Download Moderate Systemic Hypotension During

Moderate Systemic Hypotension During
Reperfusion Reduces the Coronary
Blood Flow and Increases the Size of
Myocardial Infarction in Pigs*
John N. Nanas, MD; Elias Tsolakis, MD; John V. Terrovitis, MD;
Ageliki Eleftheriou, MD; Stavros G. Drakos, MD; Argirios Dalianis, MD; and
Christos E. Charitos, MD
Study objectives: To examine the effects of low arterial BP (ABP) during reperfusion on the extent
of myocardial infarction and on coronary blood flow (CBF) in an occlusion/reperfusion experimental model.
Design: Prospective, randomized animal study.
Setting: University hospital.
Participants: Normal pigs that were anesthetized, intubated, and mechanically ventilated.
Interventions: Twenty-seven open-chest pigs underwent occlusion of the mid left anterior
descending (LAD) coronary artery for 1 h followed by reperfusion for 2 h. During reperfusion,
the animals were randomly assigned to either continuous infusion of nitroglycerin in therapeutic
doses and fluid infusion at rates to maintain a mean ABP > 80 mm Hg (group 1, n ⴝ 13), or
continuous nitroglycerin infusion at rates to maintain a mean ABP between 60 mm Hg and 75 mm
Hg (group 2, n ⴝ 14).
Measurements and results: The hemodynamics and the coronary ABP distal to the occlusion were
recorded throughout the experiment. In addition, the LAD CBF and peak hyperemia CBF before
occlusion and during reperfusion periods were measured by transit-time flowmetry. At the end
of the experiment, the infarcted left ventricular myocardial size was measured. There were no
significant hemodynamic differences, including the distal coronary arterial pressure, between the
two groups before or during the LAD artery occlusion period. During reperfusion, mean ABP was
90 ⴞ 3 mm Hg in group 1 vs 69 ⴞ 3 mm Hg in group 2 (p < 0.001). In group 1, the infarcted
myocardium represented 50.3 ⴞ 4.3% of the myocardium at risk, vs 69.4 ⴞ 7.2% in group 2
(p < 0.001). During reperfusion, CBF and peak hyperemia CBF were significantly higher in
group 1 than in group 2.
Conclusions: Low ABP during reperfusion increases the size of myocardial infarction and
decreases CBF.
(CHEST 2004; 125:1492–1499)
Key words: blood flow; BP; collateral circulation; infarction; reperfusion
Abbreviations: ABP ⫽ arterial BP; CBF ⫽ coronary blood flow; LAD ⫽ left anterior descending; LV ⫽ left ventricular; MR ⫽ myocardium at risk; DCAP ⫽ distal coronary arterial pressure
xperimental studies have shown that infarct
E size
and rate of infarct progression in dogs with
1,2
chronic hypertension and left ventricular (LV) hypertrophy are markedly influenced by the level of LV
systolic pressure during coronary arterial occlusion,
*From the University of Athens School of Medicine, Department
of Clinical Therapeutics, “Alexandra” Hospital, Athens, Greece.
Manuscript received March 5, 2003; revision accepted August 29,
2003.
Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail:
[email protected]).
