Figure 7.

Anti-anginal activity of F 15845 in a canine model of demand-ischaemia-induced epicardial ST segment changes. Following the placement of a critical stenosis on a branch of the LAD coronary artery, heart rate was increased to 80–90 bpm over baseline by left atrial pacing and then allowed to recover for 30 min. Drugs were administered as i.v. bolus after the first period of pacing and infused throughout the subsequent three periods. (A) Maximal inhibition (%) of ST segment elevation obtained by F 15845 (0.16 and 0.63 mg·kg⁻¹ i.v. bolus and infusion) and diltiazem (0.16 mg·kg⁻¹ i.v. bolus and infusion). Note equivalent maximal anti-ischaemic effects of F 15845 and diltiazem. (B–C) Mean maximal changes in mean arterial pressure (B) and heart rate (C) induced by F 15845 and diltiazem. Note absence of effects of F 15845 at either dose, and marked effects of diltiazem. Data are mean ± SEM. *P < 0.05 vs. corresponding vehicle. F 15845 was given as a 0.16 mg·kg⁻¹ i.v. bolus and 0.16 mg·kg⁻¹·h⁻¹ infusionor as a 0.63 mg·kg⁻¹ i.v. bolus and 0.63 mg·kg⁻¹·h⁻¹ infusion. Similarly, diltiazem was given as a 0.16 mg·kg⁻¹ i.v. bolus and 0.16 mg·kg⁻¹·h⁻¹ infusion. F 15845, 3-(R)-[3-(2-methoxyphenylthio-2-(S)-methylpropyl]amino-3,4-dihydro-2H-1,5 benzoxathiepine bromhydrate; LAD, left anterior descending.