Reduced sympathetic innervation underlies adjacent noninfarcted region dysfunction during left ventricular remodeling

J Am Coll Cardiol. 1997 Oct;30(4):1079-85. doi: 10.1016/s0735-1097(97)00244-1.


Objectives: We examined the association of sympathetic denervation and reduced blood flow with mechanical dysfunction in adjacent noninfarcted regions late after myocardial infarction (MI).

Background: Using a well characterized ovine model of left ventricular (LV) remodeling after transmural anteroapical MI, we previously showed that histologically normal adjacent noninfarcted regions demonstrate mechanical dysfunction.

Methods: Ten sheep underwent coronary ligation. Magnetic resonance imaging was performed before and 8 weeks after infarction for measurement of LV mass, volumes, ejection fraction and regional intramyocardial circumferential shortening (%S). Iodine-123 metaiodobenzylguanidine (I-123 MIBG) and fluorescent microspheres before and after administration of adenosine were infused before death for measurement of sympathetic innervation, blood flow and blood flow reserve from matched postmortem regions.

Results: From baseline to 8 weeks after infarction, LV end-diastolic volume increased from (mean +/- SD) 1.5 +/- 0.3 to 2.6 +/- 0.5 ml/kg (p < 0.001), and LV mass increased from 2.0 +/- 0.3 to 2.6 +/- 0.5 g/kg (p = 0.001). Regionally, the decline in subendocardial %S was greater in adjacent (19 +/- 5% to 8 +/- 5%) than in remote noninfarcted regions (20 +/- 6% to 19 +/- 6%, p < 0.002). No difference in regional blood flow or blood flow reserve was found between adjacent and remote regions, whereas I-123 MIBG uptake was lower in adjacent than in remote myocardium (1.09 +/- 0.30 vs. 1.31 +/- 0.40 nmol/g, p < 0.003). Topographically, from apex to base at 8 weeks after infarction, %S correlated closely with I-123 MIBG uptake (r = 0.93, p = 0.003).

Conclusions: In mechanically dysfunctional noninfarcted regions adjacent to chronic transmural myocardial infarction in the remodeled left ventricle, blood flow and blood flow reserve are preserved, yet sympathetic innervation is reduced. Chronic sympathetic denervation in adjacent noninfarcted regions, in association with regional mechanical dysfunction, may contribute to LV remodeling after infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Iodobenzylguanidine
  • Adrenergic Fibers / pathology*
  • Animals
  • Contrast Media
  • Coronary Circulation / physiology*
  • Disease Models, Animal
  • Female
  • Heart / innervation*
  • Hemodynamics*
  • Magnetic Resonance Imaging
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / pathology*
  • Myocardial Infarction / physiopathology*
  • Radionuclide Imaging
  • Sheep


  • Contrast Media
  • 3-Iodobenzylguanidine