| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Heart Institute, Good Samaritan Hospital, University of Southern California, Los Angeles, California 90017-2395
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
No reflow
after acute myocardial infarction is an important predictor of infarct
size and clinical outcome. However, the exact relationship between no
reflow and infarct size remains to be determined, particularly because
no reflow may progress during the time course of reperfusion. Control
groups of five previous protocols using the anesthetized, open-chest
rabbit model of coronary artery occlusion and reperfusion were
retrospectively analyzed with respect to the correlation between
regional myocardial blood flow (RMBF; radioactive microspheres) and
infarct size (triphenyltetrazolium chloride) in the course of
reperfusion. After 30 min of occlusion, reflow (defined as the ratio of
RMBF in the risk area divided by the nonischemic area) declined
from hyperemic values after 30 min of reperfusion (reflow ratio:
1.33 ± 0.81; RMBF in the risk area at the same time point:
2.25 ± 1.04 ml · g
1 · min1) to
0.47 ± 0.22 after 120 min and 0.46 ± 0.13 after 180 min of reperfusion. After 120 min of ischemia, reflow at 30 min of
reperfusion was 0.49 ± 0.24 and deteriorated by 120 min of
reperfusion (0.26 ± 0.15). In every group, there was a strong
correlation between infarct size and reflow (correlation coefficients:
0.62 to 0.82). The lines of regression for the groups with
assessment of RMBF after 120 or 180 min of reperfusion were nearly
identical regardless of the duration of ischemia. Thus
microvascular reperfusion injury led to a striking decrease in RMBF
within the first 2 h of reperfusion, with infarct size as the
major determinant of reflow at a given time point of reperfusion.
myocardial blood flow; rabbit; microvasculature
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
AFTER TEMPORARY CORONARY ARTERY OCCLUSION, reperfusion to the previously ischemic tissue may remain incomplete despite complete reopening of the epicardial artery, due to microvascular damage. This "no-reflow" phenomenon is characterized by decreased resting myocardial blood flow, ultrastructural vascular alterations, and distinct areas of hypoperfusion (11, 12). The degree of no reflow worsens with longer durations of ischemia (12); however, a further progression of no reflow with ongoing reperfusion seems to be characteristic (2). This increasing impairment of myocardial reflow during reperfusion can be interpreted as a form of reperfusion injury at the microvascular level.
In clinical studies, compromised tissue perfusion and distinct areas of microvascular hypoperfusion after successful thrombolysis or primary angioplasty for acute myocardial infarction were demonstrated as well. Recent investigations using the Thrombolysis in Myocardial Infarction (TIMI) grading of myocardial perfusion by coronary angiography (16) or myocardial contrast echocardiography (8, 19) revealed evidence for a close relationship among the incidence or degree of no reflow and clinical outcome, myocardial viability, and left ventricular function at follow-up. In addition, some clinical investigations provided evidence for a progression of microvascular damage with ongoing reperfusion by measurement of intracoronary flow velocities (10) or coronary venous flow (14) after reperfusion therapy for acute myocardial infarction.
However, the exact relationship between the amount of no reflow, as influenced by different durations of ischemia and reperfusion, and myocardial infarct size remains to be determined in both clinical and experimental animal studies. In the present analysis, control experiments of five protocols were retrospectively grouped to gain insight into the relationship between no reflow and myocardial infarct size and to determine to what degree this relationship depends on the duration of ischemia and reperfusion.
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Animal preparation. All experiments were conducted in accordance with the institutional and national Guide for the Care and Use of Laboratory Animals (17). Animals that served as control groups for other protocols were analyzed retrospectively for the current study.
