title: Intramyocardial adiposity after myocardial infarction: new implications of a substrate for ventricular tachycardia.
abstract: BACKGROUND
  Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI.
  
  
  RESULTS
  Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI-; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT-; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass-independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation (r) with conduction velocity (r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude (r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups (P>0.29). However, the MI+VT+ group demonstrated a significant (all P≤0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT- group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength (P<0.001).
  
  
  CONCLUSIONS
  Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI.
authors.affiliation: Department of Cardiology, Westmead Hospital, Sydney, Australia (J.P., W.W.B.C., G.S., M.A.B., P.N.A.F., C.M., J.L., E.K., S.P.T., A.T., P.K.); University of Sydney, Sydney, Australia (W.W.B.C., A.K., G.S., P.N.A.F., E.K., S.P.T., A.T., P.K.); and Westmead Millennium Institute, Westmead, Australia (P.N.A.F., E.K.).
authors.forename: Jim
authors.initials: J
authors.lastname: Pouliopoulos
authors.forename: William W B
authors.initials: WW
authors.lastname: Chik
authors.forename: Ajita
authors.initials: A
authors.lastname: Kanthan
authors.forename: Gopal
authors.initials: G
authors.lastname: Sivagangabalan
authors.forename: Michael A
authors.initials: MA
authors.lastname: Barry
authors.forename: Peter N A
authors.initials: PN
authors.lastname: Fahmy
authors.forename: Christine
authors.initials: C
authors.lastname: Midekin
authors.forename: Juntang
authors.initials: J
authors.lastname: Lu
authors.forename: Eddy
authors.initials: E
authors.lastname: Kizana
authors.forename: Stuart P
authors.initials: SP
authors.lastname: Thomas
authors.forename: Aravinda
authors.initials: A
authors.lastname: Thiagalingam
authors.forename: Pramesh
authors.initials: P
authors.lastname: Kovoor
mesh_terms: D050154:Adiposity; D000818:Animals; D003094:Collagen / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D017629:Gap Junctions / Q000378:metabolism / Q000473:pathology; D006329:Heart Conduction System / Q000378:metabolism / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009919:Orchiectomy; D012756:Sheep; D017180:Tachycardia, Ventricular / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D018031:Connexin 43; D003094:Collagen
keywords: adipose tissue; cicatrix; connexin 43; electrophysiology; myocardial infarction; scar; tachycardia, ventricular