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Therapeutic effect of urapidil on myocardial perfusion in patients with
ST-elevation acute coronary syndrome
Dao-kuo Yaoa,⁎, San-qing Jiaa, Lei Wanga, Hong-wei Lia, Yu-chen Zhanga,
Yong-liang Wanga, Le-xin Wangb,⁎
aHeart & Blood Vessel Center of Beijing Friendship Hospital, Capital Medical University, Beijing, China
bSchool of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia
Received 3 March 2008; received in revised form 5 May 2008; accepted 9 June 2008
Available online 21 July 2008
Objectives: To evaluate the effect of urapidil on myocardial perfusion, and ventricular function in patients with ST-elevation acute coronary
syndrome (ACS) treated with primary percutaneous coronary intervention (PCI).
Methods: Fifty-four patients were randomized into urapidil (12.5 mg, ic, n=27) or control group. Infarct related artery (IRA) was targeted with
PCI following urapidil administration. TIMI blood flow, corrected TIMI frame count (cTFC), myocardial blush grade (MBG), ST resolution
(STR) on ECG, creatine kinase MB (CK-MB) and cardiac troponin T (cTnT) were measured before, and after PCI.
Results: cTFC (18.38±3.30 vs 21.44±4.26, P=0.005), in the treatment group was lower than the placebo group, whereas MBG was higher
(P=0.04). More patients in the urapidil group achieved significant STR following PCI (93% vs 70%, P=0.04). Left ventricular ejection fraction
(LVEF), measured with echocardiography, in the urapidil group was higher than the control group 30 days after PCI (0.58±0.06 vs 0.54±0.06,
P=0.04). Peak CK-MB and peak cTnT in the urapidil group was lower than the control group (Pb0.01). Myocardial nitric oxide concentration in
the urapidil group was higher than that of the control group (Pb0.01). Following PCI, the endothlin-1 level did not change in the urapidil group
(PN0.05) but it was increased in the control group (Pb0.05).
Conclusions: Urapidil treatment improves coronary flow, myocardial perfusion and left ventricular function following PCI in patients with ST-
elevation ACS. These beneficial effects are associated with an enhanced biosynthesis of nitric oxide.
Crown Copyright © 2008 Published by Elsevier B.V. on behalf of European Federation of Internal Medicine. All rights reserved.
Keywords: Acute coronary syndrome; Percutaneous coronary intervention; Urapidil; Nitric oxide; Endothelins
Percutaneous coronary intervention (PCI) has become a
major treatment for patients with acute coronary syndrome
(ACS) [1,2]. Successful PCI reduces the incidence of death,
myocardial infarction and hospitalization in patients with ACS
[1,2]. However, slow-flow or no-reflow is present in up to 30%
of patients following the successful PCI, and reopening of the
infarct-related artery [3,4]. The “mismatch” between the
patency of the artery, and the reperfusion of the myocardium
may be due to a number of causes, such as microvascular
constriction [5–7]. The primary purpose of this study is to
evaluate the effect of urapidil, a selective α1-adrenoceptor
blocker, on the perfusion of myocardium and the left ventricular
function following PCI in patients with ACS.
2. Patients and methods
2.1. Patient selection
This study was approved by the Human Research Ethics
Committee of Beijing Friendship Hospital. Informed consent in
European Journal of Internal Medicine 20 (2009) 152–157
⁎Corresponding authors. Wang is to be contacted at School of Biomedical
Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
Tel.: +61 2 69332905; fax: +61 2 69 332587. Yao, Heart & Blood Vessel Center
of Beijing Friendship Hospital, Capital Medical University, Beijing, China.
E-mail addresses: email@example.com (D. Yao), firstname.lastname@example.org
0953-6205/$ - see front matter. Crown Copyright © 2008 Published by Elsevier B.V. on behalf of European Federation of Internal Medicine. All rights reserved.
Author's personal copy
a written form was obtained from all participants. The
procedures were in accordance with the ethical standards of
the responsible committee on human experimentation.
The selection criteria are: 1) age N18 years; 2) onset of chest
pain less than 12 h; 3) ST-elevation in at least two adjacent ECG
leads, or presence of newly developed left bundle branch block.
All patients must have an elevation of plasma creatine kinase
MB (CK-MB) or cardiac troponin T (cTnT).
Patients with one or more of the following conditions were
excluded from the study: systemic infection, anaemia, renal or
hepatic dysfunction, cancer, systemic thromboembolic disease,
autoimmune disease or pregnancy, and patients who did not
give written consent to participate the study.
