Skip to main content
Erschienen in: Cardiovascular Toxicology 9/2022

23.06.2022

An Improved Monkey Model of Myocardial Ischemic Infarction for Cardiovascular Drug Development

verfasst von: Keke Wang, Pengfei Han, Lu Huang, Ying Xiao, Jianglong Hou, Pingliang Yang, Yuping Xie, Jindan Cai, Hongge Wang, Y. James Kang

Erschienen in: Cardiovascular Toxicology | Ausgabe 9/2022

Einloggen, um Zugang zu erhalten

Abstract

Non-human primate monkey model of myocardial ischemic infarction is precious for translational medicine research. Ligation of the left anterior descending (LAD) artery is a common procedure to induce myocardial ischemic infarction. However, the consistency of the myocardial infarction thus generated remains problematic. The present study was undertaken to critically evaluate the monkey model of myocardial ischemic infarction to develop a procedure for a consistent cross-study comparison. Forty male Rhesus monkeys were divided into 4 groups and subjected to LAD artery ligation at different levels along the artery. In addition, the major diagonal branch was selectively ligated parallel to the ligation site of the LAD artery according to the diagonal branch distribution. Analyses of MRI, echocardiography, cardiac hemodynamics, electrocardiography, histopathology, and cardiac injury biomarkers were undertaken to characterize the monkeys with myocardial infarction. Ligation at 40% of the total length of the artery, measured from the apex end, produced variable infarct areas with inconsistent functional alterations. Ligation at 60% or above coupled with selective ligation of diagonal branches produced a consistent myocardial infarction with uniform dysfunction. However, ligation at 70% caused a lethal threat. After a thorough analysis, it is concluded that ligation at 60% of the total length coupled with selective ligation of diagonal branches, enables standardization of the location of occlusion and the subsequent ischemic area, as well as avoids the influence of the diagonal branches, are ideal to produce a consistent monkey model of myocardial ischemic infarction.