New Zealand White rabbits, weighing between 2.0 and 3.6 kg, were anesthetized with an intramuscular injection of ketamine (400 mg) and xylazine (200 mg). After the rabbits were shaved, tracheotomy or endotracheal intubation was followed by mechanical ventilation using room air enriched with 1.5 l/min oxygen. Initial tidal volumes were adjusted after thoracotomy. Fluid-filled catheters were inserted into the jugular vein and carotid artery for additional intravenous anesthesia (pentobarbital, as needed) and continuous monitoring of arterial blood pressure. After a thoracotomy via the fourth intercostal space and pericardial incision, a major branch of the circumflex coronary artery was encircled by a suture. The two ends of the suture were threaded through a piece of plastic tubing, forming a snare. Thereafter, a fluid-filled catheter was inserted into the left atrial appendage and fixed by a clamp. Rectal temperature was monitored, and a heating pad was used to maintain body temperature. After registration of baseline parameters, the coronary artery was occluded by tightening the snare for either 30 or 120 min. Reperfusion was then allowed by release of the coronary occlusion. At different time points, regional myocardial blood flow (RMBF) was measured by intra-atrial injection of radioactive labeled microspheres (see Regional myocardial blood flow). At the end of reperfusion, the coronary artery was reoccluded, and 4 ml of 50% Uniperse blue (Ciba-Geigy; Hawthorne, NY) were injected into the left atrial appendage. The rabbits were euthanized by an intravenous overdose of xylazine followed by 12 meq of potassium chloride (intraatrial).Assessment of ischemic risk area and infarct size. After removal of the right ventricle and the major vessels, the left ventricle was transversely sliced into six to eight sections and photographed. The slices were incubated in 1% triphenyltetrazolium chloride for ~15 min and rephotographed. After projection of the slides, the contour of each slice, the risk area, visualized as tissue not stained by the blue dye, and the area of necrosis (not stained by triphenyltetrazolium) were traced manually. After computerized planimetry, the percentages of the risk area and necrotic area were multiplied by the weight of the slice; the risk area was expressed as a percentage of the weight of the left ventricle, and the area of necrosis was expressed as a percentage of the risk area.
Regional myocardial blood flow. RMBF was measured by intra-atrial injection of ~500,000 microspheres per measurement labeled with 96niobium, 141cerium, or 103ruthenium. Simultaneously, a reference blood sample was withdrawn through the arterial catheter at a rate of 2.06 ml/min. At the end of the protocol, the hearts were cut into samples stained by the blue dye (nonischemic tissue) and not stained by the blue dye (risk area). Tissue and blood sample radioactivity was counted using a multichannel pulse-height analyzer (model ND62, Nuclear Data; Schaumburg, IL). After correction for background and crossover, RMBF was calculated as the ratio of counts in the myocardial tissue and the blood sample multiplied by the reference flow rate and divided by the weight of the tissue sample. The amount of reflow was defined as the ratio of RMBF in the risk area divided by the RMBF in the nonischemic tissue.
Experimental protocols.
Table 1 summarizes the experimental
protocols for the five groups. Primary data of group IV have
been published as a control group of another study (7),
and primary data for group I are part of a study under
consideration for publication in the journal Coronary Artery
Disease.
|
1 · min1, because
this group served as a control group for a drug study. For the same
reasons, an intravenous bolus of saline was given in group
III at 20 min of occlusion.
Statistical analysis. The measured parameters are expressed as means ± SD. To assess whether the groups are comparable with respect to baseline parameters, risk area, hemodynamics, and temperature, a one-way ANOVA for independent measurements was applied. RMBF at different time points and infarct size was analyzed by one-way ANOVA testing with subsequent Tukey's honestly significant difference post hoc test, provided that the F value revealed a significant difference among the groups. Correlation analysis between the amount of reflow and infarct size was performed using Pearson's correlation coefficient with subsequent ANOVA analysis for significance. A P value of <0.05 was considered statistically significant.
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Comparison of the five groups.
The five groups did not significantly differ with respect to body
weight, heart rate, or systolic blood pressure at baseline and during
occlusion (Table 2). In addition,
hemodynamics at 30 min of reperfusion did not significantly differ
among the groups with equal time of ischemia. However, the
animals in group IV tended to have higher diastolic blood
pressure at baseline and during early occlusion (Fig.
1). Importantly, the risk area was nearly
equal in all the five groups. Rectal temperature in group V
was slightly lower than in the other groups.
|
|
Hemodynamics. Figure 1 demonstrates blood pressure and heart rate during the experimental procedure in the five groups. In every group, coronary occlusion was followed by a marked decrease of blood pressure, and heart rate tended to increase slightly. Hemodynamics remained relatively stable until the end of the protocol.
Infarct size.
