(Circulation. 1995;91:1135-1142.)
© 1995 American Heart Association, Inc.
Articles |
Opposing Effects of Plasma Epinephrine and Norepinephrine on Coronary Thrombosis In Vivo
Correspondence to Huabao Lin, PhD, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216-4505.
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Abstract |
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Background It is well known that plasma catecholamines and myocardial infarction have a close relation and that coronary artery thrombosis is a major cause of myocardial infarction. In addition, epinephrine is known to be a prothrombogenic agent in vivo. However, the role of the other major circulating catecholamine, norepinephrine, in the development of coronary thrombosis is somewhat uncertain, although the role of norepinephrine is often considered analogous to the role of epinephrine. Therefore, the present study was designed to investigate the effect of norepinephrine and its interaction with epinephrine on coronary thrombosis.
Methods and Results To compare the effects of epinephrine and norepinephrine on coronary thrombosis, we analyzed the frequency of cyclic blood flow reductions (CFRs) in an anesthetized canine model of coronary thrombosis (n=25). Three experiments were used in the present study. In the first experiment with epinephrine infusion, plasma epinephrine was elevated from 0.46±0.25 to 27.7±1.85 nmol/L. The frequency of CFRs increased by more than 60%, from 7.1±0.5 to 11.5±0.7 in 40 minutes (P<.01). The second experiment included three experimental periods: control, norepinephrine infusion, and norepinephrine infusion plus epinephrine infusion. Norepinephrine was infused to raise plasma norepinephrine from 1.3±0.2 to 32.4±4.3 nmol/L. The frequency of CFRs in the dogs was markedly reduced, from 7.89±0.42 to 2.41±1.08 in 40 minutes (P<.01), whereas arterial pressure was elevated from 88±3 to 118±5 mm Hg (P<.01). However, when epinephrine infusion was added to the norepinephrine infusion, the frequency of CFRs increased from 2.41±1.08 to 7.74±1.12 in 40 minutes (P<.01). In the third experiment, a servocontrol device was used during the norepinephrine infusion to prevent rises in coronary arterial pressure. As a result of the norepinephrine infusion, the frequency of CFRs was reduced from 7.47±0.71 to 0.83±0.65 in 40 minutes (P<.01), even though the coronary arterial pressure was not altered.
Conclusions The present study demonstrated that infusion of epinephrine stimulated coronary artery thrombosis, whereas infusion of norepinephrine inhibited coronary artery thrombosis. In addition, the inhibitory effect of norepinephrine on coronary thrombosis is independent of increases in coronary arterial pressure. Therefore, the present findings suggest that epinephrine and norepinephrine have opposing effects on coronary thrombosis in dogs.
Key Words: catecholamines • thrombosis • coronary disease • circulation • platelets
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Introduction |
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Much evidence from previous studies has revealed a close relation between plasma catecholamines and myocardial infarction.1 2 3 4 Since coronary artery thrombosis is widely accepted as a major cause of myocardial infarction,5 6 7 the effect of catecholamines on thrombus formation may play a central role in this relation. It is well known that epinephrine is a stimulatory factor for platelet aggregation in vitro and a prothrombogenic agent for artery thrombosis in vivo. The stimulatory effect of epinephrine on platelet functions has been linked to activation of
2-adrenoceptor in the membrane of the
platelets, since the effect can be blocked by yohimbine, a specific
antagonist of 2-adrenoceptor.8 9 In
addition, activation of 2-adrenoceptor reduces platelet
cAMP and increases intracellular calcium concentration, and both are
known to be associated with platelet activation.10 11
In
several in vitro studies, epinephrine has been found to activate
platelet aggregation in the range of 0.1 to 10
µmol/L.10 12 13 14 Under
in vivo conditions, epinephrine
per se may not act as an aggregating agent because of its relatively
low plasma concentration but it may contribute to activation of
platelets through its synergistic action with other agonists. Some
studies reported that epinephrine potentiated the platelet aggregation
induced by ADP, collagen, serotonin, thrombin, and
arachidonate.15 16 17 Therefore, plasma
epinephrine does not
need to exceed the level that is believed to have a direct stimulatory
effect on platelets before it contributes significantly to the onset of
coronary thrombosis.16
Despite the fact that plasma norepinephrine concentration is usually
much greater than that of epinephrine under most
conditions,18 19 20 many studies have
focused on the action
of epinephrine rather than norepinephrine at the onset of coronary
thrombosis. Previous studies demonstrated that epinephrine and
