A Novel Large Animal Model of Thrombogenic Coronary Microembolization

Figures

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  Figure 1. Study design. Myocardial infarction (MI) was induced by occlusion of the mid LAD using an over-the-wire coronary balloon. (A) Coronary microembolization using autologous thrombus injection group (CMET): 60 min after LAD occlusion and with the balloon still inflated, autologous thrombus was injected through the balloon wire lumen. After the injection, the balloon was deflated to allow tissue reperfusion. (B) Ischemia reperfusion (I/R) group: the coronary balloon was deflated after 90 min to allow tissue reperfusion. In both groups, cardiac functional measurements were performed 1 week after the MI. LAD, left anterior descending artery; Echo, echocardiography; PV, pressure volume.

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  Figure 2. CMET leads to higher mortality. Survival curve of the pigs in I/R and CMET groups. I/R, ischemia/reperfusion; CMET, coronary microembolization using autologous thrombus injection; MI, myocardial infarction.

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  Figure 3. Representative coronary angiogram images of a pig injected with autologous thrombus. (A) Left anterior descending artery (LAD) before occlusion. (B) LAD during occlusion with an intracoronary balloon (Arrow). (C) LAD post-autologous thrombus injection and reperfusion in the RAO 90° and (D) LAO 30° projection. LAO, left anterior oblique; RAO, right anterior oblique. Angiogram movies are available in Supplemental Movie 1.

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  Figure 4. CMET leads to increased left ventricular remodeling and reduced left ventricular function. (A) LV volume indices and the EF of the animals before and 1 week after myocardial infarction. CMET leads to significant reduction of LV EF. Measurements were performed using 3D echocardiography, n = 8 each for the CMET and I/R group, n = 3 for the sham group. Change over time was evaluated by the time × group interaction by repeated measures ANOVA (*). Comparison between the study groups (CMET vs. I/R vs. sham) was performed using one-way ANOVA (†). (B) Load dependent parameters of LV function: cardiac output, maximum and minimum left ventricular dP/dt (dP/dt max and -dP/dt min, respectively), as measured using the pressure volume catheter, n = 7 for the CMET, n = 8 for the I/R and n = 3 for the sham group. P-values were determined by the one-way ANOVA. CMET, coronary microembolization using autologous thrombus injection; I/R, ischemia/reperfusion; LV, left ventricular; EDVI, end-diastolic volume index; ESVI, end-systolic volume index; EF, ejection fraction; CO, cardiac output. All data reported as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, †p < 0.05, †††p < 0.001.

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  Figure 5. Pressure-volume relationships 1 week after MI. (A) Representative LV pressure-volume loops during preload reduction 1 week after CMET and (B) after I/R. (C) Load independent parameters of LV function: ESPVR was adjusted to Ea to evaluate LV/arterial coupling. ESPVR/Ea was numerically lower in the CMET group without statistical difference. PRSW was significantly lower in the CMET group. EDPVR slope as a parameter of diastolic function was significantly steeper in the CMET group. ESPVR, end-systolic pressure-volume relationship; Ea, arterial elastance; PRSW, preload-recruitable stroke work; EDPVR, end-diastolic pressure-volume relationship; LV, left ventricular, n = 7 for the CMET, n = 8 for the I/R and n = 3 for the sham group. *p < 0.05 determined by 1-way ANOVA or Kruskal Wallis test.

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  Figure 6. CMET leads to larger scar size compared to I/R. (A) Cross-section of the left ventricle from one pig of each group (CMET and I/R). Note the intramyocardial hemorrhage in the apical part of the CMET heart. (B) Scar size 1 week after I/R or CMET, n = 3. CMET, coronary microembolization using autologous thrombus injection; I/R, ischemia/reperfusion.