During
ischemia, cardiac gap junctions close and neighboring cells uncouple. This leads to slow conduction, increased dispersion of APD90 (duration from action potential beginning to 90% of repolarization), nonuniform anisotropy, and unidirectional conduction block, all of which favor the induction of reentry arrhythmias. It has been suggested that
anti-arrhythmic peptides increase gap junction conductance during states of reduced coupling. The aim of this study was to test the effect of the
anti-arrhythmic peptide N-3-(4-hydroxyphenyl)propionyl Pro-Hyp-Gly-Ala-Gly-
OH (HP-5) (10(-10) ) on dispersion of epicardial APD90 during both normokalemic and hypokalemic
ischemia/reperfusion in isolated perfused rabbit hearts. HP-5 did not affect average APD90, heart rate, left ventricular contractility (LVP dP/dtmax), or mean coronary flow. HP-5 significantly reduced the epicardial APD dispersion during hypokalemic
ischemia (HP-5 treated: 24.1 +/- 3.4 ms, untreated: 33.9 +/- 3.1 ms, p < 0.05 versus untreated) and during normokalemic reperfusion but not during normokalemic
ischemia or control conditions. In addition, among untreated hearts subjected to hypokalemic
ischemia/reperfusion, seven of 10 developed
ventricular fibrillation, whereas only three of nine hearts perfused with HP-5 developed
ventricular fibrillation. These results show that HP-5 is able to reduce APD90 dispersion during hypokalemic
ischemia in rabbit hearts.