norepinephrine both have a high affinity for
2-adrenoceptors of platelets21 and can
inhibit activation of the platelet adenylate cyclase and elevation of
cytosolic cAMP by prostacyclin.11 In addition,
norepinephrine in vitro also has a stimulatory effect similar to that
of epinephrine on platelet aggregation through activation of
2-adrenoceptor,21 22 although its
potency
is considered less than that of epinephrine.21 Therefore,
norepinephrine undoubtedly may play a significant role in platelet
function and coronary artery thrombosis. Yet the role of norepinephrine
in the development of coronary artery thrombosis has not been well
described and is often considered analogous to the role of
epinephrine.21 22 Norepinephrine and epinephrine have
been
known to play very important roles in the regulation of many
physiological functions, and the interactive effects between them can
be synergistic, additive, and even opposite for many of these
functions. Although much in vitro data indicated that norepinephrine
and epinephrine have a similar effect on platelet aggregation, it is
premature to conclude that they can affect coronary artery thrombosis
in the same way under physiological and pathological conditions. In
addition, the disparate effects of norepinephrine and epinephrine on
blood pressure and other physiological functions may have complex
indirect influences on coronary thrombosis. Therefore, the present
study was designed to investigate the effect of norepinephrine and its
interaction with epinephrine on coronary thrombosis in an animal model
in which blood pressure in the coronary artery under study could be
servocontrolled.
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Methods |
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The experiments were performed on mongrel dogs of either sex (n=25) from the Research Animal Facilities of the University of Mississippi Medical Center. The dogs were housed in the animal facilities before use and fed a standard laboratory diet. The food was removed from their cages 15 hours before surgery, but the dogs were given free access to water. The dogs initially were sedated with 10 mg IM acepromazine maleate and were anesthetized 10 minutes later with approximately 30 mg/kg IV sodium pentobarbital.
Surgical Procedure and Experimental Measurements
The surgical
procedure and experimental measurements in the
present experiment have been described previously in
detail.23 Briefly, we used a canine model with a stenosed
coronary artery and damaged endothelium. This model originally was
developed by Folts et al.24 The frequency of cyclic blood
flow reductions (CFRs) resulting from thrombus formation in the artery
was analyzed. The heart was exposed by means of a left thoracotomy and
was suspended in a pericardial cradle. A catheter was inserted into the
left atrium through the left auricle for catecholamine or saline
infusion. A coronary artery (either the circumflex or left anterior
descending coronary artery) was gently isolated. An electromagnetic
flowmeter (model FM-501, Carolina Medical Electronics) was used to
measure coronary blood flow. A section of the coronary artery distal to
the probe was compressed firmly to damage the endothelium, and a
polished Plexiglas constrictor was placed around the damaged section of
the vessel. The constrictors were 
3 to 4 mm long and had various
internal diameters. The size of the constrictor was selected for each
dog individually to produce a critical stenosis in the circumflex
artery without reducing the resting flow. This maneuver abolished any
increase in flow in response to the release of an upstream complete
occlusion, ie, a reactive hyperemia. When an appropriate constrictor
was placed on the damaged circumflex artery, a cyclical reduction in
coronary blood flow occurred every 3 to 8 minutes, which indicated
periodic formations of platelet thrombi in the coronary artery. After
the blood flow reached nearly complete cessation, the thrombus was
dislodged by gentle mechanical agitation, and the flow immediately
returned to the initial level. Then the flow started another cyclical
reduction as a new thrombus formed. Part of the left anterior
descending coronary artery was also isolated. Another electromagnetic
flow probe was placed around the vessel to measure normal coronary
blood flow without critical stenosis and damaged endothelium.
In the
experiment in which coronary arterial blood pressure was
servocontrolled, a silicone-rubber cuff occluder was placed around the
coronary artery proximal to the flow probe. A PE-50 catheter was
inserted into the artery between the cuff occluder and flow probe
through a small branch of the coronary artery (see Fig 1
). The
catheter was used to determine coronary arterial
blood pressure, which served as a feedback control signal for a
servocontrol device.25 The cuff occluder was connected to
a pump that was controlled by the servocontrol device to maintain
coronary arterial blood pressure below the occluder at any desired
level.
