Evidence for an active inflammatory process in the hibernating human myocardium.
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 ((201)Tl 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/mm(2), n = 12 versus 8.6 +/- 0.9 cells/mm(2), 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.
Frangogiannis
Nikolaos G
NG
Department of Medicine, Baylor College of Medicine, the Methodist Hospital, Houston, Texas 77030, USA. ngf@bcm.tmc.edu
Shimoni
Sarah
S
Chang
Su Min
SM
Ren
Guofeng
G
Shan
Kesavan
K
Aggeli
Constandina
C
Reardon
Michael J
MJ
Letsou
George V
GV
Espada
Rafael
R
Ramchandani
Mahesh
M
Entman
Mark L
ML
Zoghbi
William A
WA
D000368:Aged; D000911:Antibodies, Monoclonal; D002452:Cell Count; D003094:Collagen / Q000378:metabolism; D005260:Female; D006321:Heart / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D008407:Mast Cells / Q000473:pathology; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology; D017682:Myocardial Stunning / Q000473:pathology* / Q000503:physiopathology; D009205:Myocarditis / Q000473:pathology* / Q000503:physiopathology; D020127:Recovery of Function; D013194:Staining and Labeling
D000911:Antibodies, Monoclonal; D003094:Collagen