Diadenosine polyphosphates (ApnA) are platelet-derived compounds with potent cardiac electrophysiological effects. We have described their effects on cardiac electrophysiology manifest as changes to action potential duration and refractoriness in sub-epicardial myocytes (Stavrou et al. 2001). The purpose of this study was to characterise the action of diadenosine tetraphosphate (Ap₄A) and pentaphosphate (Ap₅A) on sub-endocardial tissue to determine if changes to action potential configuration are variable in different regions of the heart. Such variability has been shown to be an important factor in exacerbating the development of cardiac arrhythmias.

The experiments used left ventricular trabeculae or papillary muscles from male guinea-pigs (300-400 g); the animals had been killed humanely by cervical dislocation. Preparations were superfused with a HCO₃^–/CO₂-Tyrode solution at 36°C, pH 7.35. Muscles were field stimulated with 0.5 ms pulses at either 1 Hz or 3.3 Hz, to compare data with our previous studies; action potentials were recorded with 3 M KCl-filled microelectrodes. Control data were recorded before and after addition of 1 nM or 1 µM Ap₄A or Ap₅A for 30 min. All data are shown as means ± S.D., n is number of experiments, and the differences between data sets were tested for significance (P < 0.05) using Student’s unpaired t test.

At 3.3 Hz stimulation Ap₄A increased action potential duration (APD) by only a small amount: 1 nM, 105 ± 2 % of control (178 ± 2 to 187 ± 2 ms, n = 7) and 1 µM 107 ± 3 % of control (178 ± 2 to 190 ± 3 ms, n = 8). By contrast the increase of APD by 1 µM Ap₄A at 1 Hz stimulation rate was proportionately much greater (134 ± 18 % of control; 198 ± 8 to 290 ± 14 ms, n = 9), although there was no significant effect at 1 nM. Similar results were seen with Ap₅A. No significant effect was observed at 1 nM using 1 Hz or 3.3 Hz stimulation. However, at 1 µM concentration a modest prolongation was recorded at 3.3 Hz (109 ± 3 % of control; 173 ± 3 to 188 ± 4 ms, n = 12) but a much greater effect at 1 Hz stimulation (130 ± 8 % of control; 204 ± 14 to 295 ± 27 ms, n = 5).

These data are different from those observed on sub-epicardial cells where at 3.3 Hz stimulation frequency 1 nM Ap₄A and Ap₅A increased slightly APD. With 1 µM of the respective compounds only Ap₄A generated a small prolongation; Ap₅A had no effect. These data therefore show that the effects of Ap₄A and Ap₅A on action potential configuration are frequency and regionally dependent. Thus these agents would contribute to heterogeneity of conduction in the ventricle and exacerbate the likelihood of arrythmogenesis.

We are grateful to the British Heart Foundation for financial assistance