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Plasma catecholamines of the dogs were analyzed in the present experiment at the end of each experimental period. Blood (4 to 5 mL) was withdrawn from an arterial catheter and used for analyses of plasma epinephrine and norepinephrine. The blood samples were placed into iced tubes containing EDTA and stored on crushed ice until the experiment was completed. The samples were centrifuged at 4°C. The concentrations of norepinephrine and epinephrine were measured by high-performance liquid chromatography with electrochemical detection. Before assay, the catecholamines were absorbed on alumina.
Experimental Protocol
Experiment With the Infusion of
Epinephrine
In this experiment, each dog (21.3±1.0 kg body wt,
n=7) was
subjected to two experimental periods, control and epinephrine
infusion. After instrumentation of the coronary artery, a stabilization
period of approximately 20 minutes was observed before the start of a
40-minute control period, during which the following variables were
recorded: frequency of CFRs, maximal circumflex arterial blood flow,
heart rate, blood pressure, hematocrit, and plasma catecholamines.
During the control period, saline solution was infused continuously at
a rate of 1.0 mL/min. At the completion of the control period,
epinephrine (Warner-Lambert Co) infusion was given by an infusion pump
(Buchler Instrument, Inc) through a left atrial catheter at 0.5 µg/kg
per minute. Then, data on the variables listed above were collected a
second time in a manner similar to that in the control period.
Experiment With the Interaction Between Norepinephrine
Infusion and
Epinephrine Infusion
The experiment was designed to investigate the
effect of infused
norepinephrine (Winthrop Pharmaceuticals) and its interaction with
infused epinephrine on coronary thrombosis in dogs (21.0±0.7 kg body
wt, n=12). The experimental protocol was similar to that mentioned
above, except that each experiment had three periods: control,
norepinephrine infusion, and norepinephrine infusion plus epinephrine
infusion. The control period included a stabilization period of 20
minutes before the start of a 40-minute experimental measurement
period, during which data on the following variables were recorded:
frequency of CFRs, maximal coronary blood flow, heart rate, blood
pressure, hematocrit, and plasma catecholamines. During the control
period, a saline solution was continuously infused at a rate of 1.0
mL/min. At the completion of the control period, norepinephrine was
given from a left atrial catheter through an infusion pump at a rate of
0.5 µg/kg per minute. After 10 minutes, data were collected on all
the variables measured during the control period during a 40-minute
experimental observation period. During the period of infusion of
norepinephrine and epinephrine, epinephrine was infused with
norepinephrine through an atrial catheter. After 10 minutes of the
combined infusion, data were collected on the variables noted above a
third time during a 40-minute period.
Experiment With
Infusion of Norepinephrine and Servocontrolled
Coronary Arterial Pressure
The experiment was designed to analyze the
effect of
norepinephrine on coronary thrombosis in the absence of an increase in
coronary arterial pressure. This experiment on six dogs (19.9±0.7 kg
body wt) included two experimental periods: a control period and period
of infusion of norepinephrine during which coronary arterial pressure
was controlled. During the control period, the same data were collected
as in the control period previously described. After these measurements
were made, norepinephrine (0.5 µg/kg per minute) was infused as in
the previous experiment, which elevated arterial blood pressure. Once
the arterial blood pressure began to increase, a servocontrol device
was activated to reduce the blood pressure in the coronary artery to
the level observed before infusion of norepinephrine. The coronary
arterial blood pressure was maintained at a constant level throughout
the experimental measurement despite increases in systemic arterial
blood pressure. Data were then collected for a second time for 40
minutes on the same variables as in the control period.
Data Analysis
Group means±SEMs are presented in the
text and figures.
Statistical comparisons of all the data were performed with a
single-factor ANOVA. Dunnett's test was used post hoc to determine the
statistical probability of differences between individual means. A
value of P<.05 was accepted as indicating statistically
significant differences. Values of P<.01 were also
indicated in the results.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Effect of Infused Epinephrine on Coronary Thrombosis
Epinephrine (0.5 µg/kg per minute) was infused through the left atrium, which elevated plasma epinephrine concentrations in the dogs from 0.46±0.25 to 27.67±1.85 nmol/L (see Fig 2
).
