chen, Y. and Moreno, A. (1969). Flow through a collapsible tube. Experimental analysis and mathematical model. Biophys. J. 9,1261 -1279.[Medline]
Kitano, Y., Takata, M., Sasaki, N., Zhang, Q., Yamamoto, S. and
Miyasaka, K. (1999). Influence of increased abdominal
pressure on steady-state cardiac performance. J. Appl.
Physiol. 86,1651
-1656.
Kresh, E. and Noordergraaf, A. (1972). Cross-sectional shape of collapsible tubes. Biophys. J. 12,274 -294.[Medline]
Lynch, F., Ochi, T., Scully, J., Williamson, M. and Dudgeon, D. (1974). Cardiovascular effects of increased intra-abdominal pressure in newborn piglets. J. Pediatr. Surg. 9,621 -626.[CrossRef][Medline]
Madger, S. (1995). Venous mechanics of
contracting gastrocnemius muscle and the muscle pump theory. J.
Appl. Physiol. 79,1930
-1935.
Masey, S., Koehler, R., Ruck, J., Pepple, J., Rogers, M. and Traystman, R. (1985). Effect of abdominal distension on central and regional hemodynamics in neonatal lambs. Pediatr. Res. 19,1244 -1249.[Abstract]
Mitchell, G., Gleeson, T. and Bennett, A. F. (1981). Pulmonary oxygen transport during activity in lizards. Resp. Physiol. 43,365 -375.[CrossRef][Medline]
Moreno, A., Katz, A., Gold, L. and Reddy, R. (1970). Mechanics of distension of dog veins and other very thin-walled tubular structures. Circ. Res. 27,1067 -1080.
Neudecker, J., Sauerland, S., Neugebauer, E., Bergamaschi, R., Bonjer, H. J., Cushieri, A., Fuchs, K. H., Jacobi, C. H., Jansen, F. W., Koivusalo, A. M. et al. (2002). The european association for endoscopic surgery clinical practice guideline on the pneumoperitoneum for laparoscopic surgery. Surg. Endosc. 16,1121 -1143.[CrossRef][Medline]
Owerkowicz, T., Farmer, C. G., Hicks, J. W. and Brainerd, E.
L. (1999). Contribution of gular pumping to lung ventilation
in monitor lizards. Science
284,1661
-1663.
Richardson, J. and Trinkle, J. (1976). Hemodynamic and respiratory alterations with increased intra-abdominal pressure. J. Surg. Res. 20,401 -404.[Medline]
Ritter, D. (1996). Axial muscle function during
lizard locomotion. J. Exp. Biol.
199,2499
-2510.
Rowland, T. (2001). The circulatory response to exercise: role of the peripheral pump. Int. J. Sports. Med. 22,558 -565.[CrossRef][Medline]
Saltin, B. (1985). Hemodynamic adaptations to exercise. Am. J. Cardiol. 55,42D -47D.[Medline]
Schaffner, F. (1998). The liver. In Biology of the Reptilia, vol.19 (ed. A. Gaunt), pp.485 -531. Ithaca, New York, USA: Society for the Study of Amphibians and Reptiles.
Scharf, S. (1995). The effect of decreased intrathoracic pressure on ventricular function. J. Sleep. Res. 4,53 -58.[Medline]
Secor, S., Hicks, J. and Bennett, A. (2000).
Ventilatory and cardiovascular responses of a python (Python molurus)
to exercise and digestion. J. Exp. Biol.
203,2447
-2454.
Takata, M., Wise, R. and Robotham, J. (1990).
Effects of abdominal pressure on venous return: abdominal vascular zone
conditions. J. Appl. Physiol.
69,1961
-1972.
Taylor, C. R. and Weibel, E. R. (1981). Design of the mammalian respiratory system. I. Problem and strategy. Resp. Physiol. 44,1 -10.[CrossRef][Medline]
Wagner, P. (1988). An integrated view of the determinants of maximal oxygen uptake. In Oxygen Transfer from Atmosphere to Tissues, vol. 227 (ed. M. Fedde), pp. 245-256. New York, USA: Plenum.
Wagner, P., Hoppeler, H. and Saltin, B. (1997). Determinants of maximal oxygen uptake. In The Lung, Scientific Foundations, vol. 2 (ed. P. Barnes), pp.2033 -2041. Philadelphia, USA: LippincottRaven.
Wang, T., Carrier, D. and Hicks, J. (1997).
Ventilation and gas exchange in lizards during treadmill exercise.
J. Exp. Biol. 200,2629
-2639.
Weibel, E., Taylor, C., Gehr, P., Hoppeler, H., Mathieu, O. and Maloiy, G. (1981). Design of the mammalian respiratory system. IX. Functional and structural limits for oxygen flow. Resp. Physiol. 44,151 -164.[CrossRef][Medline]
Weibel, E., Taylor, C. and Hoppeler, H. (1991). The concept of symmorphosis: a testable hypothesis of structurefunction relationship. Proc. Natl. Acad. Sci. USA 88,10357 -10361.[Abstract]
Wexler, L., Bergel, D. H., Gabe, I. T., Makin, G. S. and Mills, C. J. (1968). Velocity of blood flow in normal human vena cavae. Circ. Res. 23,349 -359.[Medline]
Wittmann, D. H. and Iskander, G. A. (2000). The compartment syndrome of the abdominal cavity: a state of the art review. J. Intestive Care Med. 15,201 -220.[CrossRef]