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(Circulation. 1995;92:2109-2112.)
© 1995 American Heart Association, Inc.
Articles |
Limb Vasoconstriction After Successful Angioplasty of the Left Anterior Descending Coronary Artery
From the Division of Cardiology, Department of Medicine, University Federico II, Napoli, Italy.
Correspondence to Ciro Indolfi, MD, Division of Cardiology, University Federico II, Via St Pansini 5, 80131 Napoli, Italy.
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Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background Coronary vasoconstriction has been described after uncomplicated percutaneous transluminal coronary angioplasty (PTCA). However, it is still unknown whether this phenomenon is limited to coronary circulation. The present study was planned to assess the effects of a successful PTCA on forearm blood flow (FBF) and resistance. The role of
-adrenoceptors and calcium antagonist agents on
PTCA-induced limb blood flow changes was also investigated. Methods and Results We prospectively studied 37 patients scheduled for elective single PTCA of the left anterior descending coronary artery. All patients had evidence of exercise-induced myocardial ischemia. All vasoactive drugs were withdrawn for at least 48 hours before the study. FBF was measured by calibrated venous occlusion plethysmography. A significant reduction of FBF was observed at 1, 5, and 15 minutes after PTCA (from 3.7±1.2 to 2.7±1.5, 3.0±1.6, and 2.9±1.9 mL/100 mL tissue per minute, respectively; all P<.05 versus baseline). Vascular forearm resistance also increased at 1, 5, and 15 minutes after PTCA (from 27±8 to 42±16, 37±10, and 43±19 U, respectively; all P<.05 versus baseline). Phentolamine (12 µg · kg-1 · min-1, n=7) or verapamil (3.5 µg · kg-1 · min-1, n=7) also was infused intra-arterially. PTCA-induced forearm vasoconstriction was completely abolished by pretreatment with regional infusion of phentolamine or verapamil.
Conclusions After an uncomplicated PTCA of the left anterior
descending coronary artery, a reduction in FBF and an increase
in forearm vascular resistance were observed. This
peripheral vasoconstrictive response was
probably due to -adrenergic stimulation and was abolished by
intra-arterial infusion of calcium
antagonist agents.
Key Words: angioplasty • blood flow • verapamil • receptors • adrenergic • alpha
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Spontaneous coronary artery vasoconstriction after percutaneous transluminal coronary angioplasty (PTCA) occurs routinely at and distal to the site of balloon dilation despite pretreatment with aspirin.1 2 3 4
Previous studies suggested that the mechanism(s) responsible for this vasoconstriction might be related to the phenomenon of coronary autoregulation,1 the release of vasoactive substances from aggregating platelets at the site of intimal injury,4 5 or sympathetic activation.2 6 However, it is still unknown whether this vasoconstriction is limited to the coronary circulation. Demonstration of the presence or absence of the vasoconstriction after PTCA in the forearm vasculature might be important to clarification of this phenomenon.
We recently reported a pronounced reduction in coronary and
forearm blood flow (FBF) after regional 1- or
2-adrenoceptor stimulation.7 8
Activation
of cardiac sympathetic afferents has also been described extensively
during myocardial ischemia in different animal
preparations9 10 11 and
humans.12 In a previous
study, we demonstrated that after PTCA a significant vasoconstriction
occurs in a vessel distal to a dilated stenosis and in
the control coronary segment not manipulated by the guide wire
or balloon catheter.2 Because this vasoconstriction was
abolished by pretreatment with intracoronary
phentolamine, we hypothesized that significant
-adrenoceptor–mediated coronary vasoconstriction
occurs after balloon dilation.2 Thus, neural and hormonal
mechanisms may participate in the coronary constriction
associated with an uncomplicated coronary angioplasty.
The aim of this study was to test this hypothesis by examining the effects of uncomplicated PTCA of the left anterior descending coronary artery (LAD) on FBF and vascular resistance.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Population
Thirty-seven patients (34 men and 3 women, 43 to 72 years of age [mean, 54.6±8.4 years]) scheduled for elective single lesion angioplasty of the LAD were prospectively included in the study. The study was approved by the Institutional Review Board of the University of Naples, and written informed consent was obtained from all patients before the study. No patients had unstable angina, angina at rest, previous or acute myocardial infarction, diabetes mellitus, hypertrophic cardiomyopathy, systemic hypertension, congestive heart failure, visible collateral circulation, or high plasma cholesterol levels. All patients had evidence of exercise-induced myocardial ischemia despite medical therapy. We included only patients from whom we could withdraw all vasoactive drugs for at least 48 hours before the study. No premedication was given before the procedure.
