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Distal coronary embolization following acute myocardial infarction increases early infarct size and late left ventricular wall thinning in a porcine model.

Thomas RM, Lim SY, Qiang B, Osherov AB, Ghugre NR, Noyan H, Qi X, Wolff R, Ladouceur-Wodzak M, Berk TA, Butany J, Husain M, Wright GA, Strauss BH - J Cardiovasc Magn Reson (2015)

Bottom Line: Animals were sacrificed at 3 h (n = 5), 3 days (n = 20) or 6 weeks (n = 20) post-AMI.Cardiovascular magnetic resonance (CMR), serum troponin-I, and cardiac gelatinase (MMP) and survival kinase (Akt) activities were assessed.The significance of the later remodelling changes (ventricular thinning and transmurality) following DCE, possibly due to changes in MMP-2 activity and Akt activation, merits further study.

View Article: PubMed Central - PubMed

Affiliation: Schulich Heart Centre, Sunnybrook Health Sciences Center, 2075 Bayview Avenue, Room D-406, Toronto, ON, M4N 3M5, Canada. reuben.thomas@mail.utoronto.ca.

ABSTRACT

Background: Distal coronary embolization (DCE) of thrombotic material occurs frequently during percutaneous interventions for acute myocardial infarction and can alter coronary flow grades. The significance of DCE on infarct size and myocardial function remains unsettled. The aims of this study were to evaluate the effects of DCE sufficient to cause no-reflow on infarct size, cardiac function and ventricular remodeling in a porcine acute myocardial infarction model.

Methods and results: Female Yorkshire pigs underwent 60 min balloon occlusion of the left anterior descending coronary artery followed by reperfusion and injection of either microthrombi (prepared from autologous porcine blood) sufficient to cause no-reflow (DCE), or saline (control). Animals were sacrificed at 3 h (n = 5), 3 days (n = 20) or 6 weeks (n = 20) post-AMI. Cardiovascular magnetic resonance (CMR), serum troponin-I, and cardiac gelatinase (MMP) and survival kinase (Akt) activities were assessed. At 3d, DCE increased infarct size (CMR: 18.8% vs. 14.5%, p = 0.04; serum troponin-I: 13.3 vs. 6.9 ng/uL, p < 0.05) and MMP-2 activity levels (0.81 vs. 0.49, p = 0.002), with reduced activation of Akt (0.06 versus 0.26, p = 0.02). At 6 weeks, there were no differences in infarct size, ventricular volume or ejection fraction between the two groups, although infarct transmurality (70% vs. 57%, p< 0.04) and ventricular thinning (percent change in mid anteroseptal wall thickness:-25.6% vs. 0.7%, p = 0.03) were significantly increased in the DCE group.

Conclusions: DCE increased early infarct size, but without affecting later infarct size, cardiac function or ventricular volumes. The significance of the later remodelling changes (ventricular thinning and transmurality) following DCE, possibly due to changes in MMP-2 activity and Akt activation, merits further study.

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Related in: MedlinePlus

Schematic showing the number of animals utilized in each experimental group. Out of 51 animals, 45 survived to the desired endpoints. n = 5 animals were part of study 1 (no MRI, sacrificed 3 h post ischemia); n = 20 animals were part of study 2 (sacrificed at 3 days post ischemia); n = 20 animals were part of study 3 (sacrificed 6-weeks post ischemia). A subset of animals in study 3 (Control n= 5, DCE n = 3) were imaged at 3 days post ischemia and included with the results from study 2
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Fig1: Schematic showing the number of animals utilized in each experimental group. Out of 51 animals, 45 survived to the desired endpoints. n = 5 animals were part of study 1 (no MRI, sacrificed 3 h post ischemia); n = 20 animals were part of study 2 (sacrificed at 3 days post ischemia); n = 20 animals were part of study 3 (sacrificed 6-weeks post ischemia). A subset of animals in study 3 (Control n= 5, DCE n = 3) were imaged at 3 days post ischemia and included with the results from study 2

Mentions: Animals were subsequently imaged and sacrificed (overdose of pentobarbital sodium injected IV) at one of three time points: immediate (3 h post procedure (no CMR imaging), n = 5 including control = 3 and DCE = 2), early (3d post procedure, n = 20, 10 per group) and late (6 weeks post procedure, n = 20, control = 11, DCE = 9). The study scheme and sample sizes are indicated in Fig. 1. Troponin-I levels were measured at baseline and at 3d.Fig. 1


Distal coronary embolization following acute myocardial infarction increases early infarct size and late left ventricular wall thinning in a porcine model.

