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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 27, No 6, November/December 2016
AFRICA
381
As was the case in the 20-minute GI model, FTY720 elicited
a much more evident effect when administered at 2.5
µ
M (Fig.
8), showing a profound effect on functional recovery during
reperfusion. Pre-treatment was associated with a reduction in
aortic output (only one heart recovered sufficiently to generate
AO: control: 27.86
±
13.22% vs PreFTY: 0.62%,
n
=
6;
p
<
0.05)
and work recovery (control: 40.74
±
9.98% vs PreFTY: 15.07
±
5.69%,
n
=
6;
p
<
0.05), while reperfusion administration
significantly reduced cardiac output (control: 46.56
±
10.25%
vs PostFTY: 15.02
±
5.38%,
n
=
6;
p
<
0.05) and work recovery
(control: 40.74
±
9.98% vs PostFTY: 11.84
±
4.59%,
n
=
6;
p
<
0.05).
Although reperfusion treatment did not statistically reduce
aortic output recovery, it is noteworthy that of the six hearts
included in the group, only one recovered sufficiently to actually
generate an aortic output. These profound inhibitory effects of
reperfusion-administered FTY720 on post-ischaemic CO and
work are especially intriguing in the light of the increase in CF
shown to be associated with FTY720 administration (Fig. 6).
These combined observations suggest a direct effect of FTY720
on contractility
per se
.
Since 2.5
µ
M FTY720 elicited such a strong detrimental
effect on functional recovery, we also analysed two additional
functional parameters: heart rate and systolic pressure.
Unexpectedly, FTY720 treatment was not associated with a
significant reduction in heart rate recovery (control: 95.00
±
1.85% vs PreFTY: 56.92
±
18.69% and PostFTY: 60.73
±
19.46%,
n
=
6;
p
=
NS) or systolic pressure recovery (control: 84.79
±
2.69% vs PreFTY: 48.89
±
17.03% and PostFTY: 50.96
±
16.58%,
n
=
6;
p
=
NS).
Control
PreFTY PostFTY
Functional recovery (%)
50
40
30
20
10
0
@
Control
PreFTY PostFTY
Functional recovery (%)
60
50
40
30
20
10
0
@
Control
PreFTY PostFTY
Functional recovery (%)
60
50
40
30
20
10
0
@
@
Fig. 8
The effect of 2.5
μ
M FTY720 on functional recovery following 35 minutes’ regional ischaemia (RI) in terms of (A) aortic output,
(B) cardiac output, and (C) total work.
@
p
<
0.05 vs control,
n
=
6.
A
B
C
Control
PreFTY PostFTY
1
μ
m FTY720
Infarct size (% of area at risk)
70
60
50
40
30
20
10
0
p
=
0.0663
@
Control
PreFTY PostFTY
1
μ
m FTY720
Area at risk (% of total area)
60
50
40
30
20
10
0
Control
PreFTY PostFTY
2.5
μ
m FTY720
Infarct size (% of area at risk)
60
50
40
30
20
10
0
@
@
Control
PreFTY PostFTY
2.5
μ
m FTY720
Area at risk (% of total area)
50
40
30
20
10
0
Fig. 9
Effect of FTY720 on infarct size in hearts exposed to 35 minutes of regional ischaemia. At a dose of 1
μ
M (A), FTY720
reduced infarct size when administered at the onset of reperfusion, while pre-ischaemic treatment seemed to aggravate the
ischaemic injury. At a higher dose of 2.5
μ
M, FTY720 however reduced infarct size (C) irrespective whether it was adminis-
tered prior to ischaemia or during early reperfusion. Area at risk, an indication of the ischaemic intervention experimentally
induced did not differ between any of the groups ((B) and (D)).
@
p
<
0.05 vs control,
n
=
6–8.
A
C
B
D