alpha-Tocopherol Pretreatment Reduces Ischaemia/Reperfusion Injury in Rabbit Skeletal Muscle

Abstract

Summary: Background: Ischaemia/reperfusion (I/R) injury is characterized by the production of oxygen free radicals and the loss of high energy phosphates. α‐Tocopherol (vitamin E) has been reported to play a protective role against free radical damage. Therefore, its i. v. supplementation prior to onset of ischaemia was investigated in an established I/R injury model. Methods: New Zealand white rabbits were subjected to a bilateral hind limb ischaemia/reperfusion of 2.5 h/2 h without any treatment (IR group), whereas in the VE group the vitamin E emulsion Tocovenös® was given i. v. for 10 min in a dose of 3 mg/kg bw. A SHAM group served as a control. Intramuscular phosphocreatine (PCr) and adenosine triphosphate (ATP), muscle interfibre area (MIFA), and microvessel cross‐sectional area (MVCSA) were determined and electron microscopy was performed. Results: In the IR group, PCr decreased by 65 % of the initial level after 2.5 h of ischaemia and a further depletion was noticed after 2 h of reperfusion (20.9 ± 1.1 vs 6.3 ± 3.0 µmol/g wet wt, P < 0.01). By contrast, ATP remained stable after ischaemia but dropped dramatically after reperfusion (6.5 ± 0.2 vs 2.1 ± 8.0 µmol/g wet wt, P < 0.05). In the VE group, PCr and ATP did not differ significantly from the SHAM group at the end of reperfusion. Consequently, ATP in this group was significantly higher as compared with the IR group (4.9 ± 0.9 vs 2.1 ± 8.0 µmol/g wet wt, P < 0.05). In the IR group, prominent interstitial oedema formation was found after reperfusion expressed by the increase in MIFA (28.2 ± 4.2 vs 13.7 ± 1.6 %, P < 0.05). In the VE group, only a moderate interstitial oedema was found (18.7 ± 3.4 %). Severe microvessel constriction was observed after reperfusion in both experimental groups. Electron microscopy revealed fewer tissue changes in the VE group as compared with the IR group. Conclusions: α‐Tocopherol pretreatment had a protective effect on I/R injury in skeletal muscle expressed by recovery of PCr after reperfusion and by prevention of ATP depletion. Although microvascular constriction could not be prevented, antioxidative treatment reduced interstitial oedema and preserved muscle morphology.

Combined Enzymatic and Antioxidative Treatment Reduces Ischemia-Reperfusion Injury in Rabbit Skeletal Muscle

“…Moreover, the antioxidant potential of quercetin has been shown to be more effective than that of vitamin E or ascorbate [43]. These observations can be confirmed by our earlier studies on I/R injury of skeletal muscle [13,14].…”

“…Supplementation of NO or its precursor L-arginine aims at prevention of derangement of cNOS and excessive O 2 Ϫ production [4,11], whereas radical scavengers such as antioxidative vitamins [12,13] and bioflavonoids [14,15] annihilate OFR. A combination of both strategies was reported to have an additional beneficial effect on I/R injury [16].…”