Regional myocyte hypertrophy parallels regional myocardial dysfunction during post-infarct remodeling.
After large myocardial infarction (MI), left-ventricular (LV) remodeling is characterized by cavity dilatation, eccentric hypertrophy, and regional mechanical dysfunction. We wished to correlate cellular hypertrophy chronically after MI with in vivo function on a regional basis within non-infarcted myocardium. Twelve sheep were studied. Seven underwent coronary ligation to create an anteroapical MI. Magnetic resonance imaging (MRI) was performed once in controls, and prior to and 8 weeks after infarction, for measurement of LV mass, volumes, ejection fraction, and regional intramyocardial circumferential shortening (%S). Myocyte morphometric indices (cell volume, length, cross-sectional area, width, and length/width ratios) were measured from myocytes isolated from regions adjacent to (within 2 cm of the infarct border) and remote from the infarct and at corresponding loci in the control animals. From baseline to 8 weeks after infarction in the infarcted animals, end-diastolic volume increased from (mean+/-s.d.) 1.9+/-0.4 ml/kg to 2.6+/-0.4 ml/kg (P<0.02) and EF fell from 49+/-6 to 35+/-6% (P<0.02). LV mass trended upwards from 2.2+/-0.4 to 2.6+/-0.4 g/kg (P=n.s.). Regionally, %S in the region adjacent to the infarct fell (from 19+/-3 to 13+/-3%, P<0.003) while remote %S did not change. Cell volume in adjacent non-infarcted regions was greater than that in remote non-infarcted regions (3.8+/-0.9x10(4) micrometer3 v 2.6+/-0. 8x10(4) micrometer3, P<0.006) and this difference (+1.2+/-0.7x10(4) micrometer3) was greater than the corresponding regional difference in controls (+0.4+/-0.2x10(4) micrometer3, P<0.05). Similarly, myocytes in adjacent non-infarcted regions were longer (138.0+/-10.1 micrometer) than in remote regions (123.7+/-10.1 micrometer, P<0.002), and this difference (+14.3+/-7.2 micrometer) was greater than that in controls (-1.4+/-5.6 micrometer, P<0.003). Adjacent %S correlated inversely with adjacent myocyte cell volume (r=-0.72, P<0.009) and cell length (r=-0.70, P<0.02). In mechanically dysfunctional non-infarcted regions adjacent to chronic transmural myocardial infarction in the remodeled LV, disproportionate cellular hypertrophy occurs, predominantly due to an increase in cell length. Mechanical dysfunction in these regions correlates with cell lengthening and hypertrophy.
Department of Medicine, Allegheny General Hospital, Pittsburgh, PA, USA.
C M
CM
Kramer
W J
WJ
Rogers
C S
CS
Park
P S
PS
Seibel
A
A
Shaffer
T M
TM
Theobald
N
N
Reichek
T
T
Onodera
A M
AM
Gerdes
D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology*; D048429:Cell Size; D005260:Female; D006321:Heart / Q000503:physiopathology*; D009203:Myocardial Infarction / Q000503:physiopathology*; D012756:Sheep; D013318:Stroke Volume; D020257:Ventricular Remodeling