Venous tone and cardiac function in the South American rattlesnake Crotalus durissus: mean circulatory filling pressure during adrenergic stimulation in anaesthetised and fully recovered animals
1 Department of Zoophysiology, Institute of Biological Science, Aarhus
University, Denmark
2 Departamento de Zoologia, Centro de Aquicultura, UNESP, Rio Claro,
Sâo Paulo, Brazil
* Author for correspondence (e-mail: marianne.skals{at}biology.au.dk)
Accepted 9 August 2005
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Summary |
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VS decreased significantly when MCFP was lowered by
reducing blood volume in anaesthetised snakes, whereas increased MCFP through
infusion of blood (up to 3 ml kg-1) only led to a small rise in
VS. Thus, it seems that end-diastolic volume is not
affected by an elevated MCFP in rattlesnakes. To investigate adrenergic
regulation on venous tone, adrenaline as well as phenylephrine and
isoproterenol (- and ß-adrenergic agonists, respectively) were
infused as bolus injections (2 and 10 µg kg-1). Adrenaline and
phenylephrine caused large increases in MCFP and PCV,
whereas isoproterenol decreased both parameters. This was also the case in
fully recovered snakes. Therefore, adrenaline affects venous tone through both
- and ß-adrenergic receptors, but the
-adrenergic receptor
dominates at the dosages used in the present study. Injection of the nitric
oxide donor SNP caused a significant decrease in PCV and
MCFP. Thus, nitric oxide seems to affect venous tone.
Key words: reptile, Crotalus durissus, cardiovascular control, adrenergic regulation, venous tone, mean circulatory filling pressure, venous return
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Introduction |
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Venous tone, which reflects the tonic contraction of the venous blood
vessels, is a determining parameter for venous return and cardiac filling and
can be assessed as the central venous pressure (PCV)
during a brief cessation of blood flow from the heart
(Guyton, 1955;
Pang, 2001
). When cardiac
output has stopped, blood will be redistributed between the arterial and
venous system and pressures within the entire systemic circulation equalise
(Rothe, 1993
). This pressure,
defined as mean circulatory filling pressure (MCFP) by Guyton et al.
(1954
), is determined by blood
volume and compliance of the entire circulatory system. Importantly, MCFP
represents the pressure in the small venules and is the best available
estimate of the upstream pressure driving blood towards the heart (Guyton,
1955
,
1963
;
Rothe, 1993
). Thus, at a given
right atrial pressure, venous return is proportional to MCFP
(Tabrizchi and Pang, 1992
). An
increase in MCFP can be induced by increasing sympathetic tone or by
increasing total blood volume. Conversely, a decrease in MCFP can be induced
by decreasing sympathetic tone or decreasing total blood volume
(Pang, 2000
). By altering
blood volume and, thereby, changing MCFP, it is possible to evaluate the
effect of a changed venous tone on stroke volume.
Changes in venous return through blood volume alterations markedly affect
stroke volume in anaesthetised turtles and that venous return was
significantly affected by adrenergic stimulation (S. Warburton, D. C. Jackson,
V. T. Bobb and T. Wang, unpublished data). However, it is not known whether
this response is mediated by - or ß-adrenergic receptors.
Therefore, the present study was undertaken to investigate the role of these
receptors on venous tone in anaesthetised rattlesnakes. Also, the effect of
changed venous tone on cardiac filling was investigated. This was accomplished
by the use of specific adrenergic agonists and antagonists and by blood
infusions and withdrawals. Because anaesthetics may have depressive effects on
the cardiovascular system, we also measured PCV and MCFP
during adrenergic stimulation in fully recovered snakes.
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Materials and methods |
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Surgery and instrumentation
Anaesthetised snakes
Twelve snakes were anaesthetised by an injection of 30 mg kg-1
pentobarbital (Mebumal, Sygehusapotekerne, Denmark) into the red muscle in the
tail. When all reflexes had disappeared, the animals were tracheostemised and
artificially ventilated at 4 breaths min-1 and a tidal volume of 35
ml kg-1 using a Harvard Apparatus mechanical ventilator (Cambridge,
MA, USA).