The
plasma norepinephrine concentration was not altered by the epinephrine
infusion (0.83±0.26 versus 0.80±0.33 nmol/L). Heart rate and
hematocrit were increased from 117±9 to 133±9 beats per minute
(bpm)
and from 36.4% to 45.4%, respectively, as a result of epinephrine
infusion. However, arterial blood pressure was reduced from 93.1±2.3
to 85.0±1.8 mm Hg (P<.01). Blood flow in the coronary
artery was also increased in the epinephrine infusion period (30.2±4.2
versus 36.6±4.9 mL/min, P<.01). As a result of increases
in plasma epinephrine concentration, coronary thrombosis was stimulated
in the dogs and the frequency of CFRs increased by >60%, from
7.1±0.5 to 11.5±0.7 in the 40-minute period after administration
of
epinephrine (P<.01, see Fig 3).
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Effect of Norepinephrine Infusion and Its Interaction With
Epinephrine Infusion on Coronary Thrombosis
Fig 4 shows
plasma epinephrine and norepinephrine
concentrations during the three experimental periods. Plasma
epinephrine and norepinephrine concentrations were 0.49±0.27 and
1.32±0.23 nmol/L, respectively, during the control period. During the
norepinephrine infusion, plasma norepinephrine and epinephrine
increased to 32.35±4.29 and 2.81±0.58 nmol/L
(P<.01),
respectively. During the norepinephrine plus epinephrine infusion
period, plasma norepinephrine and epinephrine were elevated to
38.2±5.67 and 32.87±3.88 nmol/L, respectively. As a result of
the
norepinephrine infusion, the frequency of CFRs decreased and arterial
blood pressure and blood flow in the left anterior descending coronary
artery increased (see Fig 5). In 10 of 12 animals used
in this experiment, the frequency of CFRs was severely or completely
inhibited by the norepinephrine infusion. The other 2 dogs showed
little or no response to the norepinephrine infusion. The frequency of
CFRs was not observed to increase in any dog. Fig 6
presents a summary of the experimental results. The
frequency of CFRs was 7.89±0.42 cycles per 40 minutes during the
control period; this was reduced to 2.41±1.08 cycles per 40 minutes
during the norepinephrine infusion period. The coronary blood flow,
heart rate, and hematocrit all increased significantly during the
norepinephrine infusion period compared with the control period (see
the Table). Arterial blood pressure was significantly
elevated, from 88±3 to 118±5 mm Hg, as a result of infusion of
norepinephrine (P<.01).
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Fig 7 shows a blood
flow recording of the CFRs in
response to the infusions of norepinephrine and of norepinephrine plus
epinephrine. Although norepinephrine infusion had a potent inhibitory
effect on the CFRs, this effect was overcome by an additional infusion
of epinephrine. As shown in Fig 6
, the frequency of the CFRs
increased
from 2.41±1.08 to 7.74±1.12 cycles per 40 minutes during the
norepinephrine plus epinephrine infusion period (P<.01).
The latter value was not different from that in the control period
(P>.05). Coronary blood flow, heart rate, and hematocrit
measurements during the norepinephrine plus epinephrine infusion period
were not significantly different from the norepinephrine infusion
period (see the Table). However, arterial blood pressure
decreased
significantly, from 118±5 to 104±4.4 mm Hg, because of the
additional infusion of epinephrine (P<.05).
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Effect of Norepinephrine Infusion With Servocontrolled Coronary
Arterial Pressure
In this experiment, a servocontrol system was used
to maintain
coronary arterial pressure at the level observed before infusion of
norepinephrine. Fig 8 shows coronary and systemic
arterial pressures in response to norepinephrine infusion. During the
control period, both systemic and coronary arterial pressures were
85.8±3.4 mm Hg. After infusion of norepinephrine at the same rate as
above (0.5 µg/kg per minute) and activation of the servocontrol
device, the systemic arterial pressure increased from 85.8±3.4 to
120.8±3.5 mm Hg (P<.01), whereas the coronary arterial
pressure was maintained at 86.3±3.4 mm Hg, which was not different
from the level before infusion of norepinephrine. The norepinephrine
infusion also increased the heart rate (123±9 versus 156±7 bpm,
P<.01) and hematocrit (36.8±1.0% versus 45.8±0.8%,
P<.01) measurements. However, maximal coronary blood flow
was not different and was 34.8±4.1 mL/min during the control period
and 36.3±3.6 mL/min during the norepinephrine infusion period
(P>.05).