Correspondence to: John N. Nanas, MD, Makedonias 24, 104 33
Athens, Greece; e-mail: [email protected]
while normotension induced by renal anastomosis or
nitroprusside during myocardial ischemia resulted in
infarct size similar to normotensive dogs without LV
hypertrophy. However, in observations made in the
For editorial comment see page 1179
thrombolytic era, a systolic arterial BP (ABP) ⬍ 120
mm Hg in patients with acute myocardial infarction
was associated with a higher mortality than in patients with ABP ⬎ 120 mm Hg. Surprisingly, an ABP
even higher than 160 mm Hg did not influence
survival.3
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Laboratory and Animal Investigations
In experimental studies4 –10 using a canine model,
the administration of various pharmacologic agents
that reduced the ABP during coronary artery occlusion with or without reperfusion showed conflicted
effects on the extent of myocardial infarction. These
differences could be attributed to the proved cytoprotective effect of those agents that reduced the
infarct size4 –7 and to the absence of such effect in
those that failed to eliminate the infarct size.4,6,8 The
IV infusion of nitroglycerin in dogs after coronary
artery ligation in doses that reduced the BP by
⬎ 10% of the baseline value was not associated with
reduced infarct size.9,10 However, in that experimental model, nitroglycerin in doses that decreased the
BP by a mean of 10% of the baseline value increased
collateral blood flow and decreased the extent of
myocardial infarction.10 Neither experimental nor
clinical data are available regarding the effects of a
decreased ABP during reperfusion on the extent of
myocardial infarction. The purpose of this study was
to examine the effects of lowering the systemic BP
during reperfusion only, on myocardial infarct size
and coronary blood flow (CBF) in an occlusion/
reperfusion porcine model.
Materials and Methods
Surgical Preparation
All animals used in this study received humane care in
compliance with the guidelines for care and use of laboratory
animals of the US National Institutes of Health. Twenty-seven
pigs weighing 22 to 35 kg were premedicated with ketamine
hydrochloride (15 mg/kg IM) and midazolam (0.5 mg/kg IM),
anesthetized with thiopental sodium (9 mg/kg IV bolus) and
fentanyl citrate (0.5 mg IV bolus), followed by continuous IV
infusions of thiopental sodium (1 mg/min), fentanyl citrate (4
mg/min), pancuronium bromide (0.25 mg/min), and lidocaine (2
mg/min), throughout the experiment. After intubation, respiration was controlled with a Soxitronic volume respirator (Soxil
S.P.A.; Segrate, Italy), supplying a mixture of room air and
oxygen. Tidal volume, respiratory rate, and percentage of inspired oxygen were adjusted to maintain an arterial pH between
7.35 and 7.45, Pco2 between 35 mm Hg and 45 mm Hg, and Po2
⬎ 100 mm Hg. The chest was opened via a midline sternotomy,
and the heart was suspended in a pericardial cradle. Catheters
were placed in the aortic arch via the right carotid artery, in the
right atrium via the right external jugular vein, and in the left
atrium directly through the left atrial appendix. The proximal to
mid left anterior descending (LAD) coronary artery was dissected
free and instrumented from proximal to distal with an ultrathin
catheter (0.018 inches) for infusion of adenosine, a transit time
flowmeter probe, a loose ligature and, distally, an ultrathin
catheter to measure distal coronary artery pressure (DCAP). The
temperature was kept within 0.5°C of the baseline value. ECG,
for severe rhythm disturbances, and aortic pressure were continuously monitored. No pharmacologic agents other than anesthetics, lidocaine, sodium bicarbonate, nitroglycerin, heparin, and
normal saline solution were infused. However, in the experiments
in which the CBF was recorded, in order to achieve peak
hyperemia CBF, on each occasion (eight times during the
experiment), intracoronary adenosine (40 ␮g/kg/min) was infused
for approximately 2 min. All experimental animals underwent
occlusion of the LAD for 1 h followed by reperfusion for 2 h.
Physiologic Measurements
After the completion of the preparation, a few minutes were
allowed for hemodynamic stabilization before the baseline recordings of aortic and right atrial pressures, DCAP, LAD CBF,
and peak hyperemia CBF. Subsequently, pressures were recorded immediately after the occlusion, and every 15 min during
the 1-h period of occlusion. The CBF was recorded at the second
minute after the onset of reperfusion and thereafter at 5, 15, 30,
60, 90, and 120 min of reperfusion, along with peak hyperemia
CBF and pressures.