Between December 2005 and October 2006, 54 consecutive
patients with ST-elevation ACS were recruited into this study.
Patients were randomised , according to their order of
hospitalization, into treatment group (urapidil, n=27) and
control (normal saline, n=27) group.
2.2. Pharmacological management and PCI
Patients from both groups were treated with 300 mg aspirin,
and 300 mg clopidogrel before PCI. Clopidogrel 75 mg per day
was administered following PCI as a maintenance therapy.
Coronary angiography was performed before balloon angio-
plasty or stent implantation to demonstrate infarct-related artery
(IRA). When coronary flow higher than TIMI-1 was present in
the IRA, urapidil (12.5 mg in 5 mL normal saline, ALTANA
Pharma, Germany), or 5 mL normal saline was injected into the
IRA followed by PCI. In patients who were taken blood sample
to measure NO and ET-1, nitroglycerin was not used before and
during the PCI procedure.
In patients undergoing PCI, target-lesion revascularization
was always attempted, and complete revascularization was
performed as clinically appropriate. Results of PCI were
assessed by visual estimation of the angiograms before, and
after the procedure. Success of PCI was defined as less than
50% stenosis in the luminal diameter after balloon angioplasty,
and less than 20% stenosis after coronary stent implantation.
Other major cardiac drugs following PCI are used listed in
2.3. Assessment of coronary flow and myocardial perfusion
The cinefilm reviewers were blinded to the treatment group
assignment and the clinical outcome of the patient. TIMI flow
grade and corrected TIMI frame count (cTFC) was conducted
using the methods reported by Gibson et al. . Myocardial
reperfusion following PCI was assessed by myocardial blush
grade (MBG), using the methods reported by the Zwolle
Myocardial Infarction Study Group .
A standard 12-lead ECG was recorded before PCI, and at
30 min, 60 min, 90 min, and 120 min following PCI. ECG was
also recorded 3 h, 4 h and 6 h following PCI. ST resolution
(STR) on the ECGs was measured. The time between
completion of PCI, and reaching significant STR was also
registered. Significant STR was defined as more than 50%
reduction in the elevated ST segment within 90 min following
Plasma CK-MB and cTnT was measured before PCI, and at
4 h, 6 h, 10 h, 16 h, 20 h, 24 h, 48 h, and 72 h following PCI.
The peak values of CK-MB, and cTnT were used as the infarct
2.4. Assessment of left ventricular function
The left ventricular systolic function was assessed 24 h and
again 30 days after PCI, using two-dimensional echocardio-
graphy (HP 7500, Philips, Netherlands). The LVEF, left
ventricular end-diastolic, and end-systolic diameters were
2.5. Measurement of nitric oxide and endothelin-1
In the last five patients of each group, nitric oxide, and
endothelin-1 was measured from blood obtained from the root
of the aorta and the coronary sinus. The difference in nitric
oxide or endothelin-1 levels between the aorta and the coronary
sinus was defined as the myocardial levels.
Blood was centrifuged at 1500 rpm for 20 min, and the
separated plasma was kept at −80 °C. Nitric oxide was
measured by chemiluminescence with a Sievers Nitric Oxide
Analyzer, model 280 (Boulder, Colorado, USA). The nitric
oxide assay was standardized by a calibration curve using
known concentrations of nitrate (0.01 to 100 µmol/L), obtained
from sodium nitrate. For each measurement, a 4-µL sample was
placed in a reducing vessel with 5 mL of 0.1 mol/L of vanadium
III chloride, 1 mol/L of hydrochloric acid, and 100 µL of
antifoaming agent at 90 °C. Each standard was analyzed three
times, and each plasma sample was analyzed at least five times.
The mean value was used for all subsequent analysis.
Plasma endothelin-1 was measured by using an ELISA kits
(RapidBio lab, CA, USA). The efficacy of the extraction
procedure was 81%; inter-assay variations were 9%, and intra-
assay variations were 5%. In this assay, cross-reactivities were
less than 5% for endothelin-2, less than 3% for endothelin-3,
and less than 37% for proendothelin.
2.6. Clinical outcomes
The cardiac events during hospitalization and within 30 days
of PCI were monitored. These events included cardiac
arrhythmia (excluding reperfusion arrhythmia), recurrent myo-
cardial infarction, post-infarct angina, left ventricular dysfunc-
tion, cardiogenic shock or cardiac death.