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Fig 9 shows a recording of the CFRs
in response to the
norepinephrine infusion when the coronary arterial pressure was
prevented from rising; Fig 9A and 9B represent
the recordings
in the same animals with or without activation of the servocontrol
device, respectively. Coronary thrombosis was inhibited by the
norepinephrine infusion even though the increase in coronary arterial
pressure was prevented; the frequency of CFRs was reduced from
7.47±0.71 to 0.83±0.65 cycles per 40 minutes (P<.01,
see
Fig 10).
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Discussion |
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Although the plasma epinephrine concentration in the present study was greater than a physiological concentration (a venous plasma concentration that occurred with exercise) that has been reported to be as high as 7 to 8 nmol/L,20 it was still far below the level that is believed to have a directly stimulatory effect on platelet aggregation in vitro. By raising the arterial plasma epinephrine concentration to approximately 27 nmol/L in the present study, epinephrine could enhance the frequency of the CFRs by >60%, which is consistent with the belief that epinephrine is a strong prothrombogenic factor for coronary thrombosis.26 27 Such a potent effect of epinephrine on coronary thrombosis is probably due to its effect on platelet function, since Larsson et al28 demonstrated that increases in plasma epinephrine concentration from 0.14 to 3.41 nmol/L elevated platelet aggregability in vivo. However, other studies21 29 30 showed that epinephrine cannot act as an aggregating agent unless its concentration reaches micromolar levels. One possible explanation is that epinephrine may potentiate other thrombogenic factors, such as serotonin, ADP, and thromboxane A2, since some of these factors are believed to play an active role in the development of CFRs in this model.31 32 Bush et al31 and Yao et al32 reported that ketanserin (a serotonin receptor blocker) and apyrase (an ADP-removing enzyme), respectively, could effectively inhibit CFRs in this model, which suggests that serotonin and ADP are thrombogenic factors for eliciting coronary thrombosis. Additionally, evidence from several in vitro studies15 16 17 has shown that epinephrine potentiated platelet aggregation induced by low doses of agonists, including serotonin, arachidonate, and thrombin. Another possibility is that hemodynamic changes resulting from the epinephrine infusion may also contribute to the enhancement of coronary thrombosis. The increase in coronary blood flow caused by the epinephrine infusion in the present study may play a role in this effect, since shear stress has been known to stimulate platelet aggregation.33 Moreover, epinephrine infusion could increase platelet numbers by recruitment of platelets sequestered in the spleen,34 35 which can facilitate coronary thrombosis. Although the platelet number was not determined in the present study, the 25% increase in the hematocrit indicates constriction of the spleen.
By infusing norepinephrine at a rate of 0.5 µg/kg per minute,
the plasma norepinephrine concentration was elevated to approximately
32 nmol/L. To our surprise, this increment of plasma norepinephrine
abolished the CFRs in most of the dogs used in this experiment (Figs
5 and 7). The plasma norepinephrine
concentration in the present
study was obviously greater than that under resting conditions, but
this concentration is comparable to the level observed under certain
other conditions, such as during intense exercise. In healthy humans,
plasma norepinephrine concentrations have been reported to increase by
more than 45 nmol/L during exercise.19 20 Therefore,
this
inhibitory effect by raised plasma norepinephrine on coronary
thrombosis should be functionally significant and relevant under
physiological conditions. However, the present finding appears to
be difficult to reconcile with the fact that norepinephrine can
activate the 2-adrenoceptor in platelets in the same
manner as epinephrine. It is well recognized that the stimulatory
effect of epinephrine on platelet aggregation is attributed to the
activation of 2-adrenoceptor, which also has a high
affinity to bind
norepinephrine.10 12 13 21 In
addition,
norepinephrine had been shown to stimulate platelet aggregation in
vitro.16 21 28 Yet the high plasma
norepinephrine
concentration in the present study did not increase the frequency
of the CFRs; instead, norepinephrine significantly inhibited coronary
thrombosis. This suggests that the mechanism by which plasma
norepinephrine inhibits coronary artery thrombosis does not depend on
the effect of norepinephrine on 2-adrenoceptor in
platelets and also may not be manifest in vitro. When a similar dose of
epinephrine was added to the norepinephrine infusion, the frequency of
CFRs returned to control levels (see Fig 7), which indicates
that the
plasma epinephrine and norepinephrine have opposite effects on coronary
artery thrombosis.