A 5 cm ventral incision was made to expose the heart and major vessels. To measure systemic arterial blood pressure (Psys), the vertebral artery was occlusively cannulated with a PE50 catheter containing heparinised saline (50 IU ml-1). To measure central venous blood pressure (PCV) a small vein running to the jugular vein was occlusively cannulated with a PE50 or PE90 catheter containing heparinised saline, and the tip of the catether was advanced into the sinus venosus. Both catethers were connected to Baxter Edward disposable pressure transducers (model PX600; Irvine, CA, USA) and the signals were amplified using an in-house-built preamplifier. Both transducers were positioned at the level of the heart of the animal and calibrated daily against a static water column.
For measurements of systemic and pulmonary blood flows, transit-time ultrasonic blood flow probes (2R or 2S; Transonic System, Inc., Ithaca, NY, USA) were placed around the left aortic arch (LAo) and the pulmonary artery. Flow probes were connected to a Transonic dual-channel blood flow meter (T206). Acoustic gel was infused around the flow probes to enhance the signal.
For measurements of MCFP, a 0.51 cm incision was made in the pericardium and a suture (1-0 silk) was placed around the common outflow tract of the heart, which included both aortic arches and the common pulmonary artery. The pericardium was subsequently closed with one or two sutures (4-0 silk).
Signals from the pressure transducers and flow meters were recorded with a Biopac MP100 data acquisition system (Biopac System, Inc., Goleta, CA, USA).
Recovered snakes
Eight snakes were anaesthetised with CO2
(Wang et al., 1993) and given
a local injection of lidocain ventrally above the heart. In all animals, a 5
cm incision was made ventrally to expose the heart and major vessels, and
catheters were inserted to measure Psys and
PCV as described for the anaesthetised snakes. In four
snakes, a 0.51 cm incision was made in the pericardium, and a vascular
occluder (In Vivo Metric, Healdsburg, CA, USA) was placed around the common
outflow tract of the heart. The pericardium was subsequently closed with one
or two sutures (4-0 silk). The animals were allowed to recover for 24 h after
surgery before measurements started.
Experimental protocols
Anaesthetised snakes
The 12 anaesthetised animals were divided into two groups with two
different experimental protocols. In protocol 1, the adrenergic control of the
venous system was investigated by injection of adrenaline and specific
- and ß-agonists (phenylephrine and isoproterenol, respectively).
In this series of experiments, blood volume alterations were also made to
investigate the effect on PCV, MCFP and blood flows. The
second protocol was designed to characterise the effect of blood volume
alterations after
-adrenergic receptor blockade by injection of
phentolamine, an
-antagonist. The effect of NO on the venous system was
also investigated in the second series by injection of the NO donor sodium
nitroprusside (SNP).
When all haemodynamic variables had stabilised following surgery, baseline values were recorded. Then, arterial outflows from the heart were occluded by tightening the suture around the common outflow tract, until both PCV and Psys had stabilised. This normally occurred within 35 s, and the stable and elevated PCV during the occlusion was taken to indicate MCFP. Blood pressures and flows returned to baseline values within minutes after releasing the occlusion, and drugs were now administered in the manner described below for the two protocols. In all cases, MCFP was measured when the effect of the drug on Psys was maximal. All haemodynamic variables were allowed to return to baseline values, and MCFP was measured before each subsequent injection. Repeated measurements of MCFP were performed at the beginning of each experiment to show that repeated occlusions of blood flow did not affect haemodynamic variables.
When haemodynamic variables had returned to baseline values after the last injection, MCFP was recorded and blood was infused or withdrawn, as described for the two protocols below, and MCFP was measured immediately after each volume change. Each infusion or withdrawal was completed as quickly as possible. Infused blood came from a donor snake and the order of infusion or withdrawal was randomised. All injections were given through the systemic catheter, and the catheter was flushed with heparinised saline immediately following all injections.
