Treatment with non-selective drugs (eg, long-chain
alcohols,
halothane) that reduce gap junction intercellular communication (GJIC) is associated with reduced
infarct size after
myocardial infarction (MI). Therefore, it has been suggested that gap junction intercellular communication stimulating compounds may increase
infarct size. The
antiarrhythmic peptide analogue
rotigaptide (ZP123) increases cardiac gap junction intercellular communication and the purpose of the present study was to examine the effects of
rotigaptide treatment on
infarct size.
Myocardial infarction was induced in male rats by
ligation of the left anterior descending artery (LAD). Rats (n = 156) were treated with
rotigaptide at three dose levels or vehicle from the onset of
ischemia and for 3 weeks following LAD occlusion.
Infarct size was determined using histomorphometry after 3 weeks treatment.
Rotigaptide treatment producing steady state plasma levels of 0.8 +/- 0.1, 5.5 +/- 0.5, and 86 +/- 8 nmol/L had no effect on mortality, but reduced
infarct size to 90 +/- 10% (P = 0.41), 67 +/- 7% (P = 0.005), and 82 +/- 7% (P = 0.13), respectively relative to vehicle-treated
myocardial infarction rats (100 +/- 12%). In contrast to what was predicted, our data demonstrates that
rotigaptide treatment was associated with a significant
infarct size reduction. We conclude that whereas treatment with non-selective inhibitors of gap junction intercellular communication cause a reduction in
infarct size, this information cannot be extrapolated to the effects of compounds that selectively increase gap junction intercellular communication.