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VALUE AND LIMITATIONS OF NITRIC OXIDE IN
SKELETAL MUSCLE REPERFUSION INJURY
Serviço: Maiomonides medical Center
- Brooklin - NY
Autores: Elke Lorensen; Robert Pollina; Mark Gennaro &
Enrico Ascer
Since a post ischemic reduction in endothelium dependent
relaxation has been demonstrated in coronary and intact hind limb vasculature
it is believed that nitric oxide (NO) may aiso have a protective role
in skeletal muscle ischemia/ reperfusion injury. Conversely, NO has been
shown to be detrimental in sepsis by causing severe vaso dilatation. To
investigate lhe role of NO on the development of skeletal muscle reperfusion
injury, we studied the effects of sodium nitroprusside (NO donor) in a
standard canine gracilis model. Twelve adult mongrel dogs underwent bilateral
isolated gracilis muscle preparation subjected to 6 hours of ischemia
and 48 hours of reperfusion. One muscle served as a control, while the
experimental side received intraarterial sodium nitroprusside (lOmcg/kg/min)
15 minutes prior to ischemia, Group l PRÉ (n=5), or 15 minutes
prior to reperfusion, Group 2 POST (n=6). After 48 hours of reperfusion,
gracilis blood flow was documented by Doppler and gracilis muscle function
was evaluated by recording isometric contractíle force in response
to stímulation with 200 msec tetani at 100 Hz and an amplitude
of80 volts. The muscles were harvested, weighed, and the extent of muscle
necrosis determined by nitroblue tetrazolium staining, sectioning and
computerized planimetry. Results expressed as mean ± SEM are as
follows:
| Function (per gm) |
Weight Gain (%) |
Necrosis (%) |
|
| Control |
6.9±3.9g |
30.2 ±13.5 |
20.1 ± 8.1 |
| Group l PRE |
1.7±1.6g* |
64.7 ± 14.5** |
74.6 ± 8.2** |
| Group 2 POST |
6.8 ± 4.0g |
27.0 ± 14.2 |
21.2 ± 8.5 |
* p < 0.05 vs control and Group 2
POST ** p < 0.01 vs. control and Group 2 POST
Administration of sodium nitroprusside prior to reperfusion
of ischemic skeletal muscle in this model did not attenuate the degree
of muscle injury as measured by function, necrosis and edema. When given
before the onset of ischemia, sodium nitroprusside increased the extent
of muscle injury. These data suggest that anincreasein NO in the period
prior to reperfusion does not protect against skeletal muscle reperfusion
injury. Furthermore, NO exerts a deleterious effect when increased prior
to ischemia in this model probably by its ability to increase oxygen free
radical production.
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