In the groups with 30 min of occlusion, infarct size as a percentage of
the risk area amounted to 36 ± 16%, 40 ± 17%, and 45 ± 14% (means ± SD) in groups I, II, and
III, respectively. In the groups with 120 min of
occlusion, mean infarct size was 72 ± 10% and 68 ± 12% in
groups IV and V, respectively (Fig.
2). Pairwise comparison of the groups
with equal duration of ischemia did not reveal significant
differences; however, all comparisons between the individual groups
with 30 min of occlusion versus 120 min of occlusion were significantly
different. Hence, as expected, infarct size was larger with 120 min of
ischemia than with 30 min of ischemia.
|
RMBF at baseline and during occlusion.
Baseline RMBF, determined in group II, was 1.81 ± 0.37 ml · g1 · min1 in the
nonischemic area. RMBF during occlusion was determined in
groups I, III, and IV and ranged
between 0.02 ± 0.03 and 0.04 ± 0.02 ml · g1 · min1 in the risk
area, which is consistent with negligible collateral blood flow to the
risk area in the rabbit heart. At the same time points, RMBF in the
nonischemic tissue ranged between 1.47 ± 0.54 and
1.90 ± 0.61 ml · g1 · min1.
RMBF after reperfusion of a 30-min occlusion (groups I-III).
Mean RMBF in the risk area at 30 min of reperfusion was hyperemic in
group I (30 min of occlusion) and amounted to 2.25 ± 1.04 ml · g1 · min1 (RMBF
in the nonischemic area: 1.80 ± 0.38 ml · g1 · min1). But when
RMBF was measured after 120 or 180 min of reperfusion (groups
II and III), a marked decrease of tissue perfusion
within the risk area was apparent (Fig. 2).
|
RMBF after reperfusion of a 120-min occlusion (groups IV and V).
After 120 min of ischemia, RMBF after 30 min of reperfusion did
not reach hyperemic values (0.65 ± 0.28 ml · g1 · min1 in the risk
area versus 1.43 ± 0.50 ml · g1 · min1 in the
nonischemic area) (Fig. 2). Average reflow was 0.49 ± 0.24 after 120 min of occlusion and 30 min of reperfusion (group IV; Fig. 3) and was further reduced after 120 min of occlusion and
120 min of reperfusion (0.26 ± 0.15, group V).
Correlation between reflow and infarct size.
Correlation analysis between infarct size and the amount of reflow
revealed a strong correlation in each of the five groups with the
Pearson correlation coefficient ranging from 0.62 to 0.82 (Fig. 3).
This correlation did not reach statistical significance in group
II (P < 0.086) and group V
(P < 0.065) but did in the other groups.
Interestingly, the lines of regression were nearly equal for
groups II, III, and V when RMBF was
measured after 120 or 180 min of reperfusion, which on the one hand
suggests that the amount of no reflow did not further deteriorate after
120 min of reperfusion, and on the other hand that the reduced reflow after longer times of occlusion but equal time of reperfusion was
solely explained by the larger infarct size. Reflow after 30 min of
reperfusion was characterized by a higher variability in both groups
after 30 and 120 min of ischemia (groups I and IV). The lines of regression of groups I and
IV had a steeper slope, and hyperemic reflow was
predominantly apparent in the animals with small infarcts. Although the
two lines of regression at 30 min of reperfusion differed more than the
lines of regression in the groups with longer reperfusion, the amount
of reflow after 30 min of reperfusion seemed to be mainly determined by
infarct size as well.
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The main results of this analysis are as follows. First, the amount of reflow to the previously ischemic myocardium after release of a coronary artery occlusion decreased with ongoing reperfusion and reached a stable value after 2 h of reperfusion. Second, the impairment of reflow was more pronounced after 2 h of ischemia than after 30 min of ischemia. Third, at every time point of reperfusion, there was a strong correlation between infarct size and the amount of reflow after both 30 and 120 min of ischemia. Finally, at 120 min of reperfusion, the depressed reflow after 2 h of ischemia compared with 30 min of ischemia seemed to be solely explained by the increased size of necrosis. Similarly, after 30 min of reperfusion, infarct size seemed to be the major determinant of reflow.
