RESUMEN
The ability of skeletal muscle to recover high energy phosphate compounds in response to pretreatment with vitamin E was investigated in a rabbit hindlimb ischemia/reperfusion model (2. 5 h/2 h). High energy metabolites were measured in the adductor magnus muscle of untreated animals and compared to the treatment group (all rac-alpha-tocopheryl acetate, 3 mg/kg body weight, supplemented i.v. before the onset of ischemia). Phosphocreatine (PCr) levels decreased after ischemia more than 65% in untreated and treatment groups, but tended to recover in treatment group after reperfusion. Adenosine triphosphate (ATP) values decreased by 50% of basal level after reperfusion in the untreated group, whereas alpha-tocopherol pretreatment prevented ATP depletion.
Asunto(s)
Metabolismo Energético/efectos de los fármacos , Isquemia/metabolismo , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Reperfusión , Vitamina E/análogos & derivados , alfa-Tocoferol/análogos & derivados , Adenosina Trifosfato/metabolismo , Animales , Miembro Posterior , Masculino , Músculo Esquelético/efectos de los fármacos , Fosfocreatina/metabolismo , Conejos , Tocoferoles , Vitamina E/administración & dosificación , Vitamina E/sangre , Vitamina E/farmacologíaRESUMEN
This study investigated the effect of a multivitamin preparation administered before ischemia or before reperfusion, on ischemia-reperfusion (I/R) injury of skeletal muscle. An in vivo hindlimb skeletal muscle I/R model (2.5 h/2 h) was carried out on adult New Zealand white rabbits. Animals used as I/R models were treated with a multivitamin preparation (0.4 ml/kg bw i.v. bolus), containing alpha-tocopherol, ascorbic acid, retinol, vitamin B complex, 30 min before starting ischemia (group MV(isc)) or 5 min before reperfusion (group MV(rep)) and compared to animals with I/R without treatment (group IR) and sham operated animals (group SHAM). Interstitial edema (muscle interfiber area, %MIFA) and changes in microvessel size (microvessel cross sectional area, MVCSA, microm(2)) were measured. Plasma malondialdehyde concentrations (MDA-TBA, nmol/ml) served as a measure of lipid peroxidation. After 2h of reperfusion, ischemia-reperfusion developed a significant microvascular constriction and an interstitial edema (IR, vs SHAM;P<< 0.01), but administration of antioxidative vitamins before the onset of ischemia reduced microvascular constriction and edema formation (P<< 0.05 vs IR group). In a similar manner, administration of vitamins before ischemia lowered plasma MDA-TBA levels as compared to the untreated group during reperfusion (p<< 0. 05). In animals treated with vitamins before reperfusion, the biochemical and morphological results showed no differences as compared to the untreated group. Antioxidative treatment with a multivitamin preparation exerted a beneficial effect on I/R injury of skeletal muscle when the aforementioned vitamins were administered before ischemia but not before the onset of reperfusion.
Asunto(s)
Músculo Esquelético/efectos de los fármacos , Daño por Reperfusión/prevención & control , Vitaminas/uso terapéutico , Animales , Edema/prevención & control , Isquemia/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/sangre , Músculo Esquelético/ultraestructura , Conejos , Daño por Reperfusión/patología , Vasoconstricción/efectos de los fármacos , Vitaminas/administración & dosificaciónRESUMEN
We tested whether treatment with exogenous L-arginine, the precursor of nitric oxide (NO), could protect the skeletal muscle from ischemia/reperfusion (I/R) injury. A rabbit hindlimb I/R model (2.5 h ischemia/2 h reperfusion) was used. Morphological changes were elucidated by morphometry. Plasma concentrations of malondialdehyde (pMDA), as well as L-arginine and L-citrulline content in the plasma and skeletal muscle were measured. I/R injury in the skeletal muscle was manifested by development of prominent interstitial edema (fraction of interfiber area was 26.23% vs 15.09% in sham operated control, p < .005) and severe microvascular constriction (capillary area was 11.41 microns2 vs 16.92 in control, p <.005). These changes were accompanied by increased pMDA levels, indicating a process of lipid peroxidation in the cell membranes. L-arginine treatment (4 mg/kg/min intravenously, for 1 h, infusion initiated 30 min before reperfusion) caused an intracellular accumulation of this amino acid in the SM. Intracellular concentrations of L-citrulline increased (201.0 mumol/dm3 after reperfusion vs 176.0 before ischemia onset, p < .005), suggesting stimulated endogenous NO synthesis. L-arginine treatment protected capillary constriction (capillary area was 17.64 microns2 vs 11.41 in the untreated animals, p < .0005) and reduced interstitial edema after reperfusion (fraction of interfiber area was 17.80% vs 26.23 in untreated animals, p < 0.005). The protective effect of L-arginine treatment on I/R injury of SM may be related to its ability to prevent microvascular constriction and reduce permeability disorders by the stimulation of endogenous NO production.
