Ligation of ameroid-stenosed coronary artery leads to reproducible myocardial infarction

a pilot study in a porcine model

Tuija Ikonen, Tommi Pätilä, Kari Virtanen, Jyri Jukka Lommi, Kimmo Lappalainen, Esko Markus Kankuri, Leena Krogerus, Ari Harjula

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    Objective. Myocardial gene and cellular therapies have revived the use of porcine ischemic heart models. Commonly applied ameroid-obstruction produces inconsistent coronary stenoses and myocardial lesions, whereas abrupt coronary occlusion causes arrhythmias and sudden death. To produce a constant myocardial lesion after adaptation to ischemia, we surgically modified the ameroid-model by ligation. As a pilot study for further cell therapy research, the spontaneous myocardial response is described. Materials and methods. Simultaneously with ameroid application, a loose loop of nonabsorbable thread was placed around the left circumflex artery (LCx) on 11 domestic piglets. Three weeks later, the loop was tightened. Coronary arteriograms with Rentrop collateral grading from 0 to 3, and 99mTc-single photon emission computerized tomography studies were performed I to 5 wk after ligation. At autopsy, the hearts were analyzed macroscopically, histologically, and with von Willebrandt factor-staining. Results. LCx-banding was well-tolerated in nine animals, of which angiographic occlusion was gained in eight. Postmortem analysis revealed a 5 to 10 cm(2) transmural or subendocardial lateral myocardial infarction in all except one heart. One week after occlusion, LCx showed well-developed collateral filling (Rentrop-grade 2.7 :+/-: 0.4), which remained unchanged at 5 wk. On single photon emission computerized tomography-scans, lateral wall perfusion increased spontaneously between 1 and 5 wk (P = 0.02), and von Willebrandt factor revealed clusters of neovascularization at the borders of infarct areas. Conclusions. This new modification of ameroid model standardizes myocardial lesion, which might reduce animal number in preclinical studies, thus having ethical aspect. The remarked potential for spontaneous recovery in ischemic porcine myocardium should be considered in preclinical therapeutic studies. (c) 2007 Elsevier Inc. All rights reserved.
    Original languageEnglish
    JournalJournal of Surgical Research
    Volume142
    Issue number1
    Pages (from-to)195-201
    Number of pages7
    ISSN0022-4804
    DOIs
    Publication statusPublished - 2007
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine

    Cite this

    Ikonen, Tuija ; Pätilä, Tommi ; Virtanen, Kari ; Lommi, Jyri Jukka ; Lappalainen, Kimmo ; Kankuri, Esko Markus ; Krogerus, Leena ; Harjula, Ari. / Ligation of ameroid-stenosed coronary artery leads to reproducible myocardial infarction : a pilot study in a porcine model. In: Journal of Surgical Research. 2007 ; Vol. 142, No. 1. pp. 195-201.
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    title = "Ligation of ameroid-stenosed coronary artery leads to reproducible myocardial infarction: a pilot study in a porcine model",
    abstract = "Objective. Myocardial gene and cellular therapies have revived the use of porcine ischemic heart models. Commonly applied ameroid-obstruction produces inconsistent coronary stenoses and myocardial lesions, whereas abrupt coronary occlusion causes arrhythmias and sudden death. To produce a constant myocardial lesion after adaptation to ischemia, we surgically modified the ameroid-model by ligation. As a pilot study for further cell therapy research, the spontaneous myocardial response is described. Materials and methods. Simultaneously with ameroid application, a loose loop of nonabsorbable thread was placed around the left circumflex artery (LCx) on 11 domestic piglets. Three weeks later, the loop was tightened. Coronary arteriograms with Rentrop collateral grading from 0 to 3, and 99mTc-single photon emission computerized tomography studies were performed I to 5 wk after ligation. At autopsy, the hearts were analyzed macroscopically, histologically, and with von Willebrandt factor-staining. Results. LCx-banding was well-tolerated in nine animals, of which angiographic occlusion was gained in eight. Postmortem analysis revealed a 5 to 10 cm(2) transmural or subendocardial lateral myocardial infarction in all except one heart. One week after occlusion, LCx showed well-developed collateral filling (Rentrop-grade 2.7 :+/-: 0.4), which remained unchanged at 5 wk. On single photon emission computerized tomography-scans, lateral wall perfusion increased spontaneously between 1 and 5 wk (P = 0.02), and von Willebrandt factor revealed clusters of neovascularization at the borders of infarct areas. Conclusions. This new modification of ameroid model standardizes myocardial lesion, which might reduce animal number in preclinical studies, thus having ethical aspect. The remarked potential for spontaneous recovery in ischemic porcine myocardium should be considered in preclinical therapeutic studies. (c) 2007 Elsevier Inc. All rights reserved.",
    keywords = "311 Basic medicine",
    author = "Tuija Ikonen and Tommi P{\"a}til{\"a} and Kari Virtanen and Lommi, {Jyri Jukka} and Kimmo Lappalainen and Kankuri, {Esko Markus} and Leena Krogerus and Ari Harjula",
    year = "2007",
    doi = "10.1016/j.jss.2007.01.022",
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    Ligation of ameroid-stenosed coronary artery leads to reproducible myocardial infarction : a pilot study in a porcine model. / Ikonen, Tuija; Pätilä, Tommi; Virtanen, Kari; Lommi, Jyri Jukka; Lappalainen, Kimmo; Kankuri, Esko Markus; Krogerus, Leena; Harjula, Ari.

