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Cardiac function in a long-term follow-up study of moderate and severe porcine model of chronic myocardial infarction.

de Jong R, van Hout GP, Houtgraaf JH, Takashima S, Pasterkamp G, Hoefer I, Duckers HJ - Biomed Res Int (2015)

Bottom Line: At 12 weeks of follow-up the heart was excised for histological analysis and infarct size calculations.Directly following AMI, LVEF was severely reduced compared to baseline in the LAD group (-17.1 ± 1.6%, P = 0.009) compared to only a moderate reduction in the LCx group (-5.9 ± 1.5%, P = 0.02) and this effect remained unchanged during 12 weeks of follow-up.Two models of chronic MI, representative for different patient groups, can reproducibly be created through clinically relevant ischemia-reperfusion of the mid-LAD and proximal LCx.

View Article: PubMed Central - PubMed

Affiliation: Molecular Cardiology Laboratory, Erasmus University Medical Center, Room 2389a, P.O. Box 2040, 3000 CA Rotterdam, Netherlands.

ABSTRACT

Background: Novel therapies need to be evaluated in a relevant large animal model that mimics the clinical course and treatment in a reasonable time frame. To reliably assess therapeutic efficacy, knowledge regarding the translational model and the course of disease is needed.

Methods: Landrace pigs were subjected to a transient occlusion of the proximal left circumflex artery (LCx) (n = 6) or mid-left anterior descending artery (LAD) (n = 6) for 150 min. Cardiac function was evaluated before by 2D echocardiography or 3D echocardiography and pressure-volume loop analysis. At 12 weeks of follow-up the heart was excised for histological analysis and infarct size calculations.

Results: Directly following AMI, LVEF was severely reduced compared to baseline in the LAD group (-17.1 ± 1.6%, P = 0.009) compared to only a moderate reduction in the LCx group (-5.9 ± 1.5%, P = 0.02) and this effect remained unchanged during 12 weeks of follow-up.

Conclusion: Two models of chronic MI, representative for different patient groups, can reproducibly be created through clinically relevant ischemia-reperfusion of the mid-LAD and proximal LCx.

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Related in: MedlinePlus

Pressure-volume loop analysis, troponin I, and infarcts size. (a)–(e) Pressure-volume loop analysis. (a) End-systolic pressure (ESP) is significantly lower at follow-up in the LAD group; (b) time to peak ejection rate (tPER); (c) time to peak filling rate (tPFR); (d) Tau: relaxation constant; (e) increase in pressure over time (dP/dt+); (f) troponin I levels 6 hours after myocardial infarction are higher in the LAD group. (g)–(i) Infarct size. (g) Example of infarct by left circumflex artery infarct (LCx) ischemia-reperfusion model. Viable myocardium is red; infarct is depicted in white (arrow). (h) Infarct size in left anterior descending artery (LAD) group is significantly higher; (i) example of an LAD infarct. LCx indicates left circumflex artery. LAD: left descending anterior artery; BL: baseline; FU: follow-up. *P < 0.05.
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fig5: Pressure-volume loop analysis, troponin I, and infarcts size. (a)–(e) Pressure-volume loop analysis. (a) End-systolic pressure (ESP) is significantly lower at follow-up in the LAD group; (b) time to peak ejection rate (tPER); (c) time to peak filling rate (tPFR); (d) Tau: relaxation constant; (e) increase in pressure over time (dP/dt+); (f) troponin I levels 6 hours after myocardial infarction are higher in the LAD group. (g)–(i) Infarct size. (g) Example of infarct by left circumflex artery infarct (LCx) ischemia-reperfusion model. Viable myocardium is red; infarct is depicted in white (arrow). (h) Infarct size in left anterior descending artery (LAD) group is significantly higher; (i) example of an LAD infarct. LCx indicates left circumflex artery. LAD: left descending anterior artery; BL: baseline; FU: follow-up. *P < 0.05.

Mentions: Invasive real-time PV loop analysis was also performed at baseline and 12 weeks of FU. dP/dt− (relaxation of the ventricle) and ESPVR (derivative of contractility) were significantly decreased in the LAD group but not in the LCx group (Figure 5). Indices of diastolic dysfunction, Tau and tPFR (time to peak filling rate), and systolic indices tPER (time to peak ejection rate) increased in both groups. Troponin I levels 6 hours after infarct induction in the LCx group were lower than in the LAD group (358.6 ± 79.9 μg/L versus 560.0 ± 79.9 μg/L, P = 0.02; Figure 5). Post-AMI decrease in cardiac function and troponin levels 6 hours after infarct correlated significantly (R = −0.763; P = 0.028). The average infarct size in the LAD group was significantly higher than in the LCx group (23.4 ± 2.1% in the LAD group versus 9.5 ± 1.7% in the LCx group, Figure 5). There were no differences in collagen density, capillary density, and arteriole density in all myocardial segments (Table 2). A trend towards an increase in arteriole density was observed in the LAD group (P = 0.09).