No reflow and experimental myocardial infarction. As demonstrated by Ambrosio et al. (2) in a canine model of myocardial infarction, anatomic no reflow increased more than twofold between 2 min and 3.5 h of reperfusion, which was accompanied by a parallel progressive decrease of RMBF. Interestingly, the progressive decline of regional blood flow in this study was predominantly observed in zones of low collateral blood flow.
The data presented in our rabbit model, which is characterized by negligible collateral flow, are consistent with these findings and extend the concept of microvascular reperfusion injury by specifying its time course and its relationship to different durations of ischemia and infarct size. While Ambrosio et al. (2) found an inverse correlation between the size of anatomic no reflow and the size of necrosis after 90 min of ischemia and 3.5 h of reperfusion, the results of the present analysis provide evidence for a strong inverse correlation between reflow and infarct size at different time points of reperfusion and after different durations of ischemia. In addition, the increase in no reflow with longer times of ischemia is mainly explained by the increased infarct size notwithstanding the duration of coronary occlusion. As the susceptibility of the microvasculature and cardiomyocytes to both the ischemic insult and reperfusion injury may be different (12), this relationship is not self-evident. On the other hand, the present analysis suggests that the marked progression of no reflow during reperfusion predominantly develops during the first 2 h of reperfusion, with no further deterioration with 3 h of reperfusion. In this context, it should be emphasized that the no-reflow phenomenon is characterized by distinct areas of microvascular perfusion defects; therefore, the data on RMBF within the risk area in this study represent an average value of zones of no or low reflow and normal or even hyperemic regional flow. Hence, RMBF in the risk area is influenced by the size and uniformity of areas of no reflow as well as functional integrity and vasomotor tone in the rest of the previously ischemic tissue. The mechanisms responsible for no reflow and its progression during reperfusion have not yet been fully elucidated, and a characterization of the time course of no reflow during reperfusion might help to estimate the importance of different potential mechanisms. Ischemia-related morphological alterations of the microvascular bed, such as localized endothelial swelling or membrane-bound intraluminal bodies, may contribute to compromised blood flow, probably directly after release of the coronary occlusion (11). With ongoing reperfusion, leukocyte-mediated mechanisms, whether solely confined to mechanical plugging (6) or more likely underlying complex interactions with endothelial cells, platelets, and myocytes (20), have been put forward to explain the progression of microvascular damage during reperfusion. After 90 min of ischemia and 3 h of reperfusion in the canine model, Tanaka et al. (21) demonstrated a marked accumulation of neutrophils in the risk area and beneficial effects of anti-neutrophil treatment on blood flow at 45 min of reperfusion. However, accumulation of granulocytes in the risk area of dog hearts, characterized by higher collateral flow, may already commence during ischemia (5). Hence, the apparently parallel development of no reflow does not necessarily apply to the rabbit model with its lack of collateral flow. Reactive oxygen species (1, 13, 18), originating from leukocytes (4) or the xanthine-oxidase reaction (3), are considered to play a crucial role in microvascular reperfusion injury. Whether the development of tissue edema, which is considered to occur mainly within the first minutes of reperfusion, with subsequent compression of the microvasculature is significantly involved in the progression of microvascular injury during reperfusion appears to be doubtful (15).Microvascular reperfusion injury and infarct size in clinical studies. Recent clinical studies (8, 16, 19) confirm a close correlation among no reflow after reperfusion therapy for myocardial infarction and myocardial viability, clinical outcome, and left ventricular function. Angiographic no reflow after coronary angioplasty for acute myocardial infarction, defined as TIMI grade 0-2 flow on the final coronary angiogram, was shown to be a strong predictor of adverse clinical outcome (16). Ito et al. (9) demonstrated sizable contrast defects by myocardial contrast echocardiography even with TIMI grade 3 flow after primary percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction, and recovery of regional contractile function was only observed in patients without perfusion defects. However, it still remains to be clarified whether the correlation between no reflow and clinical outcome simply reflects the size of the infarct or whether this correlation in addition is directly related to microvascular damage, which might impede infarct healing, promote ventricular remodeling, or potentially reduce collateral formation. A recent study (23) using magnetic resonance imaging for visualization of microvascular obstruction suggested that no reflow might be a prognostic predictor in addition to its relationship to myocardial viability.
