Hearts from
streptozotocin (STZ)-induced diabetic rats have previously been shown to have impaired intercellular electrical coupling, due to reorganization (lateralization) of
connexin43 proteins. Due to the resulting reduction in conduction reserve, conduction velocity in diabetic hearts is more sensitive to conditions that reduce cellular excitability or intercellular electrical coupling. Diabetes is a known risk factor for cardiac
ischemia, a condition associated with both reduced cellular excitability and reduced intercellular coupling. Activation of Ca(2+)-independent
phospholipase A(2) (
iPLA(2)) is known to be part of the response to acute
ischemia and may contribute to the intercellular uncoupling by causing increased levels of
arachidonic acid and lysophosphatidyl
choline. Normally perfused diabetic hearts are known to exhibit increased
iPLA(2) activity and may thus be particularly sensitive to further activation of these
enzymes. In this study, we used voltage-sensitive
dye mapping to assess changes in conduction velocity in response to acute global
ischemia in Langendorff-perfused STZ-induced diabetic hearts. Conduction slowing in response to
ischemia was significantly larger in STZ-induced diabetic hearts compared with healthy controls. Similarly, slowing of conduction velocity in response to
acidosis was also more pronounced in STZ-induced diabetic hearts. Inhibition of
iPLA(2) activity using
bromoenol lactone (BEL; 10 μM) had no effect on the response to
ischemia in healthy control hearts. However, in STZ-induced diabetic hearts, BEL significantly reduced the amount of conduction slowing observed beginning 5 min after the onset of
ischemia. BEL treatment also significantly increased the time to onset of sustained arrhythmias in STZ-induced diabetic hearts but had no effect on the time to
arrhythmia in healthy control hearts. Thus, our results suggest that
iPLA(2) activation in response to acute
ischemia in STZ-induced diabetic hearts is more pronounced than in control hearts and that this response is a significant contributor to arrhythmogenic conduction slowing.