Biomedical Engineering Reference
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procainamide, and sotalol) that cause QT prolongation or TdP did not cause
bradycardia in the assay. Where physicochemical characteristics predicted limited
absorption (a logarithm of the octanol/water partition coefficient less than 1),
microinjection was undertaken to bypass this problem and in each case bradycardia
was observed. Vehicle alone showed no significant effect on heart rate. Drug effects
are potentiated by mutation of the zebrafish KCNH2 (Fig. 5.2b and c), suggesting
200
180
160
140
120
100
80
60
40
20
0
200
*
160
120
80
40
0
*
*
*
0
250
500
750
[Morplolling] (g/m)
(
a
)
(
b
)
160
140
120
100
80
60
40
20
0
160
140
120
100
80
60
40
20
0
Eryth romycli
1000-g/mL
TUAB - MO
TUAB + MO
100-g/mL
10-g/mL
0
1
10
100
[Temperature] (g/mL)
0
1
10
(
c
)
(
d
)
[Clsapride] (g/mL)
160
140
120
100
80
Clmettldlie
60
100
μ
g/mL
40
31
μ
g/mL
10
μ
g/mL
20
0
μ
g/mL
0
0.1
1
10
100
(
e
)
[Temperature] (g/mL)
Figure 5.2
Mean heart rates and standard deviations are shown throughout. (a) The effects of drug
microinjection on HR. An asterisk denotes statistically significant difference from control (p
0.05).
(b) The effect of ZF KCNH2 antisense morpholino on HR. (c) The additive effect of KCNH2 morpholino
and terfenadine. (d) Interaction between erythromycin and cisapride. Atrial heart rate in bpm is plotted
against increasing doses of cisapride for each concentration of erythromycin shown in the box.
(e) Interaction between cimetidine and terfenadine. Atrial heart rate in bpm is plotted against
increasing doses of terfenadine for each concentration of cimetidine shown in the box. (Figure adapted
from Milan et al., 2003.)
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