Cardiac function in a long-term follow-up study of moderate and severe porcine model of chronic myocardial infarction.

de Jong R, van Hout GP, Houtgraaf JH, Takashima S, Pasterkamp G, Hoefer I, Duckers HJ - Biomed Res Int (2015)

Pressure-volume loop analysis, troponin I, and infarcts size. (a)–(e) Pressure-volume loop analysis. (a) End-systolic pressure (ESP) is significantly lower at follow-up in the LAD group; (b) time to peak ejection rate (tPER); (c) time to peak filling rate (tPFR); (d) Tau: relaxation constant; (e) increase in pressure over time (dP/dt+); (f) troponin I levels 6 hours after myocardial infarction are higher in the LAD group. (g)–(i) Infarct size. (g) Example of infarct by left circumflex artery infarct (LCx) ischemia-reperfusion model. Viable myocardium is red; infarct is depicted in white (arrow). (h) Infarct size in left anterior descending artery (LAD) group is significantly higher; (i) example of an LAD infarct. LCx indicates left circumflex artery. LAD: left descending anterior artery; BL: baseline; FU: follow-up. *P < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4352740&req=5

fig5: Pressure-volume loop analysis, troponin I, and infarcts size. (a)–(e) Pressure-volume loop analysis. (a) End-systolic pressure (ESP) is significantly lower at follow-up in the LAD group; (b) time to peak ejection rate (tPER); (c) time to peak filling rate (tPFR); (d) Tau: relaxation constant; (e) increase in pressure over time (dP/dt+); (f) troponin I levels 6 hours after myocardial infarction are higher in the LAD group. (g)–(i) Infarct size. (g) Example of infarct by left circumflex artery infarct (LCx) ischemia-reperfusion model. Viable myocardium is red; infarct is depicted in white (arrow). (h) Infarct size in left anterior descending artery (LAD) group is significantly higher; (i) example of an LAD infarct. LCx indicates left circumflex artery. LAD: left descending anterior artery; BL: baseline; FU: follow-up. *P < 0.05.
Mentions: Invasive real-time PV loop analysis was also performed at baseline and 12 weeks of FU. dP/dt− (relaxation of the ventricle) and ESPVR (derivative of contractility) were significantly decreased in the LAD group but not in the LCx group (Figure 5). Indices of diastolic dysfunction, Tau and tPFR (time to peak filling rate), and systolic indices tPER (time to peak ejection rate) increased in both groups. Troponin I levels 6 hours after infarct induction in the LCx group were lower than in the LAD group (358.6 ± 79.9 μg/L versus 560.0 ± 79.9 μg/L, P = 0.02; Figure 5). Post-AMI decrease in cardiac function and troponin levels 6 hours after infarct correlated significantly (R = −0.763; P = 0.028). The average infarct size in the LAD group was significantly higher than in the LCx group (23.4 ± 2.1% in the LAD group versus 9.5 ± 1.7% in the LCx group, Figure 5). There were no differences in collagen density, capillary density, and arteriole density in all myocardial segments (Table 2). A trend towards an increase in arteriole density was observed in the LAD group (P = 0.09).

Bottom Line: At 12 weeks of follow-up the heart was excised for histological analysis and infarct size calculations.Directly following AMI, LVEF was severely reduced compared to baseline in the LAD group (-17.1 ± 1.6%, P = 0.009) compared to only a moderate reduction in the LCx group (-5.9 ± 1.5%, P = 0.02) and this effect remained unchanged during 12 weeks of follow-up.Two models of chronic MI, representative for different patient groups, can reproducibly be created through clinically relevant ischemia-reperfusion of the mid-LAD and proximal LCx.

View Article: PubMed Central - PubMed

Affiliation: Molecular Cardiology Laboratory, Erasmus University Medical Center, Room 2389a, P.O. Box 2040, 3000 CA Rotterdam, Netherlands.

ABSTRACT

Background: Novel therapies need to be evaluated in a relevant large animal model that mimics the clinical course and treatment in a reasonable time frame. To reliably assess therapeutic efficacy, knowledge regarding the translational model and the course of disease is needed.

Methods: Landrace pigs were subjected to a transient occlusion of the proximal left circumflex artery (LCx) (n = 6) or mid-left anterior descending artery (LAD) (n = 6) for 150 min. Cardiac function was evaluated before by 2D echocardiography or 3D echocardiography and pressure-volume loop analysis. At 12 weeks of follow-up the heart was excised for histological analysis and infarct size calculations.

Results: Directly following AMI, LVEF was severely reduced compared to baseline in the LAD group (-17.1 ± 1.6%, P = 0.009) compared to only a moderate reduction in the LCx group (-5.9 ± 1.5%, P = 0.02) and this effect remained unchanged during 12 weeks of follow-up.

Conclusion: Two models of chronic MI, representative for different patient groups, can reproducibly be created through clinically relevant ischemia-reperfusion of the mid-LAD and proximal LCx.

Show MeSH
Related in: MedlinePlus