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May 1, 1991Journal of Clinical Investigation239 citationsOpen Access

Remodeling of ventricular conduction pathways in healed canine infarct border zones.

RLRobert A. LukeJSJeffrey E. Saffitz

Key Result

In healed canine infarct border zones, the number of cells connected by intercalated disks to a single myocyte was significantly reduced to 6.5 compared to 11.2 in normal myocardium.

Key Points

  • This research aims to understand how myocyte interconnections change in regions adjacent to healed cardiac infarcts and their potential role in causing ventricular tachycardia.
  • Quantitative electron microscopy was used to analyze 10 canine left ventricles 3-10 weeks after coronary occlusion.
  • Three normal canine left ventricles served as control for ultrastructural comparison.
  • Three-dimensional reconstructions of myocyte interconnections were created using high-resolution quantitative light microscopy.
  • Fewer gap junctions were observed in infarct border zones compared to normal myocardium (9.6% of total profiles but 40% of total length in transverse plane).
  • The number of cells connecting to a single myocyte decreased significantly from 11.2 to 6.5 (P<0.001).
  • Connections between cells in side-to-side apposition decreased by 75%, while end-to-end connections reduced by 22% (P<0.05).

Structured PICO

P
Population
10 canine left ventricles 3-10 weeks after coronary occlusion and 3 normal canine left ventricles
I
Intervention
Coronary occlusion (infarct border zone tissues)
C
Comparator
Normal canine left ventricles
O
Outcome
Distribution of gap junctions and myocyte interconnectionssurrogate

Infarct border zones in canine models show significant remodeling and reduction of gap junctions, particularly side-to-side connections, which may enhance axial resistivity and contribute to reentrant arrhythmias.

Main Result

Absolute Event Rate: 6.5% vs 11.2%

p-value: p=<0.001

Limitations

  • Border zone regions were not sampled randomly due to wide variability in structural composition.
  • A causal relationship between mechanical forces from collagen accumulation and the disruption of gap junctions has not been definitively established.

Abstract

Remodeling of myocyte interconnections may be an important determinant of ventricular tachycardia in regions bordering healed infarcts. We used quantitative electron microscopy to characterize the distribution of gap junctions in 10 canine left ventricles 3-10 wk after coronary occlusion. In three normal canine left ventricles analyzed ultrastructurally, myocardial gap junctions were distributed anisotropically; gap junction profile length was significantly greater in the transverse than in longitudinal planes of section. In infarct border zone tissues, the normal anisotropic distribution was completely abolished and fewer gap junctions per unit intercalated disk length were observed. Analysis of individual gap junction profile length distributions revealed selective disruption of the largest gap junctions that collectively comprised only 9.6% of total junction profiles, but encompassed nearly 40% of aggregate gap junction length in the transverse plane of section. Three-dimensional reconstructions of myocyte interconnections by high resolution quantitative light microscopy of serial sections demonstrated a reduction in the number of cells connected by intercalated disks to a single myocyte from 11.2 +/- 1.0 in normal myocardium to 6.5 +/- 1.3 in border zone tissues (P less than 0.001). Connections of cells in primarily side-to-side apposition were reduced by 75%, whereas primarily end-to-end connections were reduced by only 22% (P less than 0.05). These alterations would disproportionately enhance axial resistivity in the transverse direction, potentially contributing to development of reentrant arrhythmias.

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Cite This Study

Luke et al. (1991) studied Healed myocardial infarction (n=13). Coronary occlusion (infarct border zone) vs. Normal myocardium was evaluated on Number of cells connected by intercalated disks to a single myocyte (p=<0.001). In healed canine infarct border zones, the number of cells connected by intercalated disks to a single myocyte was significantly reduced to 6.5 compared to 11.2 in normal myocardium.

synapsesocial.com/papers/6a081c6e280cd4e998e8a6cehttps://doi.org/10.1172/jci115173
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