Experimental Protocol
The LAD artery was then occluded for 1 h when the snare was
released, and reperfusion was established for 2 h. The animals
were excluded from the study if the baseline mean ABP was ⬍ 75
mm Hg. Two groups were studied. In group 1 (n ⫽ 13), IV
nitroglycerin was infused during the reperfusion period at a rate
of 2.5 ␮g/min, along with a crystalloid solution titrated to
maintain a mean ABP ⱖ 80 mm Hg. In group 2 (n ⫽ 14), IV
nitroglycerin was infused during the reperfusion period at a mean
rate of 100 ⫾ 87 ␮g/min to decrease the mean ABP by ⬎ 20% of
baseline, and to maintain it between 60 mm Hg and 75 mm Hg.
Collateral circulatory function was monitored during the occlusion period by measuring peripheral coronary arterial pressure
in seven group 1 and eight group 2 experiments. In the remaining
experiments (n ⫽ 6 in each group), LAD CBF was measured.
The peak hyperemia CBF was obtained after a transient 10 s of
coronary occlusion, during a plateau of hyperemia achieved with
intracoronary adenosine infusion at a rate of 40 ␮g/kg/min,11 and
corresponded to the higher CBF obtained with these interventions.
Three hours after the initial occlusion, the LAD coronary
artery was reoccluded and gentian violet (1%, 3 mL/kg) was
injected into the left atrium over 30 s. Within the next 5 s, the
heart was electrically fibrillated and immediately excised.
Morphometric Measurements
The left ventricle, including the septum, was separated from
the remainder of the heart and cut into 1-cm-thick sections
perpendicular to the apex-base axis. The LV area at risk of
infarction was identified by the absence of gentian violet dye. The
borders of the area at risk were traced with sinice dye on the
heart slices. All sections were placed into a 1% triphenyltetrazolium chloride solution at 37° C for 20 min, allowing the identification of the infarcted area, which remains unstained due to
lack of nicotinamide-adenine dinucleotide or substrate stores.12
Tracings of both sides of each ventricular section, as outlined by
the gentian violet and the triphenyltetrazolium chloride reaction,
were drawn on transparent plastic sheets, and the areas of each of
the demarcated regions of each ventricular section underwent
planimetry.
All slices were weighed. For each experiment, the myocardium
at risk (MR) was calculated as a percentage of the whole left
ventricle; the infarcted myocardium, including the hemorrhagic
myocardium, was calculated as a percentage of the MR, as
previously described in detail.13 The morphometric measurements, including the tracing, planimetry, and final calculations,
were performed by an investigator unaware of the experimental
assignment.
