Table 3.
Drug | Dose mg/kg | Genotype | N | Baseline BPM | 10% O2 Peak BPM | 10% O2 Declined BPM |
---|---|---|---|---|---|---|
Saline | WT | 73 | 224.05 ± 32.61 | 495.13 ± 66.98 | 268.31 ± 47.62 | |
NULL | 78 | 268.11 ± 36.67+ | 488.02 ± 39.95 | 403.26 ± 46.53+ | ||
L-DOPA | 30 | WT | 8 | 200.73 ± 9.13 | 440.01 ± 82.86 | 259.72 ± 29.84 |
60 | WT | 6 | 243.66 ± 33.19 | 514.42 ± 56.40 | 295.82 ± 70.39 | |
100 | WT | 8 | 227.36 ± 10.04 | 411.19 ± 71.78* | 259.53 ± 35.82 | |
30 | NULL | 8 | 260.29 ± 21.86+ | 478.68 ± 56.41 | 407.29 ± 50.06+ | |
60 | NULL | 8 | 296.08 ± 36.12 | 501.84 ± 20.95 | 426.62 ± 22.63+ | |
100 | NULL | 8 | 266.57 ± 45.23 | 427.66 ± 55.62 | 326.09 ± 61.47* | |
L-DOPA + 10mg/kg Carbidopa | 30 | WT | 12 | 251.99 ± 38.75 | 444.94 ± 71.41 | 233.39 ± 57.62 |
60 | WT | 5 | 205.61 ± 21.63 | 338.77 ± 88.41* | 169.07 ± 37.00* | |
100 | WT | 34 | 204.61 ± 28.59* | 324.14 ± 48.14* | 177.01 ± 26.05* | |
30 | NULL | 12 | 334.14 ± 22.04*+ | 492.57 ± 35.02 | 359.78 ± 57.40+ | |
60 | NULL | 7 | 244.11 ± 100.76 | 340.40 ± 111.44* | 212.76 ± 64.47* | |
100 | NULL | 36 | 219.16 ± 44.74* | 312.25 ± 48.87* | 221.92 ± 39.24*+ | |
Desipramine | 3 | WT | 4 | 199.18 ± 23.82 | 507.59 ± 70.93 | 261.73 ± 33.77 |
10 | WT | 4 | 206.82 ± 14.09 | 529.00 ± 72.21 | 275.64 ± 29.45 | |
30 | WT | 6 | 219.48 ± 12.72 | 420.68 ± 35.47 | 247.50 ± 14.73 | |
3 | NULL | 4 | 266.09 ± 58.38 | 469.60 ± 22.87 | 385.83 ± 36.08 | |
10 | NULL | 4 | 289.39 ± 33.26 | 516.58 ± 33.67 | 403.16 ± 27.52+ | |
30 | NULL | 6 | 326.75 ± 67.87* | 470.95 ± 22.90 | 351.02 ± 17.90+ | |
Tiagabine | 3 | WT | 22 | 194.53 ± 12.25* | 430.29 ± 55.97* | 216.92 ± 48.17* |
10 | WT | 15 | 189.07 ± 18.67* | 376.44 ± 51.35* | 175.68 ± 19.50* | |
30 | WT | 4 | 256.41 ± 16.18 | 357.73 ± 16.94* | 146.38 ± 21.06* | |
3 | NULL | 20 | 289.96 ± 28.97+ | 460.32 ± 30.31 | 326.91 ± 47.03*+ | |
10 | NULL | 16 | 282.39 ± 30.76+ | 472.42 ± 56.26+ | 310.40 ± 49.91*+ | |
30 | NULL | 4 | 250.37 ± 23.00 | 465.69 ± 18.79+ | 294.49 ± 17.80*+ | |
Baclofen | 1 | WT | 8 | 200.67 ± 16.42 | 537.31 ± 39.75 | 245.95 ± 39.75 |
2 | WT | 7 | 195.51 ± 11.63 | 517.88 ± 34.51 | 218.01 ± 39.98 | |
3 | WT | 4 | 204.46 ± 4.26 | 396.02 ± 86.35 | 187.62 ± 54.11* | |
1 | NULL | 8 | 209.96 ± 26.95* | 446.94 ± 29.74+ | 348.51 ± 37.86+ | |
2 | NULL | 6 | 237.42 ± 44.36 | 350.07 ± 78.26*+ | 240.36 ± 75.99* | |
3 | NULL | 4 | 143.58 ± 35.03* | 197.42 ± 14.49* | 146.77 ± 56.90* | |
Muscimol | 1 | WT | 8 | 217.09 ± 9.16 | 495.59 ± 73.38 | 248.87 ± 34.29 |
2 | WT | 8 | 171.61 ± 30.81* | 387.34 ± 86.31* | 153.70 ± 66.62* | |
3 | WT | 7 | 148.70 ± 49.41* | 396.39 ± 71.50* | 150.34 ± 32.11* | |
1 | NULL | 8 | 277.90 ± 54.56 | 507.23 ± 87.24 | 393.38 ± 76.74+ | |
2 | NULL | 7 | 234.31 ± 20.17+ | 365.48 ± 68.62* | 268.45 ± 54.91* | |
3 | NULL | 8 | 188.31 ± 36.68* | 370.08 ± 38.41* | 241.65 ± 97.85* | |
Ketamine | 10 | WT | 4 | 241.09 ± 15.72 | 501.78 ± 53.76 | 272.85 ± 22.41 |
30 | WT | 4 | 223.04 ± 15.88 | 510.12 ± 83.80 | 251.58 ± 25.55 | |
10 | NULL | 4 | 282.47 ± 40.02 | 482.83 ± 53.74 | 410.80 ± 59.30 | |
30 | NULL | 2 | 292.04 ± 14.25 | 513.16 ± 18.61 | 434.15 ± 5.37+ |
Mean breath per minute (BPM) values are presented, +/– SD. *p < 0.05 effect of drug versus saline. +p < 0.05 effect of genotype within the same drug and dosage as determined by ANOVA with Bonferroni post-hoc correction for 61 multiple comparisons (40 for effect of drug vs. saline and 21 for effect of genotype at each drug and dose). Additional parameters including Irregularity Score, Apnea Index, and uncompensated Tidal Volume were also quantified (Supplementary Table 3).