Asunto(s)
Arginina/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Animales , Arginina/metabolismo , Miembro Posterior/irrigación sanguínea , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Conejos , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patologíaRESUMEN
BACKGROUND: I.V. infusions of vitamin E emulsion (all-rac-alpha-tocopherol) may reduce ischaemia-reperfusion injury after elective cardiac surgery. METHODS: Forty patients participated in a prospective, double-blind, placebo-controlled, randomized trial, receiving either placebo or four doses (270 mg each) of all-rac-alpha-tocopherol between 16 h before and 48 h after surgery. We determined plasma concentrations of vitamin E, vitamin C, malondialdehyde, creatine kinase, troponin I and interleukin 6 and other measures of clinical outcome. RESULTS: Infusion of vitamin E caused normalization of vitamin E plasma concentrations during and after surgery, but had no effect on the early increase in malondialdehyde concentration or the decreases in antioxidative capacity and the water-soluble antioxidant vitamin C. CONCLUSIONS: Normalization of plasma vitamin E concentrations with parenteral vitamin E emulsion does not affect biochemical markers of myocardial injury and does not affect clinical outcome after cardiac surgery.
Asunto(s)
Antioxidantes/administración & dosificación , Daño por Reperfusión Miocárdica/prevención & control , Estrés Oxidativo/efectos de los fármacos , Vitamina E/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Ácido Ascórbico/sangre , Procedimientos Quirúrgicos Cardíacos , Método Doble Ciego , Femenino , Humanos , Infusiones Intravenosas , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Daño por Reperfusión Miocárdica/sangre , Daño por Reperfusión Miocárdica/fisiopatología , Estudios Prospectivos , Vitamina E/sangreRESUMEN
BACKGROUND: Constitutive nitric oxide synthase (cNOS) may produce species involved in ischemia/reperfusion (I/R) injury: NO in the presence of sufficient L-arginine and superoxide at the diminished local L-arginine concentration accompanying I/R. METHODS AND RESULTS: During hindlimb I/R (2.5 hours/2 hours), in vivo NO was continuously monitored (porphyrinic sensor), and L-arginine (chromatography), superoxide (chemiluminescence), and I/R injury were measured intermittently. Normal rabbits were compared with those infused with L-arginine 4 mg x kg(-1) x min(-1) for 1 hour. In both groups, approximately 6 minutes into ischemia, a rapid increase of NO from its basal level of 50+/-17 to 115+/-7 nmol/L, P<.005 (microvessels), was observed. In animals not treated with L-arginine, NO dropped below basal to undetectable levels (<1 nmol/L) during reperfusion. In animals treated with L-arginine, the decrease of NO was slower, such that substantial amounts accumulated during reperfusion (25 nmol/L). Decreased NO during I/R was accompanied by increased superoxide, which during reperfusion reached 50 nmol/L without or 23 nmol/L with L-arginine treatment. Calcium-dependent cNOS was a major source of superoxide release (inhibited 70% by L-NMMA and 25% by L-NAME) during I/R. CONCLUSIONS: L-Arginine treatment decreased superoxide generation by cNOS while increasing NO accumulation, leading to protection from constriction (microvessel area, 17.77+/-0.95 versus 11.66+/-2.21 microm2 untreated, P<.0005) and reduction of edema after reperfusion (interfiber area, 16.56+/-2.13% versus 27.68+/-7.70% untreated, P<.005).