Although some clinical studies (10, 14) have provided evidence for a deterioration of no reflow during reperfusion, its significance and time course are not well defined. A progressive decrease of coronary vein flow was demonstrated in 9 of 19 patients, after acute myocardial infarction, over the first 24 h (14). Intracoronary Doppler flow measurement demonstrated characteristic changes within the first 10 min after primary PTCA (10). Also, different or additional mechanisms of no reflow compared with animal models of mechanical coronary artery ligation and reperfusion have to be considered in the clinical situation, which is associated with atherosclerotic and thrombotic vascular alterations. In particular, coronary microembolization in acute myocardial infarction and unstable angina, or as a side effect of thrombolysis or primary PTCA, may significantly compromise microvascular perfusion (22). The present analysis of regional myocardial flow after experimental infarction confirms a close correlation between the amount of necrosis and reflow, which parallels clinical observations. This relation seems to be present after different durations of ischemia and reperfusion. When the same time points of reperfusion are compared, the amount of reflow appears to be predominantly determined by infarct size regardless of the duration of ischemia.Limitations. This analysis was performed retrospectively. Significant differences of diastolic blood pressure at baseline and during early occlusion, as well as temperature, are not reflected by corresponding differences of infarct size or RMBF but may weaken the analysis. Risk area, as one of the major determinants of infarct size in the rabbit, was nearly equal in the five groups.
The overall duration of reperfusion was 2 h in groups II and V but 3 h in the other groups. The determination of infarct size by triphenyltetrazolium staining may depend on the duration of reperfusion; however, average infarct size did not significantly differ from groups with identical duration of ischemia but longer duration of reperfusion in this set of data. In conclusion, resting RMBF after temporary coronary artery occlusion and reperfusion was characterized by a progressive decrease within the first 2 h in the rabbit heart. The amount of reflow closely correlated with the amount of necrosis at any duration of reperfusion. This relation between infarct size and reflow at a given time point of reperfusion seems to be mainly determined by infarct size regardless of the duration of ischemia. These investigations parallel clinical observations that suggest a close relation between the incidence and amount of no reflow and myocardial viability, recovery of regional contractile function, and clinical outcome.| |
FOOTNOTES |
|---|
Address for reprint requests and other correspondence: R. A. Kloner, The Heart Institute, Good Samaritan Hosp., Univ. of Southern California, 1225 Wilshire Blvd., Los Angeles, CA 90017-2395 (E-mail: RKloner{at}goodsam.org).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
10.1152/ajpheart.00767.2001
Received 27 August 2001; accepted in final form 15 October 2001.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Ambrosio, G,
Becker LC,
Grover M,
Hutchins GM,
Weisman H,
and
Weisfeldt ML.
Reduction in experimental infarct size by recombinant human superoxide dismutase: insights into the pathophysiology of reperfusion injury.
Circulation
74:
1424-1433,
1986.
2.
Ambrosio, G,
Weisman HF,
Mannisi JA,
and
Becker LC.
Progressive impairment of regional myocardial perfusion after initial restoration of postischemic blood flow.
Circulation
80:
1846-1861,
1989.
3.
Chambers, DE,
Parks DA,
Patterson G,
Roy R,
McCord JM,
Yoshida S,
Parmley LF,
and
Downey JM.
Xanthine oxidase as a source of free radical damage in myocardial ischemia.
J Mol Cell Cardiol
17:
145-152,
1985.
4.
Duilio, C,
Ambrosio G,
Kuppusamy P,
DiPaula A,
Becker LC,
and
Zweier JL.
Neutrophils are primary source of O2 radicals during reperfusion after prolonged myocardial ischemia.
Am J Physiol Heart Circ Physiol
280:
H2649-H2657,
2001.
5.
Engler, RL,
Dahlgren MD,
Peterson MA,
Dobbs A,
and
Schmid-Schonbein GW.
Accumulation of polymorphonuclear leukocytes during 3-h experimental myocardial ischemia.
Am J Physiol Heart Circ Physiol
251:
H93-H100,
1986.
6.
Engler, RL,
Schmid-Schonbein GW,
and
Pavelec RS.
Leukocyte capillary plugging in myocardial ischemia and reperfusion in the dog.
Am J Pathol
111:
98-111,
1983.
7.
Hale, SL,
and
Kloner RA.