Protocol 1. Two dosages of adrenaline (2 µg kg-1 and 10 µg kg-1), two dosages of phenylephrine (2 µg kg-1 and 10 µg kg-1) and two dosages of isoproterenol (2 µg kg-1 and 10 µg kg-1) were injected. Blood was infused in steps of 9±0.5, 16.8±0.9 and 30.5±1.3 ml kg-1. Blood was withdrawn in steps of 8.6±0.5, 14.8±0.5 and 23.1±1.1 ml kg-1.
Protocol 2. Adrenaline (10 µg kg-1), two dosages of SNP (2.5 µg kg-1 and 25 µg kg-1), phentolamine (2 mg kg-1) and adrenaline (2 µl kg-1) were injected. Blood was infused in steps of 8±0.4, 15.7±0.7 and 29.6±0.4 ml kg-1. Blood was withdrawn in steps of 8.4±0.8, 16.2±1.1 and 23.2±0.3 ml kg-1. Each drug was dissolved in saline (0.9% w/v) and was administered in 1 ml kg-1 aliquots.
Recovered snakes
When the snakes had remained undisturbed for 2 h andexhibited stable
haemodynamic variables, baseline values were recorded and adrenergic agonists
were administered as described for protocol 1 for anaesthetised snakes. In the
four animals with vascular occluders, MCFP was measured during rest and when
the effects of the various drugs on Psys were maximal by
inflating the occluder. Haemodynamic variables normally returned to control
values within 60 s after releasing the occlusion. Manipulation of blood volume
and administration of SNP were not performed in the recovered snakes.
Calculation of cardiac output, heart rate, stroke volume and vascular resistance
Systemic cardiac output
(sys) can be calculated as
3.3 times the flow in the LAo (Galli et al.,
2005a
,b
).
Since rattlesnakes only have a single pulmonary artery, pulmonary cardiac
output (
pul) can be
measured using a single flowprobe. Total cardiac output
(
tot) was calculated as
sys+
pul.
Heart rate (fH) was derived from the flow trace of the
LAo, and total stroke volume (VStot; systemic
and pulmonary) was calculated as
tot/fH.
Systemic vascular resistance (Rsys) was calculated from
the difference between arterial and central venous blood pressures divided by
the systemic cardiac output
[Rsys=(PsysPCV)/
sys].
Venous resistance (Rven) was calculated from the
difference between MCFP and PCV divided by systemic
cardiac output
[Rven=(MCFPPCV)/
sys;
for details on venous resistance see
Guyton et al., 1952
; Pang,
2000
,
2001
].
Data analysis and statistics
All data are presented as means ± S.E.M. Blood pressure
and flow recordings were analysed using AcqKnowledge data analysis software
(version 3.7.1; Biopac, Goleta, CA, USA). Effects on haemodynamic variables
after injections of the various drugs were tested using a paired
t-test. Differences between the anaesthetised and recovered snakes
were tested using a t-test. Effects on haemodynamic variables after
infusion and withdrawal of blood within each protocol were tested using a
one-way analysis of variance (ANOVA) for repeated measurements, followed by a
Dunnet's post hoc test to identify values that were significantly
different from control values. Differences in MCFP during blood volume
alterations between the two protocols were tested using a two-way ANOVA. A
limit for significance of P<0.05 was applied.
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Results |
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Injection of the ß-agonist isoproterenol caused significant decreases
in Psys, PCV, MCFP,
Rsys and Rven. Thus, isoproterenol
seemed to cause an overall relaxation of both the arterial system and the
venous system. Furthermore, isoproterenol caused significant increases in
fH and systemic blood flow and a decrease in pulmonary
blood flow. As a consequence,
pul/
sys
decreased.
Effects of nitric oxide
The effects of injecting the NO donor SNP are shown in
Table 1. SNP caused a
significant decrease in Psys, PCV,
MCFP and a decrease in both Rsys and
Rven, reflecting an overall relaxation of the vasculature.
Regarding blood flows, SNP caused no changes in
sys but did affect
pul, resulting in a
decrease in
tot and
VStot.
|
MCFP at blood volume alterations
The effects of manipulating blood volume by withdrawal and infusion of
blood are shown in Figs 4,
5,
6 for untreated animals (black
symbols) and the group of snakes where the -adrenergic receptors had
been blocked by phentolamine (grey symbols). Before treatment with
phentolamine, both groups responded similarly to adrenaline
(Table 2; Figs
2,
3), and the efficacy of the
-adrenergic blockade was evident from the lack of vasoconstriction
following infusion of adrenaline (Table
2).