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1493
6.8 ⫾ 2.2
6.5 ⫾ 2.8
6.7 ⫾ 3.0
6.4 ⫾ 2.7
4.5 ⫾ 2.9
7.8 ⫾ 3.1
7.3 ⫾ 2.5
7.1 ⫾ 2.6
6.7 ⫾ 2.4
6.9 ⫾ 2.3
6.3 ⫾ 2.5
6.4 ⫾ 2.9
6.4 ⫾ 3.0
6.6 ⫾ 3.2
6.3 ⫾ 2.0
8.3 ⫾ 3.0
8.2 ⫾ 3.2
7.5 ⫾ 2.5
7.8 ⫾ 3.0
7.4 ⫾ 2.4
12.4 ⫾ 3.4
13.0 ⫾ 4.0
11.9 ⫾ 2.9
13.4 ⫾ 3.1
12.1 ⫾ 3.1†
11.1 ⫾ 2.5†
10.5 ⫾ 2.2†
11.7 ⫾ 1.8†
11.8 ⫾ 2.5†
11.2 ⫾ 1.9†
12.7 ⫾ 3.7
13.0 ⫾ 4.1
12.6 ⫾ 3.6
13.8 ⫾ 3.8
15.9 ⫾ 4.0
14.1 ⫾ 4.7
14.3 ⫾ 3.8
15.8 ⫾ 4.1
14.5 ⫾ 4.0
14.6 ⫾ 3.6
94.2 ⫾ 16.8
91.1 ⫾ 17.9
91.9 ⫾ 11.4
95.1 ⫾ 12.1
70.5 ⫾ 9.0†
68.4 ⫾ 7.3†
66.1 ⫾ 9.3†
68.1 ⫾ 6.9†
72.8 ⫾ 13.6†
68.2 ⫾ 5.4†
98.8 ⫾ 20.3
96.3 ⫾ 19.5
97.5 ⫾ 18.9
97.3 ⫾ 15.4
94.5 ⫾ 12.6
85.6 ⫾ 19.1
88.1 ⫾ 12.0
93.2 ⫾ 13.0
89.4 ⫾ 8.6
93.0 ⫾ 10.3
80.2 ⫾ 17.1
77.4 ⫾ 16.8
78.1 ⫾ 12.2
80.1 ⫾ 11.1
59.7 ⫾ 6.3†
55.6 ⫾ 7.9†
56.3 ⫾ 7.9†
60.5 ⫾ 6.7†
61.7 ⫾ 10.6†
57.7 ⫾ 6.1†
84.5 ⫾ 20.6
82.0 ⫾ 19.9
83.2 ⫾ 17.4
82.9 ⫾ 15.8
79.8 ⫾ 13.3
77.3 ⫾ 14.9
76.9 ⫾ 10.2
79.7 ⫾ 12.6
72.9 ⫾ 10.4
77.4 ⫾ 11.9
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*Data are presented as mean ⫾ SD.
†p ⬍ 0.05 compared with group 1 at the same time point.
107.9 ⫾ 17.1
104.9 ⫾ 18.5
106.1 ⫾ 12.3
111.2 ⫾ 12.6
84.7 ⫾ 10.4†
78.8 ⫾ 10.1†
80.8 ⫾ 10.4†
86.2 ⫾ 9.6†
85.7 ⫾ 12.7†
84.6 ⫾ 6.2†
114.4 ⫾ 17.1
122.6 ⫾ 24.7
111.9 ⫾ 24.2
120.2 ⫾ 25.1
142.3 ⫾ 30.3
139.6 ⫾ 21.5
130.4 ⫾ 22.3
136.0 ⫾ 21.0
137.3 ⫾ 19.4
132.0 ⫾ 18.1
110.6 ⫾ 17.1
116.4 ⫾ 17.4
111.6 ⫾ 16.5
119.5 ⫾ 18.1
138.3 ⫾ 24.2
136.0 ⫾ 27.1
136.4 ⫾ 24.3
140.9 ⫾ 20.6
135.9 ⫾ 29.9
132.2 ⫾ 22.8
Baseline
15-min occlusion
30-min occlusion
60-min occlusion
5-min reperfusion
15-min reperfusion
30-min reperfusion
60-min reperfusion
90-min reperfusion
120-min reperfusion
114.7 ⫾ 24.5
111.0 ⫾ 23.9
112.2 ⫾ 22.4
114.5 ⫾ 20.4
115.0 ⫾ 18.5
103.0 ⫾ 23.1
104.3 ⫾ 17.3
110.9 ⫾ 17.5
106.5 ⫾ 11.5
110.4 ⫾ 17.8
Group 2
(n ⫽ 14)
Group 1
(n ⫽ 13)
Group 2
(n ⫽ 14)
Group 1
(n ⫽ 13)
Group 2
(n ⫽ 14)
Group 1
(n ⫽ 13)
Group 2
(n ⫽ 14)
Diastolic Arterial
Pressure, mm Hg
Group 1
(n ⫽ 13)
Group 2
(n ⫽ 14)
Group 1
(n ⫽ 13)
Group 2
(n ⫽ 14)
The amount of infarcted myocardium, including
the hemorrhagic myocardium, was significantly
Group 1
(n ⫽ 13)
Morphometric Results
Systolic Arterial Pressure,
mm Hg
The hemodynamic measurements at baseline and
during the 1-h period of coronary occlusion were
similar in the two groups (Table 1). DCAP was
identical to the mean aortic pressure before occlusion of the coronary artery and during the reperfusion period in both groups. During the 1 h of LAD
artery occlusion, mean DCAP was 17.4 ⫾ 3.2 mm Hg
in group 1 vs 17.9 ⫾ 4.7 mm Hg in group 2 (p ⫽ 0.721)
and mean coronary arterial perfusion pressure
(DCAP ⫺ right atrial pressure) was 9.7 ⫾ 2.5 mm Hg
in group 1 vs 9.4 ⫾ 3.0 mm Hg in group 2 (p ⫽ 0.644).
