Evidence for an active inflammatory process in the hibernating human myocardium

Nikolaos G. Frangogiannis, Sarah Shimoni, Su Min Chang, Guofeng Ren, Kesavan Shan, Constandina Aggeli, Michael J. Reardon, George V. Letsou, Rafael Espada, Mahesh Ramchandani, Mark L. Entman, William A. Zoghbi

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Abstract

Myocardial hibernation refers to a state of prolonged impairment of left ventricular function in the presence of coronary artery disease, which may be reversed by revascularization. In this study we present evidence for a local inflammatory reaction in hibernating myocardial segments from patients undergoing coronary revascularization. We obtained transmural myocardial biopsies guided by transesophageal echocardiography from patients with ischemic ventricular dysfunction undergoing bypass surgery. Among the 28 biopsied segments included in the study, 23 showed evidence of systolic dysfunction. The majority of dysfunctional segments (85.7%) were viable (201Tl uptake ≥ 60%). The samples were stained with markers for mast cells, mature resident macrophages, and the monoclonal antibody Mac387 that labels newly recruited myeloid cells. Dysfunctional segments showed more extensive fibrosis and higher macrophage density than normal segments. Among the 23 dysfunctional segments, 12 recovered function as assessed with echocardiograms 3 months after revascularization. Segments with postoperative functional recovery had comparable macrophage and mast cell density with those showing persistent dysfunction. However, biopsied segments that subsequently recovered function contained significantly higher numbers of newly recruited Mac387-positive leukocytes (18.7 ± 3.1 cells/mm2, n = 12 versus 8.6 ± 0.9 cells/mm2, n = 11; P = 0.009). In addition, monocyte chemotactic protein-1, a potent mononuclear cell chemoattractant, was predominantly expressed in segments with recovery of function. Myocardial hibernation is associated with an inflammatory response leading to active leukocyte recruitment. Dysfunctional myocardial segments that show an active inflammatory reaction have a greater potential for recovery of function after revascularization. We postulate that revascularization may promote resolution of the ongoing inflammation, preventing further tissue injury and fibrosis.

Original languageEnglish (US)
Pages (from-to)1425-1433
Number of pages9
JournalAmerican Journal of Pathology
Volume160
Issue number4
StatePublished - 2002
Externally publishedYes

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Myocardial Stunning
Myocardium
Macrophages
Recovery of Function
Mast Cells
Leukocytes
Fibrosis
Ventricular Dysfunction
Chemokine CCL2
Chemotactic Factors
Transesophageal Echocardiography
Myeloid Cells
Left Ventricular Function
Coronary Artery Disease
Cell Count
Monoclonal Antibodies
Inflammation
Biopsy
Wounds and Injuries

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Frangogiannis, N. G., Shimoni, S., Chang, S. M., Ren, G., Shan, K., Aggeli, C., ... Zoghbi, W. A. (2002). Evidence for an active inflammatory process in the hibernating human myocardium. American Journal of Pathology, 160(4), 1425-1433.

Evidence for an active inflammatory process in the hibernating human myocardium. / Frangogiannis, Nikolaos G.; Shimoni, Sarah; Chang, Su Min; Ren, Guofeng; Shan, Kesavan; Aggeli, Constandina; Reardon, Michael J.; Letsou, George V.; Espada, Rafael; Ramchandani, Mahesh; Entman, Mark L.; Zoghbi, William A.

In: American Journal of Pathology, Vol. 160, No. 4, 2002, p. 1425-1433.

Research output: Contribution to journalArticle

Frangogiannis, NG, Shimoni, S, Chang, SM, Ren, G, Shan, K, Aggeli, C, Reardon, MJ, Letsou, GV, Espada, R, Ramchandani, M, Entman, ML & Zoghbi, WA 2002, 'Evidence for an active inflammatory process in the hibernating human myocardium', American Journal of Pathology, vol. 160, no. 4, pp. 1425-1433.
Frangogiannis, Nikolaos G. ; Shimoni, Sarah ; Chang, Su Min ; Ren, Guofeng ; Shan, Kesavan ; Aggeli, Constandina ; Reardon, Michael J. ; Letsou, George V. ; Espada, Rafael ; Ramchandani, Mahesh ; Entman, Mark L. ; Zoghbi, William A. / Evidence for an active inflammatory process in the hibernating human myocardium. In: American Journal of Pathology. 2002 ; Vol. 160, No. 4. pp. 1425-1433.
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AU - Frangogiannis, Nikolaos G.

AU - Shimoni, Sarah

AU - Chang, Su Min

AU - Ren, Guofeng

AU - Shan, Kesavan

AU - Aggeli, Constandina

AU - Reardon, Michael J.

AU - Letsou, George V.

AU - Espada, Rafael

AU - Ramchandani, Mahesh

AU - Entman, Mark L.

AU - Zoghbi, William A.

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N2 - Myocardial hibernation refers to a state of prolonged impairment of left ventricular function in the presence of coronary artery disease, which may be reversed by revascularization. In this study we present evidence for a local inflammatory reaction in hibernating myocardial segments from patients undergoing coronary revascularization. We obtained transmural myocardial biopsies guided by transesophageal echocardiography from patients with ischemic ventricular dysfunction undergoing bypass surgery. Among the 28 biopsied segments included in the study, 23 showed evidence of systolic dysfunction. The majority of dysfunctional segments (85.7%) were viable (201Tl uptake ≥ 60%). The samples were stained with markers for mast cells, mature resident macrophages, and the monoclonal antibody Mac387 that labels newly recruited myeloid cells. Dysfunctional segments showed more extensive fibrosis and higher macrophage density than normal segments. Among the 23 dysfunctional segments, 12 recovered function as assessed with echocardiograms 3 months after revascularization. Segments with postoperative functional recovery had comparable macrophage and mast cell density with those showing persistent dysfunction. However, biopsied segments that subsequently recovered function contained significantly higher numbers of newly recruited Mac387-positive leukocytes (18.7 ± 3.1 cells/mm2, n = 12 versus 8.6 ± 0.9 cells/mm2, n = 11; P = 0.009). In addition, monocyte chemotactic protein-1, a potent mononuclear cell chemoattractant, was predominantly expressed in segments with recovery of function. Myocardial hibernation is associated with an inflammatory response leading to active leukocyte recruitment. Dysfunctional myocardial segments that show an active inflammatory reaction have a greater potential for recovery of function after revascularization. We postulate that revascularization may promote resolution of the ongoing inflammation, preventing further tissue injury and fibrosis.

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