2.7. Statistical analysis
Data were expressed as means±SD. Student t test was used
to analyze the differences between the urapidil, and control
groups. Comparison of categorical data between the two
groups before or after the treatment was performed by Chi-
square test, and Fisher exact test. Logistic regression analysis
was also performed to asses the predicting factors for cTFC,
153 D. Yao et al. / European Journal of Internal Medicine 20 (2009) 152–157
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MBG and STR. Pb0.05 was considered to be statistically
3.1. General findings
Between the two groups, there was no significant difference
in age, sex, medical history, left ventricular function, time from
onset of the symptoms to PCI, or pharmacological therapies
(Tables 1, 2).
Intracoronary administration of urapidil had no significant
effect on systolic blood pressure (BP 131±11 vs 134±12 mm
Hg, PN0.05), or heart rate (HR 92±5 vs 90±7 bpm, PN0.05).
The blood pressure (BP 128±15 vs 129±14 mm Hg, PN0.05),
and heart rate (HR 93±10 vs 94±8, PN0.05) of the control
group also remained unchanged.
In the urapidil group we found 12 cases of reperfusional
arrhythmia (including 8 cases of accelerated idioventricular
rhythm and 4 sinus bradycardia), compared to 13 cases of
reperfusional arrhythmia (including 9 cases of accelerated
idioventricular rhythm , 3 sinus bradycardia and 1 atrioven-
tricular block in the control group) (PN0.05).
During the 30-day follow up, there was no cardiac death,
recurrent infarction or re-hospitalization in either group of the
3.2. Coronary angiography
There was no significant difference in the coronary
angiography between the two groups prior to urapidil admin-
istration and PCI. TIMI flow, cTFC, MBG and, the diameter of
IRA or the reference coronary artery was similar between the
two groups (PN0.05, Table 3).
After urapidil administration, there was no significant
difference between the two groups in TIMI flow grades
(Table 3, PN0.05). However, a lower cTFC (Pb0.01), and a
higher MBG (Pb0.05), was observed in the urapidil group
(Table 4, Pb0.01).
Logistic regression analysis showed that administration of
urapidil, the duration of chest pain, sex, and cTFC before PCI
are the factors were associated with post-PCI cTFC (Table 5).
Administration of urapadil (OR, 0.126; 95% CI, 0.019–0.847;
P=0.033), and the duration of chest pain (OR, 1.384; 95%CI,
Baseline patient characteristics.
Urapidil (n=27) Control (n=27) P
Smoking history (%)
History of MI (%)
Onset of symptom to PCI (h)
Left ventricular function (Killip) (%)
Medical treatment following PCI.
Urapidil (n=27)Control (n=27)P
GP IIb/IIIa receptor blockers
ACEI: angiotensin-converting enzyme inhibitor, ARB: angiotensin receptor
blocker, LMWH: low molecular weight heparin.
Results of coronary angiography.
Urapidil (n=27)Control (n=27)P
Target vessel (%)
Number of stents used (%)
TIMI flow (%) before PCI
TIMI flow (%) after PCI
LAD: left anterior descending, LCX: left circumflex, RCA: right coronary
artery, RD: reference artery diameter, MLD: minimum luminal diameter, DS:
Reperfusion after PCI and urapidil administration.
Urapadil (n=27)Control (n=27)P
cTFC before PCI
cTFC after PCI
MBG (%) before PCI
MBG (%) after PCI
cTFC: corrected TIMI frame count, MBG: myocardial blush grade.
154 D. Yao et al. / European Journal of Internal Medicine 20 (2009) 152–157
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1.059–1.808; P=0.017) are the independent predictors of
3.3. ST resolution, myocardial biomarkers and left ventricular
In the urapidil group, more patients achieved ST resolution
within 90 min of PCI (Table 6, Pb0.01). Logistic regression
analysis showed that urapidil is the independent predictor of
improved ST resolution (OR, 0.148; 95%CI, 0.025–0.8767;
The peak values of CK-MB and cTnT was lower in the
urapidil group (Table 6, Pb0.01). There was no significant
difference in hypersensitive C reactive protein between the two
groups (Table 6, PN0.05).
LVEF was higher in the urapidil group 24 h, and 30 days
after PCI (Table 6, Pb0.01).
3.4. Levels of nitric oxide and endothelin-1
Prior to PCI, there was no significant difference in the levels
of nitric oxide or endothelin-1 in the plasma obtained from the
aorta or coronary sinus between the two groups (Tables 7 and 8,
PN0.05). After PCI, the nitric oxide levels in the coronary sinus
were elevated in the two groups (Pb0.01, Table 7). It was also
elevated in the aorta in the urapidil group (Pb0.01, Table 7).