During reperfusion, mean aortic pressure and
double product (systolic BP ⫻ heart rate), an index
of the afterload, were significantly higher in group 1
than in group 2: 90 ⫾ 3 mm Hg vs 69 ⫾ 3 mm Hg
(p ⬍ 0.001) and 14,648 ⫾ 657 mm Hg/min vs
11,256 ⫾ 504 mm Hg/min (p ⬍ 0.001). The baseline
CBF was 24 ⫾ 9 mL/min in group 1 and 30 ⫾ 20
mL/min in group 2 (p ⫽ 0.509). In group 1, a high
CBF was measured during the first 5 min of reperfusion, and gradually decreased though remained
above baseline and significantly higher than in group
2 throughout the 2 h of reperfusion (Fig 1). In group
2, CBF increased significantly above baseline at the
onset of reperfusion, though it returned to baseline
levels at 15 min, and continued to decrease gradually
thereafter throughout the 2 h of reperfusion (Fig 1).
In group 1, peak hyperemia CBF was moderately
lower at 5 min after the onset of reperfusion than at
baseline, and remained stable thereafter throughout
the experiment (Fig 2). In group 2, peak hyperemia
CBF at 5 min after the onset of reperfusion was
markedly decreased to less than half of the baseline
level and, after a significant further fall, reached a
plateau at 15 min of reperfusion (Fig 2). During the
2 h of reperfusion, peak hyperemia CBF was significantly lower than at baseline in both groups and, in
group 1, remained significantly higher than in group
2 (Fig 2).
Table 1—Results of Hemodynamic Measurements in Group 1 and Group 2
Hemodynamics
Heart Rate, beats/min
Results
Mean Arterial Pressure,
mm Hg
Rate Pressure Product,
(mm Hg/min ⫻ 1,000)
The LAD CBF and the peak hyperemia CBF were each
normalized to their baseline values. Data for each group were
expressed as mean ⫾ SD. Unpaired Student t test was used to
examine differences between the two experimental groups with
respect to hemodynamic measurements, size of infarcted myocardium, and size of MR. Repeat measurements analysis was
used to evaluate differences between hemodynamic results
within each experimental group at baseline, during coronary
occlusion, and during reperfusion.
Variables
Right Atrial Pressure,
mm Hg
Statistical Analysis
Laboratory and Animal Investigations
Figure 1. Coronary blood flow during reperfusion (CBFr) normalized to baseline one (CBFb).
†p ⬍ 0.05 compared to group 2; ‡p ⱖ 0.05 and ⬍ 0.1 compared to group 2.
smaller in group 1 (50.3 ⫾ 4.3%) than in group 2
(69.4 ⫾ 7.2%, p ⬍ 0.001; Fig 3). This difference
remained significant when including the intracoronary adenosine infusion experiments (54.5 ⫾ 12.8%
and 64.8 ⫾ 11.7%, respectively [p ⫽ 0.047]). The extent of MR, expressed as percentage of the LV myocardium, was similar in both groups (26.8 ⫾ 9.6% vs
27.3 ⫾ 10.3% of the LV myocardium in group 1 vs
group 2, p ⫽ 0.940).
In this study, IV infusion of nitroglycerin was used as
an experimental tool to decrease the ABP during
reperfusion in group 2; in the absence of experimental confirmation of the above hypothesis, our study
design included the infusion of nitroglycerin during
reperfusion in both experimental groups, in therapeutic doses in group 1 and in moderately hypotensive doses in group 2.