Norepinephrine infusion increased coronary blood flow and
hematocrit in the same manner as epinephrine infusion. It is unlikely
that these two factors contributed to the inhibition of CFRs, for the
reasons described above. However, the norepinephrine infusion increased
systemic and coronary arterial pressures by 30 mm Hg, whereas
epinephrine significantly reduced these pressures. These differences in
arterial pressures raise the possibility that an increase in coronary
arterial pressure caused by norepinephrine infusion may inhibit CFRs in
the present study. The role of blood pressure in the development of
coronary thrombosis has not been well addressed, although its
importance has been suggested previously by Folts et al24
and Bush and Shebuski.36 Folts et al proposed that the
coronary pressure gradient across the stenosed artery increases as the
platelet thrombus develops and eventually may dislodge the thrombus.
Elevations in the coronary arterial pressure caused by norepinephrine
infusion could further increase the pressure gradient across the
thrombus in the present study, and this increment could dislodge
the thrombus as soon as it formed.
To examine this possibility, it was necessary to use a servocontrol system to prevent coronary arterial pressure from increasing during infusion of norepinephrine. By use of a servocontrol device, we were able to maintain coronary arterial pressure at the level observed before infusing norepinephrine, despite the >35 mm Hg increase in the systemic arterial pressure. However, controlling the coronary perfusion pressure did not prevent or attenuate the inhibitory effect of norepinephrine on coronary thrombosis. The frequency of CFRs was reduced from 7.47 to 0.83 cycles per 40 minutes after infusion of norepinephrine. Therefore, this finding indicates that the elevation of coronary arterial pressure is not involved in this inhibitory effect.
The present study demonstrated opposing effects of plasma epinephrine and norepinephrine on coronary artery thrombosis, which suggests that the ratio of plasma epinephrine to norepinephrine rather than the overall levels of plasma catecholamines may be the mechanism that affects coronary artery thrombosis. Although plasma epinephrine and norepinephrine are known to increase during sympathetic activation, the responses of epinephrine and norepinephrine can vary under different conditions. Previous studies37 reported that increases in plasma norepinephrine tended to be greater than those in plasma epinephrine during exercise, whereas plasma epinephrine was likely to be more elevated than plasma norepinephrine during smoking and mental stress. On the basis of our findings in the present study, we propose that activities and conditions such as smoking and mental stress, in which a greater proportional increase is observed in epinephrine than norepinephrine, are associated with an elevated risk of coronary artery thrombosis.
The present study did not directly reveal the mechanism by which plasma norepinephrine inhibits coronary thrombosis. On the basis of the findings of previous studies, it is reasonable to speculate that this inhibitory effect may exist only during the administration of norepinephrine in vivo. Several studies have already demonstrated that epinephrine and norepinephrine stimulated platelet aggregation in vitro; however, ex vivo data have shown that the platelet aggregations differed in response to infusions of epinephrine versus norepinephrine. In healthy human subjects, infusion of epinephrine increased platelet aggregability to agonists such as ADP,14 35 whereas increases in plasma norepinephrine from infusion could significantly reduce the platelet aggregation with low-dose collagen, epinephrine, and ADP ex vivo.37 These results indicate the possibility that increases in plasma norepinephrine may stimulate the body to release some factors that can inhibit platelet aggregation. Norepinephrine has been reported to be able to stimulate endothelial cells to release prostacyclin and nitric oxide,38 39 40 both of which are known to be potent inhibitors of platelet aggregation.41 42 However, it remains to be determined whether these two endothelium-derived factors are responsible for the inhibitory effect of increases in plasma norepinephrine on coronary artery thrombosis in the present study.
In summary, the present study shows that a high rate of epinephrine infusion significantly increased the frequency of CFRs in dogs, indicating that plasma epinephrine can stimulate the onset of coronary thrombosis. More importantly, the present findings demonstrate that an elevation in plasma norepinephrine exerts a potent inhibitory effect on the development of coronary thrombosis that is independent of elevated coronary arterial pressure. Thus, a high level of sympathetic activity per se may not promote coronary thrombosis, but a high level of epinephrine combined with a relatively low level of norepinephrine can stimulate coronary thrombosis when the coronary artery has a preexisting pathological condition.
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Acknowledgments |
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This work was supported by National Heart, Lung, and Blood Institute grants HL-21435 and HL-51971. We greatly thank Drs Thomas Lohmeier and Glen Reinhart for conducting the catecholamine assays.
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Footnotes |
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Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson.
Received June 13, 1994; revision received September 14, 1994; accepted September 28, 1994.
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