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As shown in Fig. 4, MCFP
increased significantly for both the untreated and the -blocked snakes
when blood volume was elevated by blood infusion and tended to decrease when
blood was withdrawn. This presentation of MCFP as a function of blood volume
represents `capacitance curves', and the inverse slope of the capacitance
curve represents the overall compliance (C) of the vasculature, under
the assumption that there is no transcapillary fluid movement during
manipulation of blood volume (Samar and
Coleman, 1978
). In the present study, compliance was estimated to
be 3.3±0.3 and 3.9±0.7 ml kg-1
cmH2O-1 for untreated and
-blocked snakes,
respectively. Unstressed blood volume (USBV), the blood volume at zero
distending pressure, can also be estimated from the capacitance curves by
extrapolating the curve to a MCFP value of zero
(Samar and Coleman, 1978
;
Rothe, 1993
;
Fig. 4). We did not measure
total blood volume, but using the value of 54 ml kg-1 measured on
the closely related Crotalus viridis
(Smits and Lillywhite, 1984
),
we estimate USBV to be 20.7±1.8 and 18.3±7.1 ml kg-1
for the untreated and
-blocked snakes, respectively
(Fig. 4). There were no
significant differences between C and USBV between the two groups;
i.e. untreated and
-blocked snakes.
Figs 5,
6 show the effect of changing
blood volume on the various haemodynamic parameters in untreated snakes (black
symbols), where the haemodynamic variables are presented as a function of MCFP
at each blood volume. In these snakes, Psys,
PCV,
pul,
sys,
tot,
VSpul, VSsys and
VStot were significantly affected by MCFP.
Increased MCFP by volume loading did not lead to a significant rise in
or VS, but a
lowering of MCFP by blood withdrawal generally resulted in a decline of
and VS. Blood
volume did not affect fH and Rven, but
there was tendency of Rsys to increase in response to low
blood volume.
The effects of phentolamine at normal blood volume are listed in
Table 2, and the relationships
between haemodynamic variables and MCFP, obtained after manipulation of blood
volume, are also included in Figs
5,
6 (grey symbols). The group of
snakes that received -blockade had higher
sys and
VSsys than the group of untreated snakes; as a
consequence, these snakes had significantly higher
pul/
sys
than untreated snakes. At normal blood volume, the snakes responded to
phentolamine by reductions in Psys and
Rsys, but these changes were not statistically significant
(Table 2). During the
subsequent manipulation of blood volume, the phentolamine-treated snakes
responded qualitatively similarly to the untreated snakes, but
sys and
tot as well as
VSsys and VStot
remained elevated at all MCFPs. As a major difference, the
phentolamine-treated snakes had significantly lower Rsys
and Rven, and there was no compensatory increase in
Rsys during volume depletion of the
-blocked
snakes.
Recovered snakes
Measurements of MCFP before and after injections of adrenergic agonists
from one animal are shown in Fig.
7. The three other animals with vascular occluders responded
similarly. Blood pressures and fH for the two groups of
snakes with and without vascular occluders are illustrated in
Fig. 8, where the left
hand-panel (Fig. 8AD)
shows data from snakes with a vascular occluder, whereas results from the
animals without an occluder are shown in the right-hand panel
(Fig. 8EG). Baseline
values for heart rates and blood pressures were similar in the two groups, and
they responded similarly to adrenergic agonists, although the group without a
vascular occluder generally showed more pronounced responses. As in the
anaesthetised snakes, adrenaline caused a marked rise in
Psys, PCV and MCFP, which was mirrored
after injection of phenylephrine, while isoproterenol caused a decrease in
Psys and a rise in fH.
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Discussion |
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The haemodynamic variables of the anaesthetised rattlesnakes in our study
were similar to those reported previously on the same species using
pentobarbital as anaesthetic (Galli et al.,
2005a,b
).
