Cardiac electrophysiologic study in anesthetized African green monkey
Effects of sequential does intravenous administration of DPO-1 (mg/kg i.v.) on heart rate, mean arterial pressure, and electrocardiographic and cardiac electrophysiologic parameters, measured at baseline and both immediately (Immed) and 15 min (15 min) after dosing. Data are mean ± S.E.M. with n = 7.
Parameter | DPO-1 | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Baseline | 1.0 | 3.0 | 10.0 | ||||||||||
| Immed | 15 min | Immed | 15 min | Immed | 15 min | ||||||||
| Heart rate (bpm) | 154 ± 7 | 139 ± 4 | 133 ± 5 | 129 ± 3 | 131 ± 6 | 125 ± 3 | 130 ± 5 | ||||||
| MAP (mm Hg) | 96 ± 13 | 117 ± 10 | 118 ± 13 | 122 ± 10 | 118 ± 12 | 125 ± 10 | 121 ± 10 | ||||||
| PR interval (ms) | 112 ± 4 | 125 ± 3 | 122 ± 3 | 128 ± 2 | 122 ± 3 | 131 ± 3 | 123 ± 3 | ||||||
| QRS interval (ms) | 46 ± 2 | 49 ± 2 | 48 ± 1 | 51 ± 2 | 48 ± 2 | 52 ± 2 | 48 ± 2 | ||||||
| QTc interval (ms/√s) | 370 ± 7 | 366 ± 14 | 376 ± 14 | 374 ± 12 | 376 ± 15 | 380 ± 12 | 386 ± 15 | ||||||
| AET (mA) | 0.07 ± 0.01 | 0.06 ± 0.01 | 0.06 ± 0.01 | 0.06 ± 0.01 | 0.06 ± 0.01 | 0.06 ± 0.01 | 0.06 ± 0.01 | ||||||
| ARP (ms) | 118 ± 5 | 120 ± 5 | 127 ± 4** | 130 ± 5** | 131 ± 5** | 132 ± 4** | 136 ± 5** | ||||||
| VFT (mA) | 0.13 ± 0.01 | 0.14 ± 0.01 | 0.15 ± 0.02 | 0.16 ± 0.02 | 0.17 ± 0.02 | 0.18 ± 0.02 | 0.19 ± 0.02 | ||||||
| VRP (ms) | 130 ± 6 | 128 ± 5 | 128 ± 5 | 130 ± 5 | 133 ± 4 | 134 ± 4 | 136 ± 4 | ||||||
↵** p < 0.01 using a two-way ANOVA to detect test agent-specific changes differing significantly from the vehicle profile (see Table 2), including a within-test agent treatment group repeated measures followed by a post hoc Fisher's protected least significant difference test to identify statistically significant changes from baseline value.