All patients underwent catheterization of the right and left sides of the heart in the morning, after an overnight fast. After a local anesthesia was administered, femoral arterial (8F) and femoral venous (7F) sheaths were placed, and 5000 U IV heparin was given. Diagnostic coronary angiograms were performed by a standard percutaneous femoral approach with the Judkins technique. After diagnostic coronary angiographies were obtained to select the best projection (in which the stenosis was dilated and the distal and control vessels were recorded), a second bolus of heparin (5000 U IV) was administered, followed by 500 mg IV acetylsalicylic acid and lysine salt. The angioplasties were performed by use of an over-the-wire balloon catheter system. Balloon size was chosen to match the diameter of the "normal" coronary segment adjacent to the stenosis to be dilated, which is common during routine angioplasty. The inflation time of the balloon was always 90 seconds.
Study Protocol
Baseline FBF was measured twice at 15 and 30
minutes after the
end of the diagnostic angiography. FBF was measured 1, 5,
and 15 minutes after balloon deflation (n=23). In 14 patients, the same
protocol was performed during intra-arterial continuous
infusion of phentolamine (n=7) or verapamil (n=7).
In these groups of patients, the brachial artery was cannulated under
local anesthesia with 2% (wt/vol) procaine with a 20-gauge
polyethylene catheter (Vasculon 2), and phentolamine (12
µg · kg-1 · min-1) or
verapamil (3.5
µg · kg-1 · min-1) was
infused by a
Harvard pump to keep the flow rate <0.8 mL/min.
Aortic pressure and heart rate were measured in the control state and 5 and 15 minutes after PTCA and recorded by a computer-aided system for cardiac catheterization (Siecor, Siemens). Pressure waveform analysis was performed within a user-definable analysis window over eight consecutive beats.13
FBF Measurement
The studies were conducted at a constant
temperature of 20°C
to 24°C. Forearm volume was determined by water displacement before
the study. FBF was measured with a mercury-in-Silastic-rubber
strain gauge applied around to the left forearm supported above heart
level.7 8 9 10 11 12 13 14
The gauge was connected to a calibrated
plethysmograph (Vasculab, model SPC 16, Meda Sonics), which was
connected to a strip-chart recorder to record flow
measurements in the forearm. A venous occlusion pressure of 40 mm Hg
was used in the upper arm cuff, and FBF was measured as the slope of
the change in forearm volume.7 The mean of at least three
measurements was obtained at each time point. Forearm vascular
resistance was calculated by dividing the mean blood pressure (in
millimeters of mercury) by FBF and was expressed in units. Mean blood
pressure was calculated by adding one third of the difference between
systolic and diastolic pressures to the
diastolic pressure.
Statistical Analysis
Results are expressed as mean±SD.
Statistical analysis
was performed by ANOVA for repeated measures by use of a
SYSTAT program.15 When a significant overall
effect was detected, Tukey's test was applied to compare single mean
values.16 Comparisons of FBF data between the two groups
were done by two-way ANOVA. Significant differences were assumed to
be present when P<.05.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Twenty-nine patients experienced angina pectoris, and 30 patients showed ST-segment changes during balloon inflation. The systolic aortic pressure did not change significantly 1, 5, and 15 minutes after PTCA (from 135±18 to 138±19, 136±19, and 134±17 mm Hg, respectively); neither did the diastolic and mean aortic pressures. Heart rate was also unchanged 1, 5, and 15 minutes after PTCA (from 70±6 to 71±7, 69±8, and 69±8 beats per minute, respectively).
Effects of PTCA on FBF and Resistance
No significant
variations in FBF or resistance were detected in
the 15-minute period immediately preceding balloon inflation. Fig
1
(top) shows the FBF changes after PTCA. At 1, 5, and
15 minutes after PTCA, FBF was reduced from 3.7±1.2 to 2.7±1.5,
3.0±1.6, and 2.9±1.9 mL/100 mL tissue per minute (-27%,
-19%, and
-22% versus baseline, respectively; all P<.05).
Calculated forearm vascular resistance increased in response to PTCA
from 27±7 to 42±16, 37±10, and 43±19 U at 1, 5,
and 15 minutes
after PTCA, respectively (all P<.05 versus baseline; Fig
1,
bottom).
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In contrast, in patients treated with intra-arterial
infusion of phentolamine, an increase in FBF was observed: from
4.1±1.0 to 6.7±10 mL/100 mL tissue per minute before PTCA
(P=NS) and to 8.8±2.6, 8.0±2.1, and
8.7±1.3 mL/100 mL
tissue per minute at 1, 5, and 15 minutes after PTCA, respectively
(P<.05; Fig 2, top), whereas forearm
resistance decreased from 22.9±2.7 to 14.4±3.0 U before PTCA
(P=NS) and to 12.0±3.7, 13.1±5.6, and
11.3±3.6 U at 1, 5,
and 15 minutes after PTCA, respectively (P<.05; Fig
2,
bottom).