Anaesthetised snakes had higher Psys and
fH than fully recovered snakes, and it is likely that
anaesthesia lowers parasympathetic tone and increases sympathetic tone as in
turtles (Crossley et al.,
1998
). However, PCV and MCFP were not
significantly affected by anaesthesia in rattlesnakes.
Measurements of MCFP
In rattlesnakes, PCV and Psys
usually stabilised at equal values within 35 s after occlusion, and
PCV at that time was taken to indicate MCFP. It is
possible that vascular tone changed shortly upon occlusion in response to the
lowered arterial blood pressure and ischemia of vascular beds, and such
compensatory mechanisms could affect our estimation of MCFP
(Guyton, 1963;
Pang, 2001
). Compensatory
mechanisms are rapidly activated in mammals, which is evident from a rise in
PCV after approximately 10 s of occlusion
(Guyton, 1963
;
Rothe and Dress, 1976
;
Hainsworth, 1986
), and trout
also appear to have fast compensatory responses
(Sandblom and Axelson, 2005
).
In our study, however, there was no rise in PCV within 35
s of occlusion, indicating that compensatory reflexes were not yet activated
and that our assessment of MCFP is valid.
After infusion of adrenaline and phenylephrine, the marked rise in resistance often delayed the equilibration between systemic and venous pressures. In these instances, PCV after no more than 40 s of occlusion was taken to indicate MCFP, although PCV and Psys were not equal. However, given that the venous compliance is approximately six times higher than the arterial compliance in this species (estimated from the decline in Psys relative to the rise in PCV during occlusion; Psys declined from 49.0±4.6 to 11.0±1.1 cm H2O (1 cm H2O=0.098 kPa), while PCV increased from 3.3±0.4 to 9.5±1.0 cm H2O), the lack of complete equilibration would only have minor effects on the estimated MCFP.
It was necessary to open the pericardium to place the occluder for measurement of MCFP. This could influence haemodynamic variables, so we determined Psys, PCV and fH in a group of recovered snakes without a vascular occluder and an intact pericardium. At rest and when undisturbed, both groups had similar blood pressures and heart rates, but, after injection of the various adrenergic drugs, the group without a vascular occluder exhibited larger blood pressure responses.
Adrenergic effects on blood pressures
Adrenaline increased Psys, PCV and
MCFP in both anaesthetised and recovered snakes, reflecting a marked rise in
overall vascular tone, and elicited a small tachycardia. Similar responses
have been reported in recovered rats and fish
(Trippodo, 1981;
Zhang et al., 1998
). The
-agonist phenylephrine elicited similar, albeit less pronounced,
responses without affecting fH. In recovered dogs,
phenylephrine caused large changes in Psys but had little
effect on PCV (Bennett
et al., 1984
). The smaller response to phenylephrine compared with
adrenaline in rattlesnakes could be due to a lower
-receptor affinity
of phenylephrine relative to adrenaline. Generally, isoproterenol elicited
opposite responses and was associated with a fall in Psys,
PCV and MCFP. Therefore, the constriction of the arterial
and venous vasculature in response to adrenaline is primarily mediated by
-adrenergic receptors, which is consistent with previous studies on the
arterial vasculature of other reptiles
(Nilsson, 1983
;
Overgaard et al., 2002
). Our
results clearly show that activation of ß-receptors can decrease
PCV and MCFP through dilatation of the venous system, and
ß-receptors in the veins may contribute to regulating the venous system
in rattlesnakes. Isoproterenol, however, does not significantly affect
PCV or MCFP in dogs
(Rothe et al., 1989
).
The pressure gradient for venous return and its effect on stroke volume during adrenergic stimulation
In untreated anaesthetised snakes, the pressure gradient of venous flow
(MCFPPCV) was 6.2 cm H2O and increased
to 10.1 cm H2O after the high dose of adrenaline. Surprisingly,
VStot did not increase in response to the
higher pressure gradient for venous return and the higher filling pressure
(PCV) but actually tended to decrease from 2.0±0.4
to 1.6±0.1 ml kg-1. VStot,
the difference between end-diastolic and end-systolic volumes, is determined
by cardiac filling, contractility and afterload (Psys).