Adenosine and Extent of Myocardial Infarction
Discussion
Experimental Animals and Collateral Circulation
The pigs used as experimental models in the
present study are considered to have no, or only
minimal, collateral flows on abrupt occlusion of a
coronary artery.14 Our recording of a low peripheral
coronary arterial perfusion pressure in both groups
of animals was consistent with the presence of a
negligible collateral circulation in this model, as has
been described by other investigators.14
Nitroglycerin and Extent of Myocardial Infarction
In the thrombolytic era, large clinical trials15,16 of
nitrate therapy in acute myocardial infarction found
no independent effect of nitrates on mortality, suggesting that nitroglycerin has no direct effect on
infarct size when administered during reperfusion.
In this study, the peak hyperemia was evaluated
during reperfusion after 1 h of ischemia; therefore,
the coronary vascular function was severely impaired. In order to ascertain the achievement of
maximum coronary vasodilation, the peak hyperemia
was obtained after transient ischemia during intracoronary adenosine infusion. Adenosine induces preconditioning and reduces infarct size if administered
before coronary artery occlusion,17 and inhibits
neutrophil-mediated endothelial cell injury, reduces
infarct size,18,19 prevents the no-reflow phenomenon, and improves ventricular function20 if administered at the time of reperfusion. It is possible that
the infusion of adenosine before arterial occlusion
prolonged the duration of occlusion necessary to
cause infarction,18 and that its repeated infusion
during reperfusion may have mitigated reperfusion
injury and limited infarct size.19
In the present study, the extent of myocardial
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Figure 2. Peak hyperemia coronary blood flow during reperfusion (phCBFr) normalized to baseline
one (phCBFb). †p ⬍ 0.05 compared to group 2; ‡p ⱖ 0.05 and ⬍ 0.1 compared to group 2.
infarction was significantly smaller in group 1 than in
group 2, with and without inclusion of the experiments in which adenosine was used. The differences
in infarct size between animals with high normal
levels (group 1) vs animals with low normal levels
(group 2) of arterial pressure during reperfusion
seems likely to be due to a negative effect of the
lower ABP on the extent of myocardial infarction.
ABP
The present study is the first to prospectively
examine the effects of moderately reduced aortic
pressure during the myocardial reperfusion on the
extent of myocardial infarction. Neither experimental nor clinical data are available regarding the effects
of a decreased ABP during reperfusion on the extent
of myocardial infarction. However, increasing the
diastolic aortic pressure during reperfusion in normotensive dogs reduced the size of myocardial infarction.13 The level of ABP during reperfusion may
influence the extent of the reperfusion injury.
Reperfusion Injury and Postischemic CBF
Experimentally and clinically, reperfusion after
severe myocardial ischemia or infarction precipitates
postreperfusion hemorrhage.21 In this study, the
hemorrhagic component of myocardial infarction
was a fraction of the whole calculated area of
infarcted myocardium. Another factor known to limit
the beneficial effects of blood flow restoration after
ischemia is the inability of myocardial tissue to be
reperfused. It is well established that blood flow
distribution to previously ischemic myocardium is
heterogeneous and may be lower than flow to the
nonischemic region. This multifactorial “no-reflow”
phenomenon is the consequence of severe ischemic
damage to the microvasculature,22 resulting in its
obstruction at the moment of reperfusion23 from
capillary compression by myocardial edema,24 myocardial ischemic contracture,25 direct ischemic microvascular injury with endothelial cell swelling,26
and an increased vasomotor tone.27 Microvascular
obstruction by erythrocyte and leukocyte plugging28
or platelet aggregation29 also seems to participate in
the development of no-reflow, which influences
infarct size and CBF during reperfusion.30
In our study, the CBF and peak hyperemia CBF
during reperfusion were lower in the animals with a
decreased ABP than in animals with a stable ABP
during reperfusion. The decrease in CBF below
baseline values after a brief initial increase in group
2, in contrast to the gradual decrease and maintenance to above baseline values throughout the 2 h of
reperfusion in group 1, is particularly noteworthy.