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Intra-arterial infusion of verapamil also
completely abolished PTCA-induced limb vasoconstriction. The FBF
increased after verapamil infusion from 3.9±1.5 to
16.0±2.6 mL/100 mg tissue per minute before PTCA (P<.05)
and to 19.0±6.0, 19.0±5.3, and 20.0±5.0 mL/100 mg tissue
per minute
at 1, 5, and 15 minutes after PTCA, respectively (P<.05;
Fig 3, top). After PTCA, the FBF and vascular resistance
were not significantly changed compared with the values after
verapamil infusion (Fig 3).
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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The primary finding of the present study is that an uncomplicated PTCA of the LAD induced a reduction in FBF.
Several studies described distal coronary vasoconstriction after coronary angioplasty.1 2 3 4 6 17 However, it is unknown whether this phenomenon is limited to coronary circulation.
Our study, performed in patients with a single LAD stenosis during pharmacological washout, demonstrates for the first time that significant vasoconstriction also occurs in the forearm vessels. We previously showed that after successful PTCA a coronary constriction occurs not only in the segment distal to the dilated stenosis but also in the control coronary segment not manipulated by the catheter or guide wire.2 This finding was also confirmed by other investigators.6 The present study definitely demonstrates that a systemic vasoconstriction occurs after PTCA.
Mechanisms of Coronary and Forearm Vasoconstriction
After PTCA
The first and probably the most important mechanism of
generalized
vasoconstriction after PTCA is related to the sympathetic stimulation
induced by PTCA. The temporary coronary occlusion during
coronary angioplasty may be associated with anginal pain,
ischemic ST changes, regional wall motion abnormalities, and
elevation of norepinephrine levels. An increase in plasma
norepinephrine levels after PTCA was found in a previous
study.18 The cardiac spillover of
noradrenaline did not change during balloon occlusion but
increased almost threefold during early reperfusion.18
Activation of arterial wall stretch receptor is another
potential source of cardiac afferent neural
activity.19
Several studies have demonstrated that both
1- and
2-adrenoceptors mediate constriction of epicardial
coronary
arteries.8 20 21 22 23 24
The presence of
1- and 2-adrenoceptor–mediated
vasoconstriction was also documented in peripheral human
vessels.7 25 26 Therefore, the increase
in circulating
catecholamine- and neuronal-mediated sympathetic
tone may induce coronary and peripheral
vasoconstriction after PTCA through –adrenoceptor stimulation.
On the other hand, the increased concentration of vasoactive substances
released from platelets has been indicated as another explanation
for PTCA-induced coronary
vasoconstriction.5 17
It is unlikely, however,
that this is the primary mechanism responsible
for PTCA-induced limb vasoconstriction. In fact, although
serotonin is released during coronary angioplasty
and may cause coronary vasoconstriction,17 it is
rapidly inactivated by the lungs.27 Therefore,
it is unlikely that serotonin produces vasoconstriction in
the forearm circulation. Finally, thromboxane concentration
does not increase in the coronary sinus after
PTCA.28 On the other hand, after –adrenoceptor
blockade, a forearm vasodilation was observed after PTCA, suggesting
activation of unblocked ß-adrenoceptors.29
Study Limitations and Advantages
We studied our patients in
the morning (between 8 AM
and 1 PM). A circadian rhythm in basal vascular tone,
caused either partly or entirely by -adrenoceptor sympathetic
vasoconstrictor activity during the morning, has been
described.14 Therefore, a more pronounced vasoconstriction
might be present in the afternoon.
In the present study, we used venous occlusion plethysmography, which is an accurate and reliable method to quantify the actual FBF changes in humans.7 14
Conclusions
The present study demonstrated that forearm
vasoconstriction
occurs after balloon occlusion that is completely abolished by
calcium-antagonist or -adrenergic blockade
agents. This -adrenergic vasoconstriction after PTCA could
result from both direct sympathetic nerve outflow and circulating
catecholamines. Although the significance of this
peripheral vascular response after PTCA is still unclear,
this vasoconstrictive adaptation may represent
an important component of the increased sympathetic discharge
associated with coronary occlusion and may play a role in the
maintenance of systemic blood pressure during and after
coronary occlusion.
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Acknowledgments |
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We thank Salvatore Buonerba, Giuseppe D'Alise, and Arturo Bruno for excellent technical assistance.
Received December 12, 1994; revision received April 19, 1995; accepted May 13, 1995.
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