Table 4.
Parameters at Baseline and After 3 h for BMS-986231 50 μg/kg/min and BMS-986231 50 μg/kg/min + HEX, and at Baseline and After 3 h for BMS-986231 25, 50, and 75 μg/kg/min
| Animals With Normal Cardiac Function (n = 8) (%Δ From Baseline) |
Animals With Pacing-Induced Cardiomyopathy (n = 6) (%Δ From Respective Baselines) |
||||||
|---|---|---|---|---|---|---|---|
| Baseline | 50 μg/kg/min (3 h) | 50 μg/kg/min (3 h + HEX) | Baseline (Dose, μg/kg/min) | 25 μg/kg/min (3 h) | 50 μg/kg/min (3 h) | 75 μg/kg/min (3 h) | |
| CO, l/min | 1.9 ± 0.1 | 1.9 ± 0.1 (2 ± 2) | 2.2 ± 0.2∗ (17 ± 3) | 1.4 ± 0.1 (25) 1.5 ± 0 (50) 1.5 ± 0 (75) |
1.5 ± 0.1∗ (14 ± 1) | 1.8 ± 0∗† (19 ± 2) | 1.8 ± 0.1∗† (20 ± 2) |
| SV, ml | 19 ± 1 | 20 ± 1 (5 ± 3) | 22 ± 0.7∗ (16 ± 4) | 14 ± 0.6 (25) 15 ± 0.6 (50) 14 ± 0.3 (75) |
16 ± 0.8∗ (18 ± 1) | 18 ± 0.5∗ (20 ± 3) | 18 ± 0.7∗ (28 ± 5) |
| HR, beats/min | 100 ± 8 | 96 ± 8 (−4 ± 3) | 101 ± 8 (1 ± 5) | 100 ± 5 (25) 103 ± 5 (50) 109 ± 4 (75) |
94 ± 5∗ (−5 ± 2) | 102 ± 5 (−1 ± 2) | 102 ± 5∗ (−6 ± 2) |
| SW, mm Hg • l | 2 ± 0.2 | 2 ± 0.2∗ (−11 ± 4) | 2 ± 0.2 (−5 ± 2) | 1 ± 0.1 (25) 1 ± 0.1 (50) 1 ± 0 (75) |
1 ± 0.1 (12 ± 4) | 1 ± 0 (5 ± 7) | 1 ± 0.1∗ (10 ± 5) |
| LVESP, mm Hg | 113 ± 4 | 93 ± 5∗ (−18 ± 2) | 93 ± 5∗ (−17 ± 2) | 98 ± 4 (25) 107 ± 5 (50) 108 ± 2 (75) |
90 ± 4∗ (−8 ± 2) | 92 ± 3∗ (−14 ± 3) | 90 ± 3∗ (−17 ± 1) |
| LVEDP, mm Hg | 7 ± 1 | 3 ± 1∗ (−63 ± 17) | 7 ± 1‡ (0 ± 19) | 23 ± 1 (25) 26 ± 2 (50) 25 ± 2 (75) |
20 ± 2∗ (−14 ± 3) | 21 ± 2∗ (−19 ± 4) | 18 ± 1∗ (−24 ± 6) |
| LV peak +dP/dt, mm Hg/s | 2,983 ± 167 | 3,412 ± 215∗ (14 ± 4) | 3,337 ± 177 (13 ± 5) | 1,789 ± 130 (25) 1,936 ± 217 (50) 1,777 ± 140 (75) |
1,945 ± 142 (9 ± 3) | 1,975 ± 182 (3 ± 2) | 1,805 ± 160 (1 ± 2) |
| LVEF, % | 65 ± 2 | 73 ± 2∗ (12 ± 1) | 73 ± 2∗ (12 ± 1) | 37 ± 0.9 (25) 38 ± 0.8 (50) 36 ± 0.6 (75) |
45 ± 2∗ (23 ± 2) | 48 ± 0.8∗ (26 ± 5) | 51 ± 2∗† (41 ± 6) |
| LVEDV, ml | 29 ± 2 | 27 ± 2∗ (−6 ± 2) | 30 ± 1 (3 ± 3) | 37 ± 0.9 (25) 39 ± 0.8 (50) 38 ± 0.5 (75) |
36 ± 1 (−4 ± 1) | 37 ± 1∗ (−5 ± 1) | 35 ± 0.8∗ (−9 ± 2) |
| Tau, ms | 17 ± 1 | 16 ± 0.8∗ (−6 ± 1) | 15 ± 0.8∗ (−10 ± 3) | 18 ± 0.4 (25) 17 ± 0.7 (50) 17 ± 1 (75) |
