cGMP is decreased after acute ischemia in chronically ischemic canine limbs.
BACKGROUND
A chronic partially ischemic state may alter the skeletal muscle response to acute ischemia and free radical formation.


METHODS
In order to investigate this hypothesis, a chronic ischemic state was established by ligating the right femoral artery of four mongrel dogs. ABIs were decreased from 1.05 +/- 0.25 preligation to 0.54 +/- 0.14 at 6 weeks (P = 0.04). At the end of 8 weeks, the hindlimb was subjected to 3 h of acute ischemia by clamping the iliac artery. The clamp was then released for 2 h of reperfusion. Plasma samples from the right iliac vein were taken during the ischemia-reperfusion period for analysis of cGMP. Tibialis anterior biopsies for Western analysis of eNOS and iNOS were taken upon completion of reperfusion. Comparisons to control dogs subjected to the acute ischemia and reperfusion without prior femoral artery ligation were made.


RESULTS
cGMP levels were increased in the controls at 3 h of ischemia (3539 +/- 350) and 2 h of reperfusion (2880 +/- 269). The chronic ischemia group did not develop a corresponding increase in cGMP at 3 h of ischemia (2762 +/- 251) or after 2 h of reperfusion (2102 +/- 130). Western analysis of eNOS and iNOS revealed similar levels in both groups. Analysis of eNOS revealed 0.6429 +/- 0.086 and 0.5916 +/- 0.072 (densitometric units +/- SEM) for study and control dogs, respectively. Analysis of iNOS revealed 0.3401 +/- 0.067 and 0.2475 +/- 0.066 for study and control dogs, respectively.


CONCLUSIONS
Previous ligation of the femoral artery resulting in chronic partial ischemia in this model demonstrated no increase in cGMP following acute ischemia that was not accompanied by a change in eNOS or iNOS levels. Nitric oxide activity is reflected by cGMP levels, which may increase in response to free radicals in the acute setting of complete ischemia.
Eginton
M T
MT
Department of Vascular Surgery, Medical College of Wisconsin, and the, Milwaukee, Wisconsin.
Mays
B W
BW
Kelley
H
H
Hower
C D
CD
Dassow
M
M
Cambria
R A
RA
Towne
J B
JB
Seabrook
G R
GR
Freischlag
J A
JA
D000208:Acute Disease; D000818:Animals; D015153:Blotting, Western; D002908:Chronic Disease; D006152:Cyclic GMP / Q000097:blood* / Q000378:metabolism; D003720:Densitometry; D004285:Dogs; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012016:Reference Values; D013997:Time Factors
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D006152:Cyclic GMP