Adrenaline is expected to increase contractility, but also increased afterload
and could have increased end-systolic volume. The effects of adrenaline on
VStot in rattlesnakes differ from those seen in
frogs and turtles, where VStot increases (S.
Warburton, D. C. Jackson, V. T. Bobb and T. Wang, unpublished data). This rise
in VStot in frogs and turtles was ascribed to
an increased cardiac filling as MCFP rose after adrenaline. In fish,
administration of adrenaline did not significantly affect stroke volume
(Zhang et al., 1998).
VStot did not change after phenylephrine or
isoproterenol despite an increased and decreased pressure gradient,
respectively (Figs 2,
3). Contractility is unlikely
to have been affected by phenylephrine, but, as afterload and
Rven increased, it seems that the unchanged
VStot after -adrenergic stimulation
results from a balance between venous constriction and higher afterload. An
increase in Rven in response to
-adrenergic
stimulation has also been reported for anaesthetised dogs
(Imai et al., 1978
). In our
study, isoproterenol reduced afterload and venous resistance, which would be
expected to decrease end-systolic volume and to increase end-diastolic volume,
respectively. These effects would be enhanced by ß-adrenergic stimulation
of contractility. However, VStot was not
affected by isoproterenol in rattlesnakes, which may be due to shorter filling
time as fH increased. In anaesthetised dogs,
administration of isoproterenol and noradrenaline increased venous return by
decreasing venous resistance through stimulation of ß-receptors
(Imai et al., 1978
).
The marked effects of the various adrenergic drugs on MCFP and
Rven in rattlesnakes show that this species has a strong
adrenergic regulation of the venous system. This is consistent with previous
studies on isolated central veins from the ratsnake, Elaphe obsolete,
which contract in response to adrenaline
(Conklin et al., 1996). Also,
Donald and Lillywhite (1988
)
showed dense innervation of the central venous vasculature in Elaphe.
Although an increased venous tone did not increase VS in
untreated conditions in this species, it is likely that an increased
sympathetic activity could exert strong influence on venous return and,
therefore, may mediate an increased cardiac output under conditions such as
exercise, digestion or increased temperature where metabolism is elevated.
MCFP and blood volume changes in anaesthetised snakes
Neither VS nor
increased when blood volume was raised, which indicates that end-diastolic
volume is maximal at normal blood volume. Furthermore, VS
may not have been affected because PCV increased as much
as MCFP during volume loading, so that the pressure gradient for venous flow
was virtually unchanged. Decreasing blood volume, on the other hand, markedly
reduced VS, which correlated with a substantial decrease
in MCFP and a much lower pressure gradient for venous flow. Thus, as shown in
frogs, turtles and mammals (Guyton,
1955
; S. Warburton, D. C. Jackson, V. T. Bobb and T. Wang,
unpublished data), there is a clear relationship between MCFP and cardiac
filling and VS in rattlesnakes.
In rattlesnakes, blood withdrawal was accompanied by a rise in
Rsys, as previously observed in turtles and frogs (S.
Warburton, D. C. Jackson, V. T. Bobb and T. Wang, unpublished data). To
investigate whether this response was mediated by -adrenergic
stimulation, blood volume was altered in another group of snakes following
-blockade with phentolamine. Before
-adrenergic blockade, this
group of snakes had higher VStot and
tot compared with the
untreated group (compare Table
2 with values given in Fig.
3A,D), but overall they exhibited similar changes in
PCV, MCFP and VStot in
response to changes in blood volume (Figs
4,
5B,
6C). However, the rise in
Rsys in response to volume depletion was fully abolished
after
-adrenergic blockade, suggesting an increased sympathetic tone in
response to lowered blood pressure and volume.
Compliance and unstressed blood volume
The measurements of MCFP at the various blood volumes also allow for an
estimation of unstressed blood volume (USBV), vascular compliance (C)
and stressed blood volume (SBV) as the difference between total blood volume
and USBV. In doing so, we assumed that there was no net fluid movement across
the capillary wall during blood volume changes and we used the total blood
volume of 54 ml kg-1, which has been determined in Crotalus
viridis (Smits and Lillywhite,
1984). Blood was infused and withdrawn as fast as possible,
leaving the animals hypo- and hypervolemic for as short a time as possible,
and MCFP was always measured immediately after blood volume alteration to
avoid compensatory responses.