Ischemic preconditioning and myocardial hypothermia in rabbits with prolonged coronary artery occlusion.
Am J Physiol Heart Circ Physiol
276:
H2029-H2034,
1999.
8.
Ito, H,
Iwakura K,
Oh H,
Masuyama T,
Hori M,
Higashino Y,
Fujii K,
and
Minamino T.
Temporal changes in myocardial perfusion patterns in patients with reperfused anterior wall myocardial infarction. Their relation to myocardial viability.
Circulation
91:
656-662,
1995.
9.
Ito, H,
Okamura A,
Iwakura K,
Masuyama T,
Hori M,
Takiuchi S,
Negoro S,
Nakatsuchi Y,
Taniyama Y,
Higashino Y,
Fujii K,
and
Minamino T.
Myocardial perfusion patterns related to thrombolysis in myocardial infarction perfusion grades after coronary angioplasty in patients with acute anterior wall myocardial infarction.
Circulation
93:
1993-1999,
1996.
10.
Iwakura, K,
Ito H,
Nishikawa N,
Hiraoka K,
Sugimoto K,
Higashino Y,
Masuyama T,
Hori M,
Fujii K,
and
Minamino T.
Early temporal changes in coronary flow velocity patterns in patients with acute myocardial infarction demonstrating the "no-reflow" phenomenon.
Am J Cardiol
84:
415-419,
1999.
11.
Kloner, RA,
Ganote CE,
and
Jennings RB.
The "no-reflow" phenomenon after temporary coronary occlusion in dogs.
J Clin Invest
54:
1496-1508,
1974.
12.
Kloner, RA,
Rude RE,
Carlson N,
Maroko PR,
DeBoer LWV,
and
Braunwald E.
Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: which comes first?
Circulation
62:
945-952,
1980.
13.
Kolodgie, FD,
Virmani R,
and
Frab A.
Limitation of no reflow injury by blood-free reperfusion with oxygenated perfluorochemical (fluosol-DA 20%).
J Am Coll Cardiol
18:
215-223,
1991.
14.
Komamura, K,
Kitakaze M,
Nishida K,
Naka M,
Tamai J,
Uematzu M,
Koretsune Y,
Nanto S,
Hori M,
Inoue M,
Kamada T,
and
Kodama K.
Progressive decrease in coronary vein flow during reperfusion in acute myocardial infarction: clinical documentation of the no reflow phenomenon after successful thrombolysis.
J Am Coll Cardiol
24:
370-377,
1994.
15.
Manciet, LH,
Poole DC,
McDonagh PF,
Copeland JG,
and
Matthieu-Costello O.
Microvascular compression during myocardial ischemia: mechanistic basis for no-reflow phenomenon.
Am J Physiol Heart Circ Physiol
266:
H1541-H1550,
1994.
16.
Morishima, I,
Sone T,
Okumura K,
Tsuboi H,
Kondo J,
Mukawa H,
Matsui H,
Toki T,
and
Hayakawa T.
Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction.
J Am Coll Cardiol
36:
1202-1209,
2000.
17.
National Research Council.
Guide for the Care and Use of Laboratory Animals. Washington, DC: Natl. Acad. Press, 1996.
18.
Przyklenk, K,
and
Kloner RA.
"Reperfusion injury" by oxygen-derived free radicals? Effect of superoxide dismutase plus catalase, given at the time of reperfusion, on myocardial infarct size, contractile function, coronary microvasculature, and regional myocardial blood flow.
Circ Res
64:
86-96,
1989.
19.
Sakuma, T,
Otsuka M,
Okimoto T,
Fujiwara H,
Sumii K,
Imazu M,
and
Hayashi Y.
Optimal time for predicting myocardial viability after successful primary angioplasty in acute myocardial infarction: a study using myocardial contrast echocardiography.
Am J Cardiol
87:
687-692,
2001.
20.
Siminiak, T,
Flores NA,
and
Sheridan DJ.
Neutrophil interactions with endothelium and platelets: possible role in the development of cardiovascular injury.
Eur Heart J
16:
160-170,
1995.
21.
Tanaka, M,
Brooks SE,
Richard VJ,
FitzHarris GP,
Stoler RC,
Jennings RB,
Arfors KE,
and
Reimer KA.