These serial changes in blood flow in postischemic
myocardium are consistent with those observed in
previous studies. Using radioactive microspheres in
pigs undergoing 40 min of coronary artery occlusion,
Johnson et al30 found a reduction in peak CBF at 60
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Laboratory and Animal Investigations
Figure 3. Infarcted myocardium expressed as percentage of MR.
min of reperfusion comparable to that measured in
group 2 of our study; likewise, infarct size was similar
to that of our group 2. It is also noteworthy that the
systolic BP during reperfusion was unintentionally
decreased from a mean baseline value of 120 mm Hg
to 90 mm Hg, a decrease commensurate to that
measured during reperfusion in our group 2. In
addition, a close correlation (r ⫽ ⫺ 0.79) was found
between the extent of infarction and peak hyperemia
CBF. In dogs, Cobb et al31 found the CBF to be
hyperemic in all myocardial layers during the first 15
min of reperfusion after prolonged coronary occlusion, and to be significantly decreased at 4 h in
regions with ⬎ 50% infarction. Reffelmann et al32
found a significant reduction in myocardial blood
flow between 5 min and 2 h of reperfusion. Furthermore, in isolated rat hearts subjected to 30 min of
no-reflow ischemia, a reduction in coronary flow
during reperfusion enhanced the trapping of leukocytes in capillaries, and adhesion of leukocytes in
venules was inversely related to shear rate.33 Based
on these earlier data, we hypothesize that during
reperfusion, low normal BP is associated with decreased CBF because it cannot provide adequate
reperfusion in myocardial regions with severely increased coronary vascular resistance. This decreased
CBF accelerates leukocyte accumulation, enhances
the no-reflow phenomenon, and increases the extent
of myocardial infarction in group 2. This hypothesis
finds support in the observation of a decrease in
ABP, but not CBF, by prostaglandin I2 during the
reperfusion period, most likely caused by inhibition
of neutrophil function.5,7 A delayed, progressive fall
in CBF in areas that initially were properly reperfused has been observed in regions receiving no
collateral flow during coronary occlusion, which is
associated with accumulation of neutrophils and
plugging of the capillaries late in the course of
reperfusion. In that study, CBF was markedly decreased within the first 30 min of reperfusion with a
further slight reduction at 3.5 h of reperfusion.34
CBF during reperfusion in both our experimental
groups gradually decreased over time, though this
was more prominent in the group with a low ABP
during reperfusion. Since the animals had no evidence of collateral blood flow during occlusion of the
LAD artery, which predisposed them to the development of no-reflow, the pattern of CBF during
reperfusion was probably related to the accumulation of neutrophils, apparently enhanced by the
lower CBF in group 2.34
Clinical Implications
The harmful effects on infarct size of a low normal
ABP during reperfusion observed in this experimen-
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CHEST / 125 / 4 / APRIL, 2004
1497
tal study suggest that it should be avoided in a
clinical situation. Reperfusion during acute myocardial infarction is usually achieved by thrombolysis or
mechanical vessel dilatation. In normotensive patients after such interventions, a low normal ABP in
the absence of other signs of hemodynamic instability can be increased to high normal levels by the
infusion of crystalloid solutions. The results of this
study support the idea that post-myocardial infarct
preshock, defined as persistent low normal ABP in
the presence of other signs of hemodynamic instability, including sinus tachycardia and a third heart
sound, should be treated with the intra-aortic balloon pump, which augments the diastolic aortic
pressure, decreases myocardial infarct size,13,35 and
increases survival.36
Conclusion
Our experiments showed that in normotensive
animals, a decreased central ABP during myocardial
reperfusion, even when kept within normal limits, is
associated with a larger myocardial infarct size and
lower levels of CBF. This suggests that in normotensive patients a decreased ABP, in the setting of acute
myocardial infarction in the absence of other signs of
hemodynamic instability, must be corrected to high
normal levels. Previous experimental and clinical
observations,3,10 combined with the findings of the
present study, allow the formulation of a hypothesis,
to be tested in a randomized clinical study of patients
undergoing coronary reperfusion in the setting of
acute myocardial infarction.
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