TY - JOUR
T1 - Limitations of ischemic tolerance in oxidative skeletal muscle
T2 - Perfusion vs tissue protection
AU - Badhwar, Amit
AU - Dungey, Alison A.
AU - Harris, Kenneth A.
AU - Scott, Jeremy A.
AU - McCarter, Sarah D.
AU - Scott, Jeffery R.
AU - Forbes, Thomas L.
AU - Potter, Richard F.
N1 - Funding Information:
This work was supported in part by grants from the Physicians Services Incorporated of Ontario, Medical Research Council of Canada, London Health Science Centre Research Fund, and a Medical Research Council of Canada Studentship (J.A. Scott). We acknowledge Michael Carson for invaluable technical assistance in the undertaking of the experiments used in this study.
PY - 2003/1
Y1 - 2003/1
N2 - Objective. This study determined if ischemic tolerance occurs in oxidative skeletal muscle following a severe ischemia/reperfusion (I/R) insult and if such protection involves the induction of nitric oxide synthase (NOS). Methods. The soleus muscle of male Wistar rats (250-350 g) was preconditioned (PC + I/R) using five cycles of ischemia (10 min) and reperfusion (10 min) or had no PC (I/R) and 24 h later 2 h no-flow ischemia was induced. Calcium dependent (cNOS) and independent (iNOS) NOS activities were determined from PC (n = 5), or sham (n = 5) and the role of iNOS was tested by application of aminoguanidine (AMG) (100 μM; n = 4) to the muscle bath. Direct measures of the number of perfused capillaries (Npc; #/mm) during 90-min reperfusion were obtained using intravital microscopy. Tissue injury was estimated using the fluorescent vital dyes ethidium bromide (E; labels injured cells) and bisbenzimide (B; labels all cells) and expressed as the ratio E/B. Results. PC prevented microvascular flow deficits (Npc:I/R = 23.4 ± 1.3 vs PC + I/R = 29.9 ± 1.1) and resulted in a modest, but significant reduction (21%) in tissue injury (I/R = 0.82 ± 0.03 vs PC + I/R = 0.64 ± 0.04). PC led to a nine fold increase in iNOS activity, but decreased cNOS activity by 94% compared to sham. AMG prevented the parenchymal protection following PC, but had no effect on microvascular perfusion. Conclusion. Ischemic tolerance, 24 h following PC, preserved microvascular perfusion, but only modestly improved tissue viability in the soleus muscle.
AB - Objective. This study determined if ischemic tolerance occurs in oxidative skeletal muscle following a severe ischemia/reperfusion (I/R) insult and if such protection involves the induction of nitric oxide synthase (NOS). Methods. The soleus muscle of male Wistar rats (250-350 g) was preconditioned (PC + I/R) using five cycles of ischemia (10 min) and reperfusion (10 min) or had no PC (I/R) and 24 h later 2 h no-flow ischemia was induced. Calcium dependent (cNOS) and independent (iNOS) NOS activities were determined from PC (n = 5), or sham (n = 5) and the role of iNOS was tested by application of aminoguanidine (AMG) (100 μM; n = 4) to the muscle bath. Direct measures of the number of perfused capillaries (Npc; #/mm) during 90-min reperfusion were obtained using intravital microscopy. Tissue injury was estimated using the fluorescent vital dyes ethidium bromide (E; labels injured cells) and bisbenzimide (B; labels all cells) and expressed as the ratio E/B. Results. PC prevented microvascular flow deficits (Npc:I/R = 23.4 ± 1.3 vs PC + I/R = 29.9 ± 1.1) and resulted in a modest, but significant reduction (21%) in tissue injury (I/R = 0.82 ± 0.03 vs PC + I/R = 0.64 ± 0.04). PC led to a nine fold increase in iNOS activity, but decreased cNOS activity by 94% compared to sham. AMG prevented the parenchymal protection following PC, but had no effect on microvascular perfusion. Conclusion. Ischemic tolerance, 24 h following PC, preserved microvascular perfusion, but only modestly improved tissue viability in the soleus muscle.
UR - http://www.scopus.com/inward/record.url?scp=0037288596&partnerID=8YFLogxK
U2 - 10.1016/S0022-4804(02)00044-6
DO - 10.1016/S0022-4804(02)00044-6
M3 - Article
C2 - 12591237
AN - SCOPUS:0037288596
SN - 0022-4804
VL - 109
SP - 62
EP - 67
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 1
ER -