Effect of anti-CD18 antibody on myocardial neutrophil accumulation and infarct size after ischemia and reperfusion in dogs.
Circulation
87:
526-535,
1993.
22.
Topol, EJ,
and
Yadav JS.
Recognition of the importance of embolization in atherosclerotic vascular disease.
Circulation
101:
570-580,
2000.
23.
Wu, KC,
Zerhouni EA,
Judd RM,
Lugo-Olivieri CH,
Barouch LA,
Schulman SP,
Blumenthal RS,
and
Lima JAC
Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction.
Circulation
97:
765-772,
1998.
This article has been cited by other articles:
|
|
 |
|
  M. Francone, C. Bucciarelli-Ducci, I. Carbone, E. Canali, R. Scardala, F. A. Calabrese, G. Sardella, M. Mancone, C. Catalano, F. Fedele, et al. Impact of Primary Coronary Angioplasty Delay on Myocardial Salvage, Infarct Size, and Microvascular Damage in Patients With ST-Segment Elevation Myocardial Infarction: Insight From Cardiovascular Magnetic Resonance J. Am. Coll. Cardiol., December 1, 2009; 54(23): 2145 - 2153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Strande, M. E. Widlansky, N. E. Tsopanoglou, J. Su, J. Wang, A. Hsu, K. V. Routhu, and J. E. Baker Parstatin: a cryptic peptide involved in cardioprotection after ischaemia and reperfusion injury Cardiovasc Res, July 15, 2009; 83(2): 325 - 334. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Napodano, A. Ramondo, G. Tarantini, D. Peluso, S. Compagno, C. Fraccaro, A. C. Frigo, R. Razzolini, and S. Iliceto Predictors and time-related impact of distal embolization during primary angioplasty Eur. Heart J., February 1, 2009; 30(3): 305 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. G. Leshnower, H. Sakamoto, H. Hamamoto, A. Zeeshan, J. H. Gorman III, and R. C. Gorman Progression of myocardial injury during coronary occlusion in the collateral-deficient heart: a non-wavefront phenomenon Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1799 - H1804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Thibault, L. Gomez, E. Donal, G. Pontier, M. Scherrer-Crosbie, M. Ovize, and G. Derumeaux Acute myocardial infarction in mice: assessment of transmurality by strain rate imaging Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H496 - H502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Burmeister, C. Rempf, T. G. Standl, S. Rehberg, S. Bartsch-Zwemke, T. Krause, S. Tuszynski, A. Gottschalk, and J. Schulte am Esch Effects of prophylactic or therapeutic application of bovine haemoglobin HBOC-200 on ischaemia-reperfusion injury following acute coronary ligature in rats Br. J. Anaesth., December 1, 2005; 95(6): 737 - 745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Reffemann and R. A. Kloner Microvascular Alterations After Temporary Coronary Artery Occlusion: The No-Reflow Phenomenon Journal of Cardiovascular Pharmacology and Therapeutics, July 1, 2004; 9(3): 163 - 172. [Abstract] [PDF]
|
|
|
|
|
|
E. Biagini, T. W. Galema, A. F. L. Schinkel, W. B. Vletter, J. R. T. C. Roelandt, and F. J. Ten Cate Myocardial wall thickness predicts recovery of contractile function after primary coronary intervention for acute myocardial infarction J. Am. Coll. Cardiol., April 21, 2004; 43(8): 1489 - 1493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T Dirksen, G. Laarman, A. W.J van 't Hof, G. Guagliumi, W. A.L Tonino, L. Tavazzi, D. J.G.M Duncker, M. L Simoons, and on behalf of the PARI-MI Investigators The effect of ITF-1697 on reperfusion in patients undergoing primary angioplasty: Safety and efficacy of a novel tetrapeptide, ITF-1697 Eur. Heart J., March 1, 2004; 25(5): 392 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Reffelmann and R. A. Kloner Is microvascular protection by cariporide and ischemic preconditioning causally linked to myocardial salvage? Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1134 - H1141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Reffelmann and R. A. Kloner Microvascular reperfusion injury: rapid expansion of anatomic no reflow during reperfusion in the rabbit Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H1099 - H1107. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
, reflow = 
, reflow = 
, reflow =