Effect of Cold on Ischemia-Reperfusion-Induced Microvascular Permeability Increase in Cat Skeletal Muscle

Neutrophils accumulate in skeletal muscle subjected to ischemia-reperfusion and appear to contribute to reperfusion-induced microvascular dysfunction. The overall objective of this study was to assess the role of the neutrophilic hydrolytic enzyme elastase in ischemia-reperfusion-induced granulocyte accumulation and microvascular dysfunction in skeletal muscle. We examined the effect of three structurally unrelated elastase inhibitors [eglin C, MeOsuc-Ala-Ala-Val-CH2Cl (MAAPV), or L-658758], administered at the onset of reperfusion, on neutrophil content and the increase in microvascular permeability induced by 4 h of ischemia and 0.5 h of reperfusion in the isolated canine gracilis muscle. Changes in vascular permeability (1 - sigma) were assessed by determining the solvent drag reflection coefficient for total plasma proteins (sigma) in the following groups: 1) 4.5 h of continuous perfusion (nonischemic), 2) ischemia-reperfusion alone, 3) ischemia-reperfusion + eglin C, 4) ischemia-reperfusion + MAAPV, and 5) ischemia-reperfusion + L-658758. Muscle neutrophil content was monitored by assessing tissue myeloperoxidase (MPO) activity in biopsies obtained at the end of the experiments. In nonischemic muscles, 1 - sigma and MPO activity averaged 0.13 +/- 0.03 and 0.7 +/- 0.2 units/g wet wt, respectively. Ischemia-reperfusion was associated with marked increases in microvascular permeability (1 - sigma = 0.39 +/- 0.02) and muscle MPO activity (8.9 +/- 1.2 units/g wet wt) that were attenuated by eglin C, MAAPV, and L-658758 (1 - sigma = 0.21 +/- 0.01, 0.22 +/- 0.02, and 0.21 +/- 0.03, respectively; MPO activity = 2.7 +/- 0.4, 2.1 +/- 0.8, and 2.8 +/- 1.8 units/g wet wt, respectively). These results suggest that granulocyte accumulation in postischemic skeletal muscle is dependent on the release of elastase from activated phagocytic cells. Moreover, neutrophilic elastase appears to play a major role in reperfusion-induced increases in microvascular permeability in skeletal muscle.

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Role of nitric oxide in lung ischemia and reperfusion injury

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.5.h1970 ◽

1996 ◽

Vol 271 (5) ◽

pp. H1970-H1977 ◽

Cited By ~ 7

Author(s):

T. M. Moore ◽

P. L. Khimenko ◽

P. S. Wilson ◽

A. E. Taylor

Keyword(s):

Nitric Oxide ◽

Methyl Ester ◽

Ischemia Reperfusion ◽

Microvascular Permeability ◽

Protective Effects ◽

Ischemia And Reperfusion Injury ◽

Microvascular Damage ◽

Nos Inhibitors ◽

Permeability Increase ◽

Isolated Lungs

We studied the effects of nitric oxide synthase (NOS) inhibitors and nitric oxide (NO.) donors on ischemia-reperfusion (I/R)-induced microvascular permeability increase in isolated buffer-perfused rat lungs. Microvascular permeability (Kf,c) was significantly increased in lungs subjected to 45 min of ischemia followed by 30 min of reperfusion. Lungs that were pretreated with 300 and 600 microM N omega-nitro-L-arginine methyl ester (L-NAME), 1, 300, and 600 microM NG-monomethyl-L-arginine (L-NMMA), or 600 microM L-N6-(1-iminoethyl) ornithine (L-NIO) still showed significant increases in Kf,c after I/R. Lungs that were pretreated with 5 mM L-NAME or 5 mM N omega-nitro-D-arginine methyl ester showed no increase in Kf,c after I/R. However, both compounds at these concentrations produced significant decreases in perfusate pH. The decreased pH was responsible for the protective effects, since lungs pretreated with 5 mM L-NAME and supplemented with NaHCO3 to prevent the perfusate pH decrease still showed a significant elevation in Kf,c after I/R. In additional experiments, NO.donors were administered to isolated lungs at the onset of reperfusion. Spermine-NO (100 microM) and S-nitroso-N-acetylpenacillamine (300 microM) both prevented the increase in Kf,c associated with I/R. We conclude from these studies that peroxynitrite does not mediate microvascular permeability increase after lung I/R injury in this model, and exogenous NO. does not exacerbate injury; rather, it prevents microvascular damage.

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Effects ofS-nitroso-N-acetylcysteine on contractile function of reperfused skeletal muscle

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.274.3.r822 ◽

1998 ◽

Vol 274 (3) ◽

pp. R822-R829 ◽

Cited By ~ 8

Author(s):

Long-En Chen ◽

Anthony V. Seaber ◽

Rima M. Nasser ◽

Jonathan S. Stamler ◽

James R. Urbaniak

Keyword(s):

Skeletal Muscle ◽

Reperfusion Injury ◽

Contractile Function ◽

Ischemia Reperfusion ◽

Protective Role ◽

Control Group ◽

Group Vi ◽

No Donor ◽

Early Reperfusion ◽

Reconstructive Operations

The ultimate goal of replantation and microsurgical reconstructive operations is to regain or improve impaired function of the tissue. However, the data related to the influence of NO on tissue function are limited. This study evaluated the effects of the NO donor S-nitroso- N-acetylcysteine (SNAC) on contractile function of skeletal muscle during reperfusion. Forty-nine rats were divided into six groups. The extensor digitorum longus (EDL) muscles in groups I and II were not subjected to ischemia-reperfusion but were treated with a low (100 nmol/min) or high (1 μmol/min) dose of SNAC. In groups III- V, the EDL underwent 3 h of ischemia and 3 h of reperfusion and was also treated with low (100 nmol/min) or high doses (1 or 5 μmol/min) of SNAC. Group VI was a phosphate-buffered saline (PBS)-treated control group. Twenty additional animals were used to document systemic effects of SNAC and PBS only. SNAC or PBS was infused for 6.5 h, beginning 30 min before ischemia and continuing throughout the duration of reperfusion. Contractile testing compared the maximal twitch force, isometric tetanic contractile forces, fatigue, and fatigue half time of the experimental EDL and the contralateral nontreated EDL. The findings indicate that 1) SNAC does not influence contractile function of EDL muscle not subjected to ischemia-reperfusion, 2) SNAC significantly protects the contractile function of ischemic skeletal muscle against reperfusion injury in the early reperfusion period, and 3) the protective role of SNAC is critically dosage dependent; protection is lost at higher doses. The conclusion from this study is that supplementation with exogenous NO exerts a protective effect on the tissue against reperfusion injury.

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