Thomas RM, Lim SY, Qiang B, Osherov AB, Ghugre NR, Noyan H, Qi X, Wolff R, Ladouceur-Wodzak M, Berk TA, Butany J, Husain M, Wright GA, Strauss BH - J Cardiovasc Magn Reson (2015)

Schematic showing the number of animals utilized in each experimental group. Out of 51 animals, 45 survived to the desired endpoints. n = 5 animals were part of study 1 (no MRI, sacrificed 3 h post ischemia); n = 20 animals were part of study 2 (sacrificed at 3 days post ischemia); n = 20 animals were part of study 3 (sacrificed 6-weeks post ischemia). A subset of animals in study 3 (Control n= 5, DCE n = 3) were imaged at 3 days post ischemia and included with the results from study 2
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4666124&req=5

Fig1: Schematic showing the number of animals utilized in each experimental group. Out of 51 animals, 45 survived to the desired endpoints. n = 5 animals were part of study 1 (no MRI, sacrificed 3 h post ischemia); n = 20 animals were part of study 2 (sacrificed at 3 days post ischemia); n = 20 animals were part of study 3 (sacrificed 6-weeks post ischemia). A subset of animals in study 3 (Control n= 5, DCE n = 3) were imaged at 3 days post ischemia and included with the results from study 2
Mentions: Animals were subsequently imaged and sacrificed (overdose of pentobarbital sodium injected IV) at one of three time points: immediate (3 h post procedure (no CMR imaging), n = 5 including control = 3 and DCE = 2), early (3d post procedure, n = 20, 10 per group) and late (6 weeks post procedure, n = 20, control = 11, DCE = 9). The study scheme and sample sizes are indicated in Fig. 1. Troponin-I levels were measured at baseline and at 3d.Fig. 1

Bottom Line: Animals were sacrificed at 3 h (n = 5), 3 days (n = 20) or 6 weeks (n = 20) post-AMI.Cardiovascular magnetic resonance (CMR), serum troponin-I, and cardiac gelatinase (MMP) and survival kinase (Akt) activities were assessed.The significance of the later remodelling changes (ventricular thinning and transmurality) following DCE, possibly due to changes in MMP-2 activity and Akt activation, merits further study.

View Article: PubMed Central - PubMed

Affiliation: Schulich Heart Centre, Sunnybrook Health Sciences Center, 2075 Bayview Avenue, Room D-406, Toronto, ON, M4N 3M5, Canada. reuben.thomas@mail.utoronto.ca.

ABSTRACT

Background: Distal coronary embolization (DCE) of thrombotic material occurs frequently during percutaneous interventions for acute myocardial infarction and can alter coronary flow grades. The significance of DCE on infarct size and myocardial function remains unsettled. The aims of this study were to evaluate the effects of DCE sufficient to cause no-reflow on infarct size, cardiac function and ventricular remodeling in a porcine acute myocardial infarction model.

Methods and results: Female Yorkshire pigs underwent 60 min balloon occlusion of the left anterior descending coronary artery followed by reperfusion and injection of either microthrombi (prepared from autologous porcine blood) sufficient to cause no-reflow (DCE), or saline (control). Animals were sacrificed at 3 h (n = 5), 3 days (n = 20) or 6 weeks (n = 20) post-AMI. Cardiovascular magnetic resonance (CMR), serum troponin-I, and cardiac gelatinase (MMP) and survival kinase (Akt) activities were assessed. At 3d, DCE increased infarct size (CMR: 18.8% vs. 14.5%, p = 0.04; serum troponin-I: 13.3 vs. 6.9 ng/uL, p < 0.05) and MMP-2 activity levels (0.81 vs. 0.49, p = 0.002), with reduced activation of Akt (0.06 versus 0.26, p = 0.02). At 6 weeks, there were no differences in infarct size, ventricular volume or ejection fraction between the two groups, although infarct transmurality (70% vs. 57%, p< 0.04) and ventricular thinning (percent change in mid anteroseptal wall thickness:-25.6% vs. 0.7%, p = 0.03) were significantly increased in the DCE group.

Conclusions: DCE increased early infarct size, but without affecting later infarct size, cardiac function or ventricular volumes. The significance of the later remodelling changes (ventricular thinning and transmurality) following DCE, possibly due to changes in MMP-2 activity and Akt activation, merits further study.

Show MeSH
Related in: MedlinePlus