Graphical abstract

Literatur
2.
Zurück zum Zitat James, T.N. (1961). Anatomy of the coronary arteries. P.B. Hoeber. James, T.N. (1961). Anatomy of the coronary arteries. P.B. Hoeber.
8.
Zurück zum Zitat Xie, Y., Chen, J., Han, P., Yang, P., Hou, J., & Kang, Y. J. (2012). Immunohistochemical detection of differentially localized up-regulation of lysyl oxidase and down-regulation of matrix metalloproteinase-1 in rhesus monkey model of chronic myocardial infarction. Experimental Biology and Medicine (Maywood, N.J.), 237(7), 853–859. https://​doi.​org/​10.​1258/​ebm.​2012.​012070 CrossRef Xie, Y., Chen, J., Han, P., Yang, P., Hou, J., & Kang, Y. J. (2012). Immunohistochemical detection of differentially localized up-regulation of lysyl oxidase and down-regulation of matrix metalloproteinase-1 in rhesus monkey model of chronic myocardial infarction. Experimental Biology and Medicine (Maywood, N.J.), 237(7), 853–859. https://​doi.​org/​10.​1258/​ebm.​2012.​012070 CrossRef
12.
Zurück zum Zitat Anand, I. S., Sharma, P. L., Chakravarti, R. N., & Wahi, P. L. (1980). Experimental myocardial infarction in rhesus monkeys. Verapamil pretreatment in the reduction of infarct size. Advances in Myocardiology, 2, 425–433. PubMed Anand, I. S., Sharma, P. L., Chakravarti, R. N., & Wahi, P. L. (1980). Experimental myocardial infarction in rhesus monkeys. Verapamil pretreatment in the reduction of infarct size. Advances in Myocardiology, 2, 425–433. PubMed
18.
Zurück zum Zitat Haghighi, K., Kolokathis, F., Pater, L., Lynch, R. A., Asahi, M., Gramolini, A. O., Fan, G. C., Tsiapras, D., Hahn, H. S., Adamopoulos, S., Liggett, S. B., Dorn, G. W., 2nd., MacLennan, D. H., Kremastinos, D. T., & Kranias, E. G. (2003). Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human. The Journal of Clinical Investigation, 111(6), 869–876. https://​doi.​org/​10.​1172/​JCI17892 CrossRefPubMedPubMedCentral Haghighi, K., Kolokathis, F., Pater, L., Lynch, R. A., Asahi, M., Gramolini, A. O., Fan, G. C., Tsiapras, D., Hahn, H. S., Adamopoulos, S., Liggett, S. B., Dorn, G. W., 2nd., MacLennan, D. H., Kremastinos, D. T., & Kranias, E. G. (2003). Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human. The Journal of Clinical Investigation, 111(6), 869–876. https://​doi.​org/​10.​1172/​JCI17892 CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Orlic, D., Kajstura, J., Chimenti, S., Limana, F., Jakoniuk, I., Quaini, F., Nadal-Ginard, B., Bodine, D. M., Leri, A., & Anversa, P. (2001). Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proceedings for National Academics in Science USA, 98(18), 10344–10349. https://​doi.​org/​10.​1073/​pnas.​181177898 CrossRef Orlic, D., Kajstura, J., Chimenti, S., Limana, F., Jakoniuk, I., Quaini, F., Nadal-Ginard, B., Bodine, D. M., Leri, A., & Anversa, P. (2001). Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proceedings for National Academics in Science USA, 98(18), 10344–10349. https://​doi.​org/​10.​1073/​pnas.​181177898 CrossRef
24.
Zurück zum Zitat Zohlnhofer, D., Ott, I., Mehilli, J., Schomig, K., Michalk, F., Ibrahim, T., Meisetschlager, G., von Wedel, J., Bollwein, H., Seyfarth, M., Dirschinger, J., Schmitt, C., Schwaiger, M., Kastrati, A., & Schomig, A. (2006). Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: A randomized controlled trial. JAMA, 295(9), 1003–1010. https://​doi.​org/​10.​1001/​jama.​295.​9.​1003 CrossRefPubMed Zohlnhofer, D., Ott, I., Mehilli, J., Schomig, K., Michalk, F., Ibrahim, T., Meisetschlager, G., von Wedel, J., Bollwein, H., Seyfarth, M., Dirschinger, J., Schmitt, C., Schwaiger, M., Kastrati, A., & Schomig, A. (2006). Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: A randomized controlled trial. JAMA, 295(9), 1003–1010. https://​doi.​org/​10.​1001/​jama.​295.​9.​1003 CrossRefPubMed
25.
Zurück zum Zitat Tendera, M., Wojakowski, W., Ruzyllo, W., Chojnowska, L., Kepka, C., Tracz, W., Musialek, P., Piwowarska, W., Nessler, J., Buszman, P., Grajek, S., Breborowicz, P., Majka, M., Ratajczak, M. Z., & Investigators, R. (2009). Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: Results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial. European Heart Journal, 30(11), 1313–1321. https://​doi.​org/​10.​1093/​eurheartj/​ehp073 CrossRefPubMed Tendera, M., Wojakowski, W., Ruzyllo, W., Chojnowska, L., Kepka, C., Tracz, W., Musialek, P., Piwowarska, W., Nessler, J., Buszman, P., Grajek, S., Breborowicz, P., Majka, M., Ratajczak, M. Z., & Investigators, R. (2009). Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: Results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial. European Heart Journal, 30(11), 1313–1321. https://​doi.​org/​10.​1093/​eurheartj/​ehp073 CrossRefPubMed
30.
Zurück zum Zitat Schaper, W., Piek, J., Munoz-Chapuli, R., Wolf, C., & Ito, W. (1999). Collateral circulation of the heart. Angiogenesis and Cardiovascular Disease, 11, 159–198. Schaper, W., Piek, J., Munoz-Chapuli, R., Wolf, C., & Ito, W. (1999). Collateral circulation of the heart. Angiogenesis and Cardiovascular Disease, 11, 159–198.
Metadaten
Titel
An Improved Monkey Model of Myocardial Ischemic Infarction for Cardiovascular Drug Development
verfasst von
Keke Wang
Pengfei Han
Lu Huang
Ying Xiao
Jianglong Hou
Pingliang Yang
Yuping Xie
Jindan Cai
Hongge Wang
Y. James Kang
Publikationsdatum
23.06.2022
Verlag
Springer US
Erschienen in
Cardiovascular Toxicology / Ausgabe 9/2022
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI
https://doi.org/10.1007/s12012-022-09754-6

Weitere Artikel der Ausgabe 9/2022

Cardiovascular Toxicology 9/2022 Zur Ausgabe