USBV is the volume required to fill the circulatory system until a
transmural pressure of zero and is accordingly considered to be
haemodynamically inactive, whereas SBV is haemodynamically active (Pang,
2000,
2001
). USBV is determined by
the capacity and activity of the smooth muscle cells surrounding the blood
vessels, and an increased vascular tone translocates blood from USBV to SBV
(Pang, 2001
). We estimated
USBV to be 20.7±1.8 ml kg-1 and 18.3±7.1 ml
kg-1 for the untreated and
-blocked snakes, respectively.
Compliance is a measure of vascular elasticity and is defined as a change in
volume relative to a change in transmural pressure
(Rothe, 1993
;
Pang, 2001
). In rattlesnakes,
C was estimated to be 3.3±0.3 ml kg-1
cmH2O-1 for the untreated snakes and 3.9±0.7 ml
kg-1 cmH2O-1 for the
-blocked snakes.
These estimates are similar to those determined in trout and two species of
anurans (Bufo marinus and Rana catesbeiana). In recovered
trout, USBV and C are 18.3±0.7 ml kg-1 and
3.0±0.2 ml kg-1 mmHg-1, respectively
(Zhang et al., 1998
), and
another study determined C in trout to be 2.8±0.3 ml
kg-1 mmHg-1
(Minerick et al., 2003
). In
recovered Bufo, USBV and C are 2.5 ml kg-1 and
3.7 ml kg-1 mmHg-1, and in recovered Rana, USBV
and C are 14.2 ml kg-1 and 2.2 ml kg-1
mmHg-1, respectively (Hoagland,
1997
).
Neither compliance nor unstressed volume were significantly affected by
-blockade in rattlesnakes. Similarly, compliance and unstressed volume
were not affected by phentolamine in trout, but there were small rises in both
parameters after infusion of another
-antagonist, prasozin
(Zhang et al., 1998
).
The effect of NO on the venous system
To investigate the role of nitric oxide (NO) on the venous circulation, the
NO donor SNP was injected. It is well established that SNP reduces systemic
resistance in reptiles (Crossley et al.,
2000; Galli et al.,
2005a
; Skovgaard et al., in
press
) and dilates central veins from Elaphe in vitro
(Conklin et al., 1996
). The
effect of NO on the venous circulation of reptiles, however, has not been
investigated in vivo. In rattlesnakes, SNP decreased
Psys, Rsys and
VStot as previously shown in this species
(Galli et al., 2005a
) and
caused marked decreases in PCV and MCFP, which indicate
that NO has a marked effect on the veins in this species. In trout, injection
of SNP had no effect on either PCV or
VS and only slightly decreased MCFP
(Olson et al., 1997
), whereas
in toads, SNP caused dilatation of the central veins
(Broughton and Donald, 2005
).
In rattlesnakes, MCFP decreased proportionally more than
PCV, which led to a decreased venous return, reflected in
a significant decreased total VS when the low dose of SNP
was injected.
Summary
Adrenaline, phenylephrine and isoproterenol significantly affected venous
tone, reflected as a change in MCFP, in both anaesthetised and fully recovered
rattlesnakes. Since phenylephrine showed similar responses as adrenaline, we
conclude that sympathetic responses are mediated though -receptors in
rattlesnakes. Stimulation of ß-receptors with isoproterenol decreased
venous tone. Since SNP decreased PCV and MCFP, nitric
oxide seems to regulate venous tone in anaesthetised snakes. When venous
return was increased by elevating blood volume, there was only a small rise in
VS, which indicates that end-diastolic volume is maximal
during normal conditions. However, venous return clearly affected
VS when MCFP was reduced through volume depletion. Since
blocking
-receptors with phentolamine did not markedly affect MCFP,
USBV or C, rattlesnake did not appear to have a significant
-adrenergic tone during resting conditions.
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Acknowledgments |
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References |
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