    In: Journal of Surgical Research, Vol. 142, No. 1, 2007, p. 195-201.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - Ligation of ameroid-stenosed coronary artery leads to reproducible myocardial infarction

    T2 - a pilot study in a porcine model

    AU - Ikonen, Tuija

    AU - Pätilä, Tommi

    AU - Virtanen, Kari

    AU - Lommi, Jyri Jukka

    AU - Lappalainen, Kimmo

    AU - Kankuri, Esko Markus

    AU - Krogerus, Leena

    AU - Harjula, Ari

    PY - 2007

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    N2 - Objective. Myocardial gene and cellular therapies have revived the use of porcine ischemic heart models. Commonly applied ameroid-obstruction produces inconsistent coronary stenoses and myocardial lesions, whereas abrupt coronary occlusion causes arrhythmias and sudden death. To produce a constant myocardial lesion after adaptation to ischemia, we surgically modified the ameroid-model by ligation. As a pilot study for further cell therapy research, the spontaneous myocardial response is described. Materials and methods. Simultaneously with ameroid application, a loose loop of nonabsorbable thread was placed around the left circumflex artery (LCx) on 11 domestic piglets. Three weeks later, the loop was tightened. Coronary arteriograms with Rentrop collateral grading from 0 to 3, and 99mTc-single photon emission computerized tomography studies were performed I to 5 wk after ligation. At autopsy, the hearts were analyzed macroscopically, histologically, and with von Willebrandt factor-staining. Results. LCx-banding was well-tolerated in nine animals, of which angiographic occlusion was gained in eight. Postmortem analysis revealed a 5 to 10 cm(2) transmural or subendocardial lateral myocardial infarction in all except one heart. One week after occlusion, LCx showed well-developed collateral filling (Rentrop-grade 2.7 :+/-: 0.4), which remained unchanged at 5 wk. On single photon emission computerized tomography-scans, lateral wall perfusion increased spontaneously between 1 and 5 wk (P = 0.02), and von Willebrandt factor revealed clusters of neovascularization at the borders of infarct areas. Conclusions. This new modification of ameroid model standardizes myocardial lesion, which might reduce animal number in preclinical studies, thus having ethical aspect. The remarked potential for spontaneous recovery in ischemic porcine myocardium should be considered in preclinical therapeutic studies. (c) 2007 Elsevier Inc. All rights reserved.

    AB - Objective. Myocardial gene and cellular therapies have revived the use of porcine ischemic heart models. Commonly applied ameroid-obstruction produces inconsistent coronary stenoses and myocardial lesions, whereas abrupt coronary occlusion causes arrhythmias and sudden death. To produce a constant myocardial lesion after adaptation to ischemia, we surgically modified the ameroid-model by ligation. As a pilot study for further cell therapy research, the spontaneous myocardial response is described. Materials and methods. Simultaneously with ameroid application, a loose loop of nonabsorbable thread was placed around the left circumflex artery (LCx) on 11 domestic piglets. Three weeks later, the loop was tightened. Coronary arteriograms with Rentrop collateral grading from 0 to 3, and 99mTc-single photon emission computerized tomography studies were performed I to 5 wk after ligation. At autopsy, the hearts were analyzed macroscopically, histologically, and with von Willebrandt factor-staining. Results. LCx-banding was well-tolerated in nine animals, of which angiographic occlusion was gained in eight. Postmortem analysis revealed a 5 to 10 cm(2) transmural or subendocardial lateral myocardial infarction in all except one heart. One week after occlusion, LCx showed well-developed collateral filling (Rentrop-grade 2.7 :+/-: 0.4), which remained unchanged at 5 wk. On single photon emission computerized tomography-scans, lateral wall perfusion increased spontaneously between 1 and 5 wk (P = 0.02), and von Willebrandt factor revealed clusters of neovascularization at the borders of infarct areas. Conclusions. This new modification of ameroid model standardizes myocardial lesion, which might reduce animal number in preclinical studies, thus having ethical aspect. The remarked potential for spontaneous recovery in ischemic porcine myocardium should be considered in preclinical therapeutic studies. (c) 2007 Elsevier Inc. All rights reserved.

    KW - 311 Basic medicine

    U2 - 10.1016/j.jss.2007.01.022

    DO - 10.1016/j.jss.2007.01.022

    M3 - Article

    VL - 142

    SP - 195

    EP - 201

    JO - Journal of Surgical Research

    JF - Journal of Surgical Research

    SN - 0022-4804

    IS - 1

    ER -