The nitric oxide levels in the urapidil group were higher than the
control group (Pb0.01, Table 7).
After PCI, the endothlin-1 levels were increased in the
control group (Pb0.05), whereas they remained unchanged in
the urapidil group (PN0.05, Table 8).
The major findings of the study are: 1) In patients with ST-
elevation ACS, intracoronary injection of urapidil prior to PCI
improves coronary flow and myocardial perfusion following
primary PCI; 2) Urapidil treatment enhances ST resolution on
ECG and diminishes the peak values of CK-MB and cTnT; 3)
The left ventricular function in the urapidil group was greater
than the control group following PCI; and 4) Urapidil treatment
is associated with an increased cardiac biosynthesis of nitric
oxide and reduced production of endothelin-1.
4.1. Effect of urapidil on myocardial reperfusion
α-adrenergic activities impact on the ischemic myocardium
from two perspectives. First, ischemia and hypoxia often leads
to a 2–3 fold increase in α1-adrenoceptors in ventricular
myocytes . The alterations in the α1-adrenergic receptor
system may contribute significantly to arrhythmogenesis in the
ischemic heart . For these reasons there have been calls to
include α1-adrenoceptor blockers in the management
approaches to reduce the incidence of sudden cardiac death in
patients with ACS .
Second, α-adrenergic activities contribute significantly to
the vasoconstriction of the coronary circulation during myo-
cardial ischemia . The vasoconstriction after coronary
angioplasty, and the left ventricular dysfunction secondary to
the vasoconstriction, are the direct results of enhanced α-
adrenergic activities [12,13].
The present study has demonstrated that urapidil, a
selective α1-receptor blocker, is associated with further
improvement of coronary flow and myocardial perfusion
following successful PCI. The indices that we have chosen to
reflect coronary flow or myocardial perfusion (cTFC, MBG
and ST resolution rate) are commonly used in clinical trials of
similar nature [14–16]. They are relatively reliable in
Logistic regression analysis of factors associated with post-PCI cTFc.
cTFC before PCI
Duration of chest pain (h)
ST resolution, left ventricular function and myocardial biomarkers.
Uradipil (n=27)Control (n=27)P
STR N50% in 90 min (%)
Peak CK-MB (U/L)
Peak cTnT (ng/mL)
24 h LVEF
30 days LVEF
CRP: C reactive protein.
Changes in nitric oxide (µmmol/L) after PCI.
Urapidil (n=5)Control (n=5)P
Differences before and after PCI
*, P=0.001 compared with the pre-PCI level within the same group.
Changes in endothelin-1 (pg/mL) after PCI.
Urapidil (n=5)Control (n=5)P
Differences before and after PCI
*, P=0.001 compared with the pre-PCI level within the same group.
155D. Yao et al. / European Journal of Internal Medicine 20 (2009) 152–157
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demonstrating the alterations in coronary flow or myocardial
perfusion in ACS patients [14–16]. There was a significant
improvement in all three indices in the urapidil group. These
beneficial effects are likely due to the antagonism of α1-
adrenoceptors in the coronary circulation and the resultant
dilation of coronary arteries or microcirculation.
A recent study found that in patients with intermediate
coronary stenosis, urapidil induced a significant but small
decrease in fractional flow reserve, an indicator of the fraction
of hyperaemic myocardial flow that is preserved despite the
presence of epicardial coronary stenosis . The authors of the
study concluded that α1-adrenoceptor blockers unmask a small,
clinically irrelevant degree of microvascular tone in patients
with intermediate coronarystenoses. Our study was centred on a
different patient population who had AMI and underwent PCI.
Urapidil administration before PCI resulted in a significant
increase in coronary flow and myocardial perfusion after
It is important to note that urapidil treatment in the present
study was not associated with a significant improvement of
TIMI flow in the IRA. Previous studies have shown that in
healthy subjects, and in patients with stable angina, selective
α1-adrenoceptor blockers reduce the coronary resistance
[18,19]. Intracoronary injection of phentolamine, another α-
adrenoceptor blocker, diminishes the increase of coronary
resistance following coronary angioplasty . These results
indicate that although the TIMI flow was not significantly
increased after urapidil therapy, the microcirculation may have
been improved with a reduction in coronary resistance, leading
to improved coronary flow and myocardial perfusion.
4.2. Effect of urapidil on left ventricular function
Ventricular dysfunctionfollowing myocardial ischemia is the
result of the interplay of a number of factors, including the
reflex activation of sympathetic nerve system, through stimula-
tion of the receptors in the ventricular myocardium and
coronary smooth muscle cells . Following coronary
angioplasty or stenting, a transient reduction in left ventricular
function was observed in the IRA-dependent, and non-IRA-
dependent myocardium . The transient reduction in
ventricular function following PCI was diminished by pre-
treatment with α-receptor blockers, such as phentolamine or
The current study has clearly shown that urapidil treatment is
associated with reduced peak values of plasma CK-MB and
cTnT, indicating a reduction in myocardial ischemia. The left
ventricular function in the urapidil-treated patients was also
better than the placebo group following PCI. These results
indicate that in addition to the anti-adrenergic activities, urapidil
also improves ventricular function by limiting the infarct size.
4.3. Effect of urapidil on the biosynthesis of nitric oxide and
Balloon angioplasty, and stenting are effective in reopening
the occluded coronary arteries. However, the revascularization
following PCI is not always associated with the full restoration
of myocardial perfusion . As shown in our study, α-
antagonism reduced cTFC, and improved MBG following PCI,
suggesting significant improvement in coronary flow and
To explore other potential contributors to the improved
coronary flow or myocardial perfusion following urapidil
treatment, we measured the levels of nitric oxide, and
endothelin-1 following urapidil administration in five patients.
Compared with the control group, the myocardial levels of nitric
oxide in the urapidil group were clearly elevated, whereas the
biosynthesis of detrimental endothelin-1 was suppressed.
Urapidil is a peripheral α1-adrenoceptor antagonist and
central 5-HT1A agonist. We are not aware of any direct
association between α1-antagonism and nitric oxide biosynth-
esis. Therefore, the increased myocardial level of nitric oxide
following urapidil therapy is likely due to improvement in
coronary circulation or endothelial function.
Peripheral α1-adrenoceptor antagonists do not appear to have
a significant effect on circulating endothelins in healthy humans
. There is no suggestion in the literature of any relationship
between central serotoninergic stimulation and peripheral
endothelin peptides. Therefore, it is reasonable to assume that
in our patients with ST-elevation ACS, the improvement in
coronary circulation, and myocardial reperfusion, which were
initiated by urapidil, were responsible for the unchanged
circulating endothelin-1 levels.
4.4. Limitations of the study
This was a prospective study in a relatively small number of
patients. There were clear and significant evidence to show the
beneficial effect of urapidil on the coronary flow, myocardial
perfusion and left ventricular function. However, there was no
significant change in the major adverse cardiac events in either
group. Therefore, no conclusion can be drawn on the impact of
urapidil on the prognosis of ST-elevation ACS. Furthermore,
although the dosage of urapidil used in the present study was
effective, and in agreement with a previous study , it
remains to be seen if a higher dose may elicit a greater
improvement in myocardial perfusion and left ventricular
In patients with ST-elevation ACS, PCI may salvage
impaired myocardium. However, ischemia-induced activation
of α-adrenergic nerve system and the resultant vasoconstriction
may offset some of the perfusion benefits from successful PCI.
Pre-treatment with α1-adrenoceptor antagonists will improve
the coronary flow, myocardial perfusion and left ventricular
function following PCI. These hemodynamic and clinical
benefits are associated with improved levels of nitric oxide,
and suppressed biosynthesis of deleterious endothelin-1. The
impact of α1-adrenoceptor antagonists on the major cardiac
events following PCI remains unclear, and further studies are
156 D. Yao et al. / European Journal of Internal Medicine 20 (2009) 152–157
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6. Learning points
• Activation of α-adrenergic nerve system during acute ST-
elevation MI may negate some of the benefits from PCI;
• Pre-treatment with α1-adrenoceptor antagonist, such as
urapidil, will improve the coronary flow, myocardial
perfusion and left ventricular function following PCI.
 Mehta SR, Cannon CP, Fox KA, Wallentin L, Boden WE, Spacek R, et al.
Routine vs selective invasive strategies in patients with acute coronary
syndromes: a collaborative meta-analysis of randomized trials. JAMA
 Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M,
et al. American College of Cardiology. American Heart Association Task
Force on Practice Guidelines. Canadian Cardiovascular Society. ACC/
AHA guidelines for the management of patients with ST-elevation
myocardial infarction — executive summary: a report of the American
College of Cardiology/American Heart Association Task Force on Practice
Guidelines (Writing Committee to Revise the 1999 Guidelines for the
Management of Patients with Acute Myocardial Infarction). Circulation
 Prasad A, Stone GW, Aymong E, Zimetbaum PJ, McLaughlin M, Mehran
R, et al. Impact of ST-segment resolution after primary angioplasty on
outcomes after myocardial infarction in elderly patients: an analysis from
the CADILLAC trial. Am Heart J 2004;147:669–75.
 Ito H, Tomooka T, Sakai N, Yu H, Higashino Y, Fujii K, et al. Lack of
myocardial perfusion immediately after successful thrombolysis. A
predictor of poor recovery of left ventricular function in anterior
myocardial infarction. Circulation 1992;85:1699–705.
 Wilson RF, Lesser JR, Laxon DD, White SW. Intense microvascular
constriction after angioplasty of acute thrombotic coronary arterial lesions.
 Felled H, Lichstein E, Schachter J, Shani J. Early and late angiographic
findings of the “no-reflow” phenomenon following direct angioplasty as
primary treatment of anterior myocardial infarction. Am Heart J
 Piana RN, Paik GY, Moscucci M, Cohen DJ, Gibson CM, Kugelmass AD,
et al. Incidence and treatment of “no-reflow” after percutaneous coronary
intervention. Circulation 1994;89:2514–8.
 Gibson CM, Cannon CP, Daley WL, Dodge Jr JT, Alexander Jr B, Marble
SJ, et al. TIMI frame count quantitative method of assessing coronary
artery flow. Circulation 1996;93:879–88.
 Van't Hof AW, Liem A, Suryapranata H, Hoorntje JC, de Boer MJ, Zijlstra
F. Angiographic assessment of myocardial reperfusion in patients treated
with primary angioplasty for acute myocardial infarction: myocardial
blush grade. Circulation 1998;97:2302–6.
 Kurz T, Yamada KA, DaTorre SD, Corr PB. Alpha 1-adrenergic system and
 Heusch G. α-Adrenergic mechanisms in myocardial ischemia. Circulation
B, et al. Postischemic left ventricular dysfunction is abolished by alpha-
adrenergic blocking agents. J Am Coll Cardiol 1998;31:992–1001.
Effects of selective alpha1- and alpha2-adrenergic blockade on coronary
flow reserve after coronary stenting. Circulation 2002;106:2901–7.
 De Luca G, van't Hof AW, de Boer MJ, Hoorntje JC, Gosselink AT,
Dambrink JH, et al. Impaired myocardial perfusion is a major explanation
of the poor outcome observed in patients undergoing primary angioplasty
for ST-segment-elevation myocardial infarction and signs of heart failure.
 Haager PK, Christott P, Heussen N, Lepper W, Hanrath P, Hoffmann R.
Prediction of clinical outcome after mechanical revascularization in acute
myocardial infarction by markers of myocardial reperfusion. J Am Coll
 Poli A, Fetiveau R, Vandoni P, del Rosso G, D'Urbano M, Seveso G, et al.
after successful primary angioplasty: Real-time grading of microvascular
reperfusion and prediction of early and late recovery of left ventricular
function. Circulation 2002;106:313–8.
 Babarto E, Bartunek J, Aarnoudse W, Vanderheyden M, Staelens F, Wijns
W, et al. Alpha-adrenergic receptoe blockade and hyperaemia response in
patients with intermediate coronary stenoses. Eur Heart J 2004;25:2034–9.
 Lorenzoni R, Rosen SD, Camici PG. Effect of α-adrenoceptor blockade on
resting and hyperemic myocardial blood flow in normal humans. Am H
Physiol 1996;271(4 Pt 2):H1302–6.
 Kern MJ, Horowitz JD, Ganz P, Gaspar J, Colucci WS, Lorell BH, et al.
Attenuation of coronary vascular resistance by selective alpha1-adrenergic
blockade in patients with coronary artery disease. J Am Coll Cardiol
 Gregorini L, Marco J, Kozakova M, Palombo C, Anguissola GB, Marco I,
et al. Alpha-adrenergic blockade improves recovery of myocardial
perfusion and function after coronary stenting in patients with acute
myocardial infarction. Circulation 1999;99:482–90.
 Cosenzi A, Sacerdote A, Bocin E, Molino R, Plazzotta N, Seculin P, et al.
Neither physical exercise nor alpha-1 and beta-adrenergic blockade affect
plasma endothelin concentrations. Am J Hypertens 1996;9:819–22.
157D. Yao et al. / European Journal of Internal Medicine 20 (2009) 152–157