15 ± 0.9∗ (−18 ± 4) | 15 ± 0.9∗ (−14 ± 3) | 14 ± 0.8∗ (−16 ± 4) |
| PVA, mm Hg • l | 3 ± 0.3 | 3 ± 0.2∗ (−25 ± 4) | 3 ± 0.2∗ (−21 ± 3) | 6 ± 2 (25) 5 ± 2 (50) 4 ± 0.5 (75) |
3 ± 0.4∗ (−28 ± 10) | 3 ± 0.5∗ (−36 ± 6) | 2 ± 0.1∗ (−43 ± 6) |
| PRSW, mm Hg§ | 82 ± 6 | 92 ± 7∗ (12 ± 1) | 93 ± 7∗ (12 ± 1) | 51 ± 2 (25) 59 ± 6 (50) 50 ± 2 (75) |
58 ± 2∗ (10 ± 1) | 70 ± 7∗ (16 ± 1) | 61 ± 2∗ (22 ± 1) |
| MAP, mm Hg | 111 ± 4 | 96 ± 5∗ (−14 ± 1) | 98 ± 4 (−12 ± 2) | 100 ± 4 (25) 112 ± 5 (50) 108 ± 3 (75) |
93 ± 3∗ (−7 ± 2) | 97 ± 3∗ (−13 ± 2) | 92 ± 2∗ (−15 ± 1) |
| SAP, mm Hg | 129 ± 7 | 109 ± 6∗ (−15 ± 1) | 109 ± 5 (−15 ± 3) | 117 ± 4 (25) 126 ± 4 (50) 126 ± 4 (75) |
107 ± 4 (−8 ± 2) | 109 ± 4 (−14 ± 2) | 105 ± 3 (−16 ± 2) |
| DAP, mm Hg | 94 ± 4 | 85 ± 4∗ (−10 ± 2) | 87 ± 5 (−8 ± 3) | 87 ± 5 (25) 96 ± 5 (50) 92 ± 3 (75) |
82 ± 4 (−5 ± 2) | 86 ± 4 (−10 ± 2) | 79 ± 2 (−13 ± 1) |
| SVR, MAP/CO | 58 ± 5 | 49 ± 4∗ (−16 ± 2) | 42 ± 4∗‡ (−28 ± 3) | 56 ± 4 (25) 54 ± 4 (50) 56 ± 3 (75) |
46 ± 4∗ (−16 ± 3) | 38 ± 1∗ (−27 ± 3) | 40 ± 2∗ (−29 ± 2) |
| Ea, mm Hg/ml | 6 ± 0.3 | 5 ± 0.1∗ (−23 ± 3) | 4 ± 0.1∗ (−28 ± 4) | 7 ± 0.4 (25) 8 ± 0.4 (50) 8 ± 0.1 (75) |
6 ± 0.4∗ (−22 ± 1) | 5 ± 0.3∗ (−29 ± 2) | 5 ± 0.2∗ (−35 ± 2) |
| ESPVR, mm Hg/ml | 8 ± 0.9 | 9 ± 1∗ (19 ± 2) | 9 ± 1∗ (20 ± 1) | 5 ± 0.5 (25) 6 ± 0.5 (50) 5 ± 0.5 (75) |
6 ± 0.5∗ (11 ± 1) | 7 ± 0.7∗ (18 ± 1) | 7 ± 0.7∗ (29 ± 1) |
| EDPVR, mm Hg/ml | 1 ± 0.1 | 0.8 ± 0.1∗ (−28 ± 7) | 0.9 ± 0.2∗ (−18 ± 9) | 3 ± 0.4 (25) 3 ± 0.3 (50) 3 ± 0.1 (75) |
2 ± 0.4∗ (−17 ± 2) | 2 ± 0.3∗ (−22 ± 2) | 2 ± 0.2∗† (−39 ± 6) |
Values shown are mean ± SEM or mean ± SD (n).
Ea = arterial elastance; EDPVR = end-diastolic pressure-volume relationship; ESPVR = end-systolic pressure-volume relationship; HEX = Hextend (plasma volume-expanding solution); LVESP = LV end-systolic pressure; PRSW = preload-recruitable stroke work; PVA = pressure-volume area; SW = stroke work; Tau = LV relaxation time-constant; other abbreviations as in Tables 1 and 3.
∗
p < 0.05 vs. respective baseline value.
†
p < 0.05 vs. 25 μg/kg/min dose.
‡
p < 0.05 vs. 50 µg/kg/min (3